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  • Organic Chemistry  (68,935)
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  • Cat
  • Insulin
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  • 1
    Electronic Resource
    Electronic Resource
    Short-term treatment with GLP-1 increases pulsatile insulin secretion in Type II diabetes with no effect on orderliness (2000)
    Springer
    Diabetologia 43 (2000), S. 583-588 
    Details
    ISSN: 1432-0428
    Keywords: Keywords GLP-1 ; Insulin ; pulsatility ; insulin secretion ; time series ; Type II diabetes ; human.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Aims/hypothesis. The enteric incretin hormone, glucagon-like peptide-1 (GLP-1), is a potent insulin secretagogue in healthy humans and patients with Type II (non-insulin-dependent) diabetes mellitus. In this study we assessed the impact of short-term GLP-1 infusion on pulsatile insulin secretion in Type II diabetic patients. Methods. Type II diabetic patients (n = 8) were studied in a randomised cross-over design. Plasma insulin concentration time series were obtained during basal conditions and during infusion with saline or GLP-1 (1.2 pmol/l · kg–1· min–1) on 2 separate days. Plasma glucose was clamped at the initial concentration by a variable glucose infusion. Serum insulin concentration time series were evaluated by deconvolution analysis, autocorrelation analysis, spectral analysis and approximate entropy. Results. Serum insulin concentrations increased by approximately 100 % during GLP-1 infusion. Pulsatile insulin secretion was increased as measured by secretory burst mass (19.3 ± 3.8 vs 53.0 ± 10.7 pmol/l/pulse, p = 0.02) and secretory burst amplitude (7.7 ± 1.5 vs 21.1 ± 4.3 pmol/l/min, p = 0.02). A similar increase in basal insulin secretion was observed (3.6 ± 0.9 vs 10.2 ± 2.2 pmol/l/min, p = 0.004) with no changes in the fraction of insulin delivered in pulses (0.50 ± 0.06 vs 0.49 ± 0.02, p = 0.84). Regularity of secretion was unchanged as measured by spectral analysis (normalised spectral power: 5.9 ± 0.6 vs 6.3 ± 0.8, p = 0.86), autocorrelation analysis (autocorrelation coefficient: 0.19 ± 0.04 vs 0.18 ± 0.05, p = 0.66) and the approximate entropy statistic (1.48 ± 0.02 vs 1.51 ± 0.02, p = 0.86). Conclusion/interpretation. Short-term stimulation with GLP-1 jointly increases pulsatile and basal insulin secretion, maintaining but not improving system regularity in Type II diabetic patients. [Diabetologia (2000) 43: 583–588]
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001250051347
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  • 2
    Electronic Resource
    Electronic Resource
    Pharmacodynamics and pharmacokinetics of intravenous glibenclamide in Caucasian and Chinese patients with type-2 diabetes (2000)
    Springer
    European journal of clinical pharmacology 55 (2000), S. 721-727 
    Details
    ISSN: 1432-1041
    Keywords: Key words Glibenclamide ; Insulin ; Proinsulin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Objective: We analysed the kinetics and effects of glibenclamide (Gb) on glucose, insulin and proinsulin secretion in two ethnic groups (10 in each) of type-2 diabetic patients, one of Caucasian, the other of Chinese origin. Background: Diabetes mellitus type 2 is a global disease affecting all ethnic groups. There are ethnic differences in both the prevalence and metabolic characteristics of the disease. Important interethnic pharmacodynamic and pharmacokinetic differences have been reported for several drugs. With few exceptions, detailed studies on sulphonylurea are lacking. Material and methods: The patients were studied on two occasions when either no Gb (control) or 1.25 mg Gb was administered i.v., immediately before the administration of a 75-g oral glucose tolerance test. Concentrations of insulin and proinsulin were determined by means of radioimmunoassay without cross-reactivities. Gb concentration was determined using high-performance liquid chromatography. Pharmacodynamic results were calculated using net areas under the curves, with basal values set as zero. A P value less than 0.05 was considered significant. Results: When glucose was administered orally without Gb, Chinese patients had higher plasma glucose increases at 10 min (7.6 mmol/l × min vs 2.6 mmol/l × min) and higher increases of plasma insulin levels than Caucasians at both 10 min (198 pmol/l × min vs 54 pmol/l × min) and 30 min (2286 pmol/l × min vs 1198 pmol/l × min). When Gb was administered, the plasma glucose increases were reduced, and the increases of serum insulin and proinsulin levels were greater in both ethnic groups. Compared with the basal values (−1 min), proinsulin/insulin ratios (RPI) were lowest at 10–30 min, followed by an increase. Chinese patients had higher increases of serum insulin levels at 10 min (1109 pmol/l × min vs 550 pmol/l × min) and a lower RPI at 30 min (6.0% vs 7.6%) and 240 min (15.0% vs 21.0%) relative to Caucasians. Serum Gb data were best fitted to a biexponential i.v. model. There were no interethnic differences in any of the pharmacokinetic parameters. Conclusion: In summary, following oral glucose administration without Gb, Chinese type-2 diabetic patients had higher plasma insulin levels but also higher plasma glucose levels during the first 10 min, which might reflect reduced insulin sensitivity or more rapid glucose absorption. Gb augmented glucose-induced release of both insulin and proinsulin in both ethnic groups; the effect on insulin secretion was more pronounced. In conclusion, minor pharmacodynamic but no pharmacokinetic differences were found between the two groups. It seems appropriate to employ the same dosage principles when using Gb in Caucasians and Chinese.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002280050004
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  • 3
    Electronic Resource
    Electronic Resource
    Activity of respiratory laryngeal motoneurons during fictive coughing and swallowing (2000)
    Springer
    Experimental brain research 130 (2000), S. 27-34 
    Details
    ISSN: 1432-1106
    Keywords: Key words Nucleus ambiguus ; Laryngeal motoneurons ; Superior laryngeal nerve ; Coughing and swallowing ; Cat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Membrane potential changes and discharges from 28 laryngeal motoneurons were recorded intracellularly in the caudal nucleus ambiguus of decerebrate, paralyzed and ventilated cats. Electrical activities were recorded from 17 expiratory laryngeal motoneurons (ELMs) with maximal depolarizing membrane potential in early expiration, and from 11 inspiratory laryngeal motoneurons (ILMs) with maximal depolarizing membrane potential in inspiration. Activities during breathing were compared with those observed during fictive coughing and swallowing evoked by electrical stimulation of the superior laryngeal nerves. These non-respiratory behaviors were evidenced in paralyzed animals by characteristic discharge patterns of the phrenic, abdominal nerves and pharyngeal branch of the vagus nerve. We recorded the activity of 11 ELMs and 5 ILMs during coughing in which ELMs, but not ILMs, exhibited increased membrane depolarization and discharge frequencies. Membrane depolarization and discharge frequencies of all ELMs were also significantly increased during swallowing. In addition, membrane depolarization of most ELMs (15/17) was preceded by a short-lasting hyperpolarization due to chloride-dependent inhibitory mechanisms occurring at the onset of swallowing. Out of 10 ILMs tested during swallowing, 7 exhibited membrane depolarization, preceded in 5 cases by a short-lasting hyperpolarization. Discharge frequencies of ILMs were significantly reduced during swallowing. The same pattern of phasic activities of ILMs and ELMs was observed during coughing and breathing, suggesting the involvement of similar excitatory pathways in both behaviors. These results imply that the duration of activation and the discharge frequency of neurons of the central generator for breathing that drive laryngeal motoneurons are enhanced during coughing. During swallowing, in addition to central excitatory mechanisms, laryngeal motoneurons are subjected to an initial inhibition of unknown origin. This inhibition probably contributes to the temporal organization of the swallowing motor sequence.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002210050003
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  • 4
    Electronic Resource
    Electronic Resource
    Growth, puberty and hypothalamic-pituitary function in children with suprasellar arachnoid cyst (2000)
    Springer
    European journal of pediatrics 159 (2000), S. 348-355 
    Details
    ISSN: 1432-1076
    Keywords: Key words Arachnoid cyst ; Growth ; Growth hormone deficiency ; Growth hormone treatment ; Insulin ; Leptin ; Puberty ; Precocious puberty
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A suprasellar arachnoid cyst may cause disorders of growth, puberty and hypothalamic-pituitary function, due to the proximity of the cyst to the hypothalamic-pituitary area. A total of 30 patients (17 boys) with cyst diagnosed at 4.3 ± 1 years were routinely evaluated at 5.4 ± 1 years; 24 of them had one or multiple cyst derivations. Some 23 cases had an abnormal height, weight or puberty: short (〈−2SD, 5 cases) or tall (〉2SD, 10 cases) stature, overweight (body mass index, BMI, 〉2SD, 6 cases), central precocious puberty (10 cases) and/or no progression of pubertal development (3 cases). The growth hormone (GH) peaks after pharmacological stimulation test were low (〈10 μg/l) in 16 patients, confirmed by a second evaluation in 8/11 of them. The plasma free thyroxine was low in five patients, prolactin was high in two and the cortisol and concomitant plasma and urinary osmolalities were normal. BMI was correlated negatively with the GH peaks (r=−0.37, P 〈 0.01) and positively with the plasma leptin concentrations (r=0.55, P 〈 0.01). The plasma fasting insulin concentrations were also correlated negatively with the GH peaks (r=−0.55, P 〈 0.02) and positively with the plasma insulin-like growth factor I concentrations (r=0.64, P 〈 0.002). The adult height (12 cases) was at 4SD in 1 and 〈−2SD in 4 patients, two of whom had precocious puberty untreated with gonadotropin releasing hormone (GnRH) analogue, and two had untreated GH deficiency. The adult height of those treated was normal. One girl had primary amenorrhoea and two boys had low plasma testosterone, despite a normal gonadotropin response to a GnRH test. Conclusion Suprasellar arachnoid cysts may cause deficiencies of growth hormone and thyrotropin, stimulation of the hypothalamic-pituitary-gonadal axis, tall stature and/or overweight. These last two disorders may be due to hyperinsulinism, itself due to suprasellar arachnoid cyst.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004310051285
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  • 5
    Electronic Resource
    Electronic Resource
    Clinical applications of flow cytometry and cell immunophenotyping to companion animals (dog and cat) (2000)
    Springer
    Methods in cell science 22 (2000), S. 199-207 
    Details
    ISSN: 1573-0603
    Keywords: Anto-immune disease ; Cat ; Dog ; Flow cytometry ; Immunodeficiency ; Leishmaniasis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Clinical applications of flow cytometry to certain diseases of the dog and cat are now possible. The utility of such applications for diagnosis, prognosis and follow-up are illustrated here by a number of examples: feline AIDS resulting from FIV infection, Leukocyte Adhesion Deficiency in Irish setters, deep pyoderma in German shepherds, Immune-mediated Thrombocytopenia, canine Systemic Lupus Erythematosus and Leishmaniasis, Leukemia and Lymphoma.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1009800310840
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  • 6
    Electronic Resource
    Electronic Resource
    Postnatal development of thalamocortical projections upon striate and extrastriate visual cortical areas in the cat (2000)
    Springer
    Anatomy and embryology 202 (2000), S. 431-442 
    Details
    ISSN: 1432-0568
    Keywords: Key words Visual system ; Thalamocortical connections ; Postnatal development ; Retrograde axonal tracing ; Fluorescence technique ; Cat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The development of visual thalamocortical projections was analyzed quantitatively by comparing, in cresyl violet-stained brain sections of early postnatal (10–17 days) and adult cats, the cell body dimensions and total cell packing density (CPD) of neuronal populations in different laminae (A, A1 and C) of the dorsal lateral geniculate (dLGN), medial interlaminar nucleus (MIN), and in lateral (LPl), intermediate (LPi) and medial (LPm) subdivisions of the lateral posterior complex. Following injections of different fluorescent tracers (FB, NY, EB, RITC) into cortical visual areas 17/18, posterior medial (PMLS) and posterior lateral (PLLS) lateral suprasylvian and anterior ectosylvian (AEV), the thalamic distribution and densities of retrogradely labeled neurons were analyzed. Projection CPDs and ratios of projection/total CPDs were determined and compared within the different thalamic components in the kitten and adult cat. A significant decrease in total cell packing density was observed in the various thalamic components of the adult cat, varying between 43% and 65%, and a marked increase in mean cell body diameter in the A, A1 and C laminae and MIN from kitten to adult (8.4±1.8 and 11.8±2.8 µm respectively) compared to the LP subnuclei (9.0±1.3 and 9.1±1.5 µm). The ratios of projection/total CPDs decreased significantly for projections upon areas 17/18 stemming from layers A and A1 (20 and 25%, respectively) and from LPi upon both PMLS (34%) and AEV (16%). Thalamocortical projections observed in the kitten from LPi upon areas 17/18 and from the A-laminae upon PMLS were absent in the adult cat. The data indicate that, in comparison to the lateral posterior nucleus, the maturation of neurons within the dLGN and MIN is incomplete with respect to cell body size during the early postnatal period. In addition, the developmental changes observed involve both reductions in the total number of thalamic neurons and a differential loss of cortical projections. The selective elimination of early cortical connections stemming from dorsal lateral geniculate laminae A and A1 and from the intermediate division of the lateral posterior nucleus may occur through a process of axon collateral withdrawal from the expanded cortical sites, thereby giving rise to the adult pattern.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004290000125
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  • 7
    Electronic Resource
    Electronic Resource
    IGF and Insulin Action in the Mammary Gland: Lessons from Transgenic and Knockout Models (2000)
    Springer
    Journal of mammary gland biology and neoplasia 5 (2000), S. 19-30 
    Details
    ISSN: 1573-7039
    Keywords: Insulin ; transgenic ; knockout ; mammary ; IGF
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Transgenic and knockout mice have become valuable experimental systems with which tostudy specific molecular events within the mammary gland of an intact animal. These modelshave provided a wealth of information about the effects of a number of oncogenes and growthfactors. This review focuses on results obtained from the application of transgenic and knockoutmodels to determine the roles of insulin and insulin-like growth factors (IGF)3 in the regulationof mammary gland development, lactation and tumorigenesis. Transgenic models whichoverexpress IGF-I or -II display specific alterations in mammary gland development and an increasedincidence of mammary tumors. Analysis of mammary gland development in knockout micewhich are deficient in IGF-I or the IGF-I receptor supports the conclusion that the IGF systemis important for normal mammary gland development. This review discusses these observationsin detail and attempts to fit them into a larger picture of IGF and insulin action in themammary gland.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1009559014703
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  • 8
    Electronic Resource
    Electronic Resource
    Nitric Oxide, Superoxide, and Peroxynitrite Effects on the Insulin Secretion and Viability of βTC3 Cells (2000)
    Springer
    Annals of biomedical engineering 28 (2000), S. 102-109 
    Details
    ISSN: 1573-9686
    Keywords: Nitric oxide ; Superoxide ; Pancreatic cells ; Insulin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine , Technology
    Notes: Abstract The onset of insulin-dependent diabetes mellitus (IDDM) is often associated with the infiltration of pancreatic cells by macrophages. Upon activation, macrophages release nitric oxide (NO) and superoxide (O 2 - ). These species or their reactive intermediates can be cytoxic, mutagenic, or carcinogenic. Previous studies have reported both positive and negative effects of extracellularly generated NO on insulin secretion and viability of pancreatic cells. Inherent problems of several previous studies assessing the effects of NO on insulin secretion include unsteady state NO concentration exposures and the generation of other potentially damaging species. In this study, these problems were eliminated by using a modified experimental system in which NO delivery was achieved via diffusion across a gas-permeable tube and O 2 - delivery was maintained using an enzymatic reaction. The delivery rates were constant, leading to steady state concentrations of NO and O 2 - in the experimental system. Based on reaction kinetics, a model was developed to predict NO, O 2 - and peroxynitrite ONOO- concentrations during the experiment. This study showed that NO, O 2 - and ONOO- at predicted concentrations as high as 2.8 μM, 0.25 μM, and 0.1 nM, respectively, do not affect the insulin secretion rates of βTC3 pancreatic cells over short times. © 2000 Biomedical Engineering Society. PAC00: 8717-d
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1114/1.258
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  • 9
    Electronic Resource
    Electronic Resource
    Bayesian Identification of a Population Compartmental Model of C-Peptide Kinetics (2000)
    Springer
    Annals of biomedical engineering 28 (2000), S. 812-823 
    Details
    ISSN: 1573-9686
    Keywords: C-peptide ; Population model ; Compartmental model ; Bayes estimation ; Markov chain Monte Carlo ; Insulin ; System identification
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine , Technology
    Notes: Abstract When models are used to measure or predict physiological variables and parameters in a given individual, the experiments needed are often complex and costly. A valuable solution for improving their cost effectiveness is represented by population models. A widely used population model in insulin secretion studies is the one proposed by Van Cauter et al. (Diabetes 41:368–377, 1992), which determines the parameters of the two compartment model of C-peptide kinetics in a given individual from the knowledge of his/her age, sex, body surface area, and health condition (i.e., normal, obese, diabetic). This population model was identified from the data of a large training set (more than 200 subjects) via a deterministic approach. This approach, while sound in terms of providing a point estimate of C-peptide kinetic parameters in a given individual, does not provide a measure of their precision. In this paper, by employing the same training set of Van Cauter et al., we show that the identification of the population model into a Bayesian framework (by using Markov chain Monte Carlo) allows, at the individual level, the estimation of point values of the C-peptide kinetic parameters together with their precision. A successful application of the methodology is illustrated in the estimation of C-peptide kinetic parameters of seven subjects (not belonging to the training set used for the identification of the population model) for which reference values were available thanks to an independent identification experiment. © 2000 Biomedical Engineering Society. PAC00: 8715Aa, 0250Ga, 8714-g
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1114/1.1289459
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  • 10
    Electronic Resource
    Electronic Resource
    Muscle glycogen resynthesis rate in humans after supplementation of drinks containing carbohydrates with low and high molecular masses (2000)
    Springer
    European journal of applied physiology 81 (2000), S. 346-351 
    Details
    ISSN: 1439-6327
    Keywords: Key words Carbohydrate ; Osmolality ; Glycogen ; Insulin ; Glucose
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The rate of muscle glycogen synthesis during 2 and 4 h of recovery after depletion by exercise was studied using two energy equivalent carbohydrate drinks, one containing a polyglucoside with a mean molecular mass of 500 000–700 000 (C drink), and one containing monomers and oligomers of glucose with a mean molecular mass of approximately 500 (G drink). The osmolality was 84 and 350 mosmol · l−1, respectively. A group of 13 healthy well-trained men ingested the drinks after glycogen depleting exercise, one drink at each test occasion. The total amount of carbohydrates consumed was 300 g (4.2 g · kg−1) body mass given as 75 g in 500 ml water immediately after exercise and again 30, 60 ad 90-min post exercise. Blood glucose and insulin concentrations were recorded at rest and every 30 min throughout the 4-h recovery period. Muscle biopsies were obtained at the end of exercise and after 2 and 4 h of recovery. Mean muscle glycogen contents after exercise were 52.9 (SD 27.4) mmol glycosyl units · kg−1 (dry mass) in the C group and 58.3 (SD 35.4) mmol glycosyl units · kg−1 (dry mass) in the G group. Mean glycogen synthesis rate was significantly higher during the initial 2 h for the C drink compared to the G drink: 50.2 (SD 13.7) mmol · kg−1 (dry mass) · h−1 in the C group and 29.9 (SD 12.5) mmol · kg−1 (dry mass) · h−1 in the G group. During the last 2 h the mean synthesis rate was 18.8 (SD 33.3) and 23.3 (SD 22.4) mmol · kg−1 (dry mass) · h−1 in the C and G group, respectively (n.s.). Mean blood glucose and insulin concentrations did not differ between the two drinks. Our data indicted that the osmolality of the carbohydrate drink may influence the rate of resynthesis of glycogen in muscle after its depletion by exercise.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004210050053
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  • 11
    Electronic Resource
    Electronic Resource
    Insulin alters cardiac muscle creatine kinase activity (2000)
    Springer
    Heart and vessels 15 (2000), S. 23-29 
    Details
    ISSN: 1615-2573
    Keywords: Key words Creatine kinase isoenzyme ; Insulin ; Atenolol ; Diabetes mellitus ; Myocardium
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The expression of mRNAs of creatine kinase (CK)-B and CK-M has been show to be affected by insulin, and myocardial CK-MB activity is suppressed in insulin-deficient rats. We investigated the dose-related effect of insulin on CK-MB activity in cardiac and skeletal muscles. Male Wistar rats were divided into three groups: (1) control group, (2) diabetic group, injected with 65 mg/kg streptozotocin for 4 weeks, and (3) atenolol group, administered 30 mg/kg per day atenolol. Each group was further divided into three subgroups and administered either saline, or 20 (Ins 20) or 30 (Ins 30) U/kg per day insulin. After 3 weeks, the isoenzyme activity of CK and lactate dehydrogenase (LDH) in the left ventricle of the heart (LV) and the major pectoral muscle (PM) was measured. Serum insulin increased and plasma glucose decreased in Ins 20 and Ins 30, dose-dependently, in all three groups. Both CK-MB and -BB activity in LV increased dose-dependently with insulin treatment in the control, diabetes, and atenolol groups, although these changes did not occur in skeletal muscles. CK-MB in LV correlated with the serum insulin levels in all rats, while no correlation was found in the skeletal muscles. These findings suggest that insulin possibly regulates the distribution of CK isoenzymes in rat heart muscle, and that the effect of insulin is not due to the sympathetic drive induced by hypoglycemia.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s003800070044
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  • 12
    Electronic Resource
    Electronic Resource
    The autumnal fattening of the long-distance migratory garden warbler (Sylvia borin) is stimulated by intermittent fasting (2000)
    Springer
    Journal of comparative physiology 170 (2000), S. 627-631 
    Details
    ISSN: 1432-136X
    Keywords: Key words Fattening ; Food availability ; Insulin ; Glucagon ; Corticosterone
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract To investigate the proximate influence of a changing food availability on the seasonal fattening of migratory birds, garden warblers (Sylvia borin) following postnuptial moult were food restricted once a week. Body mass, food intake, plasma hormone and metabolite levels were measured and compared to birds which always had ad libitum food access. The food-restricted birds increased their body mass significantly earlier than the controls. The accelerated fattening was initially not accompanied by hyperphagia and may be due to either an increased food utilisation efficiency or a reduced metabolic rate. An increase of basal glucagon and corticosterone and a decrease of insulin levels prior to fattening were not significant, however, they resulted in a significant decrease of the insulin:glucagon ratio. This ratio was also lower in food-restricted birds than in control birds and may account for the difference in the fattening progress. We conclude that seasonal fattening may be stimulated by a catabolic impulse which could be imposed in free-living birds by a decrease of food availability and/or by an increase of energy expenditure. A negative energy balance is hypothesised to be a common proximate factor affecting migratory as well as winter fattening.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s003600000143
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  • 13
    Electronic Resource
    Electronic Resource
    Nutrient-dependent distribution of insulin and glucokinase immunoreactivities in rat pancreatic beta cells (1999)
    Springer
    Virchows Archiv 434 (1999), S. 75-82 
    Details
    ISSN: 1432-2307
    Keywords: Key words Rat ; Pancreatic beta cell ; Insulin ; GLUT2 glucose transporter ; Glucokinase
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Functional heterogeneity among pancreatic beta cells is a characteristic feature of the islets of Langerhans. Under physiological conditions, beta cells in the pancreas of fed rats exhibited heterogeneous immunohistochemical staining for insulin and glucokinase. Intracellular beta cell glucokinase staining was either faint or dense. In the pericapillary space beta cell glucokinase immunoreactivity had a polar orientation, with the highest density in cytoplasmic regions close to the blood vessels. Starvation resulted in a loss of heterogeneity with homogeneous insulin staining in all beta cells of the islets, and this was accompanied by a loss of heterogeneous glucokinase staining. The intracellular polarity of glucokinase staining in contact to blood vessels also disappeared after starvation. Refeeding resulted in the reappearance of intercellular heterogeneity. In dependence on the functional demand, the endocrine pancreas recruited insulin from beta cells according to a well-defined hierarchy, with an initial preferential mobilization of medullary beta cells. In the course of this process intracellular polarity of glucokinase staining reappeared in areas of the beta cell with functional contact to the GLUT2 glucose transporter in the plasma membrane. This can be regarded as the morphological correlate of an activation of the glucose signal recognition apparatus. Interestingly, the study also provides evidence that the changes in glucokinase distribution apparently preceded those in insulin distribution, which is in keeping with the central role of glucokinase as the glucose sensor of the pancreatic beta cell.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004280050308
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  • 14
    Electronic Resource
    Electronic Resource
    Effects of combination of insulin and acarbose compared with insulin and gliclazide in type 2 diabetic patients (1999)
    Springer
    Acta diabetologica 36 (1999), S. 93-97 
    Details
    ISSN: 1432-5233
    Keywords: Key words Type 2 diabetes mellitus ; Insulin ; Acarbose ; Gliclazide
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In this prospective study we aimed to compare insulin plus acarbose with insulin plus gliclazide with respect to their effect on insulin requirement, lipid profiles and body mass index (BMI) while achieving good glycemic control. Forty patients with type 2 diabetes mellitus who were on conventional insulin therapy (subcutaneous insulin therapy consisting of regular and NPH insulin, two times a day) were included in the study. They were randomized to double blind treatment with insulin in combination with gliclazide or acarbose for 6 months. For both groups, acceptable glycemic control was achieved at the end of study period. The mean HbA1c levels decreased from 8.32±0.26 to 7.13±0.18% in acarbose group and 8.6±0.15 to 7.48±0.21% in the gliclazide group. The difference between groups was not significant (P 0.29). In the acarbose group, total cholesterol and LDL concentration decreased significantly while other parameters did not change. In the gliclazide group, HDL levels decreased significantly from 46.6±2.48 mg/dl to 41.3±2.09 mg/dl (P 0.001) BMI increased significantly from 27.60±1.21 kg/m2 to 28.69±1.26 kg/m2. (P 0.003) Total daily insulin dose was not changed in the acarbose group significantly, but increased from 42.6±2.73 to 49.27±3.58 U/day, which was significant in gliclazide group of (P 0.016). In the acarbose group, there were no significant differences between responders and nonresponders with respect to fasting and stimulated C-peptide, HbA1c levels and baseline BMI values. But in the gliclazide group, baseline BMI values were significantly higher in the nonresponding group compared to responders (P 0.02). In conclusion, combination of insulin with acarbose can be a good alternative for type 2 diabetic patients on insulin therapy; seems more beneficial than combination with gliclazide; may have advantage of achieving good glycemic control without increasing insulin dose and BMI; also may have the advantage of providing a decrease in LDL level, which are all important to prevent atherosclerosis.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s005920050151
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  • 15
    Electronic Resource
    Electronic Resource
    Increased glucagon-stimulated insulin secretion of cryopreserved rat islets transplanted into nude mice (1999)
    Springer
    Journal of molecular medicine 77 (1999), S. 107-110 
    Details
    ISSN: 1432-1440
    Keywords: Key words Pancreatic islet transplantation ; Cryopreservation ; Conservation ; Insulin ; Nude mice
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Cryopreservation is the only available technique for long-term storage of pancreatic islets. The freezing/thawing protocol may cause considerable loss of viable islet tissue and impair its function in vivo. The aim of this study was to investigate glucose and insulin levels after transplantation of fresh and cryo/thawed rat islets. Rat pancreatic islets were isolated following intraductal collagenase injection and Ficoll gradient purification. After isolation, islets were cultured for 24 h and then either transplanted or frozen after stepwise addition of DMSO according to Rajotte et al. and stored in liquid nitrogen. After rapid thawing islets were stepwise transferred into RPMI medium and cultured for another 24 h. The recipients were athymic mice with streptozotocine-induced diabetes. Two hundred fresh (n=13) or cryo/thawed (n=15) islets were transplanted beneath the renal capsule. Glucose levels were measured for 14 days and blood samples for insulin determination were obtained 15 min after i.p. glucagon (10 mg/kg) administration on day 14. Glucose levels were normalized (〈9 mmol/l) in all recipients within 3 days since transplantation. On day 14, mean fasting values±SE in fresh and cryo/thawed islet groups were 4.0±0.6 and 4.4±0.4 mmol/l, respectively (P〉0.05). Fasting insulin levels were higher in the cryo/thaw than in the fresh islet group (1.67±0.33 vs 0.57±0.13 ng/ml; P〈0.01). Post-glucagon levels did not differ significantly (1.45±0.24 vs 0.86±0.24 ng/ml; P=0.06). While glucagon significantly increased insulin levels (P〈0.01) in the fresh islet group, no change in insulin levels was observed (P〉0.05) in the cryo/thaw group. Immunohistochemical staining demonstrated fragmentation of viable islet tissue which was more apparent in the cryo/thaw group. We conclude that in a short-term study cryo/thawed rat islets produce higher insulin levels than fresh islets transplanted into nude mice. This may be due to better islet survival or loss of feed-back regulation.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001090050313
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  • 16
    Electronic Resource
    Electronic Resource
    Saccades and multisaccadic gaze shifts are gated by different pontine omnipause neurons in head-fixed cats (1999)
    Springer
    Experimental brain research 125 (1999), S. 287-301 
    Details
    ISSN: 1432-1106
    Keywords: Key words Omnipause neurons ; OPN ; Saccade ; Gaze shift ; Tracking ; Perisaccadic drifts ; Moving target ; Cat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Pontine omnipause neurons (OPNs) have so far been considered as forming a homogeneous group of neurons whose tonic firing stops during the duration of saccades, when the head is immobilized. In cats, they pause for the total duration of gaze shifts, when the head is free to move. In the present study, carried out on alert cats with fixed heads, we present observations made during self-initiated saccades and during tracking of a moving target which show that the OPN population is not homogeneous. Of the 76 OPNs we identified, 39 were found to have characteristics similar to those of previously described neurons, ”saccade” (S-) OPNs: (1) the durations of their pauses were significantly correlated with the durations of saccades; (2) the discharge ceased shortly before saccade onset and resumed before saccade end; (3) visual responses to target motion were excitatory; and (4) during tracking, S-OPNs interrupted the discharge for the duration of saccades and resumed firing during perisaccadic ”drifts”. However, the characteristics of 37 neurons (”complex” (C-) OPNs) were different: (1) the pause duration was not correlated with the duration of self-initiated saccades; (2) time lead of pause onsets relative to saccades was, on average, longer than in the group of S-OPNs, and firing resumed after the saccade end; (3) visual target motion suppressed tonic discharges; and (4) during tracking, firing was interrupted for the total duration of gaze shifts, including not only saccades but also perisaccadic ”drifts”. We conclude that cat OPNs can be subdivided into two main groups. The first comprises neurons whose firing patterns are compatible with gating individual saccades (”saccade” OPNs). The second group consists of ”complex” OPNs whose firing characteristics are appropriate to gate total gaze displacements rather than individual saccades. The function of these neurons may be to disinhibit pontobulbar circuits participating in the generation of saccade sequences and associated perisaccadic drifts.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002210050685
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  • 17
    Electronic Resource
    Electronic Resource
    Gene transfer into insect brain and cell-specific expression of bombyxin gene (1999)
    Springer
    Development genes and evolution 209 (1999), S. 447-450 
    Details
    ISSN: 1432-041X
    Keywords: Key words Bombyxin ; Insulin ; Bombyx mori ; Electroporation ; Cell-specific expression
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract  A transgene reporter consisting of the bombyxin gene promoter and the green fluorescent protein coding region was introduced into intact brains of the silkworm Bombyx mori by in vitro electroporation. After in vitro culture of the brains, the fluorescence derived from the introduced reporter gene was observed in all cases in eight neurosecretory cells that had previously been identified as bombyxin-producing cells (BPCs). Although the fluorescence was not always observed in all cells, it was specific to BPCs, indicating that the reporter was under the control of the bombyxin gene promoter in a BPC-specific manner. Electroporatical introduction of a reporter gene was therefore found to be a suitable method for analyzing cell-specific expression in intact tissues and to be substitute for germ-line transmission of reporters in the transgenic system. Application of this technique enables us to analyze the cell-specific expression of transgene reporters within a few days and treat more than several dozens of the reporters within 1 month, which is difficult to do with the transgenic system.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004270050277
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  • 18
    Electronic Resource
    Electronic Resource
    Saccular and utricular inputs to sternocleidomastoid motoneurons of decerebrate cats (1999)
    Springer
    Experimental brain research 126 (1999), S. 410-416 
    Details
    ISSN: 1432-1106
    Keywords: Key words Vestibulocollic reflex ; Saccular nerve ; Utricular nerve ; Sternocleidomastoid motoneuron ; Cat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Connections from the otolithic organs to sternocleidomastoid (SCM) motoneurons were studied in 20 decerebrate cats. The electrical stimulation was selective for the saccular or the utricular nerves. Postsynaptic potentials were recorded from antidromically identified SCM motoneurons; these muscles participate mainly in neck rotation and flexion. Partial transections of the brainstem at the level of the obex were performed to identify the possible pathway from the otolithic organs to the SCM motoneurons. Saccular or utricular nerve stimulation mainly evoked inhibitory postsynaptic potentials (IPSPs) in the ipsilateral SCM motoneurons. Some of the sacculus-induced IPSPs were preceded by small-amplitude excitatory PSPs (EPSPs). The latencies of the PSPs ranged from 1.8 to 3.1 ms after saccular nerve stimulation and from 1.7 to 2.8 ms after utricular nerve stimulation, indicating that most of the ipsilateral connections were disynaptic. In the contralateral SCM motoneurons, saccular nerve stimulation had no or faint effects, whereas utricular nerve stimulation evoked EPSPs in about two-thirds of neurons, and no visible PSPs in about one-third of neurons. The latencies of the EPSPs ranged from 1.5 to 2.0 ms, indicating the disynaptic connection. Thus, the results suggest a difference between the two otolithic innervating patterns of SCM motoneurons. After transection of the medial vestibulospinal tract (MVST), saccular nerve stimulation did not evoke IPSPs at all in ipsilateral SCM motoneurons, but some (11/40) neurons showed small-amplitude EPSPs. Most (24/33) of the utricular-activated IPSPs disappeared after transection, whereas the other 9 neurons still indicated IPSPs. In the contralateral SCM motoneurons, no utricular-activated EPSPs were recorded after transection. These MVST transection results suggest that most of the otolith-SCM pathways are located in the MVST at the obex level. However, the results also suggest the possibility that other otolith-SCM pathways exist at the obex level.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002210050747
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  • 19
    Electronic Resource
    Electronic Resource
    The dynamics of the vestibulo-ocular reflex after peripheral vestibular damage I. Frequency-dependent asymmetry (1999)
    Springer
    Experimental brain research 125 (1999), S. 353-364 
    Details
    ISSN: 1432-1106
    Keywords: Key words Vestibulo-ocular reflex ; Vertigo ; Labyrinthectomy ; Compensation ; Motor learning ; Oculomotor ; Plasticity ; Cat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Accurate performance by the vestibulo-ocular reflex (VOR) is necessary to stabilize visual fixation during head movements. VOR performance is severely affected by peripheral vestibular damage; after one horizontal semicircular canal is plugged, the horizontal VOR is asymmetric and its amplitude is reduced. The VOR recovers partially. We investigated the limits of recovery by measuring the VOR’s response to ipsilesional and contralesional rotation after unilateral peripheral damage in cats. We found that the VOR’s response to rotation at high frequencies remained asymmetric after recovery was complete. When the stimulus was a pulse of head velocity comprising a dynamic overshoot followed by a plateau, gain was partially restored and symmetry completely restored within 30 days after the plug, but only for the plateau response. The overshoot in eye velocity remained asymmetric. The asymmetry was independent of stimulus velocity throughout the known linear velocity range of primary vestibular afferents. Sinusoidal rotation at 0.05–8 Hz revealed that, within this range, the persistent asymmetry was significant only at frequencies above 2 Hz. Asymmetry was independent of the peak head acceleration over the range of 50–500°/s2. When both horizontal canals were plugged, a small residual VOR was observed, suggesting residual signal transduction by plugged semicircular canals. However, transduction by plugged canals could not explain the enhancement of the VOR gain, at high frequencies, for rotation away from the plugged side compared with rotation toward the plug. Also, the high-frequency asymmetry was present after recovery from a unilateral labyrinthectomy. These results suggest that high-frequency asymmetry after unilateral damage is not due to residual function in the plugged canal. The findings are discussed in the context of a bilateral model of the VOR that includes central filtering.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002210050691
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  • 20
    Electronic Resource
    Electronic Resource
    Receptive-field properties of adult cat’s retinal ganglion cells with regenerated axons (1999)
    Springer
    Experimental brain research 124 (1999), S. 383-390 
    Details
    ISSN: 1432-1106
    Keywords: Key words Retinal ganglion cells ; Axonal regeneration ; Single-unit activity ; Receptive field ; Cat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Receptive-field properties of retinal ganglion cells (RGCs) that had regenerated their axons were studied by recording single-unit activity from strands teased from peripheral nerve (PN) grafts apposed to the cut optic nerve in adult cats. Of the 286 visually responsive units recorded from PN grafts in 20 cats, 49.7% were classified, according to their receptive-field properties, as Y-cells, 39.5% as X-cells, 6.6% as W-cells, and 4.2% were unclassified. The predominant representation of Y-cells is consistent with a corresponding morphological study (Watanabe et al. 1993a), which identified α-cells as the RGC type with the largest proportion of regenerating axons. Among the X-cells, we only found ON-center types, whereas both ON-center and OFF-center Y-cells were found. As in intact retinas, the receptive-field center sizes of Y-cells and W-cells were larger than those of X-cells at corresponding displacements from the area centralis. Within the 10° surrounding the area centralis, the receptive fields of X-cells with regenerated axons were larger than those in intact retinas, suggesting that some rearrangement of retinal circuitry occurred as a consequence of degeneration and regeneration. Receptive-field center responses of Y-, X-, and W-type units with regenerated axons were similar to those found in intact retinas, but the level of spontaneous activity of Y- and X-type units was, in general, less than that of intact RGCs. Receptive-field surrounds were weak or not detected in more than half of the visually responsive RGCs with regenerated axons.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002210050635
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  • 21
    Electronic Resource
    Electronic Resource
    Direct connection of the nucleus reticularis gigantocellularis neurons with neck motoneurons in cats (1999)
    Springer
    Experimental brain research 128 (1999), S. 527-530 
    Details
    ISSN: 1432-1106
    Keywords: Key words Nucleus reticularis gigantocellularis ; Reticulospinal neuron ; Neck motoneuron ; Single-neuron EPSP ; Cat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Functional connections of single reticulospinal neurons (RSNs) in the nucleus reticularis gigantocellularis (NRG) with ipsilateral dorsal neck motoneurons were examined with the spike-triggered averaging technique. Extracellular spikes of single NRG-RSNs activated antidromically from the C6, but not from the L1 segment (C-RSNs) were used as the trigger. These neurons were monosynaptically activated from the superior colliculus and the cerebral peduncle. Single-RSN PSPs were recorded in 43 dorsal neck motoneurons [biventer cervicis and complexus (BCC) and splenius (SPL)] for 21 NRG-RSNs and 135 motoneurons tested. All synaptic potentials were EPSPs, and most of their latencies, measured from the triggering spikes, were 0.8–1.5 ms, which is in a monosynaptic range. The amplitudes of single-RSN EPSPs were 10–360 µV. Spike-triggered averaging revealed single-RSN EPSPs in multiple motoneurons of the same species (SPL or BCC), their locations extending up to nearly 1 mm rostrocaudally. Synaptic connections of single RSNs with both SPL and BCC motoneurons were also found with some predominance for one of them. The results provide direct evidence that NRG-RSNs make monosynaptic excitatory connections with SPL and BCC motoneurons. It appears that some NRG-RSNs connect predominantly with SPL motoneurons and others with BCC motoneurons.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002210050875
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  • 22
    Electronic Resource
    Electronic Resource
    Neuronal pathways from low-threshold hindlimb cutaneous afferents to motoneurons innervating trunk muscles in low-spinal cats (1999)
    Springer
    Experimental brain research 128 (1999), S. 543-549 
    Details
    ISSN: 1432-1106
    Keywords: Key words Abdominal muscles ; Back muscles ; Motoneurons ; Cutaneous afferent ; Spinal cord ; Cat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Postsynaptic potentials (PSPs) evoked in motoneurons innervating the back and abdominal muscles in the lumbar part of the body by stimulating hindlimb cutaneous afferents were investigated in unanesthetized decerebate and spinal cats. Various types of PSP: pure excitatory postsynaptic potential (EPSP), pure inhibitory postsynaptic potential (IPSP), and mixed PSP (i.e., EPSP followed by IPSP, EPSP/IPSP; and IPSP followed by EPSP, IPSP/EPSP) were observed. The weak stimulation at 2 times threshold (2T) produced predominantly the EPSP, while at 5T the incidence of IPSP or EPSP followed by IPSP was increased. In about 20–50% of the various groups of motoneurons, PSPs evoked by ipsi- and contralateral nerves were qualitatively and quantitatively similar. For the other motoneurons, PSPs evoked by ipsi- and contralateral nerves were markedly different with respect to magnitude and/or polarity. These findings suggest that, within each motoneuron pool, some neurons act to increase stiffness of the trunk or to move vertically in response to an increased activity of cutaneous afferents, while the other motoneurons act to produce lateral bending of the trunk.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002210050879
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  • 23
    Electronic Resource
    Electronic Resource
    The neural substrate of the vestibulocollic reflex (1999)
    Springer
    Experimental brain research 129 (1999), S. 483-493 
    Details
    ISSN: 1432-1106
    Keywords: Key words Vestibulocollic reflex ; Short-latency pathways ; Vestibulospinal and reticulospinal pathways ; Cat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The purpose of this review is to assess the role of short-latency pathways in the vestibulocollic reflex (VCR). First the current knowledge about the disynaptic and trisynaptic pathways linking semicircular canal and otolith afferents with cat neck motoneurons is summarized. We then discuss whether these pathways are sufficient or necessary to produce the responses observed in neck muscles by natural vestibular stimulation and conclude that they are neither. Finally, alternate pathways are considered, most likely involving reticulospinal fibers, which are an important part of the neural substrate of the VCR.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002210050918
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  • 24
    Electronic Resource
    Electronic Resource
    Activity-dependent development of cortical axon terminations in the spinal cord and brain stem (1999)
    Springer
    Experimental brain research 125 (1999), S. 184-199 
    Details
    ISSN: 1432-1106
    Keywords: Key words Corticospinal tract ; Motor cortex ; Activity-dependent development ; Spinal cord ; Cat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Corticospinal (CS) axon terminations in several species are widespread early in development but are subsequently refined into a spatially more restricted distribution. We studied the role of neural activity in sensorimotor cortex in shaping postnatal development of CS terminations in cats. We continuously infused muscimol unilaterally into sensorimotor cortex to silence neurons during the postnatal CS refinement period (weeks 3–7). Using anterograde transport of WGA-HRP, we examined the laterality of terminations from the muscimol-infused (i.e., silenced) and active sides in the spinal cord, as well as in the cuneate nucleus and red nucleus. We found that CS terminations from the muscimol-infused cortex were very sparse and limited to the contralateral side, while those from the active cortex maintained an immature bilateral topography. Controls (saline infusion, noninfusion) had dense, predominantly contralateral, CS terminations. There was a substantial decrease in the spinal gray matter area occupied by terminations from the side receiving the blockade and a concomitant increase in the area occupied by ipsilateral terminations from the active cortex. Optical density measurements of HRP reaction product from the active cortex in muscimol-infused animals showed substantial increases over controls in the ratio of ipsilateral to contralateral CS terminations for all laminae examined (IV–V, VI, VII). Our findings suggest that ipsilateral dorsal horn terminations reflect new axon growth during the refinement period because they are not present there earlier in development. Those in the ventral horn are present earlier in development and thus could reflect maintenance of transient terminations. Increased ipsilateral terminations from active cortex were due to recrossing of CS axons in lamina X and not to an increase in labeled CS axons in the ipsilateral white matter. Examination of brain stem terminations suggested that, between postnatal weeks 3 and 7, development of corticocuneate terminations also is activity-dependent but that development of corticorubral terminations is not. Activity-dependent CS development is a plausible mechanism by which early motor experiences could shape the anatomical and functional organization of the motor systems during a critical postnatal period.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002210050673
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  • 25
    Electronic Resource
    Electronic Resource
    Insulin modulation of ATP-sensitive K+ channel of rat skeletal muscle is impaired in the hypokalaemic state (1999)
    Springer
    Pflügers Archiv 437 (1999), S. 235-240 
    Details
    ISSN: 1432-2013
    Keywords: Key words Hypokalaemic periodic paralysis ; ATP-sensitive K+ channels ; Insulin ; Skeletal muscle ; Patch clamp
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  In the present work, we examined the effects of in vivo administration of insulin to rats made hypokalaemic by feeding a K+-free diet. The i.p. injection of insulin in the hypokalaemic rats provoked muscle paralysis within 3–5 h. Consistent with this observation, the skeletal muscle fibres of the paralysed rats were depolarized. In contrast, in the normokalaemic animals, insulin neither provoked paralysis nor produced significant fibre hyperpolarization. In the hypokalaemic rats, insulin almost completely abolished the sarcolemma adenosine triphosphate (ATP)-sensitive K+ currents without altering the sensitivity of the channels to ATP or glibenclamide. In contrast, in the normokalaemic rats, insulin enhanced ATP-sensitive K+ currents that became also resistant to ATP and glibenclamide. Our experiments indicate that the modulation of the sarcolemma ATP-sensitive K+ channels by insulin is impaired in the hypokalaemic state. This phenomenon appears to be related to the fibre depolarization and paralysis observed in the same animals.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004240050774
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  • 26
    Electronic Resource
    Electronic Resource
    Interleukin-1β-induced nitric oxide synthesis in aortic rings from normal and hyperinsulinaemic rats: effect of physical exercise (1999)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 360 (1999), S. 63-68 
    Details
    ISSN: 1432-1912
    Keywords: Key words Arterial smooth muscle ; Glucose ; Inducible NO synthesis ; Insulin ; Lean and obese Zucker rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Insulin has been suggested to prevent the induction of nitric oxide synthase (NOS) in vitro in arterial smooth muscle, but whether such a mechanism is operative in vivo is not known. Therefore, we evaluated the sensitivity of smooth muscle NOS to induction by interleukin-1β (IL-1β) in aortic rings of lean and obese Zucker rats, a model of experimental hyperinsulinaemia. In order to modulate the insulin and glucose balance of the rats, a 22-week-long treadmill exercise was included in the study. The training attenuated weight gain and reduced blood glucose in the obese and lean rats, whereas the abnormally high plasma insulin of the obese rats remained unaffected. A 6-h incubation of aortic rings with IL-1β (10 ng/ml) increased cyclic GMP in smooth muscle by approximately threefold in all groups, and this effect was prevented by methylene blue. The contractile sensitivity of endothelium-denuded aortic rings to phenylephrine was reduced by incubation with IL-1β (1 ng/ml and 10 ng/ml) in the exercised obese and lean rats, whereas no significant change was observed in the sedentary groups. The aortic maximal contractile force induced by phenylephrine was reduced in sedentary and exercised obese rats by incubation with IL-1β, while no change was detected in the lean rats. The aortic relaxation to exogenous L-arginine was augmented by IL-1β in all groups, while the relaxation sensitivity to L-arginine after induction by IL-1β was enhanced by exercise in the obese but not in the lean rats. Finally, the relaxation to nitroprusside was not significantly affected by IL-1β in any of the study groups. In conclusion, since maximal contractile force generation to phenylephrine was reduced by IL-1β in the obese but not in the lean rats, the sensitivity of NOS to induction by IL-1β was higher in arterial smooth muscle of the obese than the lean Zucker rats. Thus, this model of hyperinsulinaemia was not associated with reduced sensitivity of smooth muscle NOS to induction by IL-1β. Regular exercise did not change plasma insulin concentrations, but it enhanced the action of insulin in both strains as reflected by reduced blood glucose, and increased the sensitivity of smooth muscle NOS to induction by IL-1β.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002109900036
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  • 27
    Electronic Resource
    Electronic Resource
    Forskolin increases apical sodium conductance in cultured toad kidney cells (A6) by stimulating membrane insertion (1999)
    Springer
    Pflügers Archiv 438 (1999), S. 195-204 
    Details
    ISSN: 1432-2013
    Keywords: Key words A6 cells ; Capacitance ; Hormones ; Insulin ; Membrane area ; Membrane traffic ; Renal epithelia ; Water permeability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The role of membrane traffic in the stimulation of apical Na+ permeability caused by increases in cytoplasmic cyclic AMP was assessed by measuring the effects of forskolin on transepithelial capacitance (C T), transepithelial conductance (G T), and short-circuit current (I sc) in A6 cultured toad kidney cells. Apical water permeability was probed by recording cell volume changes after reducing the osmolality of the apical bath. We found that forskolin does not increase the osmotic water permeability of the apical membrane of A6 cells, and thus does not stimulate the insertion of water channels. Comparison of the effects of forskolin and insulin on Na+ transport demonstrated that both agents produce reversible increases in C T, G T and I sc. G T and C T increased proportionally during the rising phase of the insulin response. However, a non-linear relationship between both parameters was recorded when forskolin was given in NaCl Ringer’s solution. The relationship between C T and G T became linear after the effects of forskolin on Cl– conductances were eliminated by substituting Cl– by an impermeant anion. In contrast, in Cl–-containing Na+-free solutions, the non-linearity became more pronounced. Successive additions of insulin and forskolin caused additive increases in C T. Because increases in C T and Na+ transport occurred in the absence of stimulation of water permeability and increases of C T and G T were directly proportional when Na+ was the major permeating ion across the apical membrane, we suggest that the increase in apical Na+ permeability in the presence of either forskolin or insulin is due to the insertion of channels residing in intracellular pools. In contrast, the increased Cl– permeability caused by forskolin may be related to the activation of channels already present in the membrane.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004240050898
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  • 28
    Electronic Resource
    Electronic Resource
    Metabolic and ultrastructural effects of cyclosporin A on pancreatic islets (1999)
    Springer
    Transplant international 12 (1999), S. 208-212 
    Details
    ISSN: 1432-2277
    Keywords: Key words Cyclosporin A ; Langerhans ; Insulin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We investigated the effect of different doses of cyclosporin A (CyA) on glucose and insulin levels, as well as its residual effects on pancreatic islets ultrastructure after discontinuation of the drug. We studied four groups of Wistar rats. One control- (n = 5) and three experimental groups, n = 10 each, were treated with different doses of CyA IM for 14 days: group I, 5 mg/Kg; group II, 15 mg/Kg; and group III, 25 mg/Kg. Five animals of each group were sacrificed after 14 days, and the remaining five after 21 days to assess residual CyA effects. On the day of sacrifice, the rats underwent maltose absorption test, and glucose and insulin levels were measured. Pancreatic biopsies were obtained on day 21 to evaluate islets ultrastructure by electron microscopy. As a result, statistically significant, dose dependent (P 〈 0.05) increases in glucose and insulin levels were observed in CyA-treated groups. Groups II and III showed insulin levels significantly higher after fasting (P 〈 0.05) on day 14 comparing to the controls, while in groups I and II values returned to normal after CyA discontinuation. Group III showed persistently increased insulin levels on day 21. Pancreatic ultrastructural changes were observed only in group III. We can conclude that CyA effects on glucose and insulin levels were temporary and reversible at low doses. Ultrastuctural changes in the pancreatic islets may occur with high doses of CyA.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001470050212
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  • 29
    Electronic Resource
    Electronic Resource
    Insulin-induzierte Hypoglycaemia factitia aus diätetischen Gründen (1999)
    Springer
    Rechtsmedizin 9 (1999), S. 190-192 
    Details
    ISSN: 1434-5196
    Keywords: Key words Hypoglycaemia factitia ; Insulin ; Diet ; Lethal outcome ; Schlüsselwörter Hypoglykaemia factitia ; Insulin ; Diät ; Tödlicher Verlauf
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine , Law
    Description / Table of Contents: Zusammenfassung Wir berichten über den Fall einer 28jährigen, nicht insulinpflichtigen nicht-Diabetikerin, in deren Anamnese eine hypoglykaemische Episode vor dem Todeseintritt bekannt wurde. Autoptisch wurde eine (heimliche) Applikation von Insulin durch letal hohe Insulinspiegel im zentralen und peripheren Blut mit Hypoglykaemie diagnostiziert. Nach der Anamnese, den Ergebnissen des Ermittlungsverfahrens und der Autopsie konnte die Applikation von Insulin aus suizidaler und homizidaler Absicht oder im Rahmen eines Münchhausen-Syndroms ausgeschlossen werden. Vielmehr handelte es sich in der Gesamtschau um eine Hypoglykaemia factitia aus diätetischen Gründen.
    Notes: Abstract The medical history of a 28-year-old non-insulin-dependent and non-diabetic patient with a hypoglycaemic episode before death is reported. At autopsy, an (surreptious) insulin administration was documented by lethally high serum insulin in central and peripheral blood during hypoglycaemia, According to the anamnesis, the judical inquiry and the autopsy findings, a suicidal intent, murder by insulin or Munchhausen-syndrome could be excluded. We therefore diagnosed a hypoglycaemia factitia caused by the diet.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001940050107
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    Effect of moderate physical activity on plasma leptin concentration in humans (1999)
    Springer
    European journal of applied physiology 79 (1999), S. 331-335 
    Details
    ISSN: 1439-6327
    Keywords: Key words Leptin ; Exercise Energy balance ; Insulin ; Glucocorticoids
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In subjects who maintain a constant body mass, the increased energy expenditure induced by exercise must be compensated by a similar increase in energy intake. Since leptin has been shown to decrease food intake in animals, it can be expected that physical exercise would increase energy intake by lowering plasma leptin concentrations. This effect may be secondary either to exercise-induced negative energy balance or to other effects of exercise. To delineate the effects of moderate physical activity on plasma leptin concentrations, 11 healthy lean subjects (4 men, 7 women) were studied on three occasions over 3 days; in study 1 they consumed an isoenergetic diet (1.3 times resting energy expenditure) over 3 days with no physical activity; in study 2 the subjects received the same diet as in study 1, but they exercised twice daily during the 3 days (cycling at 60 W for 30 min); in study 3 the subjects exercised twice daily during the 3 days, and their energy intake was increased by 18% to cover the extra energy expenditure induced by the physical activity. Fasting plasma leptin concentration (measured on the morning of day 4) was unaltered by exercise [8.64 (SEM 2.22) 7.17 (SEM 1.66), 7.33 (SEM 1.72) 1μg · l−1 in studies 1, 2 and 3, respectively]. It was concluded that a moderate physical activity performed over a 3-day period does not alter plasma leptin concentrations, even when energy balance is slightly negative. This argues against a direct effect of physical exercise on plasma leptin concentrations, when body composition is unaltered.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004210050516
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    Repeated cat-associated peritonitis in a patient on automated nocturnal intermittent peritoneal dialysis (1999)
    Springer
    Clinical and experimental nephrology 3 (1999), S. 59-61 
    Details
    ISSN: 1437-7799
    Keywords: Key words Peritoneal dialysis ; Peritonitis ; Cat ; Pasteurella multocida
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A 49-year-old man had three episodes of bacterial peritonitis in the 8 months after he started nocturnal intermittent peritoneal dialysis (NIPD) at home, using an automated cycler device. When peritonitis was first diagnosed, Enterobacter agglomerance was cultured in his peritoneal fluid. In the second and third episodes, Pasteurella multocida and alpha-Streptococcus were isolated, respectively. These bacteria are unusual pathogens in continuous ambulatory peritoneal dialysis (CAPD) peritonitis. Detailed questioning revealed that a domestic cat had bitten the dialysis tube before the patient experienced the second episode of peritonitis. Pasteurella multocida is part of the normal oral flora in cats and dogs. We isolated Pasteurella multocida from the teeth of the patient's cat. Enterobacter agglomerance is part of the common bacterial flora in animal's alimentary tract, and alpha-Streptococcus is commonly found in animal's respiratory tracts. Since the patient removed the cat from his bedroom, he has had no peritonitis. NIPD is a very convenient sysytem for patients in the final stage of renal failure; however, patients must be aware of the risks associated with keeping pets in their homes. This case is the first report of cat-associated peritonitis in Japan.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s101570050011
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    Genome-wide scanning for type 2 diabetes susceptibility in Canadian Oji-Cree, using 190 microsatellite markers (1999)
    Springer
    Journal of human genetics 44 (1999), S. 10-14 
    Details
    ISSN: 1435-232X
    Keywords: Key words Complex disease ; Carbohydrate ; Insulin ; Aboriginal populations
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract We undertook a genome-wide scan using 190 markers with an average separation of 20 cM in 49 Canadian Oji-Cree sib pairs affected with type 2 diabetes. Four of these markers, one each on chromosomes 6, 8, 16, and 22, showed both suggestive linkage and suggestive association with type 2 diabetes in the Oji-Cree. None of these markers corresponded to any chromosomal region or marker that has so far been linked with type 2 diabetes in other populations. Thus, there might be several genetic loci that confer susceptibility to type 2 diabetes in this study sample. We are following up on these preliminary leads by increasing the density of the markers within these linked and associated regions, and also by increasing the number of study subjects. Also, we found instances in which there were wide disparities between the Oji-Cree and reference Caucasians with respect to marker heterozygosity. This suggests that a particular set of markers for genome-wide scanning will have different informativeness in different ethnic groups. Thus, different marker sets will likely be required for different ethnic groups in order to maximize their information content for linkage calculations.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s100380050097
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    The effect of euglucaemic hyperinsulinaemia on forearm blood flow and glucose uptake in the human forearm (1998)
    Springer
    Acta diabetologica 35 (1998), S. 203-206 
    Details
    ISSN: 1432-5233
    Keywords: Key words Glucose ; Insulin ; Hyperinsulinaemia ; Blood flow
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Insulin-mediated stimulation of blood flow to skeletal muscle has been proposed to be of major importance for insulin-mediated glucose uptake. The aim of this study was to investigate the relative importance of blood flow and glucose extraction as determinants of insulin-mediated glucose uptake in the human forearm. Forearm blood flow (FBF), glucose extraction and oxygen consumption were evaluated for 100 min during the euglycaemic hyperinsulinaemic clamp (92 mU/l) in nine healthy subjects. FBF was measured by venous occlusion plethysmography. Forearm glucose uptake increased sevenfold during the hyperinsulinaemia (P〈0.001). Forearm glucose extraction showed a minor increase during the first 10 min of hyperinsulinaemia, but the most marked increase took place between 10 and 20 min (+170%). Thereafter, only a minor further increase was seen. During the first 10 min of hyperinsulinaemia FBF was unchanged. Thereafter, FBF increased steadily to a plateau reached after 60 min (+50%, P〈0.001). A close relationship between whole body glucose uptake and FBF was seen at the end of the clamp (r = 0.75, P〈0.02), but at this time the relationship between whole body glucose uptake and forearm glucose extraction was not significant. The modest increase in O2 consumption seen at the beginning of the clamp (+19%) was not related to FBF during the early phase of the clamp. In conclusion, the early course of insulin-mediated glucose uptake in the human forearm was mainly due to an increase in glucose extraction. However, with time the insulin-mediated increase in blood flow increased in importance and after 100 min of hyperinsulinaemia FBF was the major determinant of glucose uptake.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s005920050132
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    Functioning human insulinomas (1998)
    Springer
    Virchows Archiv 433 (1998), S. 495-504 
    Details
    ISSN: 1432-2307
    Keywords: Key words Insulinomas ; Prohormone convertases ; Carboxypeptidase H ; Insulin ; Proinsulin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Sixty-seven insulinomas were investigated by immunohistochemistry using site-directed antibodies against insulin, proinsulin, chromogranin A, HISL-19, and four proteins directly or indirectly involved in the proteolytic processing of proinsulin: the prohormone convertases PC2 and PC3, carboxypeptidase H (CPH) and 7B2. Results were expressed in a six-grade score according to the frequency of immunoreactive tumour cells. Insulin was expressed by all tumours, appearing in either a diffuse or a polarized pattern and being detected in more than 30% of tumour cells in all cases but three. Proinsulin was also expressed in all tumours, with more than 50% of tumour cells immunoreactive in all cases but 5. It was consistently localized in the Golgi apparatus. In about half the cases, moreover, it also showed diffuse cytoplasmic staining, usually with a very sparse distribution. Trabecular and solid insulinomas did not present specific, homogeneous patterns of insulin immunostaining. However, insulin immunoreactivity was much more abundant in trabecular than in solid neoplasms, being present in virtually all tumour cells (score 6) in 50% and 8% of cases, respectively. Virtually all insulinomas expressed PC2, PC3, CPH and 7B2, usually in 30–100% of tumour cells, with a frequency significantly related to that of insulin. However, detection of PC2 and 7B2 was slightly less frequent than that of PC3 and CPH. In consecutive sections these proteins were found to be mostly co-localized with insulin and chromogranin A but not with proinsulin. They were heavily expressed in all 10 tumours with more than 10% of cells showing cytoplasmic proinsulin immunoreactivity, indicating that the leakage of proinsulin from the Golgi compartment is not associated with faulty expression of converting enzymes and possibly reflects a saturated processing capacity. HISL-19 immunoreactivity was found in both Golgi apparatus and insulin stores, indicating that the relevant antigen is different from all other proteins investigated. These results do not support a defect in expression or localization of proinsulin-processing enzymes in most insulinomas.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004280050280
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    Neuropathy in diabetic BB/Wor rats treated with insulin implants (1998)
    Springer
    Acta neuropathologica 96 (1998), S. 144-150 
    Details
    ISSN: 1432-0533
    Keywords: Key words Neuropathy ; Hypoglycaemia ; Hyperglycaemia ; Insulin ; BB/Wor rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract To elucidate the pathophysiology of diabetic neuropathy many workers have examined nerve specimens from diabetic rats. While most workers found that animals with high blood glucose levels develop neuropathy, some researchers report that the peripheral nerves are normal in hyperglycaemic rats. Hypoglycaemia may also cause neuropathy. Some workers suggest that neuropathy is linked to fluctuations of the blood glucose level. In the present study we examine plantar nerves of diabetic BB/ Wor rats maintained on an eu-/hyperglycaemic or an eu-/ hypoglycaemic regime with insulin implants. Treatment with implants worked well. Light microscopic examination of nerve fibres in non-diabetic control rats and in eu-/ hyperglycaemic diabetic rats showed a normal picture. Preparations from eu-/hypoglycemic rats showed irregular myelin sheaths and signs of Wallerian degeneration. The lengths and diameters of the largest internodes were significantly subnormal. We conclude, that periodic moderate hypoglycaemia, but not periodic moderate hyperglycaemia, elicits neuropathy in diabetic BB/Wor rats treated with insulin implants.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004010050874
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    Hypoglycaemic neuropathy in BB/Wor rats treated with insulin implants: electron microscopic observations (1998)
    Springer
    Acta neuropathologica 96 (1998), S. 151-156 
    Details
    ISSN: 1432-0533
    Keywords: Key words Neuropathy ; Hypoglycemia ; Insulin ; implant ; Rat ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Insulin-dependent diabetes mellitus is a chronic metabolic disease that causes long-term secondary complications such as neuropathy. The occurrence of diabetic neuropathy has generally been thought of as being associated with hyperglycaemia. However, in a previous light microscopic examination of plantar nerves in diabetic BB/Wor rats treated with insulin implants we found that eu-/hyperglycaemic rats present a normal picture, whereas eu-/hypoglycaemic rats show severe changes. The aim of the present work is to supplement our previous light microscopic report with electron microsocpic data from the lateral plantar nerve of normal, eu-/hyperglycaemic and eu-/hypoglycaemic BB/Wor rats. Under the electron microscope lateral plantar nerves collected from eu-/hyperglycaemic rats presented a qualitatively normal picture. In addition, the fibre numbers and the size distribution of the myelinated fibres were normal. In contrast, specimens from eu-/hypoglycaemic BB/Wor rats showed severe qualitative changes, interpreted as signs of axonal de- and regeneration. The total number of axons was somewhat subnormal and the sizes of the myelinated fibres were strongly shifted towards smaller diameters. These data confirm our previous light microscopic observations. We conclude that eu-/hypoglycaemic BB/Wor rats treated with insulin implants, but not similarly treated eu-/hyperglycaemic animals, develop a neuropathy in their plantar nerves.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004010050875
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    Visual zone of the claustrum shows localizational and organizational differences among rat, guinea pig, rabbit and cat (1998)
    Springer
    Anatomy and embryology 198 (1998), S. 63-72 
    Details
    ISSN: 1432-0568
    Keywords: Key words Claustrum ; Visual cortex ; Visual zones Comparative anatomy ; Rat ; Guinea pig ; Rabbit ; Cat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The retrograde axonal transport method was used to compare the topography and organization of the visual zone of the claustrum in rat, guinea pig, rabbit and cat. First, massive Fluoro-Gold injections were placed into the primary visual cortex and the secondary areas. Experiments showed differences in the location of the visual zone among the animals under study. In rat, the visual zone occupied the posteroventral part of the claustrum and spread to its anterior pole. In guinea pig, neurons projecting to the visual cortex were located dorsally in the posterior half of the claustrum. In rabbit, similarly to the rat, they were localized in the posteroventral part; however, they did not reach the anterior pole. In cat, neurons that project to the visual cortex were concentrated dorsally in the posterior fourth of the claustrum. In double-injection experiments, Fast Blue and Diamidino Yellow were placed into the primary and secondary visual areas in various combinations. The experiments showed that in the rat and the rabbit claustral neurons project to primary visual cortex (area 17) as well as to both secondary visual areas (areas 18a and b). Populations of neurons sending axons to the primary and secondary areas showed full overlap. The presence of double-labeled neurons indicates that some claustral neurons project both to the primary and secondary fields. In cat, neurons that project to the primary visual cortex appear to be clearly separated from those connected with the secondary visual area, as no double-labeled neurons were found. In all studied species, the double injections placed into the visual and primary somatosensory cortex did not result in any double-labeling neurons. Our results indicate that the location of the visual zone in the posterior part of the claustrum is a phylogenetically stable feature, whereas its dorsoventral shift as well as the extent toward the anterior pole is related to the particular species. The overlap of neurons projecting to the primary and secondary visual areas in the rat and rabbit as well as the separation of both projections in cat appear to reflect the higher degree of complexity of the visual system in the latter.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004290050165
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    A novel member of the bombyxin gene family: structure and expression of bombyxin G1 gene, an insulin-related peptide gene of the silkmoth Bombyx mori (1998)
    Springer
    Development genes and evolution 208 (1998), S. 407-410 
    Details
    ISSN: 1432-041X
    Keywords: Key words Bombyxin ; Insulin ; Bombyx mori ; Multigene family ; Brain neurosecretory cell
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract  Bombyxin G1 gene, a novel insulin-related peptide gene of the silkmoth Bombyx mori, has been identified. The G1 gene encodes a precursor peptide which shows 41–56% and 28% sequence identities with preprobombyxins previously characterized and human preproinsulin, respectively. The G1 gene forms a pair with bombyxin C2 gene with opposite transcriptional orientation in a bombyxin gene cluster. The bombyxin G1 mRNA in Bombyx brain was shown to locate in four pairs of medial neurosecretory cells.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004270050197
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    Cyclosporin A induces apoptosis in rat hepatocytes in culture (1998)
    Springer
    Archives of toxicology 72 (1998), S. 559-565 
    Details
    ISSN: 1432-0738
    Keywords: Key words Proliferation ; Epidermal growth factor (EGF) ; Insulin ; Hepatocyte ; Cyclosporin A
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Cyclosporin A (CsA) at concentrations up to 1 μM induced apoptosis in a dose-dependent manner in cultured rat hepatocytes for 48 h in the presence of insulin and epidermal growth factor (EGF). The effect of CsA was evidenced by the DNA fragmentation pattern constituted by fragments of multiples of 180–200 base pairs, which is a characteristic of programmed cell death. The metabolic activity did not change significantly in the presence of 0.1 μM CsA and diminished to 49% of control in the presence of 1 μM CsA. Changes in the metabolic activity were correlated with a decrease in both [methyl-3H]thymidine uptake and DNA content, which reflects a decrease in the cell number. The treatment of cells with CsA (1 μM) decreased the metabolic activity/DNA content ratio by 24% with respect to dimethyl sulphoxide (DMSO) control, which also suggests, under these conditions, that the necrosis achieved is at most only 24%. In addition, the changes observed (apoptotic process, arrest of the cell cycle and apparition of a necrotic process) were correlated with an increase in the high-affinity guanosine triphosphatase (GTPase) enzymes.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002040050543
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    Distribution of glutamate-, glycine- and GABA-immunoreactive nerve terminals on dendrites in the cat spinal motor nucleus (1998)
    Springer
    Experimental brain research 118 (1998), S. 517-532 
    Details
    ISSN: 1432-1106
    Keywords: Key words Ultrastructure ; Immunohistochemistry ; Bouton ; Synaptic input ; Cat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The dendritic tree constitutes more than 93% of the receptive membrane area of a spinal motoneuron, yet little is known about its synaptic inputs. In this study we examined the distribution of glutamate-, GABA- and glycine-like immunoreactivity in boutons apposing dendrites in the L7 spinal cord motor nucleus, by use of postembedding immunohistochemistry on serial sections. We examined 799 boutons apposing 401 cross-sectioned dendrites of different calibre (range 0.2–15 µm), and 14 first-order (stem) dendrites. Thirty-five percent (35%) of the boutons were immunopositive for glutamate and 59% for GABA and/or glycine. Among the latter, 30% showed glycine immunoreactivity only and 24% were immunoreactive for both GABA and glycine. Very few were immunoreactive only for GABA (5%). As few as 6% of the boutons were judged as not enriched for any amino acid analysed. The fine structural characteristics of the boutons were in accordance with previous descriptions. The sample of dendrites was arranged in calibre bins in order to facilitate distribution analysis. Stem dendrites differed from the other bins, with a high total bouton covering (61%) and a high bouton density. Sixty-nine percent of the membrane covering was by glycine- and/or GABA-immunoreactive boutons, whereas 18% was covered by boutons enriched in glutamate. For non-stem dendrites, bouton covering fell from 33% to 12% with decreasing calibre. However, bouton apposition length decreased in parallel, yielding a fairly uniform bouton density among dendrites of different calibre. The lack of correlation between packing density and dendrite calibre was also evident when the sample of dendrites was broken down into subsamples based on content of amino acid immunoreactivity. The latter analysis also revealed that both the relative covering and density of boutons containing inhibitory amino acids (57%; glycine and/or GABA) and glutamate (38%), respectively, did not vary systematically with dendrite calibre. Combined, the data indicate that in non-stem dendrites the proportion of excitatory and inhibition inputs does not change systematically throughout the dendritic arborizations of spinal α-motoneurons. Thus, spinal motoneurons can, with respect to the general synaptic architecture, be divided into two main compartments, i.e. the proximal soma-juxtasomatic compartment (including stem dendrites) and the distal dendritc compartment. The proximal domain is under a powerful glycine and/or GABA influence. Finally, based on the data presented here and previously published data, it was calculated that spinal α-motoneurons receive in the range of 50–140×103 synaptic boutons.
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    URL: http://dx.doi.org/10.1007/s002210050308
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    A possible basic cortical microcircuit called ’’cascaded inhibition’’Results from cortical network models and recording experiments from striate simple cells (1998)
    Springer
    Experimental brain research 122 (1998), S. 318-332 
    Details
    ISSN: 1432-1106
    Keywords: Key words Cortical microcircuits ; Relative modulation ; Push-pull mechanism ; Simple cell ; Cascaded inhibition ; Cat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The robust behavior, the degree of response linearity, and the aspect of contrast gain control in visual cortical simple cells are (amongst others) the result of the interplay between excitatory and inhibitory afferent and intracortical connections. The goal of this study was to suggest a simple intracortical connection pattern, which could also play a role in other cortical substructures, in order to generically obtain these desired effects within large physiological parameter ranges. To this end we explored the degree of linearity of spatial summation in visual simple cells experimentally and in different models based on half-wave rectifying cells (’’push-pull models’’). Visual cortical push-pull connection schemes originated from antagonistic motor-control models. Thus, this model class is widely applicable but normally requires a rather specific design. On the other hand we showed that a more generic version of a push-pull model, the so-called cascaded inhibitory intracortical connection scheme, which we implemented in a biologically realistic simulation, naturally explains much of the experimental data. We investigated the influence of the afferent and intracortical connection structure on the measured linearity of spatial summation in simple cells. The analysis made use of the relative modulation measure, which is easy to apply but is limited to moving sinusoidal grating stimuli. We introduced two basic push-pull models, where the order of threshold nonlinearity and linear summation is reversed. Very little difference is observed with the relative modulation measure for these models. Alterative models, like half-wave squaring models, were also briefly discussed. Of all model parameters, the ratio of excitation to inhibition in the simple cell exerts the most crucial influence on the relative modulation. Linearity deteriorates as soon as excitatory and inhibitory inputs are imbalanced and the relative modulation drops. This prediction was tested experimentally by extracellular recordings from cat area 17 simple cells and we found that about 62% showed a significant deviation from linear behavior. The problem that individual basic push-pull models are hard to distinguish experimentally led us to suggest a different solution. In order to generically account for the observed behavior (e.g., imbalance of excitation versus inhibition), we suggested a rather generic version of a push-pull model where it no longer mattered about (the hard-to-distinguish) fine differences in connectivity. Thus, we introduced a new class of biophysically realistic models (’’cascaded inhibition’’). This model class requires very little connection specificity and is therefore highly robust against parameter variations. Up to 25 cells are connected to each target cell. Thereby a highly interconnected network is generated, which also leads to disinhibition at some parts of an individual receptive field. We showed that the performance of these models simulates the degree of linearity and its variability in recal simple cells with comparatively high accuracy. This behavior can be explained by the self-regulating properties of a cascaded inhibitory connection scheme by which the balance between excitation and inhibition at a given cell is improved by the joint network effects. The virtues and the generic design of this connection pattern, therefore, allow to speculate that it is used also in other parts of the cortex.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002210050520
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    Flexor reflex afferents reset the step cycle during fictive locomotion in the cat (1998)
    Springer
    Experimental brain research 122 (1998), S. 339-350 
    Details
    ISSN: 1432-1106
    Keywords: Key words Fictive locomotion ; Proprioception ; Flexor reflex ; Spinal cord ; Cat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The generation of locomotor-like spinal rhythms has been proposed to involve two neural centres with mutual reciprocal inhibition (Graham Brown’s ”half-centre” hypothesis). Much later a particular set of segmental flexor reflex pathways were described as being organized in accordance with this half-centre hypothesis. As these pathways became operative following injection of monoaminoxidase inhibitors and l-3,4-dihydroxyphenylalanine (l-dopa), i.e. under the same conditions under which a spontaneous locomotor activity may develop, it was assumed that these particular pathways and spinal rhythm generators involve the same neuronal networks. In order to give further evidence to this hypothesis, we investigated whether short trains to ”flexor reflex afferents” (FRA) reset the spinal locomotor rhythm, i.e. shorten or lengthen the stimulated cycle after which the regular rhythm is resumed with step cycles of the original duration. The experiments were performed in anaemically decapitated, high-spinal curarized cats. A steady locomotor rhythm was induced by injection of nialamide and l-dopa and the influence of electrical stimulation (trains of 50–1000 ms) of FRA (joint, cutaneous, and group II and III muscle afferents) onto this rhythm was tested. Stimulation of FRA induced a clear resetting of the locomotor rhythm, which was mainly characterized by a flexion reflex pattern: during the extension phase the extensor activity was interrupted and a flexion phase was initiated; during the late flexion phase mainly a prolongation of that phase with a variable change of the following extension phase was induced. In addition to this prevailing pattern, stimulation of some nerves (in particular nerves to more distal extensors and the sural nerve) could often prolong extension, when stimulated during the late extension, or terminate the flexor burst and initiate a new extension phase, when stimulated during the late flexion phase. This pattern is probably due to the concomitant stimulation of group I afferents in the case of the muscle nerves and to separate non-FRA pathways in the case of the sural nerve. The results demonstrate that the interneurones of the FRA pathways, which are operative during l-dopa-induced locomotion in spinal animals, can be considered as neuronal elements of the rhythm-generating network for locomotion.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002210050522
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    Evidence for a strychnine-sensitive mechanism and glycine receptors involved in the control of urethral sphincter activity during micturition in the cat (1998)
    Springer
    Experimental brain research 119 (1998), S. 297-306 
    Details
    ISSN: 1432-1106
    Keywords: Key words Spinal inhibition ; Interneurons ; Micturition ; Bladder-sphincter dyssynergia ; Cat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Micturition in the decerebrate cat is characterized by a coordinated bladder contraction and a simultaneous decrease in external urethral sphincter (EUS) efferent activity. Without the suppression of EUS activity, voiding is significantly impaired, resulting in a state sometimes referred to as bladder-sphincter dyssynergia. The aim of the present study was to determine whether glycinergic inhibition contributes to the suppression of EUS activity during micturition evoked by bladder distension or electrical stimulation of the pontine micturition center (PMC) in decerebrate cats. Using subconvulsive intravenous doses of strychnine (0.1–0.24 mg/kg), we examined changes in bladder and EUS electroneurographic (ENG) activity during micturition. Following subconvulsive doses of strychnine, tonic EUS ENG activity increased during bladder filling in five of six animals. In the presence of strychnine, it was possible to evoke reflex bladder contractions of similar duration and peak pressure to those observed before strychnine administration. However, there was an absence of suppression of EUS ENG activity during the bladder contractions in all the animals. To determine whether the changes in sphincter activity could be due to strychnine acting at glycine receptors on EUS motoneurons, sacral spinal tissue was processed for a structural protein (gephyrin) associated with the glycine receptor. Motoneurons in Onuf′s nucleus in S1 were identified using choline acetyltransferase immunohistochemistry and subsequently processed with a gephyrin monoclonal antibody. Abundant gephyrin labeling was evident throughout Onuf′s nucleus. Since Onuf′s nucleus is made up of EUS and other motoneuron populations, a sample of antidromically identified urethral and anal sphincter motoneurons were intracellularly labeled with tetramethylrhodamine dextran (TMR-D) and then processed with the gephyrin antibody. Using dual-beam confocal microscopy, gephyrin immunoreactivity was observed on the soma and proximal processes of individual EUS motoneurons in both male and female animals. It was concluded that a strychnine-sensitive mechanism contributes to the suppression of sphincter activity normally observed during voiding. Although glycinergic inhibition may affect several components of the circuitry responsible for micturition, it appears that the suppression of EUS motoneurons during micturition may be partly due to a direct glycinergic inhibition of the EUS motoneurons.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002210050345
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    Electronic Resource
    Activity of thoracic and lumbar epaxial extensors during postural responses in the cat (1998)
    Springer
    Experimental brain research 119 (1998), S. 315-323 
    Details
    ISSN: 1432-1106
    Keywords: Key words Stance posture ; Balance ; Epaxial muscles ; Cat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  This study examined the role of trunk extensor muscles in the thoracic and lumbar regions during postural adjustments in the freely standing cat. The epaxial extensor muscles participate in the rapid postural responses evoked by horizontal translation of the support surface. The muscles segregate into two regional groups separated by a short transition zone, according to the spatial pattern of the electromyographic (EMG) responses. The upper thoracic muscles (T5-9) respond best to posteriorly directed translations, whereas the lumbar muscles (T13 to L7) respond best to anterior translations. The transition group muscles (T10-12) respond to almost all translations. Muscles group according to vertebral level rather than muscle species. The upper thoracic muscles change little in their response with changes in stance distance (fore-hindpaw separation) and may act to stabilize the intervertebral angles of the thoracic curvature. Activity in the lumbar muscles increases along with upward rotation of the pelvis (iliac crest) as stance distance decreases. Lumbar muscles appear to stabilize the pelvis with respect to the lumbar vertebrae (L7-sacral joint). The transition zone muscles display a change in spatial tuning with stance distance, responding to many directions of translation at short distances and focusing to respond best to contralateral translations at the long stance distance.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002210050347
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  • 45
    Electronic Resource
    Electronic Resource
    The cat vertebral column: stance configuration and range of motion (1998)
    Springer
    Experimental brain research 119 (1998), S. 324-332 
    Details
    ISSN: 1432-1106
    Keywords: Key words Vertebral column ; Antigravity support ; Scapula ; Cat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  This study examined the configuration of the vertebral column of the cat during independent stance and in various flexed positions. The range of motion in the sagittal plane is similar across most thoracic and lumbar joints, with the exception of a lesser range at the transition region from thoracic-type to lumbar-type vertebrae. The upper thoracic column exhibits most of its range in dorsiflexion and the lower thoracic and lumbar in ventroflexion. Lateral flexion is limited to less than 5° at all segments. The range in torsion is almost 180° and occurs primarily in the midthoracic region, T4-T11. Contrary to the depiction in most atlases, the standing cat exhibits several curvatures, including a mild dorsiflexion in the lower lumbar segments, a marked ventroflexion in the lower thoracic and upper lumbar segments, and a profound dorsiflexion in the upper thoracic (above T9) and cervical segments. The curvatures are not significantly changed by altering stance distance but are affected by head posture. During stance, the top of the scapula lies well above the spines of the thoracic vertebrae, and the glenohumeral joint is just below the bodies of vertebrae T3-T5. Using a simple static model of the vertebral column in the sagittal plane, it was estimated that the bending moment due to gravity is bimodal with a dorsiflexion moment in the lower thoracic and lumbar region and a ventroflexion moment in the upper thoracic and cervical region. Given the bending moments and the position of the scapula during stance, it is proposed that two groups of scapular muscles provide the major antigravity support for the head and anterior trunk. Levator scapulae and serratus ventralis form the lateral group, inserting on the lateral processes of cervical vertebrae and on the ribs. The major and minor rhomboids form the medial group, inserting on the spinous tips of vertebrae from C4 to T4. It is also proposed that the hypaxial muscles, psoas major, minor, and quadratus lumborum could support the lumbar trunk during stance.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002210050348
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  • 46
    Electronic Resource
    Electronic Resource
    Slowly deteriorating insulin secretion and C-peptide production characterizes diabetes mellitus in infantile cystinosis (1998)
    Springer
    European journal of pediatrics 157 (1998), S. 738-742 
    Details
    ISSN: 1432-1076
    Keywords: Key words Diabetes mellitus ; Infantile cystinosis ; Insulin ; C-peptide ; Chronic renal failure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Infantile cystinosis, a rare lysosomal storage disease of cystine, leads to Fanconi syndrome and end-stage renal failure. After renal transplantation, no recurrence of the disease occurs in the graft, but other organ involvement becomes evident later in life. Diabetes mellitus has been associated with cystinosis, but the mechanisms of impaired glucose tolerance have not yet been characterized. Here, we studied glucose tolerance, glucose constant decay (k-values), insulin and C-peptide by intravenous glucose tolerance test (IVGTT) in eight patients with infantile cystinosis (three with impaired GFR (CRF) and five after kidney transplantation (KTX)). For comparison, 15 age-matched children with CRF and 15 age-matched KTX patients were analysed. Both early and second insulin secretion phases were diminished in patients with infantile cystinosis, whereas in CRF, k-values were no different from control patients. After renal transplantation, k-values were significantly lower in cystinotic patients with a markedly reduced early insulin secretion phase. There was a significant negative correlation between k-values and age in patients with cystinosis. Repetitive IVGTTs in these patients demonstrated progressive but rather slow loss of first phase insulin secretion and C-peptide production, suggesting a slowly reducing secretion potential of the beta cell due to cystine storage. Conclusion Unlike type I diabetes mellitus, glucose intolerance in patients with infantile cystinosis is characterized by a slow, progressive loss of insulin secretion and C-peptide production. For these patients, the data indicate a 50% risk of developing glucose intolerance by the age of 18 years. We recommend to perform intravenous glucose tolerance tests at 5-year intervals.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004310050926
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  • 47
    Electronic Resource
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    Changes in synaptology of adult cat spinal α-motoneurons after axotomy (1998)
    Springer
    Experimental brain research 118 (1998), S. 1-13 
    Details
    ISSN: 1432-1106
    Keywords: Key words Nerve injury ; Retrograde reaction ; Spinal cord ; Electron microscopy ; Cat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The aim of this electron-microscopic study was to analyze the distribution of synaptic contacts on the cell bodies and dendrites of permanently axotomized adult cat spinal α-motoneurons. Following transection and ligation of the medial gastrocnemius nerve, the synaptic covering of the cell bodies and three different dendritic compartments of homonymous α-motoneurons was analyzed quantitatively at 3, 6, and 12 weeks postoperatively. The synaptic boutons were classified according to their size and the shape of their synaptic vesicles. On the soma, a transient increase in the number of boutons was noted at 3 weeks and 6 weeks postoperatively, while after 12 weeks the bouton number had decreased to half of its normal value. The transient increase was mainly due to an increase in the number of F-type boutons. At 12 weeks postoperatively, the synaptic covering was reduced by 83% on the soma and by 57% on the proximal dendrites. In the distal dendritic regions, the values for synaptic covering remained largely unchanged. In summary, axotomized motoneurons exhibit a reduction in synaptic covering which is maximal on the cell body and becomes less pronounced centrifugally along the dendrites. However, if also taking into account the loss of distal dendritic branches that occurs in axotomized motoneurons, the total loss of boutons is several times larger in the dendrites than on the soma.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002210050249
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  • 48
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    Electronic Resource
    Differential activation of spinal dorsal horn units by subcutaneous formalin injection in the cat: an electrophysiological study (1998)
    Springer
    Experimental brain research 118 (1998), S. 14-18 
    Details
    ISSN: 1432-1106
    Keywords: Key words Subcutaneous formalin ; Dorsal horn ; Nociception ; Central neuronal changes ; Cat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  In our previous report we found that subcutaneous (s.c.) formalin injection into the cutaneous receptive field (RF) of dorsal horn wide-dynamic-range (WDR) units and nociceptive primary afferent units resulted in a tonic, long-lasting increase in firing. However, s.c. formalin injection only resulted in a short-lasting increase in firing of non-nociceptive primary afferent units. In the present study, by using extracellular single-unit recording techniques we further studied effects of s.c. formalin on response properties of identified superficial-layer nociceptive-specific (NS) units and deeper-layer, low-threshold mechanoreceptive (LTM) units of L7 dorsal horn in urethane-chloralose-anesthetized cats. s.c. formalin injection into the RF of NS units resulted in a tonic, long-lasting increase in firing (7.08 ± 0.42 spikes/s, n = 5), for more than 1 h, compared with the spontaneous background (1.42 ± 0.03 spikes/s, n = 5). Formalin injection into the RF of LTM units also resulted in an increase in firing; however, the duration was short-lasting, for 25–520 s (152.92 ± 46.73 s, n = 12). The present study demonstrated that s.c. injection of dilute formalin solution resulted in activation of not only nociceptive but also non-nociceptive dorsal horn units, suggesting that tissue injury caused by s.c. formalin results in vigorous injury discharges of peripheral nerve terminals, which subsequently leads to activation of primary afferent neurons and secondary dorsal horn neurons.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002210050250
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  • 49
    Electronic Resource
    Electronic Resource
    Short-term changes in neck muscle and eye movement responses following unilateral vestibular neurectomy in the cat (1998)
    Springer
    Experimental brain research 120 (1998), S. 439-449 
    Details
    ISSN: 1432-1106
    Keywords: Key words Antagonist neck muscles ; Eye movements ; Unilateral vestibular neurectomy ; Visual substitution ; Motor strategies ; Cat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The purpose of this study was to investigate changes in neck muscle and eye movement responses during the early stages of vestibular compensation (first 3 weeks after unilateral vestibular neurectomy, UVN). Electromyographic (EMG) activity from antagonist neck extensor (splenius capitis) and flexor (longus capitis) muscles and eye movements were recorded during sinusoidal visual and/or otolith vertical linear stimulations in the 0.05–1 Hz frequency range (corresponding acceleration range 0.003–1.16 g) in the head-fixed alert cat. Preoperative EMG activity from the splenius and longus capitis muscles showed a pattern of alternate activation of the antagonist neck muscles in all the cats. After UVN, two motor strategies were observed. For three of the seven cats, the temporal activation of the individual neck muscles was the same as that recorded before UVN. For the other four cats, UVN resulted in a pattern of coactivation of the flexor and extensor neck muscles because of a phase change of the splenius capitis. In both subgroups, the response patterns of the antagonist neck muscles were consistent for each cat independently of the experimental conditions, throughout the 3 weeks of testing. Cats displaying alternate activation of antagonist neck muscles showed an enhanced gain of the visually induced neck responses, particularly in the high range of stimulus frequency, and a gain decrease in the otolith-induced neck responses at the lowest frequency (0.25 Hz) only. By contrast, for cats with neck muscle coactivation, the gain of the visually induced neck responses was basically unaffected relative to preoperative values, whereas otolith-induced neck responses were considerably decreased in the whole range of stimulation. As concerns oculomotor responses, results in the two subgroups of cats were similar. The optokinetic responses were not affected by the vestibular lesion. On the contrary, otolith-induced eye responses showed a gain reduction and a phase lead. Deficits and short-term changes after UVN of otolith- and semicircular canal-evoked collic and ocular responses are compared.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002210050417
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  • 50
    Electronic Resource
    Electronic Resource
    Feline caudofemoralis muscle Muscle fibre properties, architecture, and motor innervation (1998)
    Springer
    Experimental brain research 121 (1998), S. 76-91 
    Details
    ISSN: 1432-1106
    Keywords: Key words Motor nucleus ; EMG ; Muscle architecture ; Muscle fiber ; Caudofemoralis ; Cat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Feline caudofemoralis (CF) is a promising preparation in which to study the properties of mammalian fast-twitch skeletal muscle, but little is known about its muscle fiber properties, architecture, and motor innervation. We used histochemical techniques to confirm that it contained predominantly type IIB fibers (95±2%, n=8, with six of eight muscles composed exclusively of type IIA and IIB fibers), but physiological experiments showed less fatiguability than for the type IIB component of medial gastrocnemius. This may be related to the surprisingly strong and regular recruitment of CF during repetitive tasks such as walking and trotting, which we demonstrated electromyographically. We measured muscle length over the anatomical range of motion for CF (∼0.6–1.2 L 0) and estimated working length during walking and trotting (∼0.95–1.15 L 0). The specific tension was similar to that of the exclusively slow-twitch soleus muscle (31.2±4.7 N/cm2 compared with 31.8±4.1 N/cm2; P〉0.8). Single fiber dissections of CF revealed a series-fibered architecture with a mean of 2.3 fibers, each 2.5 cm long, required to span the fascicle length. We identified two neuromuscular compartments in CF by cutting one of the two nerve branches innervating CF and depleting the glycogen stores in the intact motor units. These compartments were in parallel and extended the length of the muscle; their electromyographic activity was similar during various natural behaviors. CF and gluteus maximus motoneurons were labeled concurrently with a combination of fluorescent, retrograde tracers including Fluororuby, Fluorogold and Fast Blue. The CF motor nucleus was located in L7-S1, overlapping and intermingling extensively with the nucleus of the adjacent gluteus maximus muscle. Distributions of CF motoneuron diameter revealed one large peak around 50–55 µm, with relatively few small-diameter (less than 35 µm) cells. Using estimates of the total number of fibers in three muscles and the estimated number of α-motoneurons for those same muscles, we calculated a mean innervation ratio of ∼270, which is at the low end of the innervation ratios for type IIB motor units from other feline muscles and more similar to type IIA motor units. In general, CF appears to be a useful preparation in which to study the properties of fast-twitch muscle, but these properties may vary somewhat from type IIB fibers from different muscles.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002210050439
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    Indications for coupling between feline spinocervical tract neurones and midlumbar interneurones (1998)
    Springer
    Experimental brain research 119 (1998), S. 39-46 
    Details
    ISSN: 1432-1106
    Keywords: Key words Spinal cord ; Spinocervical tract ; Interneurones ; Cat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The possibility of collateral segmental actions of spinocervical tract (SCT) neurones upon interneurones with input from cutaneous and group II muscle afferents was investigated in deeply anaesthetized cats. To this end, intracellular and/or extracellular recordings were made from 35 dorsal horn and 15 intermediate zone interneurones in midlumbar segments of the spinal cord and effects of stimulation of the ipsilateral dorso-lateral funiculus (DLF) at C3 and C1 levels, i.e. below and above the lateral cervical nucleus where axons of SCT cells terminate, were compared. The stimuli applied at the C3 segment were within the range of stimuli (50–100 μA) required for antidromic activation of SCT neurones in the same experiment. Those applied at the C1 segment (200–500 μA) were at least 3 times stronger than C3 stimuli. Under the same experimental conditions, long ascending and descending tract neurones (dorsal spino-cerebellar and rubro-spinal tract neurones) with axons in the DLF were activated at similar thresholds from the C1 and C3 segments. Intracellular recordings were made from 29 interneurnoes of which 19 (65%) were dorsal horn and 10 (35%) were intermediate zone interneurones. Excitatory postsynaptic potentials (EPSPs) evoked by single stimuli applied at the C3 segment, but not the C1 segment, were found in 14 (48%) of those interneurones; their latencies (3.0–5.7 ms) and frequency following with only minimal temporal facilitation were as required for potentials being evoked monosynaptically by the fastest conducting SCT neurones. Extracellular recordings were made from 30 interneurones (24 dorsal horn and 6 intermediate zone interneurones), and in these neurones spike potentials induced from the C3, but not from the C1 segment, were evoked only by short trains of stimuli. However, their latencies from the first effective stimulus (4.3–5.4 ms) were compatible with mono- or oligosynaptically mediated collateral actions of SCT neurones. They were found in 10 (33%) of the 30 investigated interneurones. Similar effects of C3 stimuli were found in similar proportions of dorsal horn interneurones and intermediate zone interneurones. Indications were also found for synaptic actions evoked by C3 stimuli that could not be attributed to direct collateral actions of SCT neurones. In some intracellularly recorded dorsal horn interneurones, short-latency EPSPs were evoked from the C3 segment by the 2nd or 3rd stimulus in the train, but not by single stimuli. In other dorsal horn and intermediate zone interneurones, inhibitory postsynaptic potentials (IPSPs) were evoked from the C3 segment at minimal latencies (2.7–3.2 ms), which might be too short to allow their mediation via SCT neurones. We conclude that SCT neurones might be used to forward information from muscle group II and cutaneous afferents not only to neurones in the lateral cervical nucleus and via them to thalamus and cerebral cortex but also to interneurones in spinal reflex pathways. Thereby reflex actions evoked from group II and cutaneous afferents might be co-ordinated with responses mediated by supraspinal neurones. We conclude also that dorsal horn and intermediate zone mid-lumbar interneurones might contribute to the previously reported di-and poly-synaptic excitation or inhibition of postsynaptic dorsal column (PSDC), spinothalamic tract (STT) and spinomesencephalic tract (SMT) neurones by collateral actions of SCT cells. Thereby these interneurones might contribute to the co-ordination of responses mediated by various populations of supraspinal neurones.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002210050317
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    Electronic Resource
    Spatial disparity coding in the superior colliculus of the cat (1998)
    Springer
    Experimental brain research 119 (1998), S. 333-344 
    Details
    ISSN: 1432-1106
    Keywords: Key words Disparity sensitivity ; Binocular interactions ; Superior colliculus ; Stereopsis ; Cat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Cells in the superficial layers of the superior colliculus of the cat have mainly binocular receptive fields. The aim of the present experiment was to investigate the sensitivity of these cells to horizontal spatial disparity. Unit recordings were carried out in the superficial layers of the superior colliculus of paralyzed and anesthetized cats. Centrally located receptive fields were mapped, separated using prisms, and then stimulated simultaneously using two luminous bars optimally adjusted to the size of the excitatory region of the receptive fields. Only binocular cells were tested, and 65% of these units were found to be sensitive to spatial disparities. Some cells (20%) were clearly insensitive to spatial disparity and the remaining 15% showed complex, unclassifiable interactions. The sensitive cells could be divided into four classes based on their disparity-sensitivity profiles: 38% showed excitatory interactions, whereas 9% showed inhibitory interactions. Moreover, 11% and 7% of the cells responded, respectively, to crossed or uncrossed disparities, and were classified as near cells and far cells. Whereas the general shapes of the sensitivity profiles were similar to those of cells in areas 17–18, selectivity in the superior colliculus was significantly coarser. The superficial layers of the superior colliculus project topographically to the deep layers of the superior colliculus, which are known to contain circuits involved in the control of ocular movements. The results thus suggest that disparity-sensitive cells of the superior colliculus could feed information to these oculomotor neurons, allowing for the localization and fixation of objects on the appropriate plane of vision.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002210050349
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  • 53
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    Electronic Resource
    Mechanical sensitivity of muscle afferents in a nerve treated with colchicine (1998)
    Springer
    Experimental brain research 119 (1998), S. 391-398 
    Details
    ISSN: 1432-1106
    Keywords: Key words Mechanoreceptor ; Axoplasm ; Muscle spindle ; Colchicine ; Cat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The experiments reported here demonstrate that the mechanical sensitivity of peripheral nerve fibres typically seen after injury can be induced without overtly injuring the nerve, but by simply applying colchicine topically to the nerve. In cats anaesthetised with pentobarbitone sodium, the medial gastrocnemius nerve was exposed and 10 mM colchicine applied topically for 15 min. The animals recovered from the operation normally and showed no subsequent motor deficit. Six days later animals were re-anaesthetised, a laminectomy carried out and responses recorded in single afferents at the level of the dorsal root. It was found that many afferents, particularly those with conduction velocities in the group II–III range, had become sensitive to local mechanical stimulation of the nerve in the region treated with colchicine and showed slowly adapting responses to stretch of the nerve. Many of the smaller fibres exhibited spontaneous activity. Mechanically sensitive afferents exhibited impulse conduction blocks at the colchicine-treated site. Some afferents, which appeared to conduct impulses normally through the treated region, were associated with muscle receptors having normal response properties. However, other muscle receptors were clearly abnormal and were insensitive to muscle stretch or contraction or exhibited only phasic responses. When the nerve was cut proximal to the colchicine-treated site, some, but not all, spontaneous activity was abolished. It was subsequently shown using a collision technique that the activity in some axons had its origin in the cell body in the dorsal root ganglion. In one experiment, it was shown that after nerve section proximal to the colchicine-treated region three of five axons switched their activity from a peripheral to a central origin. It is postulated that colchicine disrupts fast axonal transport of mechanically sensitive or voltage-sensitive ion channels, from the cell body to the peripheral terminals of the axons, leading to an accumulation of these channels at the treated site. This induces mechanical sensitivity and spontaneous activity. It is postulated that interruption of a retrogradely transported signal induces the spontaneous activity in the cell body. These experiments suggest that an important influence is exerted by the cell body on the peripheral terminals of mechanoreceptors to confer on them their normal response properties.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002210050354
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  • 54
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    Positron emission tomography reveals changes in global and regional cerebral blood flow during noxious stimulation of normal and inflamed elbow joints in anesthetized cats (1998)
    Springer
    Experimental brain research 118 (1998), S. 439-446 
    Details
    ISSN: 1432-1106
    Keywords: Key words Positron emission tomography ; Articular nociception ; Cerebral blood flow ; Joint inflammation ; Cat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  In cats the global (gCBF) as well as the regional cerebral blood flow (rCBF) and blood pressure were measured before, during, and after noxious inward and outward rotations of normal and inflamed elbow joints. The animals were anesthetized with halothane and immobilized by gallamine triethiodide. The gCBF as well as the rCBF were measured using positron emission tomography (PET) with a camera specifically designed for use in small animals. Slow intravenous bolus injections of 15O-labeled water were followed by 3-min acquisition of regional radioactivity starting at the time of injection. In all experiments the gCBF as well as the blood pressure were increased by noxious inward-outward rotations of the normal and of the inflamed joint, whereas the blood pressure and the rCBF remained unchanged during bolus injections under control conditions (without any joint movement). Movements of the inflamed joint evoked significantly greater increases in blood pressure and gCBF than corresponding ones of the normal joint. These increases in gCBF were paralleled by increases in rCBF along the complete anterior to posterior axis of the brain. Again, the increases in rCBF were larger, more extensive and more uniform following the stimulation of the inflamed joint relative to the results obtained with stimulation of the normal joint. No significant laterality was seen, but when an atlas-based region of interest (ROI) analysis was carried out and when the individual variations in rCBF were removed with two-way ANOVA, significant differences were disclosed in rCBF between the stimulated condition and the resting condition in a large number of brain regions. In particular, noxious rotation of the normal (right) elbow joint induced a significant increase in rCBF over the cerebral cortex and in the right thalamus and hippocampus. The same stimulation of the (left) inflamed joint induced a significant increase in rCBF throughout the brain; the biggest increase being over the right posterior cortex. It is concluded that under the conditions of the present experiments the generally accepted autoregulation of the cerebral blood flow is not fully functioning, and various factors that may be responsible for this failure (which obscures rCBF differences) are discussed. The more pronounced increases in rCBF when moving inflamed joints instead of normal ones is thought to be a direct consequence of the peripheral sensitization of the articular nociceptors and the consequent central hyperexcitability induced in the articular nociceptive pathways.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002210050300
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  • 55
    Electronic Resource
    Electronic Resource
    Effect of head position on postural orientation and equilibrium (1998)
    Springer
    Experimental brain research 122 (1998), S. 175-184 
    Details
    ISSN: 1432-1106
    Keywords: Key words Balance ; Sensorimotor transformation ; Neck proprioception ; Vestibular system ; Cat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  This study examined (1) how changes in head position affect postural orientation variables during stance and (2) whether changes in head position affect the rapid postural response to linear translation of the support surface in the horizontal plane. Cats were trained to stand quietly on a moveable platform and to maintain five different head positions: center, left, right, up, and down. For each head position, stance was perturbed by translating the support surface linearly in 16 different directions in the horizontal plane. Postural equilibrium responses were quantified in terms of the ground reaction forces, kinematics, dynamics (net joint torques), body center of mass, and electromyographic (EMG) responses of selected limb and trunk muscles. A change in head position involved rotation of not only the neck but also the scapulae and anterior trunk. Tonic EMG levels were modulated in several forelimb and scapular muscles but not hindlimb muscles. Finally, large changes in head orientation in both horizontal and vertical planes did not hamper the ability of cats to maintain postural equilibrium during linear translation of the support surface. The trajectory of the body’s center of mass was the same, regardless of head position. The main change was observed in joint torques at the forelimbs evoked by the perturbation. Evoked EMG responses of forelimb and scapular muscles were modulated in terms of magnitude but not spatial tuning. Hindlimb responses were unchanged. Thus, the spatial and temporal pattern of the automatic postural response was unchanged and only amplitudes of evoked activity were modulated by head position.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002210050505
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  • 56
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    Electronic Resource
    Visually evoked cortical potentials in awake cats during saccadic eye movements (1998)
    Springer
    Experimental brain research 122 (1998), S. 203-213 
    Details
    ISSN: 1432-1106
    Keywords: Key words Saccadic suppression ; Corollary discharge ; Visually evoked potential ; Striate cortex ; Cat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Visually evoked potentials (VEPs) measured under conditions of retinal image stabilization that minimized the influences of visual masking and smearing were averaged from electroencephalographic records measured from striate cortex of three cats. The amplitudes of the VEPs increased around saccade initiation. The grating-evoked potentials obtained at different times relative to the saccade exhibited changes in waveform shape that could be attributed to a saccade-evoked potential. The changes in the shape of the waveform were reasonably accounted for by the summation of the grating-evoked potential (produced when the cat did not make a saccade) and an appropriately timed saccade-evoked potential. The fundamental amplitudes of the residual potentials were computed and found to vary across the time course of the saccade. These observations suggest that there are other influences besides visual masking that are exerted early in the visual pathway to modulate visual processing during saccadic eye movements. A corollary discharge process is the most likely candidate to exert these influences.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002210050508
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    Neuronal responsiveness to three-dimensional motion in cat posteromedial lateral suprasylvian cortex (1998)
    Springer
    Experimental brain research 122 (1998), S. 214-226 
    Details
    ISSN: 1432-1106
    Keywords: Key words Visual perception ; Three-dimensional motion ; Motion disparity ; Size change ; Posteromedial lateral suprasylvian cortex ; Cat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The neuronal responsiveness to three-dimensional (3D) motion in cat posteromedial lateral suprasylvian (PMLS) cortex was studied using a computer-controlled, stereoscopic 3D graphic display capable of reproducing the major visual cues for natural 3D motion, including motion disparity, size, texture, and shading changes. The animals were anesthetized with nitrous oxide supplemented with alphaxalone, and paralysis prevented eye movement. Systematic investigation of neuronal responsiveness to 3D motions in 26 different directions revealed that more than half of the PMLS cells were selectively responsive to approaching (AP cells, 112 of 271) or recessive motion (RC cells, 64 of 271). The remaining cells were selectively responsive to frontoparallel motion (FP cells, 49 of 271) or nonselectively responsive to motion in multiple directions (NS cells, 46 of 271). The dependency on these visual cues was investigated as a reduction in the response amplitude or the response selectivity for the removal of a single cue from the motion stimuli containing the full visual cues. The AP and RC cells showed a strong dependency on the motion disparity cue, moderate dependency on the size cue, and weak dependency on the texture and shading cues. The FP cells showed no dependency on those visual cues. The cue dependency analysis indicated the existence of nonlinear interactions between those visual cues. Comparison of the responses to a combination of the motion disparity and size cues with the summed responses to each of the individual cues revealed that the responses to the combined cues are roughly predicted as a linear sum between the preferred responses. This comparison also showed nonlinear summation between the nonpreferred responses, i.e., responses to the combined cues were smaller than the summed responses. A similar quasilinear summation of the preferred responses between the two eyes and a nonlinear summation of the nonpreferred responses were found in the AP and RC cells for the motion disparity stimulus. All of these observations indicate that quasilinear and nonlinear interactions of the responses to various stimulus elements underlie the 3D motion responsiveness of the PMLS cells.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002210050509
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    Prolonged GABAB receptor-mediated synaptic inhibition in the cat spinal cord: an in vivo study (1998)
    Springer
    Experimental brain research 121 (1998), S. 319-333 
    Details
    ISSN: 1432-1106
    Keywords: Key words Spinal cord ; Synaptic inhibition ; GABAA receptors ; GABAB receptors ; GABA antagonists ; Cat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  In pentobarbitone-anaesthetised spinal cats, a comparison was made of the effects of intravenous bicuculline hydrochloride, a GABAA-receptor antagonist, and several (-)-baclofen (GABAB-receptor) antagonists (CGP 35348, 46381, 56999A) on the prolonged inhibition of extensor-muscle monosynaptic reflexes, recorded from lumbar ventral roots, by brief or continuous tetanic stimulation of low-threshold afferent fibres of hindlimb flexor muscles. Two components of brief tetanus inhibition were detected. Whilst possibly of similar central latency, the inhibition associated with GABAB receptors had a longer time course than that reduced by bicuculline. Furthermore, whereas bicuculline reduced primary afferent depolarization, generated by the inhibitory volleys, and detected as dorsal-root potentials, such potentials were generally enhanced by intravenous baclofen antagonists. The inhibition of reflexes during and after continuous (333 Hz) tetanic flexor-nerve stimulation appeared to be predominantly associated with the activation of GABAB receptors. In the period following continuous tetanic flexor-nerve stimulation, during which monosynaptic extensor reflexes were reduced in amplitude, the action potentials of the intraspinal terminations of extensor-muscle group-Ia afferent fibres were reduced in duration, as detected by the time course of the recovery of the threshold to extracellular microstimulation following the arrival of an orthodromic impulse. A reduction in termination action-potential duration also accompanied the reduction by microelectrophoretic (-)-baclofen of the release of excitatory transmitter from group-Ia terminations, both presynaptic effects being blocked by microelectrophoretic baclofen antagonists. However, the reduction of the duration of the action potential of individual group-Ia terminations, which followed continuous flexor-nerve stimulation, was not sensitive to the baclofen antagonist CGP 55845A, but was diminished by bicuculline methochloride. Intravenously administered bicuculline hydrochloride, however, had little or no effect on the inhibition of reflexes following continuous flexor-nerve stimulation. These observations are discussed in the context of possible intraspinal pathways and pre- and postsynaptic mechanisms for GABAA and GABAB receptor-mediated inhibition of the monosynaptic excitation of spinal motoneurones and of the functional significance of central GABAB receptor-associated inhibitory processes, given the relatively minimal effects on motor activity and behaviour produced by baclofen antagonists that penetrate the mammalian blood-brain barrier.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002210050465
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    Role of the retrorubral nucleus in striatally elicited orofacial dyskinesia in cats: effects of muscimol and bicuculline (1998)
    Springer
    Psychopharmacology 140 (1998), S. 150-156 
    Details
    ISSN: 1432-2072
    Keywords: Key words Retrorubral nucleus ; A8 ; Oro-facial dyskinesia ; Striatum ; GABA ; Bicuculline ; Muscimol ; DPI (3 ; 4 dihydroxy-phenylimino)-2-imidazoline ; Cat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Orofacial dyskinesia (OFD) is a disorder characterized by involuntary movements of the oral and facial muscles. OFD attacks can be elicited acutely in cats by local injections of dopaminergic agents into the anterodorsal part (r-CRM) of the caudate nucleus. Because the dopaminergic A8 cell group, being embedded in the retrorubral nucleus (RRN), gives rise to fibres which terminate in the r-CRM, two questions arose: (1) whether the A8 cell group forms part of the circuitry that directs and/or modulates OFD, and (2) whether GABA-ergic compounds in the RRN play a role in OFD, and if so, whether a pharmacological GABA-ergic intervention of the activity in the RRN modulates or mediates OFD. For this purpose, the activity of the RRN was manipulated with local injections of the GABAA agonist muscimol and antagonist bicuculline. These local injections into the RRN were subsequently combined with manipulations of dopamine transmission in the r-CRM with local injections of the selective DAi receptor agonist (3,4-dihydroxyphenylimino)-2-imidazoline. The present study shows that local injections of GABA-ergic compounds into the RRN do not elicit OFD attacks in cats, but can modulate oral behaviour elicited from the r-CRM. The latter effect is dose dependent and GABA-ergic specific.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002130050752
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    Expression of type III hyperlipoproteinemia in patients homozygous for apolipoprotein E-2 is modulated by lipoprotein lipase and postprandial hyperinsulinemia (1998)
    Springer
    Journal of molecular medicine 76 (1998), S. 355-364 
    Details
    ISSN: 1432-1440
    Keywords: Key words Postprandial hyperlipoproteinemia ; Lipoprotein lipase ; Insulin ; Apolipoprotein E ; Hyperlipoproteinemia type III
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Type III hyperlipoproteinemia (HLP) is a multifactorial disorder associated with homozygosity for the apolipoprotein (apo) E-2 allele. Factors which may promote the development of HLP include lipoprotein lipase (LPL) and hyperinsulinemia. These factors were investigated in eight patients with type III HLP and in nine normolipidemic controls. In vitro the interaction of apoE with LPL was analyzed in cell binding assays. All type III HLP patients showed delayed triglyceride (TG) clearance and remnant lipoprotein accumulation in an oral fat tolerance test. Normolipidemic apoE-2/2 controls revealed normal TG clearance comparable to apoE3/3 controls. HLP patients showed lower LPL activity and mass than controls. Analysis of the LPL gene revealed an Asn 291→Ser mutation in three patients and a –93 T-G substitution combined with an Asp 9→Asn mutation in one control subject. In addition to LPL abnormalities, postprandial hyperinsulinemia was observed in five out of eight patients. In vitro LPL compensated the defective function of apoE-2 in mediating remnant lipoprotein binding to cells. In summary, seven out of eight patients with type III HLP showed LPL abnormalities and/or postprandial hyperinsulinemia. Together with the in vitro data these findings support a coordinate effect of apoE and LPL for the manifestation of type III HLP. Hyperinsulinemia appears to be an additional factor important for disease expression.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001090050227
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    Cellular regulation of islet hormone secretion by the incretin hormone glucagon-like peptide 1 (1998)
    Springer
    Pflügers Archiv 435 (1998), S. 583-594 
    Details
    ISSN: 1432-2013
    Keywords: Key words GLP-1 ; cAMP ; Insulin ; Calcium ; NIDDM ; Glucagon ; Islet ; GIP
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Glucagon-like peptide 1 is a gastrointestinally derived hormone with profound effects on nutrient-induced pancreatic hormone release. GLP-1 modulates insulin, glucagon and somatostatin secretion by binding to guanine nucleotide binding protein-coupled receptors resulting in the activation of adenylate cyclase and generation of cyclic adenosine monophosphate (cAMP). In the B-cell, cAMP, via activation of protein kinase A, interacts with a plethora of signal transduction processes including ion channel activity, intracellular Ca2+ handling and exocytosis of the insulin-containing granules. The stimulatory action of GLP-1 on insulin secretion, contrary to that of the currently used hypoglycaemic sulphonylureas, is glucose dependent and requires the presence of normal or elevated concentrations of the sugar. For this reason, GLP-1 attracts much interest as a possible novel principle for the treatment of human type-2 diabetes. Here we review the actions of GLP-1 on islet cell function and attempt to integrate current knowledge into a working model for the control of pancreatic hormone secretion.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004240050558
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    Asymmetry of the internal connections of the striate cortex of the cat in the projection zone of the center of the field of vision (1998)
    Springer
    Neuroscience and behavioral physiology 28 (1998), S. 211-217 
    Details
    ISSN: 1573-899X
    Keywords: Cat ; striate cortex ; internal connections ; horseradish peroxidase
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Studies were carried out on the organization of the internal connections of the striate cortex in cats in the projection zone of the center (0–5°) of the field of vision by microintophoretic application of horseradish peroxidase to electrophysiologically identified orientational columns. The area containing neurons showing retrograde labeling in most cases extended in the mediolateral direction. Labeled cells were located in the upper (II, III) and lower (V, VI) layers of the cortex, and the shapes and orientations of the areas containing labeled neurons in these layers coincided. Spatial asymmetry was detected in the distribution of labeled neurons relative to the orientational column studied. Labeled cells were located predominantly medial to the columns, regardless of the distance from the projection of the area centralis. Considering the visuotopical map of field 17, the asymmetry detected here provides evidence that neurons in orientational columns have more extensive connections with neurons of the peripheral part of the cortex. An asymmetrical distribution of “silent” zones around the receptive fields of neurons in orientational columns is suggested, and that these appear to receive influences from the periphery of the visual field.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02461970
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    Molecular imprinting technology: challenges and prospects for the future (1998)
    New York, NY [u.a.] : Wiley-Blackwell
    Chirality 10 (1998), S. 195-209 
    Details
    ISSN: 0899-0042
    Keywords: molecular imprinting ; molecular recognition ; chirality ; chromatography ; catalysis ; biosensor ; immunoassay ; antibody mimic ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Molecular imprinting is a technique for the fabrication of biomimetic polymeric recognition sites or “plastic antibodies/receptors” which is attracting rapidly increasing interest. By this technology, recognition matrices can be prepared which possess high substrate selectivity and specificity. In the development of this technology, several applications have been foreseen in which imprinted materials may be exchanged for natural recognition elements. Thus, molecularly imprinted polymers have been used as antibody/receptor binding mimics in immunoassay-type analyses, as enzyme mimics in catalytic applications and as recognition matrices in biosensors. The best developed application area for imprinted materials, though, has been as stationary phases for chromatography, in general, and chiral chromatography, in particular. This review seeks to highlight some of the more intriguing advantages of the technique as well as pointing out some of the difficulties encountered. The prospects for future development will also be considered. Chirality 10:195-209, 1998. © 1998 Wiley-Liss, Inc.
    Additional Material: 10 Ill.
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    Separation of (R)- and (S)-tert-butyl 2-tert-butyl-4-methoxy-2,5-dihydro-1,3-imidazole-1-carboxylate (building block for amino acid synthesis) by preparative high performance liquid chromatography on a polysaccharide stationary phase (1998)
    New York, NY [u.a.] : Wiley-Blackwell
    Chirality 10 (1998), S. 217-222 
    Details
    ISSN: 0899-0042
    Keywords: amylose ; 3,5-dimethylphenyl-carbamate ; polysaccharide phase ; tert-butyl 2-tert-butyl-4-methoxy-2,5-dihydro-1,3-imidazole-1-carboxylate; amino acid ester synthesis ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The preparative separation of the enantiomers of the title compound, a versatile chiral building block for the synthesis of unnatural amino acid esters, by high performance liquid chromatography on a chiral stationary phase (CSP), is reported for the first time. The CSP consists of amylose-(3,5-dimethylphenyl-carbamate), which has been coated onto the surface of macroporous aminopropyl-functionalized silica gel. The effect of mobile phase composition and the amount of amylose derivative on the silica gel has been thoroughly investigated. Using 2-propanol as organic modifier in hexane as mobile phase, on a semi-preparative column (200 mm × 40 mm ID, containing 192 g of stationary phase) about 200 mg of the racemate was separated per injection. Running the equipment under automatic conditions with repetitive injection mode allowed for the separation of 30 g per day. Both enantiomers were obtained with enantiopurities 〉99.75:0.25. Chirality 10:217-222, 1998. © 1998 Wiley-Liss, Inc.
    Additional Material: 5 Ill.
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  • 65
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    Species-dependent enantioselective pharmacokinetics of PNU-103017, a Pyrone HIV protease inhibitor (1998)
    New York, NY [u.a.] : Wiley-Blackwell
    Chirality 10 (1998), S. 210-216 
    Details
    ISSN: 0899-0042
    Keywords: enantiospecific assay ; rat ; dog ; human ; enantiomer disposition ; HIV protease inhibitor ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: PNU-103017, 4-Cyano-N-(3-(cyclopropyl(5,6,7,8,9,10-hexahydro-4-hydroxy-2-oxo-2H-cycloocta(b) pyran-3-yl)methyl)phenyl)-benzenesulfonamide, is a selective HIV aspartyl protease inhibitor under evaluation as a potential oral treatment of Acquired Immunodeficiency Diseases. PNU-103017 is a racemic mixture of two enantiomers, designated PNU-103264 (R-) and PNU-103265 (S-). Stereoselective pharmacokinetics of the two enantiomers of PNU-103017 were observed in the dog, rat, and human after single and multiple dose administration of the racemate and were apparently species-dependent. Mean enantiomeric ratios of plasma concentrations (R-/S-) at each time point were greater than 1 in the dog, ranging from 1.22 to 3.06, but less than 1 in the rat and in the human, ranging from 0.44 to 0.80 and 0.23 to 0.73, respectively. A trend towards increased or decreased (farther from 1:1, R-/S-) enantiomeric ratio of plasma concentrations with time after each administration was also observed. The enantiomeric ratio remained unchanged after multiple dose administration in the rat, dog, and human although enzyme induction and increased plasma clearance were observed for both enantiomers. Chirality 10:210-216, 1998. © 1998 Wiley-Liss, Inc.
    Additional Material: 6 Ill.
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    Chiral interaction and stochastic kinetics in stirred crystallization of amino acids (1998)
    New York, NY [u.a.] : Wiley-Blackwell
    Chirality 10 (1998), S. 238-245 
    Details
    ISSN: 0899-0042
    Keywords: chiral selectivity ; amino acid crystallization ; molecular recognition ; stochastic kinetics ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: A study of chirally selective interaction in the stirred crystallization of glutamic acid and lysine is presented. The crystallization of S-glutamic acid is influenced by the presence of S-lysine but not R-lysine. Crystal nuclei in stirred systems are produced due to secondary nucleation. Secondary nucleation is an autocatalytic process in which a crystal produces secondary nuclei due to fluid motion, and due to crystal stirrer and crystal-crystal collisions. As a result of this autocatalysis, small fluctuations in the nucleation rates are amplified and the kinetics show a marked stochastic behavior. We investigate the stochastic behavior in detail and propose a kinetic mechanism that explains both the increase and the statistical distribution of the crystallization times of S-glutamic acid due to the presence of S-Lysine. Chirality 10:238-245, 1998. © 1998 Wiley-Liss, Inc.
    Additional Material: 8 Ill.
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    Enantiomers of thalidomide: blood distribution and the influence of serum albumin on chiral inversion and hydrolysis (1998)
    New York, NY [u.a.] : Wiley-Blackwell
    Chirality 10 (1998), S. 223-228 
    Details
    ISSN: 0899-0042
    Keywords: thalidomide enantiomers ; in vitro kinetics ; blood distribution ; human serum albumin ; chiral inversion ; plasma protein binding ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The aim of this investigation was to elucidate the distribution and reactions of the enantiomers of thalidomide at their main site of biotransformation in vivo, i.e., in human blood. Plasma protein binding, erythrocyte: plasma distribution, and the kinetics of chiral inversion and degradation in buffer, plasma, and solutions of human serum albumin (HSA) were studied by means of a stereospecific HPLC assay. The enantiomers of thalidomide were not extensively bound to blood or plasma components. The geometric mean plasma protein binding was 55% and 66%, respectively, for (+)-(R)- and (-)-(S)-thalidomide. The corresponding geometric mean blood:plasma concentration ratios were 0.86 and 0.95 (at a haematocrit of 0.37) and erythrocyte:plasma distributions were 0.58 and 0.87. The rates of inversion and hydrolysis of the enantiomers increased with pH over the range 7.0-7.5. HSA, and to a lesser extent human plasma, catalysed the chiral inversion, but not the degradation, of (+)-(R)- and (-)-(S)-thalidomide. The addition of capric acid or preincubation of HSA with acetylsalicylic acid or physostigmine impaired the catalysis to varying extents. Correction for distribution in blood enhances previously observed differences between the pharmacokinetics of the enantiomers in vivo. The findings also support the notion that chiral inversion in vivo takes place mainly in the circulation and in albumin-rich extravascular spaces while hydrolysis occurs more uniformly in the body. In addition, the chiral inversion and hydrolysis of thalidomide apparently occur by several different mechanisms. Chirality 10:223-228, 1998. © 1998 Wiley-Liss, Inc.
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    Mechanistic aspects of the biogenesis of rose oxide in Pelargonium graveolens L'Héritier (1998)
    New York, NY [u.a.] : Wiley-Blackwell
    Chirality 10 (1998), S. 229-237 
    Details
    ISSN: 0899-0042
    Keywords: deuterium labelling ; menthocitronellol ; citronellol ; enantioselective multidimensional gas chromatography-mass spectrometry (enantio-MDGC-MS) ; dynamic headspace analysis ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Mechanistic aspects of the biogenesis of the chiral monoterpenoid rose oxide in Pelargonium graveolens L'Héritier are investigated using deuterium-labelled precursors. After administration of the precursors using the cut-stem method, the dynamic headspace extracts of the plants are analysed using multidimensional gas chromatography-mass spectrometry (enantio-MDGC-MS). It is unequivocally shown that this plant is able to convert citronellol and menthocitronellol into cis-/trans-rose oxide. Menthocitronellol is converted into rose oxide with a clearly detectable enantiodiscrimination. These facts may be explained with the presence of an oxidase, which is able to oxidize citronellol and menthocitronellol in allylic position. A photooxygenation mechanism including singlet oxygen as the oxidizing agent is rather unlikely. Chirality 10:229-237, 1998. © 1998 Wiley-Liss, Inc.
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    Chloroperoxidase-induced asymmetric sulfoxidation of some conformationally restricted sulfides (1998)
    New York, NY [u.a.] : Wiley-Blackwell
    Chirality 10 (1998), S. 246-252 
    Details
    ISSN: 0899-0042
    Keywords: sulfoxides ; chloroperoxidase ; asymmetric oxidation ; enantioselective ; episulfide ; gas chromatography ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Asymmetric sulfoxidation by means of a chloroperoxidase from Caldariomyces fumago and hydrogen peroxide as the oxygen source was studied for a series of sterically well-defined substrates. The stereochemistry of the sulfoxidation was the same for all substrates studied. While 2,3-dihydrobenzo[b]thiophene (1) is an excellent substrate (giving 99.5% yield and 99% e.e. of the (R)-sulfoxide), replacement of a methylene group by either a more sterically demanding group or a heteroatom caused a substantial decrease in reactivity or in reactivity as well as enantioselectivity. A further investigation of the lowered catalytic efficiency of chloroperoxidase with these substrates has been carried out in a series of competitive reactions. Thus, benzo[1,3]oxathiole (5) acted as a competitive inhibitor of the enzyme, whereas 1-thiochroman (2) and 1-thiochroman-4-one (3) were shown to be too sterically demanding to significantly compete for the active site. For the oxidation of 2, 3, and 5, it was found that in the low CPO concentration range the chemical yield after 60 min reaction time increased almost linearly with the amount of CPO used. The products from 2 and 3 could be obtained in over 80% yield with an e.e. exceeding 96%. Chloroperoxidase was also found to be an effective catalyst in the oxidation of labile episulfides, yielding the corresponding anti-sulfoxides quantitatively and giving 12% e.e. of (1R, 2R)-sulfoxide in the oxidation of propylene sulfide. Chirality 10:246-252, 1998. © 1998 Wiley-Liss, Inc.
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    1997 Chirality Medal (1998)
    New York, NY [u.a.] : Wiley-Blackwell
    Chirality 10 (1998), S. 281-281 
    Details
    ISSN: 0899-0042
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: No abstract.
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    Circular dichroism of axially chiral methaqualone, 3-Aryl-2-mercapto- and 3-aryl-2-alkylthio-4(3H)-quinazolinones: conformational dependence of CD and assignment of absolute configuration (1998)
    New York, NY [u.a.] : Wiley-Blackwell
    Chirality 10 (1998), S. 253-261 
    Details
    ISSN: 0899-0042
    Keywords: chiroptical properties ; Cotton effect ; atropisomerism ; quantum-mechanical calculation ; AM1 ; CNDO/S ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Rotational strengths calculated on the basis of quantum-mechanically obtained minimum energy geometries were used to determine the absolute configurations of axially chiral 3-aryl-4(3H)-quinazolinones from the sign of the observed Cotton effects (CEs). For the spectral data, CNDO/S calculations were used; for the geometries, ab initio (RHF/6-31G) and semiempirical (AM1) theories were used. Oscillator and rotational strengths of all excited states down to 200 nm were compared to experimental absorption and circular dichroism (CD) data. It was found that the sign of the 1Lb Cotton effects obtained for the enantiomers of methaqualone and derivatives of 3-aryl-2-alkylthio-4(3H)-quinazolinones can be correlated unambiguously with the absolute configuration. Furthermore, the sign of the Cotton effect of the π-π* transition of the thiocarbonyl chromophore of 3-aryl-2-mercapto-4(3H)-quinazolinones is suitable for a successful stereochemical correlation. Chirality 10:253-261, 1998. © 1998 Wiley-Liss, Inc.
    Additional Material: 9 Ill.
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    Sympathomimetic enantiomers and asthma (1998)
    New York, NY [u.a.] : Wiley-Blackwell
    Chirality 10 (1998), S. 262-272 
    Details
    ISSN: 0899-0042
    Keywords: airway ; beta2-agonist ; racemic ; eutomer ; distomer ; hyperreactivity ; bronchospasm ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Airways of asthma patients can become hyperresponsive to airway spasmogens following regular use of isoprenaline or β2-selective sympathomimetics. Hyperreactivity that results from acute exposure of animals to these drugs is pre-empted by vagal section (a procedure which does not influence spasmolytic efficacy of sympathomimetics), is not diminished by antagonism of β2-adrenoceptors and is not associated with loss of responsivity of β2-adrenoceptors in the airways. Since activation, modulation, or blockade of β2-adrenoceptors does not determine this form of hyperreactivity, the possibility that distomers may induce hyperreactivity must be considered. Ocular and vascular responses to distomers of sympathomimetics have long been recognised and, more recently, comparable observations have been made for the airways. Thus, reactivity of guinea-pig airways to spasmogens was increased following exposure to S-isoprenaline, S-salbutamol, or S-terbutaline and exposure to S-isoprenaline or S-salbutamol can intensify symptoms in asthmatics. Regular exposure to the racemate, especially during or following an allergic reaction, predisposes to expression of hyperreactivity, which is nullified, acutely, by the eutomer. These observations imply that biological effects of sympathomimetic distomers may contribute to morbidity and mortality in asthma patients. Chirality 10:262-272, 1998. © 1998 Wiley-Liss, Inc.
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  • 73
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    Immobilized vancomycin as chiral stationary phase in packed capillary liquid chromatography (1998)
    New York, NY [u.a.] : Wiley-Blackwell
    Chirality 10 (1998), S. 273-280 
    Details
    ISSN: 0899-0042
    Keywords: direct chiral separation ; mobile phase composition ; NSAIDs ; retention model ; vancomycin ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Fused silica-packed capillary columns containing vancomycin immobilized by reductive amination on an aldehyde-silica were used to separate enantiomers of some non-steroidal anti-inflammatory drugs. Attempts have been made to qualitatively explain the influence of various mobile phase compositions on the enantioselective retention. The effects of mobile phase pH, buffer, and organic modifier concentrations were investigated as well as the influence of salts of hydrophobic ions added to the mobile phase to induce ion pair retention. Chirality 10:273-280, 1998. © 1998 Wiley-Liss, Inc.
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    Carbamates of cellulose bonded on silica gel: Chiral discrimination ability as HPLC chiral stationary phases (1998)
    New York, NY [u.a.] : Wiley-Blackwell
    Chirality 10 (1998), S. 283-288 
    Details
    ISSN: 0899-0042
    Keywords: chiral HPLC ; cellulose carbamates ; enantiomeric resolution ; warfarin ; flurbiprofen ; lorazepam ; oxazepam ; pindolol ; tertatolol ; nicardipine ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Four cellulose mixed 10-undecenoate/carbamate derivatives, simultaneously bearing 10-undecenoyl and variously substituted phenylaminocarbonyl groups, were chemically bonded on allylsilica gel. The study of the effect of these substitutions on the performance of the resulting chiral supports, and a comparison with the recently described 10-undecenoate/3,5-dimethylphenylcarbamate derivative, are presented. In this study heptane/2-propanol or heptane/chloroform mixtures were used as mobile phases. Chirality 10:283-288, 1998. © 1998 Wiley-Liss, Inc.
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    Correlation between time reversal symmetry and chirality in certain molecular processes (1998)
    New York, NY [u.a.] : Wiley-Blackwell
    Chirality 10 (1998), S. 289-293 
    Details
    ISSN: 0899-0042
    Keywords: chirality ; time reversal symmetry ; asymmetric synthesis ; enantiomerism ; isomerism ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: If a molecule is identified not only by its static spatial constructions, but also by the motions at the sub-molecular level, application of time reversal symmetry operation to a certain molecule could lead to another distinguishable from the original in the sense of sub-molecular motions, a phenomenon now defined as time reversal isomerism. Assessment of the consideration of certain enantiomers as distinguishable time reversal isomers is suggested in order to evoke a comprehensive interpretation of a likely correlation between the two types of isomerisms. The conceptual basis of a connection between absolute asymmetric synthesis under the influence of external fields and the intrinsic time reversal symmetry violation at the molecular level is also established to encourage new experimental investigations on this theme. Chirality 10:289-293, 1998. © 1998 Wiley-Liss, Inc.
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    Synthesis of regioselectively substituted cellulose derivatives and applications in chiral chromatography (1998)
    New York, NY [u.a.] : Wiley-Blackwell
    Chirality 10 (1998), S. 294-306 
    Details
    ISSN: 0899-0042
    Keywords: cellulose ; regioselective derivatization ; chiral stationary phases ; liquid chromatography ; enantioseparation ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Various cellulose-2,3-bis-arylcarbamate-6-O-arylesters and cellulose-2,3-bis-arylester-6-O-arylcarbamates, designed to test the possible combined effects of the known tris-arylcarbamate and tris-arylester classes, were synthesized with high regioselectivity at O-C(6), and their use as CSPs in liquid chromatography for enantiomeric separations was investigated. The separations obtained with the synthesized CSPs were compared to the separations achieved on a self-packed reference column, consisting of cellulose-tris-(3,5-dimethylphenyl-carbamate) as CSP standard. Among the synthesized, regioselectively substituted cellulose derivatives, 2,3-bis-O-(3,5-dimethylphenylcarbamate)-6-O-benzoate-cellulose and 2,3-bis-O-(benzoate)-6-O-(3,5-dichlorophenylcarbamate)-cellulose gave the best CSPs for the separation of the test racemates. CSPs from regioselectively substituted cellulose derivatives seem to exhibit higher selectivities than cellulose-tris-(3,5-dimethylphenylcarbamate) for certain classes of racemic compounds. Chirality 10:294-306, 1998. © 1998 Wiley-Liss, Inc.
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    Enantiomeric separation of rac-indoprofen by a biocatalytic procedure (1998)
    New York, NY [u.a.] : Wiley-Blackwell
    Chirality 10 (1998), S. 321-324 
    Details
    ISSN: 0899-0042
    Keywords: NSAID ; esterification ; resolution ; Candida antarctica lipase ; rac-Indoprofen ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Lipase from Candida antarctica, commercially available immobilised on acrylic resin as Novozym® 435, allows for enantioselective esterification of rac-indoprofen (±)-1, with methanol in a dioxane-toluene solvent system. A double esterification process affords methyl ester (-)-(R)-2 in 85% e.e. and enantiopure (+)-(S)-1, both in good chemical yield. Chirality 10:321-324, 1998. © 1998 Wiley-Liss, Inc.
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    Kinetics of racemization of (+)- and (-)-diethylpropion: Studies in aqueous solution, with and without the addition of cyclodextrins, in organic solvents and in human plasma (1998)
    New York, NY [u.a.] : Wiley-Blackwell
    Chirality 10 (1998), S. 307-315 
    Details
    ISSN: 0899-0042
    Keywords: configurational stability ; pH ; temperature ; ionic strength ; phosphate buffer concentration ; plasma protein affinity ; native cyclodextrins ; cyclodextrin derivatives ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The configurational stability of (+)- and (-)-diethylpropion [(+)- and (-)-2-(diethyl)-1-phenyl-1-propanone or (+)- and (-)-DEP] was investigated systematically from chemical, pharmaceutical, and pharmacological aspects. The enantiomeric ratio was monitored directly with a recently developed stability-indicating enantioselective HPLC method.In aqueous solutions, the rate of racemization increased non-linearly with increasing pH and with increasing phosphate buffer concentration. The racemization rate showed a positive slope with increasing temperature and decreasing ionic strength.The racemization rates of (+)- and (-)-DEP in the presence of cyclodextrins (CDs) did not differ significantly. CDs that were added to (+)- and (-)-DEP in a molar ratio 5:1 showed the following effects after dissolution in 10 mM phosphate buffer (final pH 6.7): sulfobutyl ether-β-CD (SBE-β-CD) and methylated-β-CD (Me-β-CD) retarded racemization; whereas hydroxypropyl-β-CD (HP-β-CD), acetyl-γ-CD (Ac-γ-CD), acetyl-β-CD (Ac-β-CD), γ-CD, and β-CD showed a weak destabilising effect. In contrast to the described CDs, α-CD distinctly accelerated the rate of racemization.The configurational stability of (+)- and (-)-DEP was also studied under physiological conditions. The half-life of racemization in heparinised human plasma was for both enantiomers determined to be approximately 23-25 min.In phosphate buffer (10 mM, pH 7.4), rac-DEP showed a high, but unselective affinity towards human α1-acid glycoprotein (orosomucoid) immobilised on silica (Chiral AGP).The rate of racemization of the free base of (-)-DEP dissolved in organic solutions generally increases with the polarity of the solvating agent. Chirality 10:307-315, 1998. © 1998 Wiley-Liss, Inc.
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    Determination of the rotational barriers of atropisomeric polychlorinated biphenyls (PCBs) by a novel stopped-flow multidimensional gas chromatographic technique (1998)
    New York, NY [u.a.] : Wiley-Blackwell
    Chirality 10 (1998), S. 316-320 
    Details
    ISSN: 0899-0042
    Keywords: atropisomeric polychlorinated biphenyls (PCBs) ; Chirasil-Dex ; rotational barrier ; stopped-flow multidimensional gas chromatographic technique ; on-line enantiomerization kinetics ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The rotational barriers ΔG
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    Discrimination in resolving systems. III: Pseudoephedrine-mandelic acid (1998)
    New York, NY [u.a.] : Wiley-Blackwell
    Chirality 10 (1998), S. 325-337 
    Details
    ISSN: 0899-0042
    Keywords: diastereomeric salts ; molecular recognition ; hydrogen bonding ; thermal analysis ; crystallography ; solubility ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: (+)-(1S;2S)-Pseudoephedrine and racemic mandelic acid form three distinct diastereomeric salts from solutions in 95% ethanol. The least-soluble phase, a hemihydrate, contains the (2R)-mandelate. A salt phase of intermediate solubility is the unsolvated double salt, containing both the (2R)- and the (2S)-mandelate. The most-soluble salt phase contains the (2S)-mandelate. Mandelate configuration and order of solubility (based on the heats of fusion) is inverted from that found in the same system synthesized from chiral base and acid, and then crystallized from benzene solution. The (2R)-mandelate hemihydrate (-H2O at 349.5K, mp 391K), monoclinic, P21, a = 6.788(5), b = 29.415(35), c = 9.488(10)Å, β = 108.91(8)°, Z = 4 (2 ion-pairs/asymmetric unit). Intermediate double salt (2S)- and (2R)-mandelate, mp 377.6K, anorthic, P1, a = 7.758(4), b = 9.966(5), c = 13.366(6)Å, α = 72.99(4), β = 79.98(4), γ = 70.51(4)°, Z = 1 (2 ion-pairs/asymmetric unit). The (2S)-mandelate (mp 386.2K), orthorhombic, P212121, a = 7.079(6), b = 13.443(10), c = 18.820(14)Å, Z = 4 is identical to a salt made from a combination of enantiomeric moieties from benzene solution. While differing from ephedrine mandelates in configuration at one center, solubilities of pseudoephedrine mandelates in 95% ethanol are much larger. A comparison of molecular structure (non-polar and H-bonding) regions of pseudoephedrine and ephedrine mandelates shows similarities and differences that are tentatively linked to crystal properties. This study reemphasizes the necessity for consistency in solvent use in resolution and in phase identification and comparison because the phases produced are frequently dependent upon the solvent. Chirality 10:325-337, 1998. © 1998 Wiley-Liss, Inc.
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    Manipulation of chiral resolution for isoxazoline-based IIb/IIIa receptor antagonists using various mobile phase additives in subcritical fluid chromatography (1998)
    New York, NY [u.a.] : Wiley-Blackwell
    Chirality 10 (1998), S. 338-342 
    Details
    ISSN: 0899-0042
    Keywords: additive ; selectivity ; efficiency ; modifier ; subcritical fluid chromatography ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Subcritical fluid chromatography (SubFC) using a carbon dioxide-methanol mobile phase is used for the chiral resolution of IIb/IIIa receptor antagonist enantiomers. The chiral resolution of three analogs, each containing two chiral centers, is optimized using various mobile phase additives. The effects that acidic, basic, and neutral additives have on retention, efficiency, and resolution are examined. The additive that gives the best resolution was found to be dependent upon the functionality and charge of the chiral analyte. For charged analytes, additives that act as competing ions of the same charge as the chiral analyte dramatically improve efficiency and resolution. Resolution of neutral chiral analyte enantiomers is also greatly affected by the choice of mobile phase additive. Chirality 10:338-342, 1998. © 1998 Wiley-Liss, Inc.
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    Mechanism of chiral asymmetry generation by chiral autocatalysis in the preparation of chiral octahedral cobalt complex (1998)
    New York, NY [u.a.] : Wiley-Blackwell
    Chirality 10 (1998), S. 343-348 
    Details
    ISSN: 0899-0042
    Keywords: chiral asymmetry generation ; chiral autocatalysis ; primary nucleation ; secondary nucleation ; chiral cobalt complex ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Chiral asymmetry generation, the predominant production of one enantiomer in a non-chiral environment, could occur in the production of the chiral complex cis-[CoBr(NH3)(en)2]Br2 by the reaction of [Co(H2O)2{(OH)2Co(en)2}2](SO4)2 with ammonium bromide in an aqueous medium. The main kinetic steps in the reaction system have been determined. During the reaction, the product crystallizes at an early stage. When a very small amount of crystalline enantiomer was added to the reaction system at an early stage, the same enantiomer was produced preferentially; in addition, the enantiomeric excess of the product increased with increasing the stirring rate. Thus, it seems that each enantiomer generates chiral crystals that could self-replicate through secondary nucleation when the solution is stirred; these crystals in turn enhance the production of the same enantiomer. With a computer code that simulates such a kinetic mechanism, it is shown that enantiomeric excess observed in the experiments could be reproduced. Chirality 10:343-348, 1998. © 1998 Wiley-Liss, Inc.
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    Stereoselective renal secretion of carbenicillin in rabbits: Role of the organic anion transporter at the renal brush border membrane (1998)
    New York, NY [u.a.] : Wiley-Blackwell
    Chirality 10 (1998), S. 349-357 
    Details
    ISSN: 0899-0042
    Keywords: carbenicillin ; stereoselective ; secretion ; transport ; rabbit ; membrane vesicles ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Stereoselectivity in the renal secretion of carbenicillin (CBPC) was studied in rabbits. Significant renal secretion of CBPC was observed in vivo, with the secretion of the S-epimer being greater than that of the R-epimer. Stereoselective transport of CBPC was further studied in vitro using basolateral and brush border membrane vesicles prepared from rabbit kidneys. The transport of CBPC by the organic anion transporter into the basolateral membrane vesicles (BLMV) was not stereoselective. In contrast, a distinct stereoselectivity was observed in the transport of CBPC by the organic anion transporter into the brush border membrane vesicles (BBMV), with the transport of the S-epimer being more favorable. Significant epimer-epimer interactions were also observed in the transport into BBMV. The stereoselectivity of the transport of CBPC was calculated from the kinetic parameters with consideration of epimer-epimer interactions and was similar to that observed in vivo. It was concluded that the observed stereoselectivity in the renal secretion of CBPC in vivo reflected that of transport via the organic anion transporter located at the brush border membrane. Chirality 10:349-357, 1998. © 1998 Wiley-Liss, Inc.
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    Emanuel Gil-Av honorary issue of Chirality (1998)
    New York, NY [u.a.] : Wiley-Blackwell
    Chirality 10 (1998), S. 371-372 
    Details
    ISSN: 0899-0042
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: No abstract.
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    Determination of the enantiomeric purity of commercial Jacobsen's catalyst samples (1998)
    New York, NY [u.a.] : Wiley-Blackwell
    Chirality 10 (1998), S. 362-363 
    Details
    ISSN: 0899-0042
    Keywords: Jacobsen's catalyst ; enantiomeric purity determination ; chiral HPLC ; cyclodextrin chiral stationary phases ; enantioseparation ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: A HPLC method is described for the chiral analysis of the commercially available Jacobsen's catalyst. A hydroxypropyl β-cyclodextrin stationary phase was used in conjunction with a nonaqueous, polar-organic mobile phase. The method can be applied to control the enantiomeric purity of the catalyst, which is of great importance for quality control of that product. High accuracy in the determination of trace levels of the unwanted enantiomer in the presence of large amounts of the desired enantiomer is demonstrated. Chirality 10:362-363, 1998. © 1998 Wiley-Liss, Inc.
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    Enantiomeric separation of several cyclic imides on a macrocyclic antibiotic (vancomycin) chiral stationary phase under normal and reversed phase conditions (1998)
    New York, NY [u.a.] : Wiley-Blackwell
    Chirality 10 (1998), S. 358-361 
    Details
    ISSN: 0899-0042
    Keywords: cyclic imides ; barbiturates ; piperidine-2,6-diones ; mephenytoin ; chiral recognition ; enantioselectivity ; vancomycin chiral stationary phase ; normal-phase mode ; reversed-phase mode ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Several cyclic imidic compounds (barbiturates, piperidine-2,6-diones, and mephenytoin) are enantiomerically resolved via high-performance liquid chromatography (HPLC) on a macrocyclic antibiotic covalently bonded to a silica gel support. The Chirobiotic V chiral stationary phase (CSP) column contains the antibiotic vancomycin as the chiral selector. The results of the analysis show that the substituents at the chiral carbon position of the racemic drugs affect chiral resolution. In addition, ring size may also play a role when considering the formation of analyte-CSP inclusion complexes. Contrary to the piperidine-2,6-diones, the chromatographic parameters for the barbiturates are much the same under normal- or reversed-phase conditions. The details of these results are discussed. Chirality 10:358-361, 1998. © 1998 Wiley-Liss, Inc.
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    Emanuel Gil-Av (1916-1996): A man with a legacy (1998)
    New York, NY [u.a.] : Wiley-Blackwell
    Chirality 10 (1998), S. 373-374 
    Details
    ISSN: 0899-0042
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: No abstract.
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    Separation of nicotine and nornicotine enantiomers via normal phase HPLC on derivatized cellulose chiral stationary phases (1998)
    New York, NY [u.a.] : Wiley-Blackwell
    Chirality 10 (1998), S. 364-369 
    Details
    ISSN: 0899-0042
    Keywords: (±)nicotine ; (±)nornicotine ; chiral separation ; enantiomers ; normal phase HPLC ; mobile phase additive ; cellulose-based chiral stationary phase ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: This paper describes the enantiorecognition of (±)nicotine and (±)nornicotine by high-performance liquid chromatography using two derivatized cellulose chiral stationary phases (CSPs) operated in the normal phase mode. It was found that different substituents linked to the cellulose backbone significantly influence the chiral selectivity of the derivatized CSP. The results showed that, in general, the tris(4-methylbenzoyl) cellulose CSP (Chiralcel OJ) surpasses tris(3,5-dimethylphenyl carbamoyl) cellulose CSP (Chiralcel OD). On the former column, the resolution (±)nicotine and (±)nornicotine enantiomers depended largely on mobile phase compositions. For the separation of the nicotine enantiomers, the addition of trifluoroacetic acid to a 95:5 hexane/alcohol mobile phase greatly improved the enantioresolution, probably due to enhanced hydrogen bonding interactions between the protonated analytes and the CSP. For (±)nornicotine separation, a reduction in the concentration of alcohol in the mobile phase was more effective than the addition of trifluoroacetic acid. Possible solute-mobile phase-stationary phase interactions are discussed to explain how different additives in the mobile phase and different substituents on the cellulose glucose units of the CSPs affect the separation of both pairs of enantiomers. Chirality 10:364-369, 1998. Published 1998 Wiley-Liss, Inc.This article is a US Government work and, as such, is in the public domain in the United States of America.
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    Chiral separation of enantiomers via selector/selectand hydrogen bondings (1998)
    New York, NY [u.a.] : Wiley-Blackwell
    Chirality 10 (1998), S. 382-395 
    Details
    ISSN: 0899-0042
    Keywords: selector/selectand associates ; hydrogen bonding ; chiral separation ; chiral phases ; enantioselectivity ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The progress made in the development of chiral stationary phases based on hydrogen-bonding selector/selectand associates is reviewed here. The structure of the different selectand/selector systems was established through X-ray diffraction and other spectroscopic techniques. The structure of the energetically more stable diastereomeric-associate was then correlated to the chromatographic results, namely to the elution order and the enantioselectivity of each of the systems. Chirality 10:382-395, 1998. © 1998 Wiley-Liss, Inc.
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    A closer study of chiral retention mechanisms (1998)
    New York, NY [u.a.] : Wiley-Blackwell
    Chirality 10 (1998), S. 375-381 
    Details
    ISSN: 0899-0042
    Keywords: retention mechanisms ; separation of enantiomers ; chiral stationary phases ; equilibrium isotherms ; bonding ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The retention mechanisms and the separation of enantiomers on the classes of chiral stationary phases which are made by bonding isolated groups on the surface of an adsorbent are discussed. It is shown that retention on these phases originates from mixed mechanisms and how the individual contributions of these two mechanisms can be separated, by determining and modeling the equilibrium isotherms. A contribution originating from interactions of the isomers with the nonselective sites (type-I) and another one due to interactions with the enantioselective sites (type-II) can be determined and their importance studied as a function of several parameters, e.g., temperature or pH. This approach is illustrated with results obtained with different pairs of enantiomers on bovine serum albumin, 4-methylcellulose tribenzoate, or cellobiohydrolase immobilized on silica. Chirality 10:375-381, 1998. © 1998 Wiley-Liss, Inc.
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    Tripodal trispeptide selector as a model for establishing the importance of hydrogen-bonding in enantiomer-separation (1998)
    New York, NY [u.a.] : Wiley-Blackwell
    Chirality 10 (1998), S. 396-404 
    Details
    ISSN: 0899-0042
    Keywords: chirality ; helicity ; GC-stationary phase ; conformations ; 1H-NMR-studies ; molecular mechanics calculations ; enantiomer separation ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The manner of hydrogen-bonding to peptide selectors in enantiomer separation is examined with the help of a structural model. This model relies on a C3-symmetric trispeptide selector, which is stabilized by a network of distinct intramolecular hydrogen bonds. A combination of experimental and theoretical tools enables us to identify the lowest-energy conformation of the trispeptide selector and the sites of selector-substrate interactions. Experimental tools include temperature dependent 1H-NMR studies, 1D-NOE-measurements, and titration experiments, with the theoretical tools being EFF and CFF91 molecular mechanics calculations. The structural information deduced from these investigations is shown to bear on the enantioseparation of the corresponding chiral stationary phase towards derivatized amino acids. These observations, taken together, help to rationalize the mode of enantiomer-separation by amide phases as involving predominantly C7-hydrogen bonding sites. Chirality 10:396-404, 1998. © 1998 Wiley-Liss, Inc.
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    The chiral code: From DNA primary structures to quaternary assemblies (1998)
    New York, NY [u.a.] : Wiley-Blackwell
    Chirality 10 (1998), S. 405-414 
    Details
    ISSN: 0899-0042
    Keywords: chiral-discrimination ; homochirality ; stereospecificity ; self-assembly ; supercoiling ; cholesteric mesophase ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Nucleic acids are characterized by a predominant right-handed helical configuration that derives from the chirality of the sugar moiety. Hitherto, only “local” effects of this helical asymmetry, exemplified by DNA interactions with small compounds, have been documented. The results described in this study indicate that an enhanced asymmetry is required for the manifestation of chiral effects in DNA self-assembly processes or for chiral discrimination upon interactions with peptides. Two cases in which the intrinsic DNA asymmetry is enhanced are reported: rod-like superhelical species derived from linear DNA molecules, and topologically constrained supercoiled DNA. In the first case, the superhelical grooves within the DNA rods allow for a stereospecific complexation with peptides, resulting in chiral discrimination. In the second case, it is shown that the properties of cholesteric assemblies derived from supercoiled DNA are strictly determined by the enhanced asymmetry associated with molecular supercoiling. The results allow for new reflections on the concept of molecular complementarity, and indicate that spontaneously obtained chiral DNA mesophases might have played a key role in determining terrestrial homochirality. Chirality 10:405-414, 1998. © 1998 Wiley-Liss, Inc.
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    Aspects of spontaneous separation of enantiomers in two- and three-dimensional crystals (1998)
    New York, NY [u.a.] : Wiley-Blackwell
    Chirality 10 (1998), S. 415-424 
    Details
    ISSN: 0899-0042
    Keywords: chiral separation ; two- and three-dimensional crystals ; grazing incidence X-ray diffraction ; atomic force microscopy ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Spontaneous separation of enantiomers in two- and three-dimensional crystals is driven by the same thermodynamic and kinetic factors. However, amphiphilic crystalline monolayers at an interface cannot possess a center of inversion, the most common symmetry element in bulk crystals. This fact should, in principle, lead to better chances for spontaneous separation in the Langmuir or Langmuir-Blodgett monomolecular films. On the other hand, the monolayers of most amphiphiles studied to date incorporate long aliphatic chains that have an intrinsic tendency to pack in a herring-bone motif requiring glide plane symmetry, thus creating a bias towards racemate formation. Moreover, 2-D crystals supposedly have a much higher degree of molecular and therefore enantiomeric disorder compared to bulk crystals. All these factors necessitate a careful choice of molecules to guarantee enantiomeric separation in two dimensions. Unambiguous detection of spontaneous resolution in 2-D appears to require atomic resolution of molecular packing arrangement, which can in principle be obtained by grazing incidence X-ray diffraction or atomic force microscopy, whereas in bulk solids spontaneous resolution can be easily detected by various macroscopic methods. This short review provides analogies between spontaneous separation in 3-D and recent examples in 2-D, showing that spontaneous separation generally depends upon subtle differences in molecular structure. Chirality 10:415-424, 1998. © 1998 Wiley-Liss, Inc.
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    Determination of the rotational barriers of atropisomeric polychlorinated biphenyls (PCBs) by a novel stopped-flow multidimensional gas chromatographic techniqueThis article was orginally published in Chirality, Volume 10, Number 4, pages 316-320. As it is suited to the theme of this issue, this article appears again here. All citations to this article should use the original volume, issue, and page range. (1998)
    New York, NY [u.a.] : Wiley-Blackwell
    Chirality 10 (1998), S. 425-429 
    Details
    ISSN: 0899-0042
    Keywords: atropisomeric polychlorinated biphenyls (PCBs) ; Chirasil-Dex ; rotational barrier ; stopped-flow multidimensional gas chromatographic technique ; on-line enantiomerization kinetics ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The rotational barriers ΔG† (T) of the four atropisomeric polychlorinated biphenyls (PCBs) 2,2′,3,5′,6-pentachlorobiphenyl (PCB 95), 2,2′3,3′,4,6′-hexachlorobiphenyl (PCB 132), 2,2′,3,3′,6,6′-hexachlorobiphenyl (PCB 136), and 2,2′,3,4′,5′,6-hexachlorobiphenyl (PCB 149) were determined via on-line enantiomerization kinetics by a new stopped-flow multidimensional gas chromatographic technique (stopped-flow MDGC) employing Chirasil-Dex as chiral stationary phase for enantiomer separation. The calculated rotational barriers ΔG† (T) of the trichloro-ortho-substituted atropisomers are 184 ± 2 kJ/mol for PCB 95, 189 ± 4 kJ/mol for PCB 132, and 184 ± 1 kJ/mol for PCB 149 at 300°C. The rotational barrier ΔG† (T) of tetrachloro-ortho-substituted PCB 136 is at least (or higher than) 210 kJ/mol at 320°C. Chirality 10:425-429, 1998. © 1998 Wiley-Liss, Inc.
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  • 95
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    Chiral recognition of phthalides and lactams (1998)
    New York, NY [u.a.] : Wiley-Blackwell
    Chirality 10 (1998), S. 430-433 
    Details
    ISSN: 0899-0042
    Keywords: Whelk-O 1 ; chromatography ; HPLC ; enantiodifferentiation ; heterocycles ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: In concert with a larger study of the processes by which chiral stationary phase CSP 1 differentiates between enantiomers, we have investigated the chromatographic separation of the enantiomers of a series of aryl-substituted heterocycles of systematically varied structure. A mechanistic picture of how these and similar resolutions occur is emerging. The mechanistic hypothesis described herein is of predictive value. Chirality 10:430-433, 1998. © 1998 Wiley-Liss, Inc.
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  • 96
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    Highly enantioselective HPLC separations using the covalently bonded macrocyclic antibiotic, ristocetin A, chiral stationary phase (1998)
    New York, NY [u.a.] : Wiley-Blackwell
    Chirality 10 (1998), S. 434-483 
    Details
    ISSN: 0899-0042
    Keywords: ristocetin A ; macrocyclic antibiotic ; enantiomeric separations ; underivatized amino acids ; chiral stationary phase ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The macrocyclic glycopeptide, ristocetin A, was covalently bonded to a silica gel support and evaluated as a liquid chromatographic (LC) chiral stationary phase (CSP). Over 230 racemates were resolved in either the reversed-phase mode, the normal-phase mode, or the polar-organic mode. The retention behavior and selectivity of this CSP were examined in each mode. Optimization of separations on this column is discussed. The ristocetin A CSP appeared to be complimentary to other glycopeptide CSPs (i.e., vancomycin and teicoplanin). Column stability was excellent. The CSP was not irreversibly altered when going from one mobile phase mode to another. Chirality 10:434-483, 1998. © 1998 Wiley-Liss, Inc.
    Additional Material: 10 Ill.
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  • 97
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    Determination of the enantiomers of albuterol in human and canine plasma by enantioselective high-performance liquid chromatography on a teicoplanin-based chiral stationary phase (1998)
    New York, NY [u.a.] : Wiley-Blackwell
    Chirality 10 (1998), S. 484-491 
    Details
    ISSN: 0899-0042
    Keywords: salbutamol ; chiral separation ; validated assay ; fluorescence detection ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: A sensitive enantioselective high-performance chromatographic (HPLC) method was developed and validated to determine low levels of (-)-R and (+)-S-albuterol in plasma. Baseline resolution was achieved by using a teicoplanin-based chiral stationary phase with a polar organic mobile phase consisting of methanol/acetonitrile/glacial acetic acid/diethylamine, 40:60:0.3:0.2, (v/v/v/v) and a flow-rate of 1.0 ml/min. Enantioselectivity (α) equaled 1.18 and resolution (Rs) equaled 1.8. By using fluorescence detection maximized at 230 and 310 nm for excitation and emission, respectively, concentrations of each enantiomer could be measured down to 125 pg/ml from a 1-ml plasma sample. Initially, the method was applied to plasma samples from a small single-dose inhalation study of racemic albuterol in a human volunteer and, later, to in vivo samples from a canine inhalation study of the single enantiomer, (-)-R-albuterol. Results from the canine study showed that no chiral inversion of (-)-R-albuterol occurs in the dog. Chirality 10:484-491, 1998. © 1998 Wiley-Liss, Inc.
    Additional Material: 5 Ill.
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  • 98
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    Achiral derivatization as a means of improving the chromatographic resolution of racemic alcohols on benzoylcellulose CSPs (1998)
    New York, NY [u.a.] : Wiley-Blackwell
    Chirality 10 (1998), S. 492-498 
    Details
    ISSN: 0899-0042
    Keywords: racemate ; enantiomer ; HPLC ; chiral stationary phase ; benzoylcellulose ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The advantages that can be gained from derivatization of various racemic aliphatic and aromatic alcohols prior to enantiomeric chromatographic separation have been systematically investigated for a series of benzoate derivatives. Three cellulose-based CSPs available in the pure polymeric form - tribenzoyl cellulose (TBC), meta-methylbenzoyl cellulose (MMBC), and para-methylbenzoyl cellulose (PMBC) - were selected and several benzoate derivatives varying in the nature and the position of the substituent on the benzoyl group were prepared and analysed. TBC clearly gives the broadest application range, and among the different benzoate esters the best selectivity was generally obtained with either the 4-methoxybenzoate or the 4-methylbenzoate derivatives. Based on these results, some empirical rules could be formulated for optimizing the enantiomeric separation of racemic alcohols, which make up one of the most important classes of chemical substances used as drugs and biocides, or as building blocks for their synthesis. An application of this approach to the preparative separation of the enantiomers of a drug intermediate is also shown. Chirality 10:492-498, 1998. © 1998 Wiley-Liss, Inc.
    Additional Material: 5 Ill.
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  • 99
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    Enantioselective capillary gas chromatography in the investigation of stereochemical correlations of terpenoids (1998)
    New York, NY [u.a.] : Wiley-Blackwell
    Chirality 10 (1998), S. 499-504 
    Details
    ISSN: 0899-0042
    Keywords: enantioselective capillary gas chromatography ; cyclodextrin derivatives ; stereochemistry of terpenes ; monoterpenes ; essential oils ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Capillary gas chromatography employing the unique selectivities of specifically substituted cyclodextrins is highly suited for stereochemical investigations of terpenoid compounds. The analysis of many essential oils have shown that monoterpene derivatives regularly occur as enantiomeric mixtures. In the case of sesquiterpene hydrocarbons, liverworts (Hepaticae) and other lower organisms usually biosynthesize compounds of opposite stereochemistry as compared to higher plants and enantiomeric mixtures occur only occasionally. The investigation of diterpene hydrocarbons has so far shown no indication of the presence of both enantiomers in the same plant. Chirality 10:499-504, 1998. © 1998 Wiley-Liss, Inc.
    Additional Material: 7 Ill.
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  • 100
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    Determination of drug levels in human serum by circular dichroism (1998)
    New York, NY [u.a.] : Wiley-Blackwell
    Chirality 10 (1998), S. 507-512 
    Details
    ISSN: 0899-0042
    Keywords: chiroptical method ; drug analysis ; β-lactam antibiotics ; CD spectroscopy ; human fluids ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: A study of the applicability of circular dichroism (CD) for the determination of drug levels in human serum is described and a new method for the quantitative determination of optically active absorbing drugs having Cotton effects at wavelengths above 250 nm in human serum and/or plasma is proposed. The principal advantages of this method are speed, economy, and simplicity, no derivatization or chromatographic separation steps being needed. The validity of the CD determination was confirmed by analysis of variance, β-lactam antibiotics being chosen as model drugs. In addition, the validation studies performed confirm the accuracy and precision of the proposed method. For β-lactam antibiotics lacking Cotton effects above 250 nm, an alternative method based on the extraction of the drug from serum is considered. Chirality 10:507-512, 1998. © 1998 Wiley-Liss, Inc.
    Additional Material: 5 Ill.
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