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  • 1
    Electronic Resource
    Electronic Resource
    Effects of L-leucine on the insulin production, oxidative metabolism and mitochondrial ultrastructure of isolated mouse pancreatic islets in tissue culture (1977)
    Springer
    Diabetologia 13 (1977), S. 59-69 
    Details
    ISSN: 1432-0428
    Keywords: Pancreatic islets ; tissue culture ; ultrastructure ; morphometry ; mitochondria ; L-leucine ; B-cell function
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary This study was performed to evaluate whether L-leucine is able to relieve the structural and functional alterations previously described in pancreatic islets exposed in vitro for a prolonged time to a subnormal glucose concentration (3.3 mM). It was found that both the impairment of secretion and the decreased rate of biosynthesis of insulin characteristic, of islets cultured for one week in 3.3 mM glucose were prevented by adding 15 mM L-leucine to the culture medium. Furthermore, the rates of tritiated water production and glucose or leucine oxidation were significantly enhanced after culture in the presence of L-leucine. The rate of DNA synthesis as estimated by the incorporation of tritiated thymidine was, however, unchanged by the presence of L-leucine in the culture medium. Leucine cultured islet cells displayed ultrastructural signs of high functional activity. A detailed morphometric examination revealed fewer but hypertrophic mitochondria. The present results suggest that L-leucine can replace glucose in several respects as a long-term stimulus of the pancreatic B-cells, possibly by acting as a metabolic substrate.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00996329
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  • 2
    Electronic Resource
    Electronic Resource
    Persistent reduction of pancreatic Beta-cell mass after a limited period of protein-energy malnutrition in the young rat (1992)
    Springer
    Diabetologia 35 (1992), S. 939-945 
    Details
    ISSN: 1432-0428
    Keywords: Malnutrition-related diabetes mellitus ; kwashiorkor ; protein-calorie malnutrition ; rat ; pancreatic islets ; pancreatic Beta cell ; insulin ; light microscopy ; electron microscopy ; morphometry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Kwashiorkor, the human disease of protein-energy malnutrition, has been implicated in the aetiology of malnutrition-related diabetes mellitus, a form of diabetes not uncommon in developing countries. We have previously demonstrated that temporary protein-energy malnutrition in young rats causes a persisting impairment of insulin secretion. The present study investigates whether this secretory deficiency is accompanied by structural alterations of the endocrine pancreas. Three-week-old rats were weaned onto semi-synthetic diets containing either 15% or 5% protein and these diets were maintained for 3 weeks. From 6 weeks of age all rats were fed a commercial chow containing 18% protein. The endocrine pancreas was investigated by light and electron microscopic morphometry at 3, 6 and 12 weeks of age. In rats not subjected to protein-energy malnutrition there was a progressive increase, with age, of total pancreatic Beta-cell weight and individual Beta-cell size. In 6-week-old rats fed the low protein diet total pancreatic Beta-cell weight and individual Beta-cell size were diminished. In 12-week-old rats previously fed the low protein diet total Beta-cell weight remained lower compared to control rats. It is concluded that protein-energy malnutrition early in life may result in a diminished reserve for insulin production. This may predispose to glucose intolerance or even diabetes in situations with an increased insulin demand.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00401422
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  • 3
    Electronic Resource
    Electronic Resource
    Protection by free oxygen radical scavenging enzymes against glucose-induced embryonic malformations in vitro (1991)
    Springer
    Diabetologia 34 (1991), S. 325-331 
    Details
    ISSN: 1432-0428
    Keywords: Diabetic pregnancy ; congenital malformation ; free oxygen radicals ; rat ; whole embryo culture ; citiolone ; superoxide dismutase ; catalase ; glutathione peroxidase
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary This study addresses the possibility that the teratogenic effects of a diabetic pregnancy are associated with increased embryonic activities of free oxygen radicals. Rat embryos were cultured in 50 mmol/l glucose for 48 h and subsequently showed pronounced growth retardation and severe malformations. The enzyme inducer citiolone and the free oxygen radical scavenging enzymes Superoxide dismutase, catalase and glutathione peroxidase protected against the disturbed growth and development of the embryos at 50 mmol/l glucose when added to the culture media. Enzymatic measurements indicated that citiolone induced an increased activity of superoxide dismutase in the embryonic tissues and that the added enzymes were taken up by both the yolk sac and the embryo proper. The protection against embryonic maldevelopment was thus conferred by agents that increased the free oxygen radical scavenging capacity of the embryonic tissues. The results suggest that a high glucose concentration in vitro causes embryonic dysmorphogenesis by generation of free oxygen radicals. An enhanced production of such radicals in embryonic tissues may be directly related to the increased risk of congenital malformations in diabetic pregnancy.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00405004
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  • 4
    Electronic Resource
    Electronic Resource
    CSF and plasma pharmacokinetics of intramuscular morphine (1985)
    Springer
    European journal of clinical pharmacology 27 (1985), S. 677-681 
    Details
    ISSN: 1432-1041
    Keywords: morphine ; analgesic ; pharmacokinetics ; intramuscular administration ; CSF/plasma-morphine levels ; CSF kinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Morphine concentrations in plasma and cerebrospinal fluid (CSF) were measured in 58 elderly patients after intramuscular administration of 10 mg morphine. The assay employed gas chromatography with electron capture detection. From 49 of the patients undergoing urological procedures plasma and lumbar CSF samples were obtained simultaneously as spinal analgesia was given, and in addition, repeated venous samples were obtained over 4 hours from 35 of the patients. A plasma-morphine concentration vs time plot was drawn from the mean values and a CSF-morphine vs time plot was calculated by pooling individual CSF concentrations and using the sliding mean technique. The individual CSF/plasma-morphine concentration ratio vs time was also plotted. In addition, 2 or 3 CSF and plasma samples were collected simultaneously from 3 patients undergoing thoracotomy. Large interindividual variation in the CSF concentration was found. The peak CSF level was reached after 3 h and, following pseudoequilibrium, CSF-morphine levels appeared only slightly lower than those found in plasma. The availability to spinal CSF amounted to no more than 0.005% of the administered dose. CSF-morphine concentrations were not related to plasma protein or albumin concentrations.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00547048
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  • 5
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of epidural morphine in man (1984)
    Springer
    European journal of clinical pharmacology 26 (1984), S. 233-237 
    Details
    ISSN: 1432-1041
    Keywords: morphine ; anesthesiology ; epidural application ; pharmacokinetics ; plasma level ; CSF level
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Cerebrospinal fluid (CSF) and plasma morphine concentrations were determined in 5 patients after epidural administration of 6 mg morphine; plasma samples were collected frequently during the initial 6 h and 6–7 CSF samples were obtained from each patient over a 24 h period. Morphine was analysed using gas chromatography and electron capture detection. Individual morphine concentration-time curves were plotted for plasma and CSF and various pharmacokinetic variables were calculated. Plasma morphine concentrations after epidural injection were similar to those found after intramuscular administration; Cmax (66±8 mg/ml: mean±SEM) appeared within 12±3 min, and the terminal elimination half-life in plasma was 213±24 min. In CSF, morphine reached a peak (1575±359 ng/ml) after 135±40 min. The terminal elimination half-life for morphine in CSF was 239±10 min. The CSF bioavailability of morphine after epidural administration was calculated to be 1.9±0.5%. The study showed that epidural administration of morphine resulted in CSF concentrations many times higher than those in plasma, but still only 2% of the dose administered was available to the CSF compartment. Morphine was eliminated with similar speed from CSF and plasma.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00630291
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  • 6
    Electronic Resource
    Electronic Resource
    Repeated exposures to cobalt or chromate on the hands of patients with hand eczema and contact allergy to that metal (2000)
    Copenhagen : Munksgaard International Publishers
    Contact dermatitis 43 (2000), S. 0 
    Details
    ISSN: 1600-0536
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The present study aimed at evaluating the effects of daily repeated exposures to low cobalt or chromate concentrations on the hands of patients with hand eczema and cobalt or chromate allergy. For 2 weeks, the patients immersed a finger for 10 min daily into the appropriate metal salt solution in water. During the 1st week, this was a 10 or 50 mg/l cobalt concentration or a 10 mg/l chromate concentration, and, during the 2nd week, a 100 or 200 mg/l cobalt concentration or a 100 mg/l chromate concentration. This regimen elicited a flare of hand eczema only in the chromate-exposed chromate-sensitive patients. During the exposure period, accumulation of cobalt or chromate in the nail was demonstrated. Standardization of chemical methods of quantification of skin exposure to allergens, combined with experimental exposure studies in patients with specific contact allergy, will increase the possibility of providing evidence-based medicine in the area of allergic contact dermatitis in the future.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1034/j.1600-0536.2000.043004212.x
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  • 7
    Electronic Resource
    Electronic Resource
    Aliphatic C"6-C"1"4 dicarboxylic acids in urine from an infant with fatal congenital lactic acidosis
    Amsterdam : Elsevier
    Clinica Chimica Acta 41 (1972), S. 363-366 
    Details
    ISSN: 0009-8981
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Medicine
    Type of Medium: Electronic Resource
    URL: http://linkinghub.elsevier.com/retrieve/pii/0009-8981(72)90532-3
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  • 8
    Electronic Resource
    Electronic Resource
    Long-term effects of glibenclamide on the insulin production, oxidative metabolism and quantitative ultrastructure of mouse pancreatic islets maintained in tissue culture at different glucose concentrations (1981)
    Springer
    Acta diabetologica 18 (1981), S. 65-83 
    Details
    ISSN: 1432-5233
    Keywords: Electron microscopy ; Glibenclamide ; Glucose oxidation ; Insulin biosynthesis ; Insulin secretion ; Islets of Langerhans ; Mitochondria ; Morphometry ; Tissue culture
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In order to evaluate long-term effects of sulphonylureas on pancreatic islet structure and function, isolated mouse islets were maintained in tissue culture for one week at various glucose concentrations, and in the absence or presence of glibenclamide. When the islets were cultured at 3.3 or 5.5 mmol/1, but not at 16.7 mmol/1 glucose, it was found that the drug stimulated insulin secretion into the culture medium during the initial 3 days of culture. During the remainder of the culture period no such enhancement of secretion was demonstrated. Insulin release due to glibenclamide apparently resulted in rapid depletion of intracellular insulin stores. The finding of an enlarged B-cell Golgi apparatus in the drug-treated islets was probably associated with granule discharge. The failure of glibenclamide to promote insulin secretion during the whole culture period could reflect the adverse effects of the drug on islet insulin biosynthesis as indicated by short-term experiments performed after culture. Similar experiments showed that the impaired insulin biosynthesis could not be restored by withdrawal of the drug from the culture medium for 3 days. Furthermore, the capacity for insulin release in response to an acute glucose challenge at the end of the culture period, was abolished by culture in the presence of glibenclamide. The drug effects on insulin biosynthesis and intracellular insulin stores, which were most pronounced at 5.5 mmol/1 glucose, possibly resulted from changes in B-cell metabolism as suggested by the diminished islet glucose-oxidation rate. The spatial characteristics of islet mitochondria indicated that these changes might involve an adaptation to substrates other than glucose. In conclusion, our findings suggest that sulphonylureas have an insulinotropic effect, which is however transient. Indeed, it rather seems as if long-term exposure of islet B-cells to sulphonylureasin vitro were accompanied by functional deficiency.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02056108
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  • 9
    Electronic Resource
    Electronic Resource
    Nickel-induced cytokine production from mononuclear cells in nickel-sensitive individuals and controls (2000)
    Springer
    Archives of dermatological research 292 (2000), S. 285-291 
    Details
    ISSN: 1432-069X
    Keywords: Key words Nickel ; Allergic contact dermatitis ; T cells ; IL-4 ; IL-5
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Exposure to nickel is a major cause of allergic contact dermatitis which is considered to be an inflammatory response induced by antigen-specific T cells. Here we describe the in vitro analysis of the nickel-specific T-cell-derived cytokine response of peripheral blood mononuclear cells from 35 nickel-allergic and 30 non-nickel-allergic individuals. Peripheral blood mononuclear cells were stimulated with 10–4 and 10–5 mol/l NiSO4 for 6 days and then additionally with ionomycin and phorbol myristate acetate for 24 h. Culture supernatants were analysed for interleukin-4 (IL-4), IL-5, interferon-γ (IFN-γ) and tumour necrosis factor-α (TNF-α) by quantitative ELISA. The analysis showed that the synthesis of IL-4 and IL-5 but not of IFN-γ or TNF-α was significantly higher in the nickel-allergic individuals. The finding of preferential synthesis of Th2 cytokines was somewhat of a surprise, since previous studies have suggested a Th1 response in nickel-mediated allergic contact dermatitis. Subsequently, the nickel-allergic individuals were randomized to experimental exposure to nickel or vehicle in a double-blind design. A daily 10-min exposure of one finger to 10 ppm nickel solution for 1 week followed by 100 ppm for an additional week evoked a clinical response of hand eczema in the nickel-exposed group. Blood samples were drawn on days 7 and 14 after the start of this exposure to occupationally relevant concentrations of nickel. No statistically significant differences were observed in the nickel-induced in vitro cytokine response during the exposure period. Our results indicate the possibility that IL-4 and IL-5 are involved in the pathogenesis of nickel-mediated contact dermatitis.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004030000129
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  • 10
    Electronic Resource
    Electronic Resource
    Altered mitochondrial morphology of rat embryos in diabetic pregnancy (1995)
    New York, NY [u.a.] : Wiley-Blackwell
    The @Anatomical Record 241 (1995), S. 255-267 
    Details
    ISSN: 0003-276X
    Keywords: Rat ; Diabetic pregnancy ; Embryonic dysmorphogenesis ; Neuroepithelium ; Blood cells ; Mitochondria ; High-amplitude mitochondrial swelling ; Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: Background: Previous studies in vivo and in vitro have suggeted that the oxidative metabolism of the embryo may have a role in the treatogenicity of diabetic pregnancy. In particular, the production of reactive oxygen species by the embroyonic mitochondiria has been implicated in the teratological process. The induction of congenital malformations by the diabetic milieu occurs during the early embryonic development. The present study aimed to estimate the role of the embryonic mitochondria in the teratological process of diabetic pregnancy by studying mitochondrial morphology in the embryos exposed to a diabetic environment in vivo or in vitro during early organogenesis and late fetal development.Methods: For studies in vivo embryos of control or streptozotocin-dia-betic rats were taken at gestational days 9-11 and sujected to light and electron microscopical analysis. The brain, heart, and liver of day-15 fetuses were also observed. For studies in vitro day-9 embryos of normal rats were cultured in a whole-embryo culture system for 48 hours. The culture media were supplied with high conectration of diabetes-related substrates and metabolites, and their effect on structure of embryonic neuropeithelial cells determined.Results: The light microscopoical observations demonstrated numberous cytoplasmic vaculoes in the ectoderm of day-9 embryos and the neuroepithelium and blood cells of day-10 and day-11 embryos of diabetic rats. Ultrastructuraily, these vacuoles were found to be mitochondria undergoing large-amplitude swelling with loss of matrix density and disturbed cristae. In contrast, no Mitochondrial differences were found in the brain, heart, and liver, when day-15 fetuses from normal and diabeic rats were compared. Ultrastructural analysis of day-9 embryos cultured for 48 hours in the presnce of high conectrations of D-Glucose, pyruvate, β-hydroxybutyrate, and α-ketoisocaproate also showed high-amplitude mitochondrial swelling in the neuroepithelium. The motochondrial swelling was, however, not found in embryos cultured in a high conectration of L-glucose, excluding simple osmotic effects of the diabetes-related substrated and metabolites.Conclusions: The mitochondrial morphological changes appeared in embryos subjected to a diabetic environment during a time period when the congenital malformations in diabetic pregnancy are induced. The results support the notion that embryonic mitochondria are involved in the teratological process of diabetic pregnancy. © 1995 Wiley-Liss, inc.
    Additional Material: 7 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/ar.1092410212
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