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  • 1990-1994  (12,907)
  • 1980-1984  (8,341)
  • Analytical Chemistry and Spectroscopy  (11,781)
  • Organic Chemistry  (7,936)
  • Rat  (1,531)
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  • 101
    Electronic Resource
    Electronic Resource
    Springer
    Psychopharmacology 115 (1994), S. 213-220 
    ISSN: 1432-2072
    Keywords: Divided attention ; Scopolamine ; Chlordiazepoxide ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract “Divided attention” is a psychological construct that hinges on assumptions about a fixed finite capacity of subjects to simultaneously process multiple sets of information. A model of a crossmodal divided attention task was developed in rats. Initially, rats were trained consecutively in operant auditory and visual conditional discrimination tasks. The final task consisted of two successive blocks of 20 trials per modality (modality certainty), followed by 60 trials comprising a semi-randomized sequence of stimuli of both modalities (auditory or visual) and qualities (flashing/pulsing or constantly turned on; modality uncertainty). In comparison to unimodal blocks of trials, performance in the mixed condition was assumed to reflect the demands on the parallel processing of two sets of stimulus-response rules. While response accuracy remained unchanged, response latencies were generally longer in the bimodal condition. Administration of scopolamine (0.03, 0.06, 0.1 mg/kg) or chlordiazepoxide (1, 3, 5, 8 mg/kg) dose-dependently increased response latencies. The scopolamine-induced increase in response latencies was greater in the mixed condition. Cost-benefit analyses demonstrated that the absolute divided attention costs (in ms) were generally higher for visual than for auditory stimuli. Both drugs produced qualitatively similar effects; however, scopolamine was more potent in increasing the absolute divided attention costs than chlordiazepoxide. These data are discussed in terms of the validity of this animal paradigm, and of hypotheses about the effects of benzodiazepine receptor agonists and muscarinic antagonists on brain information processing capacity.
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  • 102
    ISSN: 1432-2072
    Keywords: Behaviour ; Olfactory recognition ; Social investigation ; Neuropeptides ; Cholecystokinin ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Modulation of learning and memory is one of the physiological roles that the neuropeptide cholecystokinin (CCK-8) may play. We have used a behavioural model of olfactory recognition among rats to test this hypothesis and to explore the relationship between CCK-A and CCK-B receptors and memory retention. Adult male rats form a transient memory of a juvenile congenere as indicated by a reduction in the duration of investigatory behaviour upon re-exposure 30 min after an initial exposure, but not when re-exposure is delayed until 120 min afterwards. In the present study, rats were treated after the first contact with various compounds; inhibition and facilitation of olfactory recognition were evaluated as the persistence in investigation 30 min and the decrease in investigation 120 min after pharmacological manipulations, respectively. Systemic injection of CCK-8, of a selective CCK-A agonist, or of non-peptide CCK-B antagonists (CI-988 and LY-262691) enhanced olfactory recognition. In contrast, the CCK-B selective agonist BC 264 and the tetrapeptide CCK-4 both disrupted it. Taken together with previous evidence of the detrimental effect of the non-peptide CCK-A antagonist devazepide on olfactory recognition, these results confirm and extend the hypothesis that there is a balance between CCK-A-mediated facilitative effects and CCK-B-mediated inhibitory effects on memory retention.
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  • 103
    ISSN: 1432-2072
    Keywords: Chronic mild stress ; Imipramine ; Animal model of depression ; Dopamine ; D1-receptors ; D2-receptors ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Chronic sequential exposure to a variety of mild stressors has previously been found to cause an antidepressant-reversible decrease in the consumption of palatable sweet solutions, associated with abnormalities of dopaminergic neurotransmission in the nucleus accumbens. In the present study, 5 weeks of treatment with imipramine (10 mg/kg b.i.d.) reversed the decreased sucrose intake of rats exposed to chronic mild stress. Stress also caused a decrease in D2-receptor binding in the limbic forebrain (but not the striatum), which was completely reversed by imipramine. In nonstressed animals, imipramine decreased D1-receptor binding in both regions. However, in stressed animals, imipramine did not significantly alter D1-receptor binding in either area. Stress alone slightly increased D1-receptor binding, in striatum only. Scatchard analysis showed that all changes in receptor binding resulted from changes in receptor number (Bmax) rather than receptor affinity (KD). The results support the hypothesis that changes in D2-receptor function in the nucleus accumbens are responsible for chronic mild stress-induced anhedonia and its reversal by antidepressant drugs. They do not support the hypothesis that the sensitization of D2-receptors seen following chronic antidepressant treatment is caused by a down-regulation of D1-receptors.
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  • 104
    ISSN: 1432-2072
    Keywords: β1-adrenergic receptors ; Rat ; Brain ; Citalopram ; Fluoxetine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Quantitative receptor autoradiography was used to study the effects of the selective serotonin reuptake inhibitors citalopram and fluoxetine and the tricyclic antidepressant imipramine on the regulation of β1-adrenergic receptors in the rat brain. Rats were treated with saline, citalopram (10 mg kg−1), fluoxetine (10 mg kg−1), or imipramine (15 mg kg−1) SC once daily for 14 days. [125I]Iodocyanopindolol binding to β1-adrenergic receptors was found to increase significantly in the caudate-putamen and the somatosensory areas of the frontal cortex after both citalopram and fluoxetine treatments. Imipramine treatment elicited a marked decrease in β1 binding in the outer laminae of the cingulate cortex, as well as in the motor and somatosensory areas of the frontal cortex. In a separate experiment, rats were treated with saline, citalopram (2.5, 10 and 20 mg kg−1) or fluoxetine (2.5, 10 and 20 mg kg−1) SC once daily for 14 days. The effects of citalopram and fluoxetine on β1 receptors in the somatosensory cortex and caudate-putamen were replicated. These results demonstrate that chronic administration of selective serotonin reuptake inhibitors, in contrast to imipramine, can cause a regional up-regulation of β1-adrenergic receptors in the rat brain.
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  • 105
    ISSN: 1432-2072
    Keywords: 5-Hydroxytryptamine ; 5,7-Dihydroxytryptamine ; Operant behaviour ; Timing ; Interval bisection procedure ; Acquisition ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract This experiment examined the effect of destroying the 5-hydroxytryptaminergic (5HTergic) pathways on the acquisition and performance of discrimination between two brief time intervals. Rats that had received injections of 5,7-dihydroxytryptamine into the dorsal and median raphe nuclei, and sham-lesioned control rats were trained in a series of discrete trials to press lever A following a 200-ms presentation of a light stimulus and lever B following an 800-ms presentation of the same stimulus. Both groups gradually acquired accurate performance, attaining 80%–85% accuracy by the end of 40 sessions. The lesioned group learnt the task significantly faster than the control group. When stable performance had been attained, “probe” trials were introduced in which the light was presented for intermediate durations. Both groups showed sigmoid functions relating percent choice of lever B to log stimulus duration. The bisection point (duration corresponding to 50% choice of lever B) did not differ significantly between the two groups; however, the Weber fraction was significantly smaller in the lesioned group than in the control group. The levels of 5HT and 5-hydroxy-indole-acetic acid were markedly reduced in the brains of the lesioned rats, but the levels of noradrenaline and dopamine were not altered. The results indicate that destruction of the 5HTergic pathways facilitates acquisition of a temporal discrimination. The lack of an effect of the lesion on the bisection point contrasts with our previous finding using longer stimulus durations; it is suggested that different behavioural processes may underlie millisecond-range and second-range temporal discrimination, and that these may be differently affected by 5HT depletion.
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  • 106
    ISSN: 1432-2072
    Keywords: Antipsychotic agents ; Acoustic startle ; Prepulse inhibition ; Schizophrenia ; Phencyclidine ; Remoxipride ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effect of various typical (haloperidol) and atypical (clozapine, raclopride, remoxipride) antipsychotics on phencyclidine (PCP)-induced disruption of sensorimotor gating was tested in rats using an acoustic startle paradigm. Clozapine (4–40 µmol/kg), haloperidol (1–5 µmol/kg) and raclopride (1–12 µmol/kg) failed to reverse PCP-induced disruption of prepulse inhibition (PPI) of the acoustic startle response. In contrast, remoxipride (12–60 µmol/kg) caused a dose-dependent block of this effect. PCP-induced disruption of PPI is a widely accepted animal model of a corresponding behavioural deficit observed in schizophrenia although little evidence has been presented that it is in fact sensitive to antipsychotic agents. The present results indicate that remoxipride behaves in a unique way in this model compared to clozapine, haloperidol and raclopride.
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  • 107
    ISSN: 1432-2072
    Keywords: Short term memory ; Delayed matching to position ; 5-HT ; 5-HT1A receptor ; 8-OH DPAT ; Ipsapirone ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A series of experiments examined the effects of 5-HT1A ligands alone and in combination with the muscarinic antagonist scopolamine on short term working memory in the rat. The behavioural paradigm was a discrete trial, operant delayed matching to position task, with delays of 0, 5, 15 and 30 s. The 5-HT1A ligands tested were the full agonist, 8-OH DPAT (0, 0.1, 0.3 and 1 mg/kg), the partial agonist, ipsapirone (0, 1, 3 and 10 mg/kg), and the purported antagonist, NAN 190 (0, 1, 2, and 4 mg/kg). 1-PP (0, 0.1, 0.3, 1 mg/kg), the major metabolite of ipsapirone, was also tested. The lowest dose of 8-OH DPAT significantly improved matching accuracy at the longest delay, whereas the highest dose impaired matching accuracy and increased the latency to respond. Ipsapirone also significantly improved the accuracy of performance at a dose of 3 mg/kg, but the doses of 1 and 10 mg/kg did not significantly affect performance. NAN-190, at the highest dose tested (4 mg/kg), impaired matching accuracy, whereas the two lower doses did not significantly affect performance. The highest dose also increased the latency to respond. 1-PP had no effect on performance. Scopolamine HBr (0.14 mg/kg) caused a delay dependent impairment in matching accuracy, and had no effect on missed trials or the latency to respond. Low doses of 8-OH DPAT (0.1 and 0.3 mg/kg) significantly attenuated the scopolamine induced accuracy impairment, whereas 1 mg/kg 8-OH DPAT potentiated the impairment. Ipsapirone (3 mg/kg) also significantly improved the performance of scopolamine impaired rats. NAN-190 increased the latency to respond and reduced the number of nose pokes made during the delays in scopolamine-treated rats, and tended to potentiate the scopolamine-induced accuracy impairment. 1-PP did not affect the performance of scopolamine treated rats. Taken together, these results suggest that modulation of 5-HT1A receptors influences short term spatial working memory in the rat.
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  • 108
    ISSN: 1432-2072
    Keywords: Neurosteroid ; Memory ; Amnesia ; NMDA receptor ; Ataxia ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The neurosteroid pregnenolone sulfate (PS) has been recently shown to positively modulate NMDA receptors and to have memory enhancing properties in mice. In the present study, we examined the ability of PS to increase retention performance and to reduce deficits induced by a competitive NMDA receptor antagonist, the 3-((±)-2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP), in a step-through passive avoidance task in rats. Pretraining administration of PS (0.84–1680 pmol, ICV) had minimal effects on retention performance assessed 24 h after training, while CPP significantly decreased retention performance at the doses of 1.2 and 1.6 nmol (ICV). However, when administered in combination with CPP (1.2 nmol), PS (0.84–840 pmol, ICV) dose-dependently blocked the deficit in passive avoidance response induced by the NMDA antagonist. At the dose of 840 nmol, PS also significantly reduced the motor impairment induced by CPP (1.2 nmol). The blockade of CPP-induced behavioral deficits by PS may result from its positive modulatory action at NMDA receptors.
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  • 109
    ISSN: 1432-2072
    Keywords: Fetus ; Prenatal drug exposure ; Schizophreniad-Amphetamine ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Recent evidence suggests that mid-pregnancy is a critical period for production of fetal abnormalities that cause behavioral and neuropathological changes in adult offspring. The present experiments provide an animal model of these effects by treating pregnant Sprague-Dawley rats during gestational days 11–14 withd-amphetamine (AM). Offspring were tested for neurological signs, foraging activity, reversal learning, and sensitivity to amphetamine challenge. In the Early Juvenile period, postnatal days (PND) 20–30, female AM offspring initially showed reductions in rearing, holepoking, and midfield activity. On later trials, and as young adults, AM females showed signs of locomotor hyperactivity despite continued poor foraging efficiency, and were also more sensitive to a 1.0 mg/kgd-amphetamine challenge. AM males showed initially slower and more perseverative responding than controls, but then developed excessive response switching. These changes continued during tests for Retention, Reversal, and Extinction in the Late Juvenile/Early Adult stage (PND 50–90), when both AM-exposed sexes showed increased eating time, significantly more perseverative lateral turning preference (right or left), and slower reversal learning than controls. Behavioral data were consistent with aberrations in thalamo-frontal and mesolimbic/nigrostriatal projection systems that have been reported in AM animals and which are also affected by maternal drug abuse and schizophrenia.
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  • 110
    ISSN: 1432-2072
    Keywords: Adenosine A2 receptor ; Dopamine D2 receptor ; Methylxanthine ; Tardive dyskinesias ; Receptor-receptor interaction ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Stimulation of adenosine A2 receptors (with the selective adenosine A2 agonist CGS 21680) in rat striatal membrane preparations, produces a decrease in both the affinity of D2 receptors and the transduction of the signal from the D2 receptor to the G protein. This intramembrane A2-D2 interaction might be responsible for the behavioural depressant effects of adenosine agonists and for the behavioural stimulant effects of adenosine antagonists such as caffeine and theophylline. Dopamine denervation induces an increase in the intramembrane A2-D2 interaction, which may underlie the observed higher sensitivity to the behavioural effects induced by adenosine antagonists found in these animals. The present study was designed to examine if chronic treatment with haloperidol, which also produces dopamine receptor supersensitivity, is also associated with an increase in the intramembrane A2-D2 interaction in the neostriatum and with a higher sensitivity to the behavioural effects induced by adenosine antagonists. The data showed that: (i) haloperidol pretreatment causes a higher binding of the D2 antagonist [3H] raclopride in striatal membrane preparations due to an increase in the number of D2 receptors without changes in their affinity for the antagonist (increase in Bmax without changes in kd); (ii) GCS 21680 decreases the affinity of dopamine for the D2 receptor, by increasing the equilibrium dissociation constants of high (Kh) and low affinity (K1) dopamine D2 binding sites and increases the proportion of high affinity binding sites (Rh); (iii) a low dose of CGS 21680 (3 nM), which is ineffective in membrane preparations from neostriatum of nontreated animals, is effective in membranes from the striatum of haloperidol-pretreated animals; (iv) the nonselective adenosine antagonist theophylline (20 mg/kg SC) causes a higher motor activation in rats pretreated with haloperidol. The possible relevance of these results for the pathophysiology and treatment of tardive dyskinesias is discussed.
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  • 111
    ISSN: 1432-2072
    Keywords: Rat ; Development ; Δ-9-Tetrahydrocannabinol ; Motor behavior ; Locomotor activity ; Grooming ; Corticosterone
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The ontogeny and the adult expression of motor behaviors were studied in male and female rats born from mothers exposed to Δ9-tetrahydrocannabinol (THC, 5 mg/kg) during gestation and lactation. Perinatal exposure to THC increased both rearing and locomotor activities in males and females at immature preweanling ages (P-15 and P-20). These effects disappeared after ceasing THC exposure (postweaning ages), but they were observed again in adult (P-70) females. The effects appeared as persistently high motor activity in familiar environments, disappearing the characteristic habituation profile in locomotor and exploratory behaviors. In novel environment condition tests, adult (P-70) THC-exposed females, but not males, exhibited lower locomotor activity in the socio-sexual approach test, and an increase in the emergence latency in the dark-light emergence test. Additionally, animals of both sexes exposed to THC showed a increase in the time spent grooming measured in novelty conditions. These findings suggest that perinatal exposure to THC affects both the development and the adult expression of motor behaviors and it resulted in a sex-dimorphic psychomotor activation very similar to that observed after perinatal exposure to other drugs of abuse. A possible role of THC-induced pituitary-adrenal (PA) axis activation was also evaluated by measuring plasma corticosterone levels in adult animals perinatally exposed: THC-exposed females exhibit a clear increase of this adrenal hormone, whereas THC-exposed males displayed lower levels of this hormone. These results confirm our previous finding of a sex-dimorphic behavioral response to perinatal exposure to hashish extracts, and they suggest a role of THC-induced PA activation in the mediation of these actions.
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  • 112
    ISSN: 1432-2072
    Keywords: Dopamine ; 5-HT2 ; 5-HT1C ; D1 ; SKF 38393 ; SKF 82958 ; SCH 39166 ; SCH 23390 ; Feeding ; Behavior ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The hypophagic effect of the D1 receptor agonist SKF 38393 is not dose-dependently antagonized by the D1 antagonist SCH 23390. Moreover, the receptor specificity of this interaction remains in question, since SCH 23390 has significant activity at both 5-HT2 and 5-HT1C receptors, and SKF 38393 also interacts with 5-HT1C receptors. To determine the relative significance of these actions, a comparison was made between the anorectic effects in rats of SCH 23390 (0.1–1.0 mg/kg) and the benzonaphthazepine SCH 39166 (0.1–3.0 mg/kg), a D1 antagonist with negligible affinity for 5-HT sites. Both compounds inhibited food-intake dose-dependently, with SCH 23390 being approximately twice as potent as SCH 39166. Behaviorally inactive and active doses of both antagonists were tested in combination with the D1 agonist SKF 38393 (10–56 mg/kg). Neither antagonist was able to produce more than a marginal attenuation of the agonist-induced hypophagia. This demonstrates that previous failures to reverse the behavioral actions of SKF 38393 by SCH 23390 were not due to specific actions of this particular antagonist. Finally, like SCH 23390, SCH 39166 (0.3 mg/kg) was able to attenuate fully the anorectic effects of the D1 agonist SKF 82958 (1.0 and 3.0 mg/kg), demonstrating that neither compound is intrinsically unable to block D1 receptor-mediated hypophagia. The results demonstrate the generality of the D1 antagonist-mediated effect on feeding and call into question the use of SKF 38393 as a D1 agonist in studies of feeding, and perhaps in other contexts as well.
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  • 113
    ISSN: 1432-2072
    Keywords: Prefrontal cortex ; Dopamine ; Acoustic startle response ; Prepulse inhibition ; 6-Hydroxydopamine ; Rat ; Schizophrenia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Prepulse inhibition (PPI) of the acoustic startle response (ASR) is impaired by dopamine (DA) overactivity in the nucleus accumbens and anteromedial striatum. Since there is evidence that DA in the medial prefrontal cortex exerts an inhibitory control on striatal DA systems, it was investigated whether depletion of prefrontal DA reduces PPI. Rats were tested for PPI both before and after injections (2 × 1 µl per side) of vehicle, a low (3.0 µg/µl) or a high (6.0 µg/µl) dose of 6-hydroxydopamine hydrobromide (6-OHDA) into the prefrontal cortex. Only the high dose of 6-OHDA, leading to an 87% depletion of prefrontal DA, impaired PPI. The ability of an acoustic prepulse (75 dB, 10 kHz) to reduce the response to a startle pulse (100 dB noise burst) was maintained in sham lesioned rats, but was significantly disturbed in rats lesioned with the high dose of 6-OHDA. The 6-OHDA treatment did not affect the ASR amplitude in the absence of a prepulse. The reduction of PPI in lesioned rats correlated with the extent of DA depletion. These results suggest that the DA innervation of the prefrontal cortex is involved in the modulation of the ASR and they provide further evidence for opposite actions of prefrontal and subcortical DA systems in the control of behaviour. The present findings are discussed with regard to the potential role of prefrontal DA in schizophrenia.
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  • 114
    ISSN: 1432-2072
    Keywords: Risperidone ; 9-Hydroxy-risperidone ; Active metabolite ; Antipsychotic ; 5-HT2 Antagonist ; Dopamine-D2 antagonist ; Pharmacokinetics ; Regional brain distribution ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Risperidone is a new benzisoxazole antipsychotic. 9-Hydroxy-risperidone is the major plasma metabolite of risperidone. The pharmacological properties of 9-hydroxy-risperidone were studied and appeared to be comparable to those of risperidone itself, both in respect of the profile of interactions with various neurotransmitters and its potency, activity, and onset and duration of action. The absorption, plasma levels and regional brain distribution of risperidone, metabolically formed 9-hydroxy-risperidone and total radioactivity were studied in the male Wistar rat after single subcutaneous administration of radiolabelled risperidone at 0.02 mg/kg. Concentrations were determined by HPLC separation, and off-line determination of the radioactivity with liquid scintillation counting. Risperidone was well absorbed. Maximum plasma concentrations were reached at 0.5–1 h after subcutaneous administration. Plasma concentrations of 9-hydroxy-risperidone were higher than those of risperidone from 2 h after dosing. In plasma, the apparent elimination half-life of risperidone was 1.0 h, and mean residence times were 1.5 h for risperidone and 2.5 h for its 9-hydroxy metabolite. Plasma levels of the radioactivity increased dose proportionally between 0.02 and 1.3 mg/kg. Risperidone was rapidly distributed to brain tissues. The elimination of the radioactivity from the frontal cortex and striatum—brain regions with high concentrations of 5-HT2 or dopamine-D2 receptors—became more gradual with decreasing dose levels. After a subcutaneous dose of 0.02 mg/kg, the ED50 for central 5-HT2 antagonism in male rats, half-lives in frontal cortex and striatum were 3–4 h for risperidone, whereas mean residence times were 4–6 h for risperidone and about 12 h for 9-hydroxy-risperidone. These half-lives and mean residence times were 3–5 times longer than in plasma and in cerebellum, a region with very low concentrations of 5-HT2 and D2 receptors. Frontal cortex and striatum to plasma concentration ratios increased during the experiment. The distribution of 9-hydroxy-risperidone to the different brain regions, including frontal cortex and striatum, was more limited than that of risperidone itself. This indicated that 9-hydroxy-risperidone contributes to the in vivo activity of risperidone, but to a smaller extent than would be predicted from plasma levels. AUCs of both active compounds in frontal cortex and striatum were 10–18 times higher than those in cerebellum. No retention of metabolites other than 9-hydroxy-risperidone was observed in any of the brain regions investigated.
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  • 115
    ISSN: 1432-2072
    Keywords: Cocaine ; Drug discrimination ; Nucleus accumbens ; Dopamine D1 and D2 receptors ; Microinjection ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Dopamine (DA) D1 and D2 receptors are involved in mediating the behavioral effects of cocaine, including its discriminative stimulus properties. The purpose of the present study was to investigate the role of the nucleus accumbens and, in particular, accum bens DA D1 receptors in modulating the stimulus effects of cocaine. Thus, rats were trained to discriminate cocaine (10 mg/kg, IP) from saline using a two-lever, water-reinforced FR 20 drug discrimination task. In substitution tests, systemic (IP) administration of cocaine (0.625–20 mg/kg) produced a dose-related increase in cocaine-appropriate responding. Microinjections of cocaine (2.5–40 µg) into the nucleus accumbens also engendered dose-dependent and complete substitutions (〉 80% drug-lever responding) for the systemic training dose of cocaine, whereas intra-accumbens artificial cerebrospinal fluid (1 µl/side) produced primarily saline-appropriate responding. In antagonism tests, pretreatment with the DA D1 antagonist SCH 23390 (3–12 µg/kg) completely antagonized (〈20% drug-lever responding) a dose of cocaine (5 mg/kg) that produced greater than 90% cocaine-lever responding when given alone. Additionally, intra-accumbens injections of SCH 23390 (0.025–0.4 µg) prior to systemic cocaine (5 mg/kg) also significantly blocked the cocaine stimulus. The present results confirm the importance of the nucleus accumbens in mediating the discriminative stimulus properties of cocaine and suggest a primary role of accumbens DA D1 receptors in modulating this behavior.
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  • 116
    Electronic Resource
    Electronic Resource
    Springer
    Psychopharmacology 115 (1994), S. 289-296 
    ISSN: 1432-2072
    Keywords: CL 284,846 ; Drug discrimination ; Sedative ; Hypnotic ; Anxiolytic ; Rat ; Benzodiazepine receptors
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract CL 284,846,N-[3-(3-cyanopyrazolo[1, 5-a]pyrimidin-7-yl)phenyl)]-N-ethylacetamide, is a novel non-benzodiazepine sedative-hypnotic with benzodiazepine-like sedative effects, but with less apparent liability for accompanying undesired side effects. In an effort to further characterize its pharmacological activity, CL 284,846 (3.0 mg/kg, IP, 30 min pretreatment) was established as a discriminative stimulus (DS) in rats (n=7). CL 284,846 (0.3–10.0 mg/kg) showed a dose-related increase in drug-appropriate responding up to the training dose and a dose-related decrease in response rate. The benzodiazepine agonist triazolam (0.1–1.0 mg/kg), the benzodiazepine partial agonist Ro 17-1812 (0.3–3.0 mg/kg) and the triazolopyridazine CL 218,872 (1.0–3.0 mg/kg) substituted for CL 284,846 in all rats, whereas the imidazopyridines zolpidem (3.0–10.0 mg/kg) and alpidem (10.0–30.0 mg/kg), the benzodiazepine partial agonist bretazenil (0.03–10.0 mg/kg) and the novel putative anxiolytic CL 273,547 (10.0–56.0 mg/kg) substituted in most, but not all, rats. Ro 17-1812, bretazenil, and CL 218,872 had no effect on response rate while the other drugs showed a concomitant decrease in rate. The 5-HT1A agonist buspirone (1.0–10.0 mg/kg) and the barbiturate pentobarbital (3.0–17.0 mg/kg) failed to substitute for CL 284,846 up to rate-decreasing doses. The benzodiazepine antagonist flumazenil (3.0–10.0 mg/kg) blocked the DS effects of CL 284,846 in most rats with no effect on response rate. Taken together, these results suggest that the DS effects of CL 284,846 are mediated via benzodiazepine receptors; however, the DS profile of CL 284,846 remains distinct from both benzodiazepine and non-benzodiazepine sedative-hypnotic drugs.
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  • 117
    Electronic Resource
    Electronic Resource
    Springer
    Psychopharmacology 115 (1994), S. 320-324 
    ISSN: 1432-2072
    Keywords: Caffeine ; Electroconvulsive shock ; Seizure ; Rat ; Electroencephalography ; Convulsions
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Caffeine has been used clinically to increase seizure length in electroconvulsive treatment (ECT). The present study was designed to establish an animal model of caffeine-augmented seizures for further study of mechanisms and effects of pharmacological manipulation of seizure length. Increasing doses of caffeine (0–200 mg/kg, IP) were given before electroconvulsive stimulation (ECS) in rats and resulting seizure lengths were quantified by timing of classical tonic-clonic convulsive movements. With this paradigm, caffeine led to a dose-dependent increase in seizure duration. This proconvulsant action of caffeine was detectable within 1 min after dosing, persisted for at least 230 min and was reversible. The results suggest that seizure length is a practicable measure in pharmacological modification of electroconvulsive seizures. They also suggest that pharmacologically-modified ECS can be modeled effectively in animals.
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  • 118
    Electronic Resource
    Electronic Resource
    Springer
    Psychopharmacology 115 (1994), S. 249-253 
    ISSN: 1432-2072
    Keywords: Penile erection ; Muscimol ; Baclofen ; Bicuculline ; Picrotoxin ; Phaclofen ; Apomorphine ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effects of GABA agonists and antagonists on penile erection (PE) induced by apomorphine were investigated in rats. Subcutaneous (SC) administration of apomorphine (0.01–0.1 mg/kg) induces a dose-dependent PE in rats. The maximum effect was obtained with 0.1 mg/kg of the drug. The response was decreased with increasing doses of apomorphine from 0.1 to 0.5 mg/kg. The response induced by apomorphine (0.1–0.5 mg/kg) was decreased in animals pretreated with either the GABA-A agonist muscimol or the GABA-B agonist baclofen. Combination of muscimol with baclofen caused a stronger inhibitory effect on apomorphine-induced PE. Bicuculline or picrotoxin but not phaclofen reduced the inhibitory effect of muscimol on PE induced by apomorphine, whereas phaclofen but not GABA-A antagonists decreased the inhibitory action of baclofen on apomorphine-induced PE. Pretreatment of animals with higher doses of the GABA-A antagonists bicuculline and picrotoxin or the GABA-B antagonist phaclofen elicited inhibition of apomorphine-induced PE. However, the inhibitory effects of GABA-A and GABA-B antagonists are lost on combination. Administration of GABA-A and GABA-B receptor stimulation inhibit PE induced by dopaminergic mechanism(s).
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  • 119
    ISSN: 1432-2072
    Keywords: Dopamine receptors ; Neuroleptics ; SCH-23390 ; Raclopride ; Response duration ; Catalepsy ; Operant behavior ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In an experiment designed to distinguish between the behavioral consequences of treatment with SCH-23390, a D1 dopamine receptor blocker, and raclopride, a D2 antagonist, rats were trained to perform a water-reinforced forelimb operant response. Response rate and the duration of each forelimb contact with the operandum were recorded. In addition, the durations of the rat's visits to the reward well were detected by a photobeam which was blocked by the rat's muzzle as it remained at the reward well. In a between-groups dosing design, separate groups of rats (11–13 rats/group) received SCH-23390 (0, 0.01, 0.02, 0.04, 0.08, 0.12 mg/kg, IP, 30 min) or raclopride (0. 0.05, 0.1, 0.2, 0.4, 0.8 mg/kg, IP, 30 min) for 21 consecutive days. Quantitative analyses indicated that for comparable amounts of operant rate reduction, raclopride had a significantly greater tendency than SCH-23390 to increase the duration of operant responses and to increase the maximum muzzle entry duration (i.e., to induce microcatalepsy). The results support the idea that at relatively low doses D2 antagonism is more likely than D1 antagonism to produce effects identified preclinically with extrapyramidal side effects.
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  • 120
    ISSN: 1432-2072
    Keywords: Cocaine ; Schedule-induced polydipsia ; Drinking ; Locomotor activity ; Nucleus accumbens ; Medial prefrontal cortex ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effects of cocaine HCl infusions into either the nucleus accumbens (NACC) or medial prefrontal cortex (PFC) were compared on the performance of schedule-induced polydipsia (SIP) and related behaviours. Food-deprived rats were exposed to a fixed-time 60-s schedule of food delivery in daily 30-min sessions until stable levels of behaviour were obtained (14 days). Rats were then bilaterally infused with cocaine into either the NACC or PFC via chronically indwelling guide cannulae. Each subject received a sequence of five cocaine infusions (0, 12.5, 25, 50, 100 µg) according to a Latin Square design. For comparison, following these intracranial infusions each rat received a sequence of five IP injections of cocaine (0, 2.5, 5, 10, 20 mg/kg) also in a counterbalanced order. NACC and PFC infusions of cocaine and IP cocaine dose-dependently reduced SIP. Cocaine infusions into the NACC, but not the PFC, increased locomotor activity but the characteristic temporal profile of locomotor activity during SIP was retained. IP cocaine also increased locomotor activity in a dose-dependent manner, but the temporal profile of activity was flattened following 20 mg/kg cocaine. NACC and PFC infusions of cocaine had little effect on the total number of panel presses to gain access to the food pellets, but did slightly decrease the high rates of responding immediately prior to the pellet delivery. IP cocaine increased the total number of panel presses at the higher doses, mainly by increasing the low rates of responding. The effects of cocaine infusions into the PFC were behaviourally the most selective, as they reduced SIP without having substantial effects either on locomotor activity or panel pressing. These data therefore implicate a role for the PFC in the performance of SIP.
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  • 121
    ISSN: 1432-2072
    Keywords: Anxiety ; Elevated zero-maze ; Rat ; Diazepam ; Chlordiazepoxide ; mCPP ; 8-OH-DPAT ; Ondansetron ; Head dips ; Stretched attend postures
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The elevated “zero-maze” is a modification of the elevated plus-maze model of anxiety in rats which incorporates both traditional and novel ethological measures in the analysis of drug effects. The novel design comprises an elevated annular platform with two opposite enclosed quadrants and two open, removing any ambiguity in interpretation of time spent on the central square of the traditional design and allowing uninterrupted exploration. Using this model, the reference benzodiazepine anxiolytics, diazepam (0.125–0.5 mg/kg) and chlordiazepoxide (0.5–2.0 mg/kg) significantly increased the percentage of time spent in the open quadrants (% TO) and the frequency of head dips over the edge of the platform (HDIPS), and reduced the frequency of stretched attend postures (SAP) from the closed to open quadrants. In contrast, the anxiogenic drugm-chlorophenyl-piperazine (mCPP; 0.25–1.0 mg/kg) induced the opposite effects, decreasing %TO and HDIPS, and increasing SAP. The 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT; 0.001–0.1 mg/kg) had no effects on either %TO or HDIPS, but did decrease SAP at 0.01 mg/kg although not at higher or lower doses. Similarly, the 5-HT3 receptor antagonist, ondansetron (0.0001–1.0 mg/kg) decreased SAP and increased %TO at 0.01 mg/kg, but not at other doses. The present data suggest that a combination of the novel “zero-maze” design and a detailed ethological analysis provides a sensitive model for the detection of anxiolytic/anxiogenic drug action.
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  • 122
    ISSN: 1432-2072
    Keywords: 5-HT1B ; 5-HT1C ; 5-HT2 receptors ; Feeding ; Satiety sequence ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Previous studies have shown that administration of 5-HT1B, 5-HT1C or 5-HT2 agonists decreases food intake in rats. However, it has not been established whether these drugs induce satiety or decrease feeding by a non-specific mechanism. In the present study the post-prandial satiety sequence was used to characterise the actions of the 5-HT2 receptor agonist, 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI), the 5-HT1B/5-HT1C receptor agonists, 1-(3-chorophenyl) piperazine (mCPP) and 1-[3-(trifluoromethyl)phenyl] piperazine (TFMPP), and the 5-HT1B agonist, 5-methoxy-3-(1,2,3,6-tetrahydro-4-pyridinyl)H-indole (RU 24969), on feeding in rats. All four compounds reduced food intake in rats that had been food deprived overnight. The 5-HT1B/5-HT1C agonists, TFMPP (at a dose of 1.0 mg/kg) and mCPP (at a dose of 3.0 mg/kg), appeared to produce satiety as their effects on the satiety sequence were similar to those induced by a food pre-load. In contrast, the 5-HT1B agonist RU 24969 and the 5-HT2 agonist DOI did not produce behavioural profiles that resembled satiety. Thus, RU 24969 elevated active behaviours and did not accelerate resting whereas DOI appeared to induce hypophagia by a non-specific fragmentation of behaviour. The results suggest that simultaneous activation of 5-HT1B and 5-HT1C receptors may be sufficient to elicit behaviourally specific satiety in the rat. In contrast, selective activation of 5-HT2 receptors does not induce satiety but elicits active behaviours and decreases feeding by response competition.
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  • 123
    ISSN: 1432-2072
    Keywords: Behavioral sensitization ; amphetamine ; NPA ; Ontogeny ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In the present study, the abilities of NPA (a direct DA receptor agonist) and amphetamine (an indirect DA receptor agonist) to induce short- and long-term behavioral sensitization were assessed in 11- and 17-day-old rats (age at initial injection). Rats were injected on 4 consecutive days with amphetamine (1.0, 2.5, or 5.0 mg/kg), NPA (1.0 mg/kg), or saline. A final test day occurred either 2 days (experiment 1) or 8 days (experiment 2) later. On the test day, rats given successive agonist injections received a single injection of the same agonist again; whereas rats given successive saline injections received either amphetamine or NPA for the first time. Five minutes after injection, locomotor activity (line-crosses), stereotyped sniffing, and vertical activity were measured during a 30-min testing session. The results showed that 11- and 17-day-old rats exhibited behavioral sensitization when tested with NPA or amphetamine after a 2-day interval. In contrast, neither NPA nor amphetamine was able to sensitize the behaviors of preweanling rats when measured 8 days after initial drug treatments. Therefore, these results show that both direct and indirect DA agonists are able to induce short-term behavioral sensitization in preweanling rats, but that the mechanisms responsible for mediating long-term behavioral sensitization have not yet matured.
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  • 124
    ISSN: 1432-2072
    Keywords: Stress ; Anxiety ; Rat ; Metabolism ; Energy expenditure ; Energy substrate utilisation ; Respiratory quotient ; Midazolam ; FG-7142 ; RO 15-1788 ; Panic ; Hyperventilation ; Sympathetic nervous system ; Benzodiazepine ; Conditioned stimulus ; Respiration
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Changes in O2 consumption, CO2 production and locomotor activity were examined in rats exposed to (1) brief footshock, (2) an aversive conditioned stimulus (CS) predicting footshock, or (3) the anxiogenic drug FG-7142. Respiratory quotient (RQ=CO2 produced/O2 consumed) and energy expenditure [EE=O2 consumed (364+113RQ)] were derived to give an estimate of the energy substrate (fat, carbohydrate or protein) being utilised and total substrate oxidation respectively. In experiment 1, footshock (4 × 5 s 0.6 mA shocks over 2 min) produced an immediate increase in RQ, EE and activity. The RQ and EE effects were attenuated by the benzodiazepine midazolam (1 mg/kg). In experiment 2, an aversive CS, consisting of flashing light and buzzer that had 24 h earlier been repeatedly paired with footshock (20 × 5 s 0.6 mA shocks) caused a pronounced drop in RQ, an increase in EE and locomotor activity suppression. The effects of the aversive CS on RQ and EE were reversed by midazolam (1 mg/kg). In experiment 3, FG-7142 (10 mg/kg) produced a steep drop in RQ that persisted for at least 2 h and which was reversed by midazolam (1 mg/kg) and delayed by the benzodiazepine antagonist RO 15-1788 (10 mg/kg). FG-7142 also tended to inhibit EE and locomotor activity, but these effects did not reach statistical significance. Overall, these data show that stress causes profound alterations in RQ, EE and activity and that the pattern of change in these parameters differs with the nature of the stressor involved.
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  • 125
    ISSN: 1432-2072
    Keywords: Kavapyrone ; Piper methysticum ; GABA ; Rat ; Brain
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Regional differences in the modulation of [3H] muscimol binding to GABAA receptor complexes by kavapyrones, compounds of the rhizome of the plantPiper methysticum which possess sedative activity, were demonstrated using membrane fractions obtained from target brain centers of kavapyrone action: hippocampus (HIP), amygdala (AMY) and medulla oblongata (MED), and from brain centers outside the main kavapyrone effects as frontal cortex (FC) and cerebellum (CER). The kava extract enhanced the binding of [3H] muscimol in a concentration-dependent manner with maximal potentiation of 358% over control in HIP followed by AMY and MED (main target brain centers). Minimal stimulation was observed in CER followed by FC. In contrast, apart from CER, the potency of kavapyrones was similar in the brain areas investigated with EC50 values ranging between 200 and 300 µM kavapyrones. Scatchard analysis revealed that the observed effects of kavapyrones were due to an increase in the number of binding sites (Bmax), rather than to a change in affinity. At a kavapyrone concentration of 500 µM the order of enhancement in Bmax was HIP=AMY〉MED〉FC〉CER. When kavapyrones are included together with pentobarbital or HPO the two classes of compounds produced a more than additive, i.e., synergetic effect on [3H] muscimol binding. Our findings suggest that one way kavapyrones might mediate sedative effects in vivo is through effects on GABAA receptor binding.
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  • 126
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    Psychopharmacology 113 (1994), S. 534-538 
    ISSN: 1432-2072
    Keywords: Nicotine ; Prenatal ; Analgesia ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effect of prenatal exposure to nicotine on nicotine-induced analgesia was studied in rats. The analgesic effect of a single dose of nicotine (1 mg/kg SC) was measured by the tail-flick technique, and two subsequent studies were carried out. In the first study, 7-month-old male rats, born to dams chronically treated with nicotine during pregnancy (NIC), exhibited prolonged nicotine-induced analgesia compared to matched controls. The second study was designed to explore whether rats prenatally exposed to nicotine (NIC rats) are born with an increased sensitivity to nicotine and whether there is any sex difference. The analgesic effect of nicotine was tested on control and NIC rats of both sexes once a month from 2 to 7 months of age. At an early age, male but not female NIC rats, exhibited shorter analgesic responses to nicotine than did the matched controls. With increasing age, however, the duration of nicotine analgesia began to be prolonged in NIC rats of both sexes. Significant differences between control and NIC rats were found at the age of 6 and 7 months, in both sexes. Thus, rats prenatally exposed to nicotine are not born with an increased sensitivity to the analgesic effect of a single dose of nicotine. This phenomenon develops later, during the course of life, independently of gender.
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  • 127
    ISSN: 1432-2072
    Keywords: 5-Hydroxytryptamine ; 5,7-Dihydroxytryptamine ; Operant behaviour ; Timing ; Fixed-interval peak procedure ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Twelve rats received injections of 5,7-dihydroxytryptamine into the dorsal and median raphe nuclei; 12 rats received sham lesions. The rats were then trained for 60 sessions under a discrete-trials fixed-interval schedule (peak procedure). In half the trials, a reinforcer became available 40 s after trial onset, and the trial was terminated upon reinforcer delivery; the remaining trials were 120 s in duration, and reinforcement did not occur in these trials. Performance during the 120-s trials was characterized by increasing response rate during the first 40 s of the trial, declining response rate between 40 s and 80 s, and a secondary increase in response rate during the final 40 s of the trial. The lesioned group showed a broader “spread” of the response rate function than the control group (time between attainment of 70% of the peak response rate and subsequent decline of response rate below this level); however, the peak response rate and the time from trial onset until attainment of the peak response rate did not differ significantly between the groups; the spread/peak-time ratio was significantly greater in the lesioned group than in the control group. The levels of 5-hydroxytryptamine (5HT) and 5-hydroxyindoleacetic acid in the parietal cortex, hippocampus, amygdala, nucleus accumbens and hypothalamus were markedly reduced in the lesioned group, but the levels of noradrenaline and dopamine were not significantly affected by the lesion. The results confirm the involvement of 5HTergic function in timing behaviour.
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  • 128
    ISSN: 1432-2072
    Keywords: Methamphetamine ; Rat ; Postnatal ; Acoustic startle ; Spatial learning
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Methamphetamine (MA) induces neurotransmitter reductions and neurotoxicity at high doses in adult animals, but its effects on early brain development and behavior have received less attention. In this experiment the effects of MA exposure during a period equivalent to the human third trimester were examined. Rats (Sprague-Dawley CD) were injected subcutaneously withd-MA (30 mg/kg b.i.d.) early in postnatal development (days 1–10), later (postnatal days 11–20), or with water during both of these periods. Both early and later MA-exposed offspring exhibited augmented acoustic startle and impaired performance in a complex multiple-T water maze. Only the early MA exposure group showed a persistent deficit in weight while only the later MA exposure group showed impaired learning in the Morris hidden platform maze. Effects on locomoter activity are reported in the accompanying article. It was concluded that the effects of MA are both long lasting and stage dependent and involve cognitive as well as arousal functions.
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  • 129
    ISSN: 1432-2072
    Keywords: Phenylpropanolamine ; Body weight ; Food consumption ; Water consumption ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The present study determined the effect of chronic PPA infusion and withdrawal on weight regulation. Male Sprague-Dawley rats received PPA (0, 90 or 180 mg/kg) via miniosmotic pumps for 2 weeks. Body weight and food and water consumption were measured daily before, during, and for 2 weeks after PPA infusion. Additionally, body weight was measured once 6 weeks after the last day of drug administration. PPA infusion produced dose-dependent reductions in body weight and food consumption throughout drug administration. During the first week of PPA termination, food consumption returned to control levels; however, body weights of drug-treated animals remained below those of controls throughout the 6-week post-drug period. PPA depressed water intake during the first week of drug administration, but tolerance to this effect developed by the second week of administration. These results suggest chronic PPA infusion produces persistent appetite suppression and weight loss and that discontinuation of PPA does not result in hyperphagia or rapid weight gain. These findings may have clinical significance for the many individuals who wish to lose weight but have difficulty reducing intake without pharmacologic assistance.
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  • 130
    ISSN: 1432-2072
    Keywords: Benzodiazepines ; Diazepam ; Morris water maze ; Place learning ; Anxiety ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Anxiolytic benzodiazepines have been shown to impair place learning in the Morris water maze. However, a clear-cut demonstration of a direct and specific effect on mnemonic processes has not yet been offered. In the present study, the effects of diazepam on place navigation in the Morris water maze were studied in rats. Three conditions were examined: learning, reversal learning and learning after familiarisation of animals with the maze. In view of the anxiolytic and sedative properties of diazepam, appropriate doses of the drug, i.e. those that produced an anxiolytic effect but no major motor impairment, were initially selected in the water-lick conflict and rotarod tests, respectively. Doses of 2.5 and 5 mg/kg PO increased punished drinking in the water-lick conflict test without significantly decreasing rotarod performance. These doses were then used to assess the effects of diazepam on spatial behaviour. Diazepam, at both doses, impaired place learning in behaviourally naive rats. Such an effect appeared to be transient: diazepam-treated rats eventually reached control performance. Moreover, analysis of the probe trial at the end of training revealed adoption of a spatial strategy to locate the submerged platform. Neither reversal learning nor learning after familiarisation was affected. These results do not replicate previous findings in the Morris water maze and provide some evidence that the diazepam-induced place learning deficit may be primarily anxiolytic in nature.
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  • 131
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    Psychopharmacology 115 (1994), S. 478-484 
    ISSN: 1432-2072
    Keywords: Aggression ; α2 Adrenoceptors ; Catecholamines ; ACTH ; Corticosterone ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effects of adrenergic activation on aggressiveness and the aggression induced endocrine changes were tested in rats. α2 adrenoceptor blockers were used for enhancing activation of the adrenergic system, and changes in aggressiveness were tested in resident-intruder contests. Three experiments were conducted. In experiment 1, saline injected rats responded to the presence of an opponent by aggression and the increase in plasma ACTH and corticosterone. Intraperitoneal administration of 1 mg/kg CH-38083 (an α2 adrenoceptor antagonist) produced a several fold increase in clinch fighting and mutual upright scores, and also further enhanced the plasma ACTH and corticosterone response. In experiment 2, the effect of three doses (0.5, 1 and 2 mg/kg) of three different α2 adrenoceptor blockers CH-38083, idazoxan and yohimbine were tested. All the substances increased aggression at 0.5 and 1 mg/kg; at 2 mg/kg the effect of idazoxan and yohimbine disappeared, while with CH-38083 an additional increase was obtained. In yohimbine treated animals the enhancement of aggression was reduced already at 1 mg/kg. In experiment 3, indomethacin, a potent inhibitor of the catecholamine-induced ACTH release completely abolished the effects of the α2 adrenoceptor antagonist CH-38083: the intensity of agonistic interactions, as well as ACTH and corticosterone plasma concentrations, returned to control levels. The possible role of catecholamines and the stress hormones in the activation of aggression is discussed.
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  • 132
    ISSN: 1432-2072
    Keywords: Isolation rearing ; α2-Adrenoceptor ; Clonidine ; Mydriasis ; Hypoactivity ; [3H]-Idazoxan binding ; cAMP ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract This study investigated central α2-adrenoceptor function in differentially reared rats. Rats reared from weaning were either housed singly or in groups of five. Measurements of spontaneous ambulatory activity at 4 weeks postweaning showed that isolates were more hyperactive on exposure to a novel environment than grouped rats. α2-Adrenoceptors were investigated using α2-adrenoceptor agonist-induced behaviours, [3H]-idazoxan binding and measurement of forskolin-stimulated cyclic AMP accumulation. Clonidine (0.001–1.0 mg/kg IP) induced mydriasis in both groups with no difference observed in the response between the isolation and group-reared animals. Clonidine (0.01–0.5 mg/kg IP) induced hypoactivity in both groups, with the effect significantly greater in the isolation-reared rats. Idazoxan markedly attenuated both responses, confirming their induction by α2-adrenoceptor stimulation. Clonidine-induced hypoactivity and mydriasis are mediated by pre- and postsynaptic α2-adrenoceptors, respectively; therefore the results suggest rats reared in isolation have enhanced presynaptic but unchanged postsynaptic α2-adrenoceptor function. Saturation binding experiments using [3H]-idazoxan were undertaken to determine α2-adrenoceptor number (Bmax) and affinity (Kd) in membranes prepared from the frontal cortex and hippocampus. Analysis of binding data revealed an increase in receptor number in the hippocampus of isolates. Cyclic AMP accumulation was measured in hippocampal slices from differentially reared rats. Isolation-rearing did not affect cyclic AMP accumulation in response to stimulation by forskolin (30 µM). However, the selective α2-adrenoceptor agonist, UK14304, produced a significantly greater inhibition of cyclic AMP accumulation in slices from isolated rats, confirming changes in α2-adrenoceptor function following isolation rearing.
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  • 133
    ISSN: 1432-2072
    Keywords: SR 48692 ; Neurotensin receptor antagonist ; Dopamine ; Apomorphine ; Bromocriptine ; (+) SKF 38393 ; (+) Amphetamine ; Turning ; Yawning ; Mouse ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract One major mechanism underlying the central action of neurotensin is an interaction with the function of dopamine (DA)-containing neurons. In addition, direct or indirect DA agonists have been reported to promote neurotensin release. We have found that SR 48692, a non-peptide neurotensin receptor antagonist (0.04 – 0.64 mg/kg orally), antagonizes (50–65%) yawning induced by apomorphine (0.07 mg/kg SC) or bromocriptine (2 mg/kg IP) in rats, and turning behaviour induced by intrastriatal injection of apomorphine (0.25 µg), (+) SKF 38393 (0.1 µg), bromocriptine (0.01 ng) or (+) amphetamine (10 µg) in mice. Other apomorphine-induced effects in mice and rats such as climbing, hypothermia, hypo- and hyper-locomotion, penile erections and stereotypies were not significantly modified by SR 48692. Taken together, these data suggest that neurotensin may play a permissive role in the expression of some but not all behavioural responses to DA receptor stimulation.
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  • 134
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    Psychopharmacology 116 (1994), S. 304-308 
    ISSN: 1432-2072
    Keywords: Intermediate stage of sleep ; Paradoxical sleep ; Spindle ; Theta rhythm ; Atropine ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Paradoxical sleep (PS) in the rat, cat and mouse is preceded and sometimes followed by a short-lasting intermediate stage (IS) characterized by high amplitude cortical spindles and low frequency theta rhythm. This stage, which is mimicked by an intercollicular transection, is massively extended at the expense of PS by low doses of barbiturates. Since the pontine cholinergic cell activation of PS is suppressed by barbiturates, we studied whether atropine, an antimuscarinic compound, extends IS at the expense of PS. Atropine sulfate was given at 5, 10 and 20 mg/kg IP. All doses increased dose dependently the occurrence latency of IS and PS. The amount of IS and PS was decreased for several hours, principally by a decrease of the number of phases. At 20 mg/kg the phase mean duration of IS and PS was also decreased. Consequently, IS and PS are similarly supported by muscarinic processes. The theta rhythm frequency was scored during IS and outside PS phasic motor activities (type 2 theta). At all doses it was significantly increased for hours. The theta rhythm frequency was also transiently increased during the hypersynchronization periods of PS (type 1 theta). At 20 mg/kg it was similarly the case for type 1 theta rhythm during waking.
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  • 135
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    Psychopharmacology 116 (1994), S. 523-528 
    ISSN: 1432-2072
    Keywords: Chronic mild stress ; Anhedonia ; Sucrose drinking ; Place conditioning ; Mianserin ; (+)-Mianserin ; Dopamine ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Chronic sequential exposure to a variety of mild unpredictable stressors has previously been found to depress the consumption of a dilute (1%) sucrose solution and to inhibit food-induced place preference conditioning. In the present study, using a simplified version of the mild stress procedure, the decreased sucrose intake was reversed by chronic (4 weeks) treatment with the atypical antidepressant mianserin. The racemic compound (±)-mianserin (5 mg/kg per day) and one of its enantiomers, (+)-mianserin (2.5 mg/kg) were effective in this model; a lower dose of (±)-mianserin (2.5 mg/kg), and the other enantiomer, (−)-mianserin (2.5 mg/kg), were ineffective. Vehicle-treated stressed animals were also subsensitive to food reward in the place conditioning procedure: normal place preference conditioning was reinstated by chronic treatment with (±)-mianserin (5 mg/kg) or (+)-mianserin, but not by the lower dose of (±)-mianserin (2.5 mg/kg) or by (−)-mianserin. Raclopride (100 µg/kg) reinstated the decrease in sucrose intake in stressed animals successfully treated with (±)- or (+)-mianserin. The results suggest that (+)-mianserin is the active enantiomer in reversing chronic mild stress-induced anhedonia, and further support the hypothesis of a dopaminergic mechanism of antidepressant action in this paradigm.
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  • 136
    ISSN: 1432-2072
    Keywords: Methamphetamine ; Rat ; Postnatal development ; Hypoactivity ; Pharmacological challenge
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Methamphetamine induces neurotransmitter reductions and neurotoxicity at high doses in adult animals, but its effects on early brain development and behavior have received little attention. In this experiment the effects of methamphetamine exposure during a period equivalent to the human third trimester were examined. Rats (Sprague-Dawley CD) were injected subcutaneously withd-methamphetamine (d-MA) (30 mg/kg b.i.d.) early in postnatal development (days 1–10), later (postnatal days 11–20), or with water during both of these periods. Both early and later MA-exposed offspring exhibited reduced locomotor activity. The effect was most evident at 30 days of age and was smaller at 45 and 60 days and only present at these latter ages in males. Only the early MA exposure group showed prolonged suppression of activity in response to a challenge dose of fluoxetine and a persistant deficit in weight while only the later MA exposure group showed attenuated suppression of activity in response to a challenge dose of fluoxetine. Based both on the present data and those in the preceding article, it was concluded that the effects of MA are both long lasting and stage dependent and involve arousal as well as cognitive functions.
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  • 137
    ISSN: 1432-2072
    Keywords: Cocaine ; Self-administration ; Calcium antagonists ; Isradipine ; Dopamine ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effect of isradipine, a dihydropyridine calcium antagonist, on cocaine intravenous self-administration in rats was investigated. Administration of (±)isradipine (1.25–5 mg/kg SC) 2 h before the cocaine self-administration session induced a significant and dose-dependent increase in the number of coacine injections with respect to basal values. This effect was sterospecific, with the (+) form of isradipine being active, while the (−) stereoisomer was ineffective. These results suggest that isradipine antagonizes the rewarding properties of cocaine, possibly by inhibiting those dopaminergic systems related to reward mechanisms. These results further indicate a possible use of isradipine, or structurally similar compounds, in the treatment of cocaine related disorders.
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  • 138
    ISSN: 1432-2072
    Keywords: Nitrogen dioxide ; Prenatal exposure ; Behavior ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Wistar female rats were exposed to low concentrations of nitrogen dioxide, NO2 (1.5 and 3 ppm) from day 0 to day 20 of pregnancy. The results show that prenatal exposure to this oxidant gas produced significant changes in the duration pattern of ultrasonic vocalizations emitted by male pups removed from their nest. In particular, a significant decrease in the length of ultrasonic calls was found in both 10- and 15-day-old rats exposed to NO2 (3 ppm) during gestation. These alterations were found at dose levels which did not significantly affect reproduction parameters, body weight gain and motor activity development. These findings suggest that gestational exposure to NO2, at concentrations below those associated with overt signs of toxicity, induces in rat offspring subtle behavioral changes characterized by altered ontogeny of ultrasonic emission.
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  • 139
    ISSN: 1432-2013
    Keywords: Brown adipose tissue ; Cold-acclimation ; Noradrenaline turnover ; Oestradiol ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract It has been shown previously that high plasma levels of oestradiol inhibit brown adipose tissue thermogenesis. Since rats and mice show a close association between thermogenic activity in and sympathetic discharge to brown fat, we measured the noradrenaline turnover in rats with high plasma levels of oestradiol to establish whether the observed inhibition of thermogenic activity is brought about by a reduction in the sympathetic drive to brown adipocytes. Oestradiol-filled Silastic capsules were implanted subcutaneously in female rats previously acclimated either to thermoneutrality or to cold. Control rats received empty implants. After 15 days treatment, noradrenaline turnover was measured by blocking its synthesis with α-methyl-p-tyrosine. As expected, noradrenaline turnover was higher in cold-acclimated rats than in rats kept at thermoneutrality. The presence of high plasma oestradiol levels did not alter sympathetic activity in any of the treated groups despite reducing thermogenic activity. This result reveals that oestradiol dissociates the thermogenic activity of brown adipose tissue from its sympathetic activation. Such dissociation has never been previously reported in rats, although it seems to be common in Syrian hamsters. However the causative factor in this species is unknown.
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  • 140
    ISSN: 1432-2013
    Keywords: Skeletal muscle ; Muscle damage ; Treadmill running ; Serum ; Enzymes ; Water content ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Male Wistar rats were made to run uphill on a treadmill 5.5° incline at 17 m min−1 for 4 h, and killed for muscle and serum sampling 2, 4, 12, 24, 48 or 96 h after the exertion. To estimate the degree of muscle damage,β-glucuronidase activity, total protein concentration, water content and morphology were examined in the red parts of quadriceps femoris (MQF) and soleus (MS) muscles, the distal white part of the rectus femoris muscle (MRF) and the superficial part of triceps brachii muscle (MTB). Simultaneous serum samples were assayed for creatine kinase (CK) activity and carbonic anhydrase III (CA III) concentration. Fibre swelling and interstitial oedema were detected in MS at 4 h and in MQF at 12 h and typical histopathological changes, including inflammation and fibre necrosis, in both muscles 12–96 h post-exertion.β-Glucuronidase activity, a quantitative marker of muscle damage, was increased in MS at 4 h, in MQF at 24 h and in MRF 48 h after the running. No increase occurred in MTB. Water and protein content increased or decreased respectively, faster in MS (2 h post-exercise) than in MQF (12 h) or MRF (12 h). Water content thus contributed to muscle damage by preceding the increase inβ-glucuronidase activity. Serum CK activity was increased 2, 4, and 48 h after the running. Changes in serum CA III concentration were rather similar to those in CK but were not significant. The increase in serum CK was not in concert with the necrotic events in the muscle but occurred considerably earlier (2 h vs. 12–24 h post-exercise). The second peak in CK, 48 h post-exercise (during the necrotic phase), was smaller than the first one. Our results show that serum CK activity is an inaccurate estimate of exercise-induced muscle damage as regards interpretation of the degree and the time course of pathological events in the muscle.
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  • 141
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    Pflügers Archiv 426 (1994), S. 183-188 
    ISSN: 1432-2013
    Keywords: Hippocampus ; Corticosterone ; Adrenalectomy ; Local cerebral blood flow ; Diurnal rhythm ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The present study examined the effect of glucocorticoid manipulations on local cerebral blood flow in the hippocampus. We measured local cerebral blood flow in the hippocampus at 1-h intervals over a 1-day period in freely moving rats, by means of the H2 clearance method, before and after sham adrenalectomy, adrenalectomy or adrenalectomy with corticosterone replacement. We also measured local cerebral blood flow in the prefrontal cortex before and after adrenalectomy. Four weeks after the adrenalectomy, hippocampal blood flow at each time of day was an average of 47% greater than before the operation, showing diurnal variation as before. After the sham adrenalectomy or adrenalectomy with corticosterone replacement, hippocampal blood flow did not change significantly with respect to either its level or its diurnal variation. Local cerebral blood flow in the prefrontal cortex increased by only 19% after adrenalectomy. The present study demonstrates that adrenalectomy causes a remarkable increase in hippocampal blood flow, probably due to a lack of corticosterone.
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  • 142
    ISSN: 1432-2013
    Keywords: Glutamine synthetase ; Kidney ; Intestine ; Glutamine ; Ammonia ; Amino acids ; Metabolism ; Rat ; In vivo
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Renal glutamine metabolism in relation to ammoniagenesis has been extensively studied during chronic metabolic acidosis, when arterial glutamine levels are reduced. However, little is known about the effects of reduced glutamine delivery on renal glutamine and ammonia metabolism at physiological systemic pH values. Therefore, a model of decreased arterial glutamine concentrations at normal pH values was developed using methionine sulphoximine (MSO). Renal glutamine and ammonia metabolism was measured by determining fluxes and intracellular concentrations after an overnight fast in ether anaesthetized normal rats, MSO-treated rats and their pair-fed controls. Moreover, fluxes and intracellular concentrations of several other amino acids were determined concomitantly. After 2 and 4 days of MSO treatment, arterial glutamine concentrations were reduced to 55%, while arterial ammonia concentrations increased by 70%. Kidney glutamine uptake reduced, but systemic pH was unchanged. Fractional extraction of glutamine remained unchanged, suggesting that also in vivo net uptake of glutamine by the kidney at subnormal levels is related to arterial glutamine concentrations. As a result, at day 2 but not at day 4, the kidney reduced the net release of ammonia into the renal vein and thus reduced net renal ammonia addition to body ammonia pools. Therefore at day 2, the kidney seems to play an important role in adaptation to both hyperammonaemia and hypoglutaminaemia.
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  • 143
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    Pflügers Archiv 426 (1994), S. 328-332 
    ISSN: 1432-2013
    Keywords: Cortical collecting duct ; K+ channel ; Rat ; Isolated tubule ; Patch clamp
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Ion channel current amplitudes (μ) and open probabilities (P o) have been analysed so far by defining a 50% threshold to distinguish between open and closed states of the channels. With this standard method (SM) it is very difficult or even impossible to analyse channels of different size in one membrane patch correctly. A stochastical model, named the hidden Markov model (HMM), separates between observation noise and the stochastic process of opening and closing of ion channels. The HMM allows the independent analysis of μ, P o, and mean dwell times (τ) of different channels in one membrane patch, without defining threshold levels. Using this method errors in the analysis are not summarized like in the SM because all different analysing procedures (e. g. filtering, setting of threshold, fitting processes) are done in one step. Two different K+ channels in excised basolateral membranes of the cortical collecting duct of rat (CCD) were analysed by the SM and the HMM. The μ value of the intermediate-conductance K+ channel (i-K+) was 3.9±0.1 pA (SM) and 3.8±0.2 pA (HMM) for 11 observations. The P o value of this channel was 10.2±4.2% (SM) and 10.1±4.0% (HMM). The mean τ values were 5.4±0.6 ms for the open state and 9.6±2.2 ms and 145±21 ms for the closed states (SM) and 7.8±1.1 ms, 7.7±0.9 ms and 148±24 ms (HMM), respectively. For seven small-conductance K+ (s-K+) channels, which were found in the same membrane patches as the i-K+, an accurate analysis of P o and τ was not possible with the SM. The μ value was 1.0±0.1 (SM), 0.9±0.1 (HMM) pA. P o was 16.6±4.6%, the open τ value was 11.1±2.8 ms, and the closed τ value was 34.9±8.5 ms. The HMM allows the analysis of single-channel currents, P o, and mean τ values when different or more than one ion channel(s) are colocalized in one membrane patch. Where analysis with the SM was possible results did not significantly differ from those obtained with the HMM. Thus for this kind of analysis the method of setting a 50% threshold appears justified.
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  • 144
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    Pflügers Archiv 426 (1994), S. 351-353 
    ISSN: 1432-2013
    Keywords: Rat ; Brown adipose tissue ; Noradrenaline responsiveness ; Oxygen consumption ; Cold acclimation ; Body temperature ; Oxidative capacity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Rectal temperature and oxygen consumption (üüO2) were monitored in female rats acclimated either to cold or to thermoneutrality and with and without chronic administration of oestradiol. The hormone is known to inactivate brown adipose tissue (BAT) and to reduce its response to noradrenaline (NA). The role of sympathetic control was studied by administering NA or the adrenergic blocker propranolol. Oestradiol treatment did not affect rectal temperature in the states of acclimation to thermoneutrality and to cold, nor did it change the hypothermic response of cold-exposed rats to temporary food deprivation. In the cold-acclimated rats, both controls and oestradiol-treated animals exhibited similar degrees of metabolic reduction after propranolol administration in the cold and similar degrees of metabolic activation by NA at thermoneutrality. Rats acclimated to thermoneutrality showed a larger metabolic response to NA when treated with oestradiol. The results suggest that oestradiol, while inactivating the BAT response to NA, activates the NA responsiveness of other metabolically active tissues in cold-induced thermogenesis. The observation of a greater oxidative capacity in the kidney and the rectus abdominis muscle of oestradiol-treated, cold-acclimated rats would be in line with this proposal.
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  • 145
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    Pflügers Archiv 426 (1994), S. 371-377 
    ISSN: 1432-2013
    Keywords: Body temperature ; Respiration ; Electrolytic lesions ; Urethrane anaesthesia ; Hypothalamus ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Urethane-anaesthetised rats were exposed to hypoxia (7% O2 in N2) for 5 min periods while body core temperature (T bc) was maintained within the normal range (37–38° C) using an abdominal heat exchanger. Animals were exposed to hypoxia and after placement of electrolytic lesions in either the anterior (n=6) or posterior hypothalamus (n=6). Neither lesion altered respiration while rats breathed air at either T bc. At normal T bc, rats responded to hypoxia with increased ventilation throughout the exposure period. This response was unchanged by lesions in either location. At reduced T bc rats responded to hypoxia with an initial increase in ventilation followed by depression to below air-breathing levels. This depressive response was unchanged after anterior hypothalamic lesions but eliminated after posterior hypothalamic lesions. It is concluded that neurons either originating in the posterior hypothalamus, or passing through it, play a role in the interaction between cold and hypoxia which leads to inhibition of respiration.
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  • 146
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    Documenta ophthalmologica 87 (1994), S. 315-329 
    ISSN: 1573-2622
    Keywords: Experimental retinal detachment ; Glial fibrillary acidic protein ; Müller cells ; Oxygen ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We conducted an extensive histological study of the retinas of newborn rats that had been exposed to hyperoxic conditions. Our aim was to verify whether it is possible, using oxygen alone, to induce retinal detachment, a lesion that is characteristic of the more advanced stages of retinopathy of prematurity (ROP). Eight litters (total number of animals: 64) of newborn, albino Wistar rats were used. Four litters (32 rats) were exposed to 80% oxygen for the first ten days of life. Some of these rats were then removed to room-air environments where they were kept for two, three or four more weeks. The other four litters (32 rats) were maintained for the entire period in room-air. On the 11th, 25th, 32nd and 39th days of life rats from both the exposed and control groups were sacrificed and 5 micron sections of their in toto eyeballs were submitted to histological evaluation and immunohistochemical studies. Folding of the internal retinal layers was observed in some of the animals exposed to hyperoxia, as well as those kept in room air. These folds did not alter the overall thickness of the retina itself and were probably congenital. Retinal folds and microdetachments were seen in many of the retinas from the exposed group of rats. Extensive detachment was observed in one of the rats sacrificed after two weeks of room-air recovery, in two of those recovered for three weeks and in two exposed to four weeks of room air. The sections containing these areas of retinal detachment showed marked increases in glial fibrillary acidic protein (GFAP) in immunocytochemical studies, suggesting that Müller cells might play a role in the pathogenesis of retinal detachment.
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  • 147
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    Urological research 22 (1994), S. 51-55 
    ISSN: 1434-0879
    Keywords: Bladder dysfunction ; Muscle strip ; Rat ; X-irradiation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Strips of rat detrusor muscle were studied in an organ bath 6 months after X-irradiation at doses of 15 and 25 Gy; cystometric studies in these animals had shown a persistent and significant reduction in compliance. The organ bath study demonstrated an increase in the purinergie sensitivity of irradiated detrusor muscle as compared with control. This was significant: p〈0.0145 for the 25 Gy dose group (n=8) and p〈0.0456 for the 15 Gy group (n=8) at an α,β-methylene-ATP concentration of 10-4 M (Mann-Whitney U-Test). There was no difference in sensitivity to cholinergic or noradrenergic stimulation, or to electrical stimulation of the transmural nerves. The finding of purinergic hypersensitivity in irradiated muscle, coupled with ultrastructural evidence of a neural injury, raises the interesting possibility that a denervation super-sensitivity phenomenon may contribute to the pathophysiology of post-irradiation bladder dysfunction.
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  • 148
    ISSN: 1434-0879
    Keywords: Kidney ; Pyelonephritis ; Rat ; Sialidase (neuraminidase) ; Urokinase
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Renal stone formation can be caused by many different and varied disturbances, some of which are poorly understood. The relationship between urinary infection and renal stone formation has not been completely clarified. It is argued that renal stones form primarily as a consequence of the hydrolysis of urea by the bacterial enzyme urease. However, no explanation is given for microorganisms that produce urease only occasionally or not at all. The question arises as to wheter the infection-induced microorganisms might not be playing a double role in renal stone formation by not only producting urease, but also by affecting in vivo urokinase (UK) and sialidase (SA) activity. With this in mind, the effect of Escherichia coli on renal UK and SA activity has been studied in male rats with a normal diet. The renal UK (P=0.208) and SA (P=0.2135) activities did not differ significantly between the two kidneys of the same rat. In contrast, when drainage from one kidney of a rat was externally obstructed, the UK and SA activities differed significantly between kidneys (P〈0.015). An increase in UK (r=0.6456, P〈0.0001) and SA (r=0.7507, P〈0.0001) activity was observed over time in the obstructed kidney. Subcutaneous injections with E. coli reduced the UK activity of the obstructed kidney significantly (p=0.0171). However, the SA activity remained the same (P=0.3929). This decrease in the UK activity in the presence of microorganisms may result in an increase in the uromucoid concentration, leading to renal stone formation in the presence of increased salt precipitation on the uromucoid as caused by the urease producing microorganisms.
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  • 149
    ISSN: 1434-0879
    Keywords: GnRH-DT vaccine ; Testosterone ; Ultrastructure ; Rat ; Prostate
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract To evaluate the effects of active immunization against gonadotropin-releasing hormone (GnRH) on the ultrastructure of the rat ventral prostate, male Sprague-Dawley rats received three consecutive intramuscular injections of 10 μg/100g body weight (D-Lys6)-GnRH-diphtheria toxoid conjugate (GnRH-DT vaccine). Following immunization, test animals developed sufficiently high antibody titres to block the pituitary gonadal axis. Consequently testosterone values dropped to the levels in castrates. This therapy leads to atrophy of the prostate. Following immunization a strong immunological response, indicating the presence of considerable amounts of a GnRH-like peptide, was observed in the ventral prostates as early as 14 days after the first injection of GnRH-DT. Immunoneutralisation of GnRH-like activity may contribute to the effects observed.
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  • 150
    ISSN: 1434-0879
    Keywords: S100 protein ; Rat ; Carcinogenesis ; Renal neoplasms
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Concentrations of α and β-subunits of S100 protein (S100-α and S100-β) in rat kidney neoplasms, including renal cell and mesenchymal tumors, were determined using a highly sensitive enzyme immunoassay, and both types immunohistochemically localized in tissue sections. Concentration of S100-α in each histological type of rat tumor were lower than in normal kidney, whereas levels of S100-β (mean±SE: 29.7±14.2 ng/mg protein, n=15) in renal cell tumors were significantly higher than in normal kidneys (0.55±0.06 ng/mg protein, n=7), or mesenchymal tumors (1.21±0.43 ng/mg protein, n=9). In normal rat kidney tissues S100-α was immunohistochemically positive in epithelial cells of the distal tubules, the thin limbs of loops of Henle, and the collecting ducts. No appreciable immunostaining for S100-β was found in any nephron segment. Both S100-α and S100-β were positive for renal cell tumors, indicating new appearance of the latter during renal carcinogenesis in rats.
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  • 151
    ISSN: 1573-7365
    Keywords: Hippocampus ; Slices ; Protein synthesis ; Ischemia ; Glutamate ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Protein synthesis was measured in hippocampal slices which were exposed to glutamate (1 mM or 10 mM) or which were deprived of glucose and oxygen (‘in vitro ischemia’) for 15 min. Glutamate at 1 mM, a concentration estimated to occur duringin vivo ischemia did not affect protein synthesis. Ten mM glutamate inhibited protein synthesis immediately after exposure (50% of control values) and reduced ATP levels to about 30% of the control. After two hours, slices fully recovered their protein synthesis and energy metabolism. The effect of 10 mM glutamate was not receptor-mediated, as NMDA, AMPA, or metabotropic receptor antagonists failed to block the glutamate effect. Immediately after ischemia, protein synthesis was reduced to 30% of control values, and 2 hours later it was still depressed to one-half of control values. Energy charge, however, recovered completely. Ischemic inhibition of protein synthesis was not reversed by glutamate receptor antagonists. The data indicate that inhibition of protein synthesis in hippocampal slices during ischemia is not glutamate-dependent.
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  • 152
    ISSN: 1439-6327
    Keywords: Hindlimb suspension ; Recovery ; Soleus muscle ; Fibre-type composition ; Myosin heavy-chain IId isoform ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We examined the changes in myosin heavy-chain (HC) isoforms and fibre-type composition in rat soleus muscle using both myosin adenosine triphosphatase staining and sodium dodecyl sulphate/polyacrylamide gel electrophoresis (SDS-PAGE) analyses during the recovery period after 4 weeks of hindlimb suspension. Although there was no change in type IIc fibres after the suspension, an increase in this type of fibres was observed during the 1- to 4-week recovery period. The increase in type Ilc fibres was considered to be due to a shift from type Ila to IIc fibres. The SDS-PAGE analysis revealed the presence of the HC IId isoform, which was not observed in the control muscle, after a 4-week hindlimb suspension. The HC IId isoform gradually decreased over 3 weeks of recovery and disappeared in the 4th week of recovery after the suspension. These results suggest that the hypogravity conditions induced by hindlimb suspension stimulated the synthesis of the HC IId isoform, whereas an increase in mechanical load to the muscle accelerated the degradation of the HC IId isoform and the synthesis of type Ilc fibres during the recovery period after hindlimb suspension.
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  • 153
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    Journal of Chemometrics 8 (1994), S. 21-36 
    ISSN: 0886-9383
    Keywords: GRAM ; Tucker ; Unfold ; NBRA ; Second-order ; Three-way ; PARAFAC ; Trilinear ; Chemistry ; Analytical Chemistry and Spectroscopy
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: If an analytical instrument or instrumental method gives a response matrix when analyzing a pure analyte, the instrument or instrumental method is called a second-order method. Second-order methods that generate a response matrix for a pure analyte of rank one are called rank-one second-order methods. If the response matrix of a pure analyte is not rank one, essentially two cases exist: medium rank (between two and five) and high rank (greater than five). Subsequently, medium- and high-rank second-order calibration tries to use medium- and high-rank second-order methods to analyze for analytes of interest in a mixture. A particular advantage of second-order methods is the ability to analyze for analytes of interest in a mixture which contains unknown interferences. Keeping this advantage is the challenge on moving away from rank-one second-order calibration methods. In this paper a medium-rank second-order calibration method is proposed based on least-squares restricted Tucker models. With this method the second-order advantage is retained.
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  • 154
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    Journal of Chemometrics 8 (1994), S. 81-93 
    ISSN: 0886-9383
    Keywords: Sensory evaluation ; Cumulative ranks ; Assessor variation ; Chemistry ; Analytical Chemistry and Spectroscopy
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: A graphical method of assessing differences between sets of rankings based on cumulative ranks is developed. The method can be used to identify rankings that differ over all or just part of the range of objects ranked. The method is applied to an example of sensory evaluation of green peas in which ten assessors scored six attributes on each of 60 samples.
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  • 155
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    Journal of Chemometrics 8 (1994), S. i 
    ISSN: 0886-9383
    Keywords: Chemistry ; Analytical Chemistry and Spectroscopy
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
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  • 156
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    Journal of Chemometrics 8 (1994), S. 155-168 
    ISSN: 0886-9383
    Keywords: Trilinear models ; Tensorial resolution ; PARAFAC ; Swamps ; Two-factor degeneracy ; Chemistry ; Analytical Chemistry and Spectroscopy
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The alternating least squares PARAFAC algorithm is a useful tool for resolving trilinear three-way data arrays. Occasionally, however, it becomes bogged down for many iterations in the vicinity of a poor quality resolution before moving on to a much superior optimum fit. We investigate this behavior in a simulation study and suggest ways of overcoming the obstacles it presents.
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  • 157
    ISSN: 0886-9383
    Keywords: Chemistry ; Analytical Chemistry and Spectroscopy
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
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  • 158
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    Journal of Chemometrics 8 (1994), S. i 
    ISSN: 0886-9383
    Keywords: Chemistry ; Analytical Chemistry and Spectroscopy
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
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  • 159
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    Journal of Chemometrics 8 (1994), S. 181-203 
    ISSN: 0886-9383
    Keywords: RAFA ; GRAM ; Eigenvalues ; Bias ; Variance ; Chemistry ; Analytical Chemistry and Spectroscopy
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Rank annihilation factor analysis (RAFA) is a method for multicomponent calibration using two data matrices simultaneously, one for the unknown and one for the calibration sample. In its most general form, the generalized rank annihilation method (GRAM), an eigenvalue problem has to be solved. In this second paper expressions are derived for predicting the bias and variance in the eigenvalues of GRAM. These expressions are built on the analogies between a reformulation of the eigenvalue problem and the prediction equations of univariate and multivariate calibration. The error analysis will also be performed for Lorber's formulation of RAFA. It will be demonstrated that, depending on the size of the eigenvalue, large differences in performance must be expected. A bias correction technique is proposed that effectively eliminates the bias if the error in the bias estimate is not too large. The derived expressions are evaluated by Monte Carlo simulations. It is shown that the predictions are satisfactory up to the limit of detection. The results are not sensitive to an incorrect choice of the dimension of the factor space.
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  • 160
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    Journal of Chemometrics 8 (1994), S. 301-302 
    ISSN: 0886-9383
    Keywords: Chemistry ; Analytical Chemistry and Spectroscopy
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
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  • 161
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    Journal of Chemometrics 8 (1994) 
    ISSN: 0886-9383
    Keywords: Chemistry ; Analytical Chemistry and Spectroscopy
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
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  • 162
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    Journal of Chemometrics 8 (1994), S. 305-331 
    ISSN: 0886-9383
    Keywords: Pyrolysis ; Mass spectroscopy ; Multivariate analysis ; Biological material identification ; Convexity ; Cones ; Subspaces ; Chemistry ; Analytical Chemistry and Spectroscopy
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: This work addresses the classification of high-dimensional time-dependent pyrolysis mass spectra of biological samples. The aim was the detection and classification of biological agents, and the developed approach resembles mixture analysis. The data were projected on to a low-dimensional subspace using singular value decomposition. Then a convex cone was formed on this subspace, showing as its corners physically meaningful components of the sample. This technique enabled separation of a biological material signal largely independent of the absolute amount of sample. The detection of the presence of any biological material could be accomplished based on the convex cone alone, without other reference to the mass spectra. Automated clustering of samples was successfully carried out using a minimal spanning tree.
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    Journal of Chemometrics 8 (1994), S. 373-373 
    ISSN: 0886-9383
    Keywords: Chemistry ; Analytical Chemistry and Spectroscopy
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
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    Keywords: Chemistry ; Analytical Chemistry and Spectroscopy
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    Topics: Chemistry and Pharmacology
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  • 165
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    Journal of Chemometrics 8 (1994), S. 37-44 
    ISSN: 0886-9383
    Keywords: Bootstrap ; Confidence interval ; Non-linear regression ; Monte Carlo methods ; Chemistry ; Analytical Chemistry and Spectroscopy
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Non-linear regression models describing the toxicity of a mixture of rotenone and pyrethrins as an insecticide, the catalytic dehydration of n-hexyl alcohol and the Michaelis-Menten model for characterizing reaction rates in enzyme systems will be used to illustrate the accuracy of bootstrap methods in non-linear regression. Classical and bootstrap confidence intervals for the parameter estimates will be presented.
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  • 166
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    Keywords: Chemistry ; Analytical Chemistry and Spectroscopy
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  • 167
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    Journal of Chemometrics 8 (1994), S. 102-102 
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    Keywords: Chemistry ; Analytical Chemistry and Spectroscopy
    Source: Wiley InterScience Backfile Collection 1832-2000
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  • 168
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    Journal of Chemometrics 8 (1994), S. 111-125 
    ISSN: 0886-9383
    Keywords: PLS regression algorithm ; Kernel ; Many-variable data sets ; Chemistry ; Analytical Chemistry and Spectroscopy
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: A fast PLS regression algorithm dealing with large data matrices with many variables (K) and fewer objects (N) is presented For such data matrices the classical algorithm is computer-intensive and memory-demanding. Recently, Lindgren et al. (J. Chemometrics, 7, 45-49 (1993)) developed a quick and efficient kernel algorithm for the case with many objects and few variables. The present paper is focused on the opposite case, i.e. many variables and fewer objects. A kernel algorithm is presented based on eigenvectors to the ‘kernel’ matrix XX TYYT, which is a square, non-symmetric matrix of size N × N, where N is the number of objects. Using the kernel matrix and the association matrices XXT (N × N) and YYT (N × N), it is possible to calculate all score and loading vectors and hence conduct a complete PLS regression including diagnostics such as R2. This is done without returning to the original data matrices X and Y. The algorithm is presented in equation form, with proofs of some new properties and as MATLAB code.
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  • 169
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    Journal of Chemometrics 8 (1994), S. 169-174 
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    Keywords: Kernel algorithm ; PLS ; SVD ; Chemistry ; Analytical Chemistry and Spectroscopy
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Lindgren et al. (J. Chemometrics, 7, 45-49 (1993)) published a so-called kernel algorithm for PLS regression of Y against X when the number of objects is very large. The algorithm is based solely on deflation of the cross-product matrices XTX, YTY and XTY. The algorithm is now described in a shorter and more transparent way and compared with a similar algorithm for the singular value decomposition of XTY.
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  • 170
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    Keywords: Chemistry ; Analytical Chemistry and Spectroscopy
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  • 171
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    Journal of Chemometrics 8 (1994), S. 241-241 
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    Keywords: Chemistry ; Analytical Chemistry and Spectroscopy
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
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  • 172
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    Journal of Chemometrics 8 (1994), S. 273-285 
    ISSN: 0886-9383
    Keywords: GRAM ; Least-squares problem ; Eigenvalue problem ; NIPALS ; Performance index ; Condition number ; Chemistry ; Analytical Chemistry and Spectroscopy
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: In this paper we discuss the practical implementation of the generalized rank annihilation method (GRAM). The practical implementation comes down to developing a computer program where two critical steps can be distinguished: the construction of the factor space and the oblique rotation of the factors. The construction of the factor space is a least-squares (LS) problem solved by singular value decomposition (SVD), whereas the rotation of the factors is brought about by solving an eigenvalue problem. In the past several formulations for GRAM have been published. The differences essentially come down to solving either a standard eigenvalue problem or a generalized eigenvalue problem. The first objective of this paper is to discuss the numerical stability of the algorithms resulting from these formulations. It is found that the generalized eigenvalue problem is only to be preferred if the construction of the factor space is not performed with maximum precision. This is demonstrated for the case where the dominant factors are calculated by the non-linear iterative partial least-squares (NIPALS) algorithm. Several performance measures are proposed to investigate the numerical accuracy of the computed solution. The previously derived bias and variance are proposed to estimate the number of physically significant digits in the computed solution. The second objective of this paper is to discuss the relevance of theoretical considerations for application of GRAM in the presence of model errors.
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  • 173
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    Journal of Chemometrics 8 (1994), S. 299-301 
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    Keywords: Chemistry ; Analytical Chemistry and Spectroscopy
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Additional Material: 2 Tab.
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  • 174
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    Journal of Chemometrics 8 (1994), S. i 
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    Keywords: Chemistry ; Analytical Chemistry and Spectroscopy
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  • 175
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    Journal of Chemometrics 8 (1994), S. 349-363 
    ISSN: 0886-9383
    Keywords: Variable selection ; PLS ; Calibration ; Modelling ; Chemistry ; Analytical Chemistry and Spectroscopy
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: A modified PLS algorithm is introduced with the goal of achieving improved prediction ability. The method, denoted IVS-PLS, is based on dimension-wise selective reweighting of single elements in the PLS weight vector w. Cross-validation, a criterion for the estimation of predictive quality, is used for guiding the selection procedure in the modelling stage. A threshold that controls the size of the selected values in w is put inside a cross-validation loop. This loop is repeated for each dimension and the results are interpreted graphically. The manipulation of w leads to rotation of the classical PLS solution. The results of IVS-PLS are different from simply selecting X-variables prior to modelling. The theory is explained and the algorithm is demonstrated for a simulated data set with 200 variables and 40 objects, representing a typical spectral calibration situation with four analytes. Improvements of up to 70% in external PRESS over the classical PLS algorithm are shown to be possible.
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  • 176
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    Journal of Chemometrics 8 (1994), S. i 
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    Keywords: Chemistry ; Analytical Chemistry and Spectroscopy
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  • 177
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    Journal of Chemometrics 8 (1994), S. 409-421 
    ISSN: 0886-9383
    Keywords: Deconvolution ; FT-IR spectroscopy ; Protein conformations ; Chemistry ; Analytical Chemistry and Spectroscopy
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: In a variety of spectroscopic techniques the fundamental problem exists of determination of the individual spectral components, intrinsically overlapped in the measured spectrum. This is a typical deconvolution problem and several methods and techniques have been proposed for its solution in the technical literature, but suggestions of new approaches are still of interest. A new deconvolution procedure is presented here based on the use of the conjugate gradient minimization algorithm with the addition of sutiable constraints directly obtained by the application to the measured spectrum of the second-derivative operator or more sophisticated resolution enhancement procedures. Since in the examined case deconvolution essentially requires the minimization of a non-convex function, the use of such constraints is extremely important to supply suitable input parameters to the conjugate gradient algorithm to avoid obtaining minimum points which have no physical meaning. In our case each spectral compoent used for deconvolution has been assumed to have a Gaussian analytical definition fully identified by three parameters (amplitude, central frequency, spectral bandwidth), so that the input values required to start the deconvolution process are the number M of Gaussian components and 3M suitable initial approximations of the parameters above. It is shown that all this information can be obtained from the measured data. The deconvolution procedure was implemented by a FORTRAN Microsoft Version 5.1 program and experimental results relative to spectroscopic data obtained by FT-IR analysis of human serum albumin are reported. The results are discussed and compared with data obtained by the use of other techniques.
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  • 178
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    Keywords: Chemistry ; Analytical Chemistry and Spectroscopy
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  • 180
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    Keywords: Chemistry ; Analytical Chemistry and Spectroscopy
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  • 181
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    Journal of Chemometrics 8 (1994), S. 243-243 
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    Keywords: Chemistry ; Analytical Chemistry and Spectroscopy
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  • 182
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    Journal of Chemometrics 8 (1994), S. 245-261 
    ISSN: 0886-9383
    Keywords: Factor analysis ; Spectral resolution ; Two-dimensional luminescence ; Chemistry ; Analytical Chemistry and Spectroscopy
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: A factor analysis algorithm that estimates the spectra of mixture components using the set of most dissimilar rows and/or columns is described and illustrated. This algorithm uses the distance as a measure of spectral similarity and is suitable for application to a variety of the bilinear matrix-formatted data types produced by hyphenated and multidimensional analytical techniqes. The algorithm requires that the data matrix contain at least one row or column that corresponds to the pure spectrum of each component to effect accurate spectral resolution. The performance of the method is illustrated using the resolution of excitation and emission spectra of up to four components from experimental fluorescence excitation-emission matrices (EEMs). In the case of the EEM, characteristic bands in an emission spectrum effect resolution of the excitation spectrum of the corresponding component, while characteristic bands in an excitation spectrum lead to resolution of the corresponding emission spectrum. The use of the set of most dissimilar rows and columns to evaluate the degree of overlap in the component spectra and compare the quality of row and column solutions is also described.
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  • 183
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    Journal of Chemometrics 8 (1994), S. 293-294 
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    Keywords: Chemistry ; Analytical Chemistry and Spectroscopy
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
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  • 184
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    Journal of Chemometrics 8 (1994), S. 303-303 
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    Keywords: Chemistry ; Analytical Chemistry and Spectroscopy
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
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  • 185
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    Journal of Chemometrics 8 (1994), S. 333-347 
    ISSN: 0886-9383
    Keywords: PLS ; ATR ; Paper ; Resolution ; Infrared ; FTIR ; Chemistry ; Analytical Chemistry and Spectroscopy
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Attenuated total reflectance Fourier transform infrared spectrometry (ATR-FTIR) has been used to determine the amount of styrene-butadiene latex on the surface of coated papers and to predict the composition of the polymer. Spectrum recording was performed on the sample in its usual form without any modification.For quantitative analysis, partial least squares (PLS) regression, principal component regression (PCR) and multi-linear regression (MLR) were used to calculate models for prediction. The best result is obtained with PLS.We analysed two series of paper samples. The first analysis concerns the measurement of the quantity of latex of a constant quality on the coating surface. For 15 samples the concentration varied between 5 and 25 parts (grams per 100g of mineral pigments). We compared the predictive results at various resolutions. We obtained a relative error of 0.15 parts in latex at 4 cm-1 resolution. The second analysis concerns the measurement of the styrene/butadiene ratio in various types of latex. We obtained a relative error of 0.156 parts for styrene determination and 0.161 parts for butadiene determination.
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  • 186
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    Journal of Chemometrics 8 (1994), S. 439-443 
    ISSN: 0886-9383
    Keywords: Pattern recognition ; Principal component analysis ; Inverse mapping ; Optimization ; Material design ; Chemistry ; Analytical Chemistry and Spectroscopy
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: An inverse mapping method called PCB (principal component backing), in which the point representing an unknown sample from a low-dimensional principal component subspace is back-projected to the high-dimensional original feature space, is proposed. Two sorts of boundary conditions, non-linear inverse mapping and linear inverse mapping, are used to obtain an accurate solution in the PCB method. The method is applied to the material design of high-Tc superconductors, predicting the composition and process conditions for the synthesis of F-doped Bi-based materials. Samples in the ‘optimal’ region with the highest Tc of the Bi-based ceramics have been predicted.
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  • 187
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    Journal of Chemometrics 8 (1994), S. 65-79 
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    Keywords: Genetic algorithms ; Full validation ; Feature selection ; Outlier detection ; Multivariate analysis ; Chemistry ; Analytical Chemistry and Spectroscopy
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Genetic algorithms have been proved to be a very efficient method in the feature selection problem. However, as for every other method, if the validation of the results is performed in an incomplete way, erroneous conclusions can be drawn. In this paper a development of a previous genetic algorithm is presented so that a full validation of the results can be obtained. Furthermore, this algorithm has been shown to perform very well also as an outlier detector, allowing easy identification of the presence of outliers even in cases where the ‘classical’ techniques fail.
    Additional Material: 6 Ill.
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  • 188
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    Journal of Chemometrics 8 (1994), S. 99-100 
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    Keywords: Chemistry ; Analytical Chemistry and Spectroscopy
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
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  • 189
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    Journal of Chemometrics 8 (1994), S. 101-101 
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    Keywords: Chemistry ; Analytical Chemistry and Spectroscopy
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
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  • 190
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    Journal of Chemometrics 8 (1994), S. 147-154 
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    Keywords: RAFA ; GRAM ; Eigenvalue problem ; Complex solution ; Degenerate solution ; Chemistry ; Analytical Chemistry and Spectroscopy
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Rank annihilation factor analysis (RAFA) is a method for multicomponent calibration using two data matrices simultaneously, one for the unknown and one for the calibration sample. In its most general form, the generalized rank annihilation method (GRAM), an eigenvalue problem has to be solved. In this first paper different formulations of GRAM are compared and a slightly different eigenvalue problem will be derived. The eigenvectors of this specific eigenvalue problem constitute the transformation matrix that rotates the abstract factors from principal component analysis (PCA) into their physical counterparts. This reformulation of GRAM facilitates a comparison with other PCA-based methods for curve resolution and calibration. Furthermore, we will discuss two characteristics common to all formulations of GRAM, i.e. the distinct possibility of a complex and degenerate solution. It will be shown that a complex solution-contrary to degeneracy-should not arise for components present in both samples for model data.
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  • 191
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    Keywords: Chemistry ; Analytical Chemistry and Spectroscopy
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  • 192
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    Journal of Chemometrics 8 (1994), S. 179-180 
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    Keywords: Chemistry ; Analytical Chemistry and Spectroscopy
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
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  • 193
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    Journal of Chemometrics 8 (1994), S. 205-219 
    ISSN: 0886-9383
    Keywords: Fractional factorial design ; Significant effects ; ANOVA ; Probability plotting ; Bayes plot ; Chemistry ; Analytical Chemistry and Spectroscopy
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: This paper presents a method for identifying significant effects in fractional factorial designs. The method is based on comparing functions of the estimated effects with a scale invariant reference distribution. The method is illustrated and compared with alternative techniques on a dataset from processed cheese production. The method corresponded well to other methods (probability plotting and Bayes plot) that do not make use of error estimates. These methods were better than F-tests with few (two or four) degrees of freedom for error.
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  • 194
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    Keywords: Chemistry ; Analytical Chemistry and Spectroscopy
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    Topics: Chemistry and Pharmacology
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  • 195
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    Keywords: Fitting ; Non-linear ; Least squares ; Refinement ; Constraints ; MSE ; Confidence ; C ls ; XPS ; Chemistry ; Analytical Chemistry and Spectroscopy
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: A non-linear least squares iterative refinement has been implemented which shows high performance on a multiple-peak spectrum including baseline or background. Constraints as well as links within a range are introduced to drive the mathematical optimization: each peak parameter (i.e. height, position, Gaussian/Lorentzian mixing ratio and HWHM on both left and right sides) has assigned to it an allowed range of variation and can be strained to be correlated with other parameters belonging either to the same peak (symmetrical peaks) or to other peaks (doublets, triplets, etc.). Peak shapes typical of XP spectra are used and applications in the field of XPS are discussed. Through emulated curves with Poisson distributed noise, the accuracy and precision of back-calculated (refined) parameters have been estimated. Moreover, a confidence level calculated from X2 and degrees of freedom has been suggested to check the overall fitting of experimental curves where the signal-to-noise ratio is a priori unknown. An application to real C ls XP spectra is described as an example and a list of suggestions is given to match operator requirements. Finally, features of NLLSRC are discussed with respect to other approaches.
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  • 196
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    Journal of Chemometrics 8 (1994), S. 263-272 
    ISSN: 0886-9383
    Keywords: Molecular descriptors ; Principal component analysis ; Chemometrics ; Pattern recognition ; Total surface area ; PCDD PCDF ; Chemistry ; Analytical Chemistry and Spectroscopy
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: New theoretical molecular indices are defined. They contain information about the whole molecular structure in terms of size, shape, symmetry and atom distribution. These indices are calcualted from the (x, y, z) co-ordinates of a molecule within different weighting schemes in a straightforward manner and represent a very general approach to describe molecules, molecular fragments, macromolecules and molecular conformations in a unitary conceptual framework. Their interpretability is quite evident and is defined by the same mathematical properties as the algorithm used for their calculation. Examples on the total surface area, toxicity of PCDD and PCDF and reaction rate of catalysed reactions show a high modelling power of these indices.
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  • 197
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    Keywords: Chemistry ; Analytical Chemistry and Spectroscopy
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  • 198
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    Journal of Chemometrics 8 (1994), S. 365-370 
    ISSN: 0886-9383
    Keywords: Censored data ; ECM and EM algorithms ; Incomplete data ; Maximum likehhood ; Chemistry ; Analytical Chemistry and Spectroscopy
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The purpose of this short communication is to illustrate the use of conditional maximization (CM) in chemometric applications. The CM algorithm is useful in reducing the computational complexity when a high-dimensional and complicated maximization problem arises from fitting chemometric models. It can also be efficiently combined with the expectation-maximization (EM) algorithm for handling incomplete data, a problem that sometimes arises when only a part of the intended data can be collected. Three models from fluorescence spectroscopy are used for illustration.
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    Keywords: Chemistry ; Analytical Chemistry and Spectroscopy
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    Topics: Chemistry and Pharmacology
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  • 200
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    Journal of Chemometrics 8 (1994), S. 391-407 
    ISSN: 0886-9383
    Keywords: Neural networks ; Non-linear multivariate regression ; Pattern classification ; Kalman filter ; Chemistry ; Analytical Chemistry and Spectroscopy
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Finding methods for the optimization of weights in feedforward neural networks has become an ongoing developmental process in connectionist research. The current focus on finding new methods for the optimization of weights is mostly the result of the slow and unreliable convergence properties of the gradient descent optimization used in the original back-propagation algorithm. More accurate and computationally expensive second-order gradient methods have displaced earlier first-order gradient optimization of the network connection weights. The global, extended Kalman filter is among the most accurate and computationally expensive of these second-order weight optimization methods. The iterative, second-order nature of the filter results in a large number of calculations for each sweep of the training set. This can increase the training time dramatically when training is conducted with data sets that contain large numbers of training patterns. In this paper an adaptive variant of the global, extended Kalman filter that exhibits substantially improved convergence properties is presented and discussed. The adaptive mechanism permits more rapid convergence of network training by identifying data that contain redundant information and avoiding calculations based on this redundant information.
    Additional Material: 9 Ill.
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