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Biomedical subjects

H Fink

Publications and source records attributed to H Fink.

At least 37 records · Page 2Linked to original sources
PubMed2000

Lesion of the median raphe nucleus: a combined behavioral and microdialysis study in rats.

The purpose of the present study was to investigate the behavioral consequences and the neurochemical correlates of a 5,7-dihydroxytryptamine (5,7-DHT) lesion of the median raphe nucleus (MRN) in rats. Anxiety-related behavior was assessed in the elevated plus maze test on days 5, 14, and 21 after lesioning. In general, behavior of MRN-lesioned rats was unchanged when compared with sham-lesioned or untreated controls. Neurochemically, microinjection of 5,7-DHT into the MRN resulted in 87.5% depletion of hippocampal 5-HT content. Using the in vivo microdialysis technique, the exposure of 5,7-DHT-lesioned rats to the elevated plus-maze failed to increase extracellular 5-HT release (94%) in the hippocampus, as shown in sham-lesioned (150%) or untreated controls (194%). Moreover, application of fenfluramine (10 mg/kg, i.p.) evoked a 10-fold increase in hippocampal extracellular 5-HT levels in sham-lesioned animals, whereas in 5,7-DHT lesioned rats 5-HT was only slightly increased. The results demonstrate, that a marked reduction of 5-HT release from the MRN is not necessarily accompanied by anxiolytic-like behavior.

5,7-Dihydroxytryptamine↗
PubMed2000

Feeding and 8-OH-DPAT-related release of serotonin in the rat lateral hypothalamus.

Based on the different effects of somatodendritic 5-HT1A agonist 8-OH-DPAT on food intake whether given to food-deprived rats or freely feeding rats, we hypothesized that the effects of 8-OH-DPAT on extracellular serotonin (5-HT) in the lateral hypothalamus (LH) will interfere with different feeding states, eventually resulting in different patterns of 5-HT release. In a microdialysis study we measured extracellular 5-HT in the LH after 8-OH-DPAT under four experimental conditions, i.e., in freely feeding rats with no food available, freely feeding rats with access to food, in food-deprived rats with no food available, and in food-deprived rats with good available after treatment. The results show a significant decrease of 5-HT release after 300 microg/kg 8-OH-DPAT (i.p.) in freely feeding rats. This effect is not seen when food is provided after drug treatment. In contrast, the same dose of 8-OH-DPAT has no effect on 5-HT release in food-deprived rats. In addition, providing food after drug treatment does not change the release pattern significantly in food-deprived rats, suggesting more complexity in the underlying mechanisms. The present study describes the effects of 8-OH-DPAT on 5-HT release in the LH, depending on feeding conditions and feeding-related behavioral states.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed2000

Sex specific behavioural alterations in Mas-deficient mice.

Male mice lacking the Mas protooncogene have been shown to exhibit an increased anxiety in the Elevated Plus Maze Task and sustained long-term potentiation in the hippocampus without effect on spatial learning in the Morris Water Maze Task. Here, we report behavioural studies in female mice lacking the Mas protooncogene. As for the males, we analysed the learning and anxiety behaviour using both behavioural tasks. With the exception of a trend to a better performance in the Morris Water Maze no differences were found in both tests between control and Mas-deficient females. This implicates that the lack of Mas protein influences spatial learning and anxiety in a sex-specific manner.

Animals↗
PubMed2000

Does increased endogenous CCK interact with serotonin to reduce food intake in rats?

The present study was aimed to test the hypothesis that increased endogenous CCK may interact with the anorectic serotonergic agent dl-fenfluramine to reduce food intake in rats. Previous studies, using selective CCK receptor antagonists, could demonstrate CCK-dependent 5-HT-induced anorexia. In the present approach, we used protease inhibitors to increase levels of endogenous CCK instead of blocking CCK receptors by antagonists. The protease inhibitors we used were soybean trypsin inhibitor (STI) and camostate. We hypothesized that combining the anorectic serotonergic drug dl-fenfluramine with either STI or camostate should result in an enhanced hypophagic effect when compared to single drug treatment. All feeding experiments were performed in non-deprived rats during night time feeding. Given alone, STI (500 mg/kg, po), camostate (200 mg/kg po) and also fenfluramine (1-9 mg/kg ip) reduced significantly food intake, with a more pronounced effect following fenfluramine. However, the experiments do not provide evidence for any additive or synergistic action between camostate or STI and the anorectic serotonergic drug dl-fenfluramine on food intake.

Animals↗
PubMed2000

Effects of xenon on cerebral blood flow and autoregulation: an experimental study in pigs.

We have investigated the effects of xenon on regional cerebral blood flow (rCBF) and autoregulation in pigs sedated with propofol 4 mg kg-1 h-1. Balloon-tipped catheters were placed into the descending aorta and inferior vena cava of 15 Göttingen Minipigs for manipulation of arterial pressure and blood sampling. rCBF was measured using the sagittal sinus outflow technique. Xenon was adjusted randomly to end-tidal fractions (FE'Xe) of 0, 0.30, 0.50 and 0.70. After baseline measurements of heart rate (HR), mean arterial pressure (MAP), rCBF, sagittal sinus pressure (SSP) and calculation of regional cerebrovascular resistance (rCVR) at each respective FE'Xe, autoregulation was tested in the MAP range 60-120 mm Hg. Increasing FE'Xe had no effect on HR, MAP, rCBF or SSP. rCVR increased with increases in MAP, regardless of FE'Xe. Autoregulation was not impaired. We conclude that xenon inhalation had no effect on rCBF and autoregulation in our model, which could suggest that xenon is an adequate adjunct for neurosurgical anaesthesia.

Anesthetics, Inhalation↗
PubMed2000

Prednisolone-induced muscle dysfunction is caused more by atrophy than by altered acetylcholine receptor expression.

UNLABELLED: Large doses of glucocorticoids can alter muscle physiology and susceptibility to neuromuscular blocking drugs by mechanisms not clearly understood. We investigated the effects of moderate and large doses of prednisolone on muscle function and pharmacology, and their relationship to changes in muscle size and acetylcholine receptor (AChR) expression. With institutional approval, 35 Sprague-Dawley rats were randomly allocated to receive daily subcutaneous doses of 10 mg/kg prednisolone (P10 group), 100 mg/kg prednisolone (P100 group), or an equal volume of saline (S group) for 7 days. A fourth group of rats was pair fed (food restricted) with the P100 rats for 7 days (FR group). On Day 8, the nerve-evoked peak twitch tensions, tetanic tensions, and fatigability, and the dose-response curves of d-tubocurarine in the tibialis cranialis muscle were measured in vivo and related to muscle mass or expression of AChRs. Rate of body weight gain was depressed in the P100, FR, and P10 groups compared with the S group. Tibialis muscle mass was smaller in the P100 group than in the P10 or S groups. The evoked peak twitch and tetanic tensions were less in the P100 group than in the P10 or S groups, however, tension per milligram of muscle mass was greater in the P100 group than in the S group. The 50% effective dose of d-tubocurarine (microg/kg) in the tibialis muscle was smaller in the P10 (33.6 +/- 5.4) than in the S (61.9 +/- 5.0) or the P100 (71.3 +/- 9.6) groups. AChR expression was less in the P10 group than in the S group. The evoked tensions correlated with muscle mass (r(2) = 0.32, P < 0.001), however, not with expression of AChR. The 50% effective dose of d-tubocurarine did not correlate with muscle mass or AChR expression. Our results suggest that the neuromuscular dysfunction after prednisolone is dose-dependent, and derives primarily from muscle atrophy and derives less so from changes in AChR expression. IMPLICATIONS: The mechanisms by which chronic glucocorticoid therapy alters neuromuscular physiology and pharmacology are unclear. We suggest that the observed effects are dose-dependent and derive primarily from muscle atrophy and derive less from changes in acetylcholine receptor expression.

Animals↗
PubMed2000

Cerebral histopathology following portal venous infusion of bacteria in a chronic porcine model.

BACKGROUND: The aim of this study was to histologically investigate brain damage after prolonged periods of bacteremia in pigs. METHODS: Twenty-one pathogen-free Göttingen minipigs were anesthetized and instrumented with a femoral arterial, a pulmonary arterial, and through midline abdominal incision with a portal venous catheter. After craniotomy the superior sagittal sinus was cannulated. A lumbosacral spinal catheter was inserted for sampling of cerebrospinal fluid. Twelve hours after instrumentation, the animals were randomized in two groups: septic and control animals. The septic group received an infusion of 107 colony-forming units per kilogram of living Escherichia coli over 0.5 h through portal venous catheter each day. The control group received saline. Postoperative intensive care treatment included 4 days of controlled mechanical ventilation, sedation, and intravenous nutrition. The brains then were removed, fixed, and processed for histology. Each pathologic alteration found in the samples was assessed and given a severity code (0-3). RESULTS: Sham-operated animals showed no alterations caused by the instrumentation and the intensive care treatment. The septic group showed typical clinical signs of sepsis. Vasopressor support and mechanical ventilation prevented systemic hypotension and hypoxemia. High serum and cerebrospinal fluid levels of interleukin-6 and tumor necrosis factor-alpha were detected. The septic group showed severe histologic abnormalities of the brain including perivascular edema, spongiform degeneration, hyperemia, and purpura. Damage of neurons was seen including eosinophilic cytoplasm, shrunken nuclei, and disintegration of the nuclear membrane. CONCLUSIONS: Abdominal sepsis induced severe brain damage that was not related to systemic hypoxia or ischemia. High cerebrospinal fluid levels of tumor necrosis factor-alpha and interleukin-6 were related to an inflammatory process in the brain resulting in cerebral edema and death of neurons.

Animals↗
PubMed2000

From genotype to phenotype--behavior of the transgenic rat TGR(mRen2)27 as an example.

Transgenic techniques provide a tool to generate animals that differ from the wild-type by one or more genes, either by introducing foreign genes (transgenic animals) or by specific mutations of genes (knock-out animals). Most transgenic and knock-out animals are mice and not rats. The frequent use of rat models in the behavioral laboratory, however, will require the increasing application of transgenic techniques in this species. This paper reviews behavioral data from our laboratory as an example of characterizing the behavioral phenotype of a particular transgenic rat, the TGR(mRen2)27 rat. By describing the anxiogenic profile of this rat we also consider some problems associated with such an analysis, with the intention to raise issues that may also apply to studies of behavior in transgenic animals in general.

Animals↗
PubMed2000

The mother-child interaction and clinical judgment during acute pediatric illnesses.

OBJECTIVES: For acutely ill children living in less than optimal environments, mothers and pediatricians may have a heightened perception of illness severity, a lower specificity of clinical judgments, and a tendency to over-utilize resources. We examined the mother-child interaction in order to understand the relation of less optimal environments to clinical judgment and resource use. STUDY DESIGN: At the 2-week and 6-, 15-, and 24-month well child visits of 316 children, the mother-well child interaction was assessed by using the Biringen's Emotional Availability Scales (EAS). Data were gathered regarding maternal depression and sense of competence, infant temperament, maternal social support, life events, the home environment, and demographics. At ill visits, the mother-ill child interaction was assessed by using the EAS, and mothers and pediatricians independently assessed illness severity using the Acute Illness Observation Scales. Resource use during the illness was evaluated. RESULTS: One thousand nine hundred eight-three acute illnesses were assessed. A less optimal mother-child interaction was significantly (P <.05 for all comparisons) associated with poorer reliability of mothers' judgments, lower specificity of mothers' judgments (71% vs 85%) and pediatricians' judgments (92% vs 97%), and greater use of resources (eg, for hospitalizations, 2.6% of visits vs 0.7%). Adverse maternal, infant, and demographic characteristics were associated with a less optimal mother-well child (r = 0.68) and mother-ill child (r = 0.80) interaction, a heightened perception of illness severity, and greater resource use. CONCLUSION: Less optimal environments adversely affect the mother-child interaction; a poor mother-child interaction is correlated with low specificity of clinical judgment and over-utilization of resources.

Acute Disease↗
PubMed1999

Cortical NADH during pharmacological manipulations of the respiratory chain and spreading depression in vivo.

The nicotinamide adenine dinucleotide (NADH) is one of the main means for energy transfer in the mitochondrial respiratory chain and is an important parameter of cellular metabolism. NADH can be measured by its fluorescence and various fluorometric methods have been developed. In this study, a pulsed nitrogen laser combined with a fibreoptic set-up and photomultipliers was used to induce and measure NADH fluorescence on the cortical surface. The aim of the study was to assess the suitability of the laser induced spectroscopy for in vivo and on-line measurement of NADH in neuroscience and particularly for the assessment of neuronal metabolism. Changes in cerebral blood flow may affect fluorescence measurement. To assess the consequences of alterations in blood flow, the vasodilators glyceryl trinitrate and nimodipine and the vasoconstrictor endothelin-1 were applied. The induced hemodynamic changes were verified by colour Doppler sonography. The tests using the vasodilators showed that an increased blood flow in the brain increased not only NADH fluorescence but also the scattered light measured. The vasoconstrictor caused opposite effects. Insertion of a compensation method (subtraction of the scattered light) allowed the exclusion of hemodynamic artifacts. Effects of changes in the cellular metabolism were induced by sodium cyanide, an inhibitor of the mitochondrial respiratory chain, or by 2,4-dinitrophenol (2,4-DNP), an uncoupler of the oxidative phosphorylation. Sodium cyanide induced a transient increase of NADH fluorescence and 2,4-DNP decreased intracellular NADH fluorescence. Furthermore, the repercussions of cortical spreading depressions (CSD), a response of the brain to noxious stimuli, on cortical NADH fluorescence were determined. A single CSD decreased cortical NADH fluorescence for about 1 min, followed by a 5- to 10-min increase. The changes in NADH levels seem to correspond with the excitation and inhibition of neuronal metabolism, respectively. In summary, the measurement of NADH fluorescence using the laser technique allows the determination of changes in oxidative phosphorylation with high regional selectivity and time resolution.

2,4-Dinitrophenol↗
PubMed1999

Perinatal elevation of hypothalamic insulin, acquired malformation of hypothalamic galaninergic neurons, and syndrome x-like alterations in adulthood of neonatally overfed rats.

Overnutrition during critical developmental periods is suggested to be a risk factor for obesity and associated metabolic disorders in later life. Underlying mechanisms are unknown. Neuropeptides are essentially involved in the central nervous regulation of body weight. For instance, hypothalamic galanin (GAL) is a stimulator of food intake and body weight gain. To investigate long-term consequences of early postnatal overfeeding, the normal litter size of Wistar rats (n=10; controls) was reduced from day 3 to day 21 of life to only 3 pups per mother (small litters, SL; overnutrition). Throughout life, SL rats displayed hyperphagia (p<0.01), overweight (p<0.0001), hyperinsulinemia (p<0.01), impaired glucose tolerance (p<0.001), elevated triglycerides (p<0.001), and an increased systolic blood pressure (p<0.05). In adulthood, an increase of GAL-neurons in the arcuate hypothalamic nucleus (ARC) was found (p<0.001), positively correlated to body weight (p<0.001). A second experiment revealed hyperinsulinemia (p<0.001) and increased hypothalamic insulin levels (p<0.05) in SL rats during early postnatal life. Already on day 21 of life, i.e., at the end of the critical hypothalamic differentiation period, in SL rats the number of GAL-neurons was increased in the ARC (p<0.001), showing a positive correlation to body weight and insulin (p<0.05). In conclusion, neonatally acquired persisting malformation of hypothalamic galaninergic neurons, induced by early overfeeding and hyperinsulinism, might promote the development of overweight and syndrome X-like alterations during life.

Animals↗
PubMed1999

Learning and anxiety in angiotensin-deficient mice.

Angiotensin II in the brain was shown to be involved in mechanisms influencing cardiovascular and electrolyte homeostasis, anxiety and learning. Here, we report behavioural studies in mice lacking angiotensinogen. We analysed learning and anxiety related behaviour using the Morris water maze task and the elevated plus maze task, respectively. In both tests no differences were found between control mice and angiotensin-deficient mice. This implicates that angiotensin does not influence learning and anxiety-related behaviour in mice under normal conditions.

Angiotensin II↗
PubMed1999

Role of cholecystokinin type B receptors in ultrasound induced behavior in rats.

The cholecystokinin-tetrapeptide (CCK-4) can induce panic attacks in humans. The present study investigates the effects of CCK-4 and the CCK-B receptor antagonist L-365.260 on ultrasound induced defense behavior in the rat that may model the unconditioned aspects of panic behavior in man. CCK-4 (50 microg/kg) increased the defense response induced by ultrasound (95 dB) an effect prevented by pretreatment with L-365.260 (10 microg/kg). Compared with other antipanic/panicogenic drugs the effects of CCK-4 and L-365.260 were relatively small. In conclusion, drugs acting at the CCK-B receptor appear to have only a minor role in the modulation of an unconditioned aversive response.

Animals↗
PubMed1999

Hippocampal 5-HT and NE release in the transgenic rat TGR(mREN2)27 related to behavior on the elevated plus maze.

The transgenic rat TGR(mREN2)27 was generated to study mechanisms involved in the hypertensive process. A characteristic of this rat is a high expression of the murine renin-2 gene in several peripheral tissues and in the brain. The high expression of the transgene is associated with increased local formation of angiotensin II. In a previous study, we studied for the first time the behavior of male TGR(mREN2)27 rat in the open field and on the elevated plus maze. There were no differences between TGR(mREN2)27 and SPRD-controls in locomotor activity measured in the open field. While placed on the elevated plus maze, however, the TGR(mREN2)27 rats showed a greater "anxiogenic" profile than the SPRD-rats. The present study was aimed to characterize neurotransmitter release involved in anxiety in hippocampus of TGR(mREN2)27 rats during exposure to the elevated plus maze. Exposure to the maze resulted in an increased intrahippocampal serotonin release with the same maximum both in the transgenic rats and in the control rats. However, the subsequent decrease was significantly faster in the TGR(mREN2)27 compared to the SPRD-controls. The latter suggests that the serotonergic system is functionally changed in the TGR(mREN2) rat, too. In contrast, norepinephrine release did not change during exposure to the maze and there were no significant differences in norepinephrine release between transgenics and controls.

Angiotensin II↗
PubMed1999

Behavioral and neurochemical differences between Fischer 344 and Harlan-Wistar rats raised identically.

Inbred Fisher 344 and outbred Harlan-Wistar rats were compared in the elevated plus maze, the black-and-white box, the social interaction test, and a modified open-field test, to assess the contribution of genetic factors to aversion-motivated behavior. All animals used were born and raised under identical conditions. Compared to the Wistar rats, the Fischer rats displayed a more pronounced fearful behavior in all tests. In a separate microdialysis study, the relationship between behavioral variations to biochemical differences was assessed, with serotonin (5-HT) release in the ventral hippocampus being measured during the elevated plus-maze test. Exposure to the elevated plus-maze induced an increase in hippocampal 5-HT in the (more anxious) Fischer rats but not in the (less anxious) Wistar rats. The results confirm the influence of genetic factors on emotionality in rats and demonstrate a close, although not simple, relationship between the serotonergic system and "anxiety-related" behavior.

Animals↗