Search PubMed⌕ Search

Biomedical subjects

R Landgraf

Publications and source records attributed to R Landgraf.

At least 55 records · Page 3Linked to original sources
PubMed2001

Post-prandial decrease of circulating human ghrelin levels.

Ghrelin, an endogenous ligand of the GH secretagogue-receptor, has recently been shown to stimulate GH secretion and to have orexigenic and adipogenic effects in rodents, but little is known about its regulation and biological function in humans. Gastric motor function is under control of the central nervous system; however, the afferent and efferent loops of this feedback control mechanism remain to be elucidated. In the study presented here we investigated the effect of nutrient intake on circulating human ghrelin levels, and a possible association between ghrelin levels and gastric emptying. Ten healthy volunteers received a standard meal after an overnight fast. Food intake significantly decreased plasma ghrelin levels from 248.5 +/- 15.0 to 179.5 +/- 17.9 fmol/ml (120 min after meal, p=0.047). Gastric emptying half-time (non-invasive 13C-octanoic acid breath test) was correlated with fasting plasma ghrelin levels (r=0.74, p=0.0013). Ghrelin appears to be one possible candidate to provide feedback signaling between nutrient intake, gastric motor function and the central nervous system.

Adult↗
PubMed2001

[Intraoperative monitoring of intact parathyroid hormone (iPTH) in surgery of primary hyperparathyroidism with a new rapid test].

OBJECTIVES: Intraoperative differentiation between adenoma and hyperplasia during surgery for primary hyperparathyroidism (pHPT) is sometimes difficult, but essential for good results. The aim of our study was to evaluate a new highly sensitive electrochemiluminescence immunoassay (ECLIA) for intraoperative monitoring of intact parathyroid hormone (iPTH) following parathyroidectomy as an adjunct for identification of solitary adenoma in patients with pHPT. METHODS: Thirty consecutive patients with pHPT (2 with recurrent pHPT) were examined following a standardized protocol: Immediately before and 5, 10 and 15 min following parathyroidectomy of the enlarged gland, iPTH was measured with a new ECLIA (Roche-Diagnostics, Mannheim, Germany). The results were available within 15-20 min. Besides 20 conventional bilateral neck explorations, parathyroidectomy was carried out in a minimally invasive video-assisted technique (MI-VAP) in 10 patients. RESULTS: Among the 30 patients we found 24 with solitary adenoma (80%), 5 with hyperplasia (17%) and one with a double adenoma (3%). Five minutes after removal of a solitary adenoma the level of iPTH had decreased by 65 (12)% [mean (+/- SD)], after 10 min by 76 (8)% and after 15 min by 81 (8)%. All patients with multiple gland disease could be clearly identified, as iPTH after 15 min did not fall below 50% of basal value. Only after removal of all hyperplastic glands did iPTH decrease to the normal range. Sensitivity and specificity for prediction of a solitary adenoma were 92% and 100% (decline of iPTH more than 50% from baseline value 5 min after parathyroidectomy). In one patient with recurrent pHPT intraoperative sampling from different sites in both internal jugular veins could predict the quadrant of the enlarged gland. Correlation (r) between the results of the quick and the conventional assay, which requires 24 h of incubation, was 0.955. All patients had normal or low calcium levels postoperatively. CONCLUSIONS: (1) Intraoperative monitoring of iPTH with this new quick assay allows safe identification of patients with solitary adenoma during surgery for pHPT. (2) It represents a valuable adjunct to surgical skill not only in primary operations for pHPT but especially in cases of recurrent surgery for pHPT. (3) With this test available minimally invasive techniques for parathyroidectomy may be employed in cases of preoperatively localized adenoma (ultrasound, sesta-mibi scan), avoiding bilateral neck exploration with its higher potential for complications.

Adenoma↗
PubMed2001

Neuroendocrine and behavioral effects of repetitive transcranial magnetic stimulation in a psychopathological animal model are suggestive of antidepressant-like effects.

The neuroendocrine and behavioral effects of repetitive transcranial magnetic stimulation (rTMS) were investigated in two rat lines selectively bred for high and low anxiety-related behavior. The stimulation parameters were adjusted according to the results of accurate computer-assisted and magnetic resonance imaging-based reconstructions of the current density distributions induced by rTMS in the rat and human brain, ensuring comparable stimulation patterns in both cases. Adult male rats were treated in two 3-day series under halothane anesthesia. In the forced swim test, rTMS-treatment induced a more active coping strategy in the high anxiety-related behavior rats only (time spent struggling; 332% vs. controls), allowing these animals to reach the performance of low anxiety-related behavior rats. In contrast, rTMS-treated low anxiety-related behavior rats did not change their swimming behavior. The development of active coping strategies in high anxiety-related behavior rats was accompanied by a significantly attenuated stress-induced elevation of plasma corticotropin and corticosterone concentrations. In summary, the behavioral and neuroendocrine effects of rTMS of frontal brain regions in high anxiety-related behavior rats are comparable to the effects of antidepressant drug treatment. Interestingly, in the psychopathological animal model repetitive transcranial magnetic stimulation induced changes in stress coping abilities in the high-anxiety line only.

Adaptation, Psychological↗
PubMed2001

Cross-fostering and cross-breeding of HAB and LAB rats: a genetic rat model of anxiety.

Recently, two Wistar rat lines, bred and selected for either high (HAB) or low (LAB) anxiety-related behavior on the elevated plus-maze, were described as a novel psychopathologic animal model. The behavioral and neuroendocrine responses to exposure to an emotional stressor were markedly enhanced in HAB rats compared with LAB rats, thus resembling patients suffering from psychiatric diseases. The present study focused on the developmental and genetic basis of the line-specific differences by using cross-fostering and cross-breeding approaches. For the cross-fostering paradigm, neonate HAB offspring were nursed by a LAB foster mother, and vice versa, until weaning. In the cross-breeding approach, HAB females were mated with LAB males, and vice versa, to create an intermediate F1 generation. Thereafter, the F1 animals were strictly sibling-mated to produce a segregating F2 generation. At 10 weeks of age, anxiety-related behavior of all animals was tested on the elevated plus-maze. The robustness of emotionality was assessed in rats of both lines throughout their entire lifetime. Serving this purpose, the frequency of ultrasound isolation calls, indicative of the emotionality of newborn rats, was monitored in regularly-fostered HAB and LAB pups on postnatal day 11. In addition, the timecourse of anxiety-related behavior was studied by repeated testing on the elevated plus-maze at the ages of 10 weeks, 6 months, 16 months, and 19 months. The cross-fostering approach failed to reveal behavioral differences between regularly and cross-fostered HAB and LAB rats, indicating no line-specific differences in maternal care or maternally-influenced development, at least after postnatal day 1. In contrast, cross-breeding resulted in F1 and F2 offspring displaying intermediate behavioral patterns on the elevated plus-maze which were exactly in between those shown in HAB and LAB control rats, thus confirming a genetic basis of the differences in anxiety. Cross-breeding revealed no differences related to the gender of the offspring or to the line-derivation of sire or dam, indicating an autosomal, rather than heterosomal, heredity of the divergent emotionality in HABs and LABs. Further, we were able to show stable and robust emotional differences in rats of both lines during their entire lifetime. HAB rats showed an enhanced frequency of ultrasound isolation calls on postnatal day 11 (p < 0.05) and a lower open arm exploration of the elevated plus-maze throughout adulthood (p < 0.01) compared with the same-aged LABs. In conclusion, the extremely divergent anxiety levels of HAB and LAB rats are maintained during their whole lives and are determined genetically, rather than being learned. These findings may be important for further studies on the genetic basis of emotionality.

Aging↗
PubMed2001

The anxiolytic effect of the CRH(1) receptor antagonist R121919 depends on innate emotionality in rats.

Hyperactivity of central corticotropin-releasing hormone (CRH) circuits appears to contribute to the symptomatology of affective and anxiety disorders and therefore CRH receptor antagonists have attracted attention as potential therapeutic agents. R121919, a novel high-affinity nonpeptide CRH(1) receptor antagonist, displaced (125)I-oCRH in rat pituitary, cortex and amygdala, but not in choroid plexus or cerebral blood vessels in vitro and in vivo, which is consistent with CRH(1) receptor antagonism. In vivo, R121919 significantly inhibited stress-induced corticotropin release in rats selectively bred for high- and low-anxiety-related behaviour but displayed anxiolytic effects in high-anxiety rats only. These data, corroborated by ex vivo receptor occupancy studies, suggest that this animal model is appropriate for the evaluation of CRH(1) receptor antagonists and that compounds such as R121919 will be beneficial whenever the central stress hormone system is hyperactive.

Adrenocorticotropic Hormone↗
PubMed2001

Social isolation after a single defeat reduces striatal dopamine transporter binding in rats.

A single social defeat in male rats has long lasting physiological and behavioural consequences, which are similar to those seen in depressive patients. In addition, the housing conditions after social defeat appear to be crucial for the development of depression-like symptoms. Because the dopaminergic system is thought to be altered in depressive illness, we investigated the impact of individual and group housing on the temporal development of changes of dopamine transporter (DAT) binding in male rats after a single social defeat. The number of striatal DAT binding sites was reduced in animals that remained isolated after being defeated. The isolation length after social defeat amplified this effect, indicating a temporal development of the changes on the striatal DAT. In animals which returned to the familiar group after social defeat the density of striatal DAT binding sites was not affected. We conclude that social isolation after a single defeat reduces the number of DAT binding sites. In contrast, a familiar environment after a single social defeat appears to prevent the stress-induced alterations on the dopaminergic system. This finding suggests that housing conditions are critical when investigating the central nervous effects of social defeat in male rats.

Animals↗
PubMed2001

Forced swimming stimulates the expression of vasopressin and oxytocin in magnocellular neurons of the rat hypothalamic paraventricular nucleus.

Previous studies have shown that a 10-min forced swimming session triggers the release of both vasopressin and oxytocin into the extracellular fluid of the hypothalamic paraventricular (PVN) and supraoptic nuclei (SON) in rats. At the same time oxytocin, but not vasopressin, was released from the axon terminals into the blood. Here we combined forced swimming with in situ hybridization to investigate whether (i) the stressor-induced release of vasopressin and oxytocin within the PVN originates from parvo- or magnocellular neurons of the nucleus, and (ii) central release with or without concomitant peripheral secretion is followed by changes in the synthesis of vasopressin and/or oxytocin. Adult male Wistar rats were killed 2, 4 or 8 h after a 10-min forced swimming session and their brains processed for in situ hybridization using 35S-labelled oligonucleotide probes. As measured on photo-emulsion-coated slides, cellular vasopressin mRNA concentration increased in magnocellular PVN neurons 2 and 4 h after swimming (P < 0.05). Similarly, oxytocin mRNA concentration was significantly increased in magnocellular neurons of the PVN at 2 and 8 h (P < 0.05). We failed to observe significant effects on vasopressin and oxytocin mRNA levels in the parvocellular PVN and in the SON. Taken together with results from previous studies, our data suggest that magnocellular neurons are the predominant source of vasopressin and oxytocin released within PVN in response to forced swimming. Furthermore, in the case of vasopressin, central release in the absence of peripheral secretion is followed by increased mRNA levels, implying a refill of depleted somato-dendritic vasopressin stores. Within the SON, however, mRNA levels are poor indicators of the secretory activity of magnocellular neurons during stress.

Animals↗
PubMed2001

Taurine selectively modulates the secretory activity of vasopressin neurons in conscious rats.

Previous experiments have shown that a 10-min forced swimming session triggers the release of vasopressin from somata and dendrites, but not axon terminals, of neurons of the hypothalamic-neurohypophysial system. To further investigate regulatory mechanisms underlying this dissociated release, we forced male Wistar rats to swim in warm (20 degrees C) water and monitored release of the potentially inhibitory amino acids gamma amino butyric acid (GABA) and taurine into the hypothalamic supraoptic nucleus using microdialysis. Forced swimming caused a significant increase in the release of taurine (up to 350%; P < 0.05 vs. prestress release), but not GABA. To reveal the physiological significance of centrally released taurine, the specific taurine antagonist 6-aminomethyl-3-methyl-4H-1,2,4-benzothiadiazine-1,1-dioxide was administered into the supraoptic nucleus via retrodialysis. Administration of this antagonist caused a significant increase in the release of vasopressin within the supraoptic nucleus and into the blood both under basal conditions and during stress (up to 800%; P < 0.05 vs. basal values), without affecting hypothalamic or plasma oxytocin. Local administration of the GABA(A) receptor antagonist bicuculline, in contrast, failed to influence vasopressin secretion at either time point. In a separate series of in vivo electrophysiological experiments, administration of the same dosage of the taurine antagonist into the supraoptic nucleus via microdialysis resulted in an increased electrical activity of identified vasopressinergic, but not oxytocinergic, neurons. Taken together our data demonstrate that taurine is released within the supraoptic nucleus during physical/emotional stress. Furthermore, at the level of the supraoptic nucleus, taurine inhibits not only the electrical activity of vasopressin neurons but also acts as an inhibitor of both central and peripheral vasopressin secretion during different physiological states.

Action Potentials↗
PubMed2001

Insulin antibodies are associated with lipoatrophy but also with lipohypertrophy in children and adolescents with type 1 diabetes.

AIM: To evaluate clinical and immunological factors that are associated with lipodystrophy, i.e. lipoatrophy and lipohypertrophy, in diabetic children and adolescents. METHODS: We investigated in a cross-sectional study 112 children and adolescents (age 1.1-19.1 yrs.) with type 1 diabetes. To grade lipodystrophy, we developed a clinical score ranging from normal (grade 0), moderate hypertrophy of subcutaneous tissue (grade 1), severe hypertrophy with increased density of tissue (grade 2) to lipoatrophy (grade 3). In all children, grade of lipodystrophy, antibodies against insulin (IA) or beta cell antigens (IA-2 and GAD) and clinical parameters were documented. RESULTS: The antibodies against insulin (IA) increased significantly after diabetes manifestation and initiation of insulin treatment, while beta cell specific antibodies (IA-2, GAD) did not. Lipoatrophy (grade 3) was seen in 4 children, severe lipohypertrophy (grade 2) in 18 and moderate lipohypertrophy (grade 1) in 27 children. No alteration of injection sites was found in 63 children. Amongst clinical and immunological parameters, IA levels were significantly associated with hypertrophy or atrophy of injection sites. CONCLUSION: The strong association of lipoatrophy and lipohypertrophy with insulin antibodies might suggest that autoimmune phenomena with insulin play a role in the development of both. Despite an association of IA and lipodystrophy in type 1 diabetic children, the causal link between the two remains unproven and requires further longitudinal exploration.

Adolescent↗
PubMed2001

Neuropeptides and anxiety-related behavior.

Behavior is shaped by a variety of genetic and epigenetic mechanisms, including those underlying anxiety and fear. Neuropeptides are ideal candidates to be involved in the regulation of emotional facets as they are released within the brain and act as neuromodulators/neurotransmitters; furthermore, their large number is prone to direct changes by mutations. A variety of approaches have been used to reveal the physiological involvement of neuropeptides in anxiety-related behavior, including those focused on behavioral effects of neuropeptides and, vice versa, the influence of behavioral phenomena on intracerebral neuropeptides. In concert with other neuropeptides and classical transmitters, particularly CRH and vasopressin are promising candidate neuropeptides to determine not only the activity of the hypothalamopituitary-adrenocortical axis, but also anxiety-related behavior including its cognitive components. CRH and vasopressin interactions with specific receptor subtypes have been shown to induce consequences on emotionality, and CRH and vasopressin responses to both anxiogenic stimuli and extreme levels of inborn anxiety confirm their critical involvement in normal and pathological anxiety. Based on behavioral and neuroendocrine data obtained from proper animal models, the neurobiological and genetic analyses of anxiety and fear will provide the prerequisites to develop novel and more causal therapeutic strategies for anxiety disorders.

Animals↗
PubMed2001

The modified hole board as a differential screen for behavior in rodents.

We describe a modified hole board (mHB) paradigm as a test for unconditioned behavior in rodents that is aimed at analyzing a variety of behavioral dimensions. We demonstrate that the mHB enables the investigation of different behavioral dimensions in rodents in only one test by reproducing the behavioral characteristics previously collected from multiple behavioral tests in rats bred for either high or low anxiety-related behavior. In addition, the test design, which allows the experimental animal to maintain social contact with its group mates during the test, was shown to minimize stress for experimental animals and, moreover, to enable the investigator to assess social affinity among group mates. In summary, the mHB test enables animal models to be comprehensively phenotyped, while simultaneously reducing the number of animals and the amount of time required. Therefore, the mHB represents an alternative to the common practice of using a series of more specific tests.

Analysis of Variance↗
PubMed2001

Dimensions of emotionality in a rat model of innate anxiety.

Emotionality is thought to be multidimensional, with "anxiety" representing one dimension. Dissecting emotional dimensions in animal models is an essential prerequisite for investigating the neurobiological mechanisms that underlie anxiety. The authors used factor analysis to investigate emotional dimensions in normal rats and rats bred for either high or low anxiety-related behavior. Hyperanxious rats were reduced in emotional dimensions in the elevated plus-maze by selection pressure, and a modified hole board test revealed a dissection of their emotionality with precisely defined dimensions. This enabled clear differentiation of "anxiety" from other emotional dimensions including risk assessment behavior and exploration. Factors extracted by analyzing data from a multiple-test battery corresponded to particular test characteristics rather than to emotional dimensions. The approach used might help to develop specific treatment strategies for anxiety disorders.

Animals↗
PubMed2000

[Increased clinical and economic advantages using PROSIT (proteinuria screening and intervention) in type 2 diabetic patients].

BACKGROUND AND OBJECTIVE: Even though there are simple and cost-effective means for the early diagnosis of diabetic nephropathy, only a small proportion of diabetics in Germany is regularly tests for microalbuminuria. On the basis of evidence-based knowledge and of international guidelines the PROSIT project (proteinuria screening and intervention) aims to make good this deficiency in the German Federal Republic by introducing nephropathy screening and a structured intervention to improve blood sugar and blood pressure regulation, optimizing lipid metabolism and nutritional intake. It was the aim of this study to assess with a computer-aided diabetes model the clinical value and cost-effectiveness of such an intervention. PATIENTS AND METHODS: From data collected for 589 diabetics who participated in the PROSIT project, the short-time effects after one year on HbA1c, systolic blood pressure and lipid levels were obtained and cost-effectiveness compared with that of standard care. Life expectancy, life-time costs to be met by health insurance and event frequency of the diabetic nephropathy stages were calculated with a Markov model for type 2 diabetics. RESULTS: PROSIT improved individual life expectancy by 0.23 years with reduction of life-time costs by DM 9,772 (ca. $4,900). The cumulative incidence of microalbuminuria was lowered by 30.5%, that of terminal renal failure by 55.9%. Even after discounting the results (i.e. the inclusion of time preference for cost and benefit) and stepwise changes of all variables by +/- 10%, PROSIT remained the more cost-effective variant. CONCLUSION: From a health economy viewpoint PROSIT is superior to standard management. Early recognition of albuminuria and the introduction of a multifactorial treatment strategy make it possible to delay progression to terminal renal failure. In addition to its clinical benefits, prevention of dialysis and transplantation would reduce the annual savings of the health care system by several billion DM.

Albuminuria↗
PubMed2000

Vasopressin, major depression, and hypothalamic-pituitary-adrenocortical desensitization.

BACKGROUND: The hypothalamic neuropeptide arginine vasopressin is thought to play an important role in the pathophysiology of affective disorders and the hyperactivity of the hypothalamic-pituitary-adrenocortical system that frequently accompanies them. Postmortem studies as well as clinical investigations have described elevated levels of vasopressin in the brain and plasma of depressed patients, and this finding has been suggested to contribute to depressive symptomatology. METHODS: The case of a 47-year-old patient displaying chronically elevated plasma vasopressin levels due to paraneoplastic vasopressin secretion by an olfactory neuroblastoma and the first episode of major depression is presented. RESULTS: Depressive symptoms improved markedly after surgical resection of the tumor and subsequent normalization of plasma vasopressin levels. Unexpectedly, neither corticotropin nor cortisol secretion could be stimulated by an intravenous corticotropin-releasing hormone challenge under the condition of chronically elevated plasma vasopressin levels in this patient. CONCLUSIONS: Chronically elevated plasma vasopressin levels may induce depressive symptomatology, and-in contrast to the potent corticotropin secretagogue effects of acute vasopressin administration-lead to a marked desensitization of the hypothalamic-pituitary-adrenocortical system.

Adrenocorticotropic Hormone↗
PubMed2000

A single social defeat experience selectively stimulates the release of oxytocin, but not vasopressin, within the septal brain area of male rats.

The naturally occurring social conflict situation to be confronted with an aggressive dominant conspecific was used to study the effects of emotional stress on the release of oxytocin (OXT) and arginine vasopressin (AVP) within the mediolateral septum of the rat brain. Male rats were chronically implanted with a microdialysis probe into this brain area. Local release patterns of both, OXT and AVP were monitored in response to a 30 min social defeat. Social defeat caused a significant increase in the release of OXT (to 254%+/-43%, P<0.01). In contrast, the release of AVP was not affected. In a preliminary experiment, to assess the physiological significance of stress-induced intraseptal OXT release, a separate group of animals received the OXT receptor antagonist des-Gly-NH(2)d(CH(2))(5)[Tyr(Me)(2)Thr(4)]OVT into the mediolateral septum via inverse microdialysis prior to and during the social defeat procedure. However, no difference could be observed in submissive freezing (passive coping) or in exploratory behavior (active coping) when compared to vehicle-treated animals, neither acutely nor 24 h after antagonist administration. Taken together, our results demonstrate that emotional stress activates the septal oxytocinergic, but not vasopressinergic, system. The physiological significance of intraseptally released OXT remains unclear and has to be elucidated in future studies.

Adaptation, Psychological↗