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R Landgraf

Publications and source records attributed to R Landgraf.

At least 19 recordsLinked to original sources
PubMed2007

Neural nitric oxide gene inactivation affects the release profile of oxytocin into the blood in response to forced swimming.

This study was undertaken to examine the importance of nitric oxide (NO) generated by the neural isoform of the nitric oxide synthase (nNOS) on the activity of the hypothalamic neurohypophyseal system in neural nitric oxide synthase knock-out (KO) and wild-type (WT) mice under basal conditions and in response to forced swimming. The intensity of the hybridisation signal for vasopressin (AVP) in the hypothalamic supraoptic nucleus (SON) was significantly higher in KO mice when compared with WT, whereas oxytocin (OXT) basal mRNA levels were similar in both groups. Although the basal peripheral release of AVP and OXT was equivalent in both genotypes, we observed in KO mice a significant drop of AVP and OXT plasma values 15 min after stressor onset and a robust increase in the OXT plasma concentration at 60 min. These findings suggest that in the male mouse, NO inhibits AVP gene transcription in magnocellular neurones of the SON and collaborates in maintaining constant AVP and OXT plasma levels following acute stressor exposure, exerting a bimodal regulatory action on OXT secretion. We conclude that NO is involved in the regulation of magnocellular neurones of the SON, and it is preferentially implicated in the attenuation of the peripheral release of OXT induced by acute stressor exposure.

Animals↗
PubMed2006

Results of the pilot study of DIADEM: a comprehensive disease management programme for type 2 diabetes.

AIMS: The purpose of the study was to evaluate the feasibility and preliminary clinical effects of the DIADEM disease management programme for type 2 diabetic patients. METHODS: The study was performed at two test sites (Cardiff, UK: Aachen, Germany) including 137 and 166 patients, respectively. In 16 study centres any patients with type 2 diabetes capable of communicating by phone and able to perform blood pressure, blood glucose or urine glucose self-measurements were included. The maximum programme duration was 6 months at Cardiff and 4 months at Aachen, during which patients were assessed for glycaemic control, cardiovascular risk profile and the presence of complications of diabetes. Data were entered via the internet to a central server. RESULTS: At entry into the programme the patient group in Cardiff had significantly lower mean age (60.3+/-9.4 years versus 64.9+/-8.7 years, p<0.001) and duration of diabetes (6.1+/-5.7 years versus 7.4+/-7.0 years, p<0.05) than in Aachen, however body mass index (31.6+/-5.2 kg/m(2) versus 29.5+/-4.9 kg/m(2), p<0.01), HbA1c (7.7+/-1.2% versus 7.1+/-1.2%, p<0.001) and systolic blood pressure (138.4+/-15.1 mmHg versus 133.5+/-11.5 mmHg, p<0.001) were significantly higher. In contrast, total cholesterol (4.7+/-1.0 mmol/l versus 5.5+/-1.1 mmol/l, p<0.001) was significantly lower in Cardiff compared to Aachen. Following entry into the programme highly significant improvements in HbA1c (Cardiff from 7.7% to 7.1%, p<0.001; Aachen from 7.2% to 6.8%, p<0.05) and total cholesterol concentrations (Cardiff: 4.66-4.46 mmol/l; Aachen: 5.33-5.15 mmol/l; both p<0.05) were observed. There were no significant changes in blood pressure at either site. CONCLUSIONS: Intensive diabetes care was delivered to DIADEM patients and relevant and significant improvements in diabetes care were achieved demonstrating that an IT-based diabetes disease management service can improve care for patients with type 2 diabetes.

Aged↗
PubMed2006

Regulation of ghrelin is related to estimated insulin sensitivity in obese children.

OBJECTIVE: To investigate whether ghrelin concentrations and their changes during weight loss in obese children are associated with parameters of glucose and insulin metabolism. DESIGN: Total plasma ghrelin, insulin and glucose were measured during oral glucose tolerance testing before and after diet-induced weight loss over 6 weeks. SETTING: In-patient rehabilitation program in a pediatric hospital. PARTICIPANTS: Twenty-three obese children (age 10-16 years) and 11 normal weight controls (age 10-15 years). OUTCOME MEASURES: Changes in ghrelin concentrations during weight loss and correlation analysis of changes in ghrelin and changes in parameters of glucose and insulin metabolism. After data collection, subgroup analysis of obese patients with high, medium and low estimated insulin sensitivity whole-body insulin sensitivity index (WBISI) was performed. RESULTS: Weight loss increased the area under the curve (AUC) of ghrelin by 26% (P<0.001). The increase in ghrelin AUC correlated significantly with improved estimated insulin sensitivity (WBISI) (r=0.69, P<0.001). The independent predicting effect of WBISI was confirmed in multivariate analysis. In children with low WBISI, ghrelin reached the level of control values after weight loss. In children with high WBISI, ghrelin increased markedly above control levels. CONCLUSIONS: Changes in ghrelin are independently associated with changes in glucose and insulin metabolism. The increase in plasma ghrelin above control levels was limited to obese children with high WBISI.

Adolescent↗
PubMed2006

Patient and provider perceptions of care for diabetes: results of the cross-national DAWN Study.

AIMS/HYPOTHESIS: We assessed country-level and individual-level patterns in patient and provider perceptions of diabetes care. METHODS: The study used a cross-sectional design with face-to-face or telephone interviews of diabetic patients and healthcare providers in 13 countries from Asia, Australia, Europe and North America. Participants were randomly selected adults with type 1 or type 2 diabetes (n=5,104), and randomly selected diabetes-care providers, including primary-care physicians (n=2,070), diabetes specialist physicians (n=635) and nurses (n=1,122). Multivariate analysis was used to examine the relationships between outcomes and both country and respondent characteristics, and the interaction between these two factors. RESULTS: Providers rated chronic-care systems and remuneration for chronic care as mediocre. Patients reported that ease of access to care was high, but not without financial barriers. Patients reported moderate levels of collaboration among providers, and providers indicated that several specialist disciplines were not readily available to them. Patients reported high levels of collaboration with providers in their own care. Provider endorsement of primary prevention strategies for type 2 diabetes was high. Patients with fewer socio-economic resources and more diabetes complications had lower access (and/or higher barriers) to care and lower quality of patient-provider collaboration. Countries differed significantly for all outcomes, and the relationships between respondent characteristics and outcomes varied by country. CONCLUSIONS/INTERPRETATION: There is much need for improvement in applying the chronic-care model to the treatment and prevention of diabetes in all of the countries studied. Each country must develop its own priorities for improving diabetes care and comparison with other countries can help identify strengths as well as weaknesses.

Adolescent↗
PubMed2006

[Comorbidities and complications of adiposis].

Overweight and obesity are associated with a high number of complications and co-morbidities. Obesity can affect almost all tissues and organs of the body. Obesity is associated with the components of the metabolic syndrome and is the leading cause of type 2 diabetes. Either obesity itself or co-morbidities of obesity are responsible for the increased cardiovascular risk. The increased overall mortality risk is due to cardiovascular and other complications like the higher prevalence and incidence of malignant tumors. Other complications of obesity like the polycystic ovary syndrome or the obstructive sleep apnea syndrome are relatively unknown but important and frequent. Medical care of people with obesity should focus not only on weight loss but also on complications and co-morbidities.

Cardiovascular Diseases↗
PubMed2006

[Therapy of diabetes mellitus. Pancreas transplantation, islet transplantation, stem cell and gene therapy].

The long-term normalization of glucose metabolism - a prerequisite for the prevention of secondary complications in patients with diabetes mellitus - is only possible by transplantation of a whole pancreas or a reasonable number of islets. An absolute indication for pancreas grafting is given in type 1 diabetic patients with end-stage renal disease. The 1-year survival after simultaneous kidney/pancreas transplantation is, according to the international registry, 94-100% for patients, 89-92% for kidneys and 85-87% for the pancreas. The high success rate with long lasting normalization of glucose metabolism leads to a stabilization and/or amelioration of secondary complications, to an increase in quality of life and, most importantly, to a significant reduction in mortality when compared to diabetic kidney recipients. The indications for islet transplantation are similar to those for pancreatic grafting. Islet grafting is only a minor surgical procedure, but islet isolation is difficult. The 1-year survival for the recipients is 98%, for the islets 82% and for insulin-independency 42%. There is a significant decline of islet function to 10% 5 years after transplantation. Stem cell therapy would provide a definitive treatment solution not only for patients with type 1 diabetes. So far, this therapeutic option is still at an early stage of development.

Combined Modality Therapy↗
PubMed2006

[HbA1c--the gold standard in the assessment of diabetes treatment?].

HbA1c is an important measure in monitoring treatment and management decisions in diabetic patients. It reflects the mean blood glucose level during the preceding 6 to 8 weeks. But this is true only for the population as a whole, not the individual patient. Differences between blood glucose and HbA1c values must be analysed precisely, because it is subject to numerous factors. HbA1c cannot replace blood glucose measurements for immediately assessing glucose metabolism and recognizing acute metabolic abnormalities. The mean HbA1c level predicts potential diabetic complications and is closely correlated with clinical angiopathic end-points. The quality of metabolic regulation can be assessed from HbA1c and blood glucose levels at defined times. But because of the numerous influencing factors HbA1c can be used as gold standard only with limitations. Developments, as in Great Britain and the USA, which take HbA1c as relevant basis for treatment ("pay for performance"), lead in a completely wrong direction and contribute neither to the validity of documented values in structured therapeutic programmes nor do they stimulate improvement in the overall management of diabetes. The quality of metabolic control should be determined entirely within the therapeutic target worked out together with the patient.

Biomarkers↗
PubMed2005

Neuropeptides in anxiety modulation.

This review is focused on the involvement of neuropeptides in the modulation of physiological and pathological anxiety. Neuropeptides play a major role as endogenous modulators of complex behaviours, including anxiety-related behaviour and psychopathology, particularly due to their high number and diversity, the dynamics of release patterns in distinct brain areas and the multiple and variable modes of interneuronal communication they are involved in. Manipulations of central neuropeptidergic systems to reveal their role in anxiety (and often comorbid depression-like behaviour) include a broad spectrum of loss-of-function and gain-of-function approaches. This article concentrates on those neuropeptides for which an involvement as endogenous anxiolytic or anxiogenic modulators is well established by such complementary approaches. Particular attention is paid to corticotropin-releasing hormone (CRH) and vasopressin (AVP) which, closely linked to stress, neuroendocrine regulation, social behaviour and learning/memory, play critical roles in the regulation of anxiety-related behaviour of rodents. Provided that their neurobiology, neuroendocrinology and molecular-genetic background are well characterized, these and other neuropeptidergic systems may be promising targets for future anxiolytic strategies.

Animals↗
PubMed2005

Differential effects of periodic maternal separation on adult stress coping in a rat model of extremes in trait anxiety.

We studied interactions of genetic and environmental factors shaping adult emotionality and stress coping, and tested the hypothesis that repeated periodic maternal deprivation (PMD) exerts differential effects on adult behavioral and neuroendocrine stress responsiveness in dependence on the genetic predisposition to either hyper- or hypo-anxiety. Exposure of male Wistar rats bidirectionally bred for either high (HAB) or low (LAB) anxiety-related behavior to PMD between postnatal days 2 and 15 resulted in a behavioral approximation of the selected lines. This was reflected by test-dependent signs of reduced anxiety-related behavior in adult HAB rats and of enhanced levels of anxiety in LAB rats compared with their corresponding unstressed controls. In addition to behavioral parameters, differential effects of PMD were also seen with respect to the responsiveness of the hypothalamo-pituitary-adrenocortical axis to acute stressor exposure (novel environment) in adulthood. The corticotrophin (ACTH) and corticosterone hyper-responses seen in control rats of the HAB line compared with those of the LAB line became attenuated in PMD-HAB rats, whereas PMD did not significantly alter neuroendocrine responses in LAB rats. Thus, as a result of PMD, both ACTH and corticosterone responses became indistinguishable between HAB and LAB rats. Although HAB dams spent more time on the nest with the litter compared with LAB dams during the first 5 days postpartum, licking and grooming behavior did not differ between the lines prior to separation, and was found to be increased to the same extent in both HAB and LAB dams during the first hour immediately after reunion with the pups. In contrast to early life stress, exposure of adult HAB and LAB rats to a 10-day unpredictable stress schedule failed to alter their emotional measures. The mitigating effect of PMD on both behavioral and neuroendocrine parameters in rats representing extremes in trait anxiety might reflect an evolutionary benefit as the genetic variability among individuals of a species is sustained while allowing adequate responses to potentially dangerous stimuli in adulthood dependent on early life conditions.

Adaptation, Psychological↗
PubMed2004

Two Wistar rat lines selectively bred for anxiety-related behavior show opposite reactions in elevated plus maze and fear-sensitized acoustic startle tests.

Two Wistar rat lines selectively bred for high (HAB), and low anxiety-related behavior (LAB) on the elevated plus maze were tested for the fear-sensitized acoustic startle response. The study of male rats from the F9 generation revealed a higher anxiety level of HAB rats on the elevated plus maze. However, the LAB rats displayed a higher baseline and fear-sensitized acoustic startle response compared to HAB rats, although the two rat lines did not differ in freezing duration during the interstimulus intervals in the startle experiment (neither before, nor after, footshocks). Counts of neurons immunoreactive for corticotropin-releasing factor and neuropeptide Y in amygdaloid nuclei did not reveal any differences between the two lines, which is in marked contrast to findings in the Roman rat lines. The data indicate that opposite types of anxiety/fear responses are elicited in HAB/LAB rats in the elevated plus maze and fear-sensitized startle tests. Moreover, the animals displayed a differential fear response in the startle experiment, as assessed by measuring the fear-sensitized startle response and freezing.

Acoustic Stimulation↗
PubMed2004

Hypothalamic neuropeptide release after experimental subarachnoid hemorrhage: in vivo microdialysis study.

OBJECTIVES: As evidence exists about independent regulation of peripheral and central release of the vasoactive and natriuretic neuropeptides arginine-vasopressin (AVP) and oxytocin (OXT), we investigated their release patterns following subarachnoid hemorrhage (SAH). MATERIALS AND METHODS: After injection of 0.1 ml arterial blood or saline into the great cistern of 33 Wistar rats, AVP and OXT levels were measured in blood and by microdialysis in the hypothalamic supraoptic (SON) and paraventricular nucleus (PVN). For statistical analysis, the analysis of variance (ANOVA) was used with Tukey HSD post hoc ANOVA tests to determine specific group differences. RESULTS: Plasma AVP and OXT peaked 2 h after SAH (P < 0.05), and normalized at 4 h. In the SON, both AVP and OXT peaked 4 h after SAH (P < 0.05). In the PVN, AVP increased in both groups (P < 0.05), while no OXT release occurred. By the sham group, any effect of experimental procedure was excluded. CONCLUSIONS: The SAH-specific central neuropeptide release, which exceeded peripheral release and continued longer, may contribute to pathophysiological events following SAH.

Animals↗
PubMed2004

Effectiveness of a disease management programme for patients with type 2 diabetes mellitus and albuminuria in primary care - the PROSIT project (Proteinuria Screening and Intervention).

Aims. To evaluate the structured PROSIT(R) disease management programme for high-risk diabetic patients in primary care with respect to the cardio-vascular risk profile and mortality. Subjects and Methods. Retrospectively 55 albuminuric Type 2 diabetic patients included into the PROSIT(R) programme from 1994 to 1999 (intervention group: age 66.6 +/- 10.5 years, known duration of diabetes 8.9 +/- 6.5 years) were compared with 58 albuminuric patients not participating in the PROSIT(R) programme (control group: age 68.5 +/- 10.4 years, known duration of diabetes 8.5 +/- 6.7 years). Within PROSIT(R) a structured multifactorial intervention programme was applied. The main characteristics of this intervention were strict follow-ups of the patient's risk profile every three months and the use of quality management methods (definition of target values, structured documentation, central data feedback with diagnostic and therapeutic recommendations based on European guidelines). The cardio-vascular risk profile, therapeutic intervention, and secondary diabetic complications were compared between both groups in 1994 and 1999. Results. In the period from 1994 to 1999 the intervention group showed a significant improvement in the vascular risk profile, while the control group did not. In 1999 the mean arterial blood pressure was significantly lower compared to the control group (115 +/- 13 mm Hg vs. 125 +/- 16 mm Hg, p < 0.05). The HbA1c improved only in the intervention group and in 1999 it was significantly lower than in the control group (7.0 +/- 1.3 % vs. 8.4 +/- 1.8 %, p < 0.01). Moreover, the occurrence of clinical endpoints in the intervention group could be reduced: Both the mortalitly rate (14.5 % vs. 34.5 %, p < 0.05) and the rate of new myocardial infarctions (6 % vs. 20 %, p < 0.05) of the intervention group were significantly lower. Conclusions. Participation of albuminuric Type 2 diabetic patients and their physicians in a structured intervention programme showed positive effects on the cardio-vascular risk profile and endpoints compared with a group of non-participating patients and physicians.

Aged↗
PubMed2003

Nitric oxide is not involved in the control of vasopressin release during acute forced swimming in rats.

Neurons of the hypothalamo-neurohypophyseal system (HNS) are known to contain high amounts of neuronal nitric oxide (NO) synthase (nNOS). NO produced by those neurons is commonly supposed to be involved as modulator in the release of the two nonapeptides vasopressin (AVP) and oxytocin into the blood stream. Previous studies showed that forced swimming fails to increase the release of AVP into the blood stream while its secretion into the hypothalamus is triggered. We investigated here whether hypothalamically acting NO contributes to the control of the AVP release into blood under forced swimming conditions. Intracerebral microdialysis and in situ hybridization were employed to analyze the activity of the nitrergic system within the supraoptic nucleus (SON), the hypothalamic origin of the HNS. A 10-min forced swimming session failed to significantly alter the local NO release as indicated both by nitrite and, the main by-product of NO synthesis, citrulline levels in microdialysis samples collected from the SON. Microdialysis administration of NO directly into the SON increased the concentration of AVP in plasma samples collected during simultaneous forced swimming. In an additional experiment the effect of the defined stressor exposure on the concentration of mRNA coding for nNOS within the SON was investigated by in situ hybridization. Forced swimming increased the expression of nNOS mRNA at two and four hours after onset of the stressor compared to untreated controls. Taken together, our results imply that NO within the SON does not contribute to the regulation of the secretory activity of HNS neurons during acute forced swimming. Increased nNOS mRNA in the SON after forced swimming and the increase in AVP release in the presence of exogenous NO under forced swimming points to a possible role of NO in the regulation of the HNS under repeated stressor exposure.

Animals↗
PubMed2003

[Neurobiology and genetics of anxiety in an animal model].

This paper presents a valid animal model of innate anxiety/depression: anxious (HAB) or non-anxious (LAB) rats, which show stable and robust responses in a variety of ethological tests. In addition to their extreme anxiety-related behavior, HAB animals are characterized by passive stress coping, an activated stress (HPA) axis, and increased stress vulnerability. The enhanced expression and release of arginine vasopressin (AVP) in the hypothalamus of HAB rats seem to underlie these phenomena. Accordingly, an AVP receptor antagonist attenuates anxiety-related behavior and normalizes the HPA axis and the dexamethasone/CRH test. Treatment with the antidepressive drug paroxetine reduces the overexpression of AVP and normalizes both the depression-like behavior and neuroendocrine correlates of anxiety/depression. The complex phenotyping led us to the conclusion that the AVP gene is likely to be a candidate gene of inborn anxiety. Partial genotyping of HAB animals results in the identification of polymorphisms (SNPs) in the promoter domain of the AVP gene, thus potentially leading to novel strategies of diagnosis and therapy of anxiety disorders and depression.

Animals↗