Subduralhämatom und Pneumatozephalus nach neuroaxialer Anästhesie

Die Anaesthesiologie -     

Vascular Endothelial Growth Factor-A and Islet Vascularization Are Necessary in Developing,but Not Adult,Pancreatic Islets

Pancreatic islets are highly vascularized mini-organs, and vascular endothelial growth factor (VEGF)-A is a critical factor in the development of islet vascularization. To investigate the role of VEGF-A and endothelial cells (ECs) in adult islets, we used complementary genetic approaches to temporally inactivate VEGF-A in developing mouse pancreatic and islet progenitor cells or in adult β-cells. Inactivation of VEGF-A early in development dramatically reduced pancreatic and islet vascularization, leading to reduced β-cell proliferation in both developing and adult islets and, ultimately, reduced β-cell mass and impaired glucose clearance. When VEGF-A was inactivated in adult β-cells, islet vascularization was reduced twofold. Surprisingly, even after 3 months of reduced islet vascularization, islet architecture and β-cell gene expression, mass, and function were preserved with only a minimal abnormality in glucose clearance. These data show that normal pancreatic VEGF-A expression is critical for the recruitment of ECs and the subsequent stimulation of endocrine cell proliferation during islet development. In contrast, although VEGF-A is required for maintaining the specialized vasculature observed in normal adult islets, adult β-cells can adapt and survive long-term reductions in islet vascularity. These results indicate that VEGF-A and islet vascularization have a lesser role in adult islet function and β-cell mass.The pancreatic islets are endocrine mini-organs with a specialized vasculature. Islets are highly vascularized, with a dense network of capillaries that are thicker and more tortuous than vessels of the exocrine tissue (1). While islets occupy only a small volume of the pancreas, they receive a disproportionally greater fraction of pancreatic blood flow (2,3). Ultrastructurally, islets have a fenestrated endothelium, which allows for the rapid exchange of nutrients and hormones between endocrine cells and the bloodstream (1,4,5). This highly vascularized state leads to a greater partial oxygen pressure in islets than in exocrine tissue (6). The polyhedral β-cells appear to have multiple faces contacting blood vessels, and hypoxia impairs glucose-stimulated insulin secretion (7,8). Furthermore, the islet vasculature and the ECs near or in the developing pancreas and islet provide critically important instructive signals necessary for islet formation and β-cell differentiation (9,10).Much work to understand the mechanisms directing normal islet vascularization has focused on the role of islet-derived angiogenic factors. Islet endocrine cells produce multiple factors from the VEGF, angiopoietin, and ephrin families, with VEGF-A being the predominant regulator of islet angiogenesis and vascularization. When VEGF-A is inactivated either in the early pancreas (5) or in newly formed β-cells (1), the intraislet capillary plexus fails to fully mature, resulting in substantial defects in insulin secretion and glucose intolerance. In contrast, overexpression of VEGF-A in developing pancreata (11) or β-cells (12) is detrimental to endocrine cell differentiation and islet formation. Therefore, VEGF-A expression must be precisely controlled in the developing pancreas for proper islet development and long-term glucose homeostasis.While existing genetic mouse models demonstrated a role for VEGF-A and ECs in islet formation, the precise role of VEGF-A in adult islets is unclear. Prior studies inactivated VEGF-A during embryogenesis, thus making it difficult to identify which phenotypes resulted from developmental defects and which reflected the role of VEGF-A and ECs in adult islets. In an alternate approach, VEGF signaling inhibitors administered to adult mice demonstrated the importance of VEGF-A in maintaining the islet vascular density and permeability (13). However, the effects of VEGF inhibitors on the vasculature of multiple tissues prevented a full understanding of the role of ECs in established islets.To investigate the role of VEGF-A and ECs in adult islet function, we used complementary genetic approaches to temporally inactivate VEGF-A in developing pancreatic and islet progenitors or in adult β-cells using a tamoxifen (Tm)-inducible Cre-loxP system. We found that adult pancreatic β-cells tolerated a significant and prolonged reduction in intraislet capillary density and still maintained relatively normal function. By comparison, inactivation of VEGF-A in early pancreas development resulted in hypovascularized islets with a sustained reduction in β-cell proliferation and mass. These data indicate that VEGF-A plays distinctive roles in developing and adult pancreatic islets.     

Somatotropic function of the adenohypophysis in hyperthyroidism

Changes in the adenohypophyseal somatotropin function and the site of their origin were studied in experimental rats with hyperthyrosis. It was determined that the adenohypophyseal somatotropin content and biosynthesis were sharply reduced. After repeated somatotropin injections these indices remained unchanged. In vitro the somatotropin-releasing activity of the hypothalamic extracts off hyperthyroid rats is enhanced, whereas somatotropin release into the medium, obtained from the adenohypophyses of hyperthyroid animals, is lowered under the extract effect. It is concluded that a decrease in the adenohypophyseal somatotropin function is caused by loss of somatotropic cell sensitivity to the action of the hypothalamic regulation factors.     

Calcified aortal stenosis and osteoporosis: bone metabolism of systemic calcium metabolism in the elderly

AIM: To examine bone tissue, systemic calcium metabolism and bone remodeling in patients with calcified aortal stenosis of degenerative origin (DAS). MATERIAL AND METHODS: The examination of 310 patients (mean age 73.2 years) was made with application of questioning, echocardiography, double energetic x-ray absorptionmetry, measurements of C-telopeptides, osteocalcin, vitamin D, parathyroid hormone with solid phase enzyme immunoassay. RESULTS: Bone tissue mineral density (BTMD) was abnormal in 71% of examinees (osteopenia--40%, osteoporosis--31%). Vitamin D concentration under 50 nmol/l was in 76.3%, parathyroid hormone elevated above 100 pg/ml in 15.8% patients. CONCLUSION: The severity of lumbar spine affection depended on severity of calcinosis of aortic valve, was associated with lowering of osteosynthetic activity and was not associated with the presence of osteoporosis risk factors, constitutional parameters, calcium metabolism changes. This suggests the existance of a special form of BTMD disorder in elderly patients with aortal stenosis.     

Long-term air pollution and traffic noise exposures and cognitive function:A cross-sectional analysis of the Heinz Nixdorf Recall study

ABSTRACT

Investigations of adverse effects of air pollution (AP) and ambient noise on cognitive functions are apparently scarce, and findings seem to be inconsistent. The aim of this study was to examine the associations of long-term exposure to AP and traffic noise with cognitive performance. At the second examination of the population-based Heinz Nixdorf Recall study (2006–2008), cognitive performance was evaluated in 4086 participants. Long-term residential exposure to size-specific particulate matter (PM) and nitrogen oxides (NOx) with land use regression, to and traffic noise (weighted 24-h (L_DEN) and nighttime (L_NIGHT) means), was assessed according to the European Union (EU) Directive 2002/49/EC. Multiple regression models were calculated for the relationship of environmental exposures with a global cognitive score (GCS) and in five cognitive subtests, using single- and two-exposure models. In fully adjusted models, several AP metrics were negatively associated with four of five subtests and with GCS. For example, an interquartile range increase in PM_2.5 was correlated with verbal fluency, labyrinth test, and immediate and delayed verbal recall. A 10 dB(A) elevation in L_DEN and L_NIGHT was associated with GCS. Similar but not significant associations were found for the cognitive subtests. In two-exposure models including noise and air pollution simultaneously, the associations did not change markedly for air pollution, but attenuated numerically for noise. Long-term exposures to AP and traffic noise are negatively correlated with subtests related to memory and executive functions. There appears to be little evidence for mutual confounding.     

Investigating air pollution and atherosclerosis in humans: concepts and outlook

Although ambient particulate matter contributes to atherosclerosis in animal models, its role in atherogenesis in humans needs to be established. This article discusses concepts, study design, and choice of health outcomes to efficiently investigate the atherogenic role of ambient air pollution, with an emphasis on early preclinical biomarkers of atherosclerosis that are unaffected by short-term exposure to air pollution (eg, carotid intima-media thickness [CIMT] and functional performance of the vessel). Air pollution studies using these end points are summarized. The CIMT is currently the most frequently used outcome in this field (6 studies). The continuous nature of CIMT, the lack of short-term variation, its relationship to atherosclerotic changes in the artery wall, its predictive value for coronary heart disease, and the noninvasiveness of the assessment make it a useful candidate for cross-sectional and longitudinal studies investigating the role of air pollution in atherogenesis.