Herzfrequenzvariabilität in der Postmenopause

Zusammenfassung: Autonomes Nervensystem und Herzfrequenzvariabilität: Sowohl eine Dysregulation des autonomen Nervensystems (ANS) als auch die Menopause sind mit einem erhöhten kardiovaskulären Risiko verbunden. Das kardiale ANS kann anhand der Herzfrequenzvariabilität (HRV) beurteilt und in Frequenzspektren aufgespalten werden, die sich dem Parasympathikus- und/oder Sympathikuseinfluss zuordnen lassen. Einfluss der endokrinen Lebensphasen: Bereits während des Menstruationszyklus zeigt sich eine zyklusabhängige Fluktuation der HRV. Mit dem menopausalen Östrogenabfall ist ein Anstieg des Sympathikotonus mit HRV-Reduktion verbunden, was mit einem erhöhten kardiovaskulären Risiko einhergeht. Das mit menopausalen Hitzewallungen verbundene erhöhte kardiovaskuläre Erkrankungsrisiko ist möglicherweise ebenso auf eine Sympathikusaktivierung zurückzuführen. Therapie: Eine Hormonersatztherapie vermag eventuell eine Wiederherstellung der autonomen Balance herbeizuführe

String Dilaton Fluid Cosmology

We investigate $(n+1)$-dimensional string-dilaton cosmology with effective dilaton potential in presence of perfect-fluid matter.We get exact solutions parametrized by the constant \gam of the state equation p=(\gam-1)\rho, the spatial dimension number $n$, the bulk of matter, and the spatial curvature constant $k$. Several interesting cosmological behaviours are selected. Finally we discuss the recovering of ordinary Einstein gravity starting from string dominated regime and a sort of asymptotic freedom due to string effective coupling.Comment: 16 pages, Latex, submitted to Int. Jou. Mod. Phys.

The mammalian Scribble polarity protein regulates epithelial cell adhesion and migration through E-cadherin

Scribble (Scrib) is a conserved polarity protein required in Drosophila melanogaster for synaptic function, neuroblast differentiation, and epithelial polarization. It is also a tumor suppressor. In rodents, Scrib has been implicated in receptor recycling and planar polarity but not in apical/basal polarity. We now show that knockdown of Scrib disrupts adhesion between Madin–Darby canine kidney epithelial cells. As a consequence, the cells acquire a mesenchymal appearance, migrate more rapidly, and lose directionality. Although tight junction assembly is delayed, confluent monolayers remain polarized. These effects are independent of Rac activation or Scrib binding to βPIX. Rather, Scrib depletion disrupts E-cadherin–mediated cell–cell adhesion. The changes in morphology and migration are phenocopied by E-cadherin knockdown. Adhesion is partially rescued by expression of an E-cadherin–α-catenin fusion protein but not by E-cadherin–green fluorescent protein. These results suggest that Scrib stabilizes the coupling between E-cadherin and the catenins and are consistent with the idea that mammalian Scrib could behave as a tumor suppressor by regulating epithelial cell adhesion and migration

Molecular analysis has allowed the definitive diagnosis of multiple acyl-CoA dehydrogenase deficiency (MADD)

Multiple acyl-CoA dehydrogenation deficiency (MADD) is a rare autosomal recessive disorder due to defects in the electron transfer flavoprotein (ETF) or in the electron transfer flavoprotein dehydrogenase (ETFDH) enzymes, involved in the mitochondrial electron transport chain. Patients with MADD fall into different clinical phenotypes, ranging from a severe neonatal presentation, with metabolic acidosis, cardiomyopathy and liver disease to a mild childhood/adult disease, with episodic metabolic decompensation, muscle weakness and respiratory failure.Nowadays, the MADD diagnosis is established by the presence of dicarboxylic organic acids and acylglycine derivatives in the urine and increased levels of medium-and long-chain acylcarnitines in the blood. Mutations in ETFA, ETFB, ETFDH genes, encoding for alpha and beta subunits of ETF and for ETF-dehydrogenase are associated with MADD. We report the case of a three years old child, affected by lethargy and asthenia associated with anorexia. Biochemical analyses showed hypoketotic hypoglycemia with remarkable increments in transaminases, lactic dehydrogenase, aldolase and creatine kinase. The chromatographic layout of urinary organic acids showed a typical dicarboxylic aciduria. Thus, based on these features, MADD was suspected. Fifteen years later, at the age of 19, MADD diagnosis was confirmed by molecular analysis, showing a compound heterozygosity for the mutations c.1074G>C (p.R358S; HGMD: CM031670 in HGMD database) and c.1073G>A (p.R358K) in the ETFDH gene. The c.1073G>A (p.R358K; rs796051959) mutation is reported in ClinVar database as pathogenic allele, although lacking link to a specific clinical condition. However, familial segregation study and in silico analysis, performed by bioinformatics tools, confirmed that this substitution is likely pathogenetic. Her parents were healthy carriers of one of the two mutations. It is known that the severity of the clinical phenotype of MADD may be related to the type of mutation in the ETFA/ETFB/ETFDH genes. Particularly, missense mutations in the ETFDH gene, leaving a detectable residual enzyme activity, may account for the milder form of the disease, as is the case here. In conclusion we suggest that molecular analysis is essential to the definitive diagnosis of MADD and to direct the adequate therapeutic management. Thus, through a close nutritional follow up, a few months ago the patient gave birth to a healthy boy. References Olsen et al. Clear relationship between ETF/ETFDH genotype and phenotype in patients with multiple acyl-CoA dehydrogenation deficiency. Hum Mutat. 2003; 22:12–23

Impact of Sleeve Gastrectomy on Weight Loss, Glucose Homeostasis, and Comorbidities in Severely Obese Type 2 Diabetic Subjects

This study was undertaken to assess medium-term effects of laparoscopic sleeve gastrectomy (LSG) on body weight and glucose homeostasis in severely obese type 2 diabetic (T2DM) subjects. Twenty-five obese T2DM subjects (10 M/15 F, age 45 ± 9 years, BMI 48 ± 8 kg/m2, M ± SD) underwent evaluation of anthropometric/clinical parameters and glucose homeostasis before, 3 and 9–15 months after LSG. Mean BMI decreased from 48 ± 8 kg/m2 to 40 ± 9 kg/m2 (P < .001) at 3 months and 34 ± 6 kg/m2 (P < .001) at 9–15 months after surgery. Remission of T2DM (fasting plasma glucose < 126 mg/dL and HbA1c < 6.5% in the absence of hypoglycemic treatment) occurred in all patients but one. There was a remarkable reduction in the percentage of patients requiring antihypertensive and hypolipidemic drugs. Our study shows that LSG is effective in producing a significant and sustained weight loss and improving glucose homeostasis in severely obese T2DM patients

Muscle sympathetic nerve activity in patients with acromegaly

Muscle sympathetic nerve activity was measured in nine acromegalic patients (age, 35 +/- 4 yr; body mass index, 28 +/- 2 kg/m2) and eight healthy subjects (age, 32 +/- 3 yr; body mass index, 25 +/- 2 kg/m2) by combining the forearm arterial-venous difference technique with the tracer method [infusion of tritiated norepinephrine (NE)]. Muscle NE release was quantified both at rest and during physiological hyperinsulinemia while maintaining euglycemia (approximately 90 mg/dL) by means of the euglycemic clamp. Arterial plasma NE was similar in the two groups at rest (197 +/- 28 and 200 +/- 27 pg/mL (-1) and slightly increased during insulin infusion. Forearm NE release was 2.33 +/- 0.55 ng x liter(-1) x min(-1) in healthy subjects and 2.67 +/- 0.61 ng x liter(-1) x min(-1) in acromegalic subjects in the basal state and increased to a similar extent during insulin infusion in both groups (3.13 +/- 0.71 and 3.32 +/- 0.75 ng x L(-1) x min(-1), P < 0.05 vs. basal), indicating a normal stimulatory effect of insulin on muscle sympathetic activity. In contrast, insulin-stimulated forearm glucose uptake was markedly lower in acromegalic patients (2.3 +/- 0.4 mg x L(-1) x min(-1)) than in control subjects (7.9 +/- 1.3 mg x L(-1) x min(-1), P < 0.001), indicating the presence of severe insulin resistance involving glucose metabolism. Our data demonstrate that patients with long-term acromegaly have normal sympathetic activity in the skeletal muscle in the basal, postabsorptive state and normal increments in NE spillover in response to the sympatho-excitatory effect of insulin. Thus, the presence of severe insulin resistance in acromegaly is not accounted for by adrenergic mechanisms

Laparoscopic reinforced sleeve gastrectomy: early results and complications

BACKGROUND: Sleeve gastrectomy (SG) was pioneered as a two-stage intervention for super and super-super obesity to minimize morbidity and mortality; it is employed increasingly as a primary procedure. Early outcomes and integrity of laparoscopic SG (LSG) against leak using a technique incorporating gastric transection-line reinforcement were studied. METHODS: Between 2003 and 2009, 121 patients underwent LSG (16, two-stage; 105, primary). Of the patients, 66% were women, mean age 38.8 ± 10.9 (15.0-64.0), and body mass index (BMI, kg/m(2)) 48.7 ± 9.3 (33.7-74.8). Bovine pericardium (Peri-Strips Dry [PSD]) was used to reinforce the staple line. Parametric and nonparametric tests were used, as appropriate. The paired t test was used to assess change from baseline; bivariate analyses and logistic regression were used to identify preoperative patient characteristics predictive of suboptimal weight loss. RESULTS: Mean operative time was 105 min (95-180), and mean hospitalization was 5.6 days (1-14). There was no mortality. There were 6 (5.0%) complications: 1 intraoperative leak, 1 stricture, 1 trocar-site bleed, 1 renal failure, and 2 wound infections. There were no postoperative staple-line leaks. Following 15 concomitant hiatal hernia operations, 3 (20%) recurred: 1 revised to RYGB and 2 in standby. Two post-LSG hiatal hernias of the two-stage series required revisions because of symptoms. BMI decreased 24.7% at 6 months (n = 55) to 37.5 ± 9.3 (22.2-58.1); %EWL was 48.1 ± 19.3 (15.5-98.9). Twelve-month BMI (n = 41) was 38.4 ± 10.5 (19.3-62.3); %EWL was 51.7 ± 25.0 (8.9-123.3). Forty-eight-month BMI (n = 13) was 35.6 ± 6.8 (24.9-47.5); %EWL was 61.1 ± 12.2 (43.9-82.1) (p 70% of patients who experienced <50% EWL at 6 months. At 2 weeks, 100% of type 2 diabetes patients (n = 23) were off medication (mean HbA(1C), 5.9 ± 0.5%; glycemia, 90.0 ± 19.9 mg/dL (p < 0.01) at 3 months). CONCLUSIONS: Laparoscopic PSD-reinforced LSG as a staged or definitive procedure is safe and effective in the short term and provides rapid type 2 diabetes mellitus reduction with a very low rate of complications

Acute noradrenergic activation induces insulin resistance in human skeletal muscle

We assessed in normal subjects the effects of an acute increase in forearm norepinephrine (NE) release, evoked by -20 mmHg lower body negative pressure (LBNP), on insulin-mediated muscle glucose uptake. Seven normal subjects underwent the following two insulin euglycemic clamps in random sequence: one during application of LBNP and the other without LBNP (control study). In the control study, hyperinsulinemia (approximately 60 microU/ml) produced a significant increment in forearm NE release, measured by using the forearm perfusion technique combined with infusion of tritiated NE (from 4.91 +/- 1 to 7.94 +/- 1.33 ng.l-1.min-1; P < 0.05). Forearm glucose uptake rose from 0.97 +/- 0.13 to 5.2 +/- 0.2 mg.l-1.min-1 in response to insulin infusion. When the insulin clamp was performed during LBNP, forearm NE release rose to significantly higher values than those of the control study (from 4.33 +/- 0.52 to 12.7 +/- 1.46 ng.l-1.min-1; P < 0.01 vs. control). Under these conditions, the stimulatory effect of insulin on forearm glucose uptake was markedly reduced (from 0.78 +/- 0.10 to 3.2 +/- 0.7 mg.l-1.min-1; P < 0.02 vs. control). Forearm blood flow and plasma epinephrine and free fatty acid concentrations were comparable in the two study sessions. These data demonstrate that an acute activation of endogenous NE release antagonizes insulin-mediated glucose uptake in forearm skeletal muscle, probably accounted for by a direct metabolic effect of NE.We assessed in normal subjects the effects of an acute increase in forearm norepinephrine (NE) release, evoked by -20 mmHg lower body negative pressure (LBNP), on insulin-mediated muscle glucose uptake. Seven normal subjects underwent the following two insulin euglycemic clamps in random sequence: one during application of LBNP and the other without LBNP (control study). In the control study, hyperinsulinemia (≃60 μU/ml) produced a significant increment in forearm NE release, measured by using the forearm perfusion technique combined with infusion of tritiated NE (from 4.91 ± 1 to 7.94 ± 1.33 ng · l -1 · min -1 ; P < 0.05). Forearm glucose uptake rose from 0.97 ± 0.13 to 5.2 ± 0.2 mg · l -1 · min -1 in response to insulin infusion. When the insulin clamp was performed during LBNP, forearm NE release rose to significantly higher values than those of the control study (from 4.33 ± 0.52 to 12.7 ± 1.46 ng · l -1 · min -1 ; P < 0.01 vs. control). Under these conditions, the stimulatory effect of insulin on forearm glucose uptake was markedly reduced (from 0.78 ± 0.10 to 3.2 ± 0.7 mg · l -1 · min -1 ; P < 0.02 vs. control). Forearm blood flow and plasma epinephrine and free fatty acid concentrations were comparable in the two study sessions. These data demonstrate that an acute activation of endogenous NE release antagonizes insulin-mediated glucose uptake in forearm skeletal muscle, probably accounted for by a direct metabolic effect of NE