Circulating sex hormones and gene expression of subcutaneous adipose tissue oestrogen and alpha-adrenergic receptors in HIV-lipodystrophy: implications for fat distribution

OBJECTIVE: Circulating oestradiol and testosterone, which have been shown to increase in human immunodeficiency virus (HIV)-infected patients following highly active antiretroviral therapy (HAART), may influence fat distribution and insulin sensitivity. Oestradiol increases subcutaneous adipose tissue in humans possibly through binding to oestrogen-receptor-alpha, which in turn activates anti-lipolytic alpha2A-adrenergic-receptor. DESIGN AND METHODS: To address these issues circulating pituitary-gonadal-axis hormones and gene expression of receptors in subcutaneous adipose tissue were determined in 31 nondiabetic HIV-infected male patients receiving HAART (16 with lipodystrophy), in whom measures of fat distribution (CT and DEXA-scans) and insulin sensitivity (hyperinsulinaemic euglycaemic clamp) were available. RESULTS: Total and free oestradiol and testosterone were decreased in lipodystrophic patients compared to nonlipodystrophic patients, whereas luteinizing hormone, follicle-stimulating hormone and prolactin were similar and normal in both study groups. Ratio of subcutaneous to total abdominal fat mass, limb fat, and insulin sensitivity, which were all decreased in lipodystrophic patients, correlated positively with both plasma oestradiol and testosterone (n = 31). Glycerol concentration during clamp (a marker of lipolysis) correlated inversely with expression of alpha2A-adrenergic-receptor, ratio of subcutaneous to total abdominal fat mass, and limb fat, respectively. Expression of alpha2A-adrenergic-receptor correlated positively with expression of oestrogen-receptor-alpha. CONCLUSIONS: The results fit the hypothesis that sex hormones play a role in altered fat distribution and insulin sensitivity of male patients with HIV-lipodystrophy. The effect of oestradiol on the subcutaneous fat depot and lipolysis may be mediated in part through binding to the oestrogen-receptor-alpha, in turn activating anti-lipolytic alpha2A-adrenergic-receptor.     

Aortic regurgitation. Detection of left ventricular dysfunction by exercise echocardiography.

Left ventricular performance was assessed in 20 symptom free patients and 10 with symptoms, all with isolated aortic regurgitation, by measuring the echocardiographic peak velocity of circumferential fibre shortening (echo peak Vcf) at rest and during graded bicycle ergometer exercise in the supine position. The normal left ventricular response during such exercise was first determined in 20 healthy controls. On the basis of their resting and exercise echo peak Vcf, the 30 patients with aortic regurgitation could be separated into three groups: Group 1 comprised 11 symptom free patients with a normal resting echo peak Vcf which increased normally with exercise; group 2 comprised nine symptom free patients with a normal resting echo peak Vcf but with a subnormal response to exercise; group 3 consisted of 10 patients with symptoms with a depressed resting echo peak Vcf which remained subnormal with exercise. Subsequent cardiac catheterisation disclosed normal ejection fractions in patients in group 1, borderline ejection fractions in those in group 2, and reduced ejection fractions in those in group 3. Echocardiographic assessment of left ventricular performance during supine isotonic exercise may provide a simple noninvasive method for the early detection of left ventricular dysfunction in symptom free patients with aortic regurgitation.     

An empirical model of the Baltic Sea reveals the importance of social dynamics for ecological regime shifts

Regime shifts triggered by human activities and environmental changes have led to significant ecological and socioeconomic consequences in marine and terrestrial ecosystems worldwide. Ecological processes and feedbacks associated with regime shifts have received considerable attention, but human individual and collective behavior is rarely treated as an integrated component of such shifts. Here, we used generalized modeling to develop a coupled social–ecological model that integrated rich social and ecological data to investigate the role of social dynamics in the 1980s Baltic Sea cod boom and collapse. We showed that psychological, economic, and regulatory aspects of fisher decision making, in addition to ecological interactions, contributed both to the temporary persistence of the cod boom and to its subsequent collapse. These features of the social–ecological system also would have limited the effectiveness of stronger fishery regulations. Our results provide quantitative, empirical evidence that incorporating social dynamics into models of natural resources is critical for understanding how resources can be managed sustainably. We also show that generalized modeling, which is well-suited to collaborative model development and does not require detailed specification of causal relationships between system variables, can help tackle the complexities involved in creating and analyzing social–ecological models.In recent decades, the world’s biological and physical systems have experienced dramatic change (1, 2). Many marine ecosystems, for example, have undergone abrupt changes known as regime shifts (3, 4). In one prominent case, the Baltic cod fishery suddenly changed in the 1980s from historically high cod biomass and catches (henceforth the “cod boom”) to a sprat-dominant ecosystem with low cod abundance (5–8). This collapse, generally understood to have been precipitated by deteriorating environmental conditions and overfishing (7), had substantial negative socioeconomic impact on Baltic Sea fisheries, including among others the small-scale coastal fishery (9).Ecological analyses of regime shifts, such as of the Baltic cod fishery (10), can capture the complex interplay of ecological and physical processes and drivers that trigger the shift. Numerous studies, however, have shown that understanding individual and collective human behavior is also critical for managing natural resources (11, 12) such as marine ecosystems (13, 14). Social–ecological system research responds to the need to incorporate humans as part of ecosystems by treating natural resource use as arising from linked systems of humans and nature, so-called social–ecological systems. Social–ecological system dynamics result from feedback loops involving biophysical processes, human behavior, and institutional processes within given social and biophysical contexts (15). Formal, quantitative analyses of the contributions of the social and biophysical subsystems to a social–ecological system’s dynamics are rare, however, because knowledge of social–ecological systems is often partial and spread over multiple disciplines (16).Here, we tested the influence of social dynamics on a regime shift in a marine ecosystem using a formal modeling framework. Specifically, we investigated the significance of fisher decision making, as influenced by psychological, economic, and regulatory factors, on the 1980s boom and collapse of the Eastern Baltic cod stock. In a significant advance for natural resource modeling, and for social–ecological modeling more generally, use of the generalized modeling approach (17, 18) enabled us to empirically parameterize, dynamically model, and analyze the qualitative social and ecological dynamics of the Baltic cod fishery at comparable levels of detail and without detailed specification of causal relationships. The Baltic cod fishery was selected because the ecological dynamics during the cod boom and collapse have been well-studied (10, 19, 20), and information about fisher behavior and institutional settings, such as regulation and subsidy policy, is available. Additionally, the cod boom and collapse are qualitatively distinct features of the social–ecological system’s dynamics that are amenable to the concepts and methods of dynamical systems theory (21), such as stability.     

Monthly or weekly bisphosphonate? Evaluation of satisfaction in patients with postmenopausal osteoporosis using OPSAT-Q questionnaire during the BOOSTER study in Croatia

A prospective, open-labelled, multicentre 6-month study was designed to assess three categories that have high impact on Health-Related Quality of Life (HR-QoL). These categories were: satisfaction, preference and drug tolerability in postmenopausal patients with osteoporosis in Croatia, at first treated with weekly oral bisphosphonates, followed by monthly oral ibandronate. Three hundred eighty-five postmenopausal women who were treated with one of the weekly bisphosphonates for at least 6?months were included into the study and after they had signed written informed consent, the therapy was changed to monthly ibandronate. Satisfaction with the treatment was assessed with the Osteoporosis Patient Satisfaction Questionnaire (OPSAT-Q). Patients completed OPSAT-Q at the baseline visit before the change of therapy (visit 1) and 6?months after the change of therapy (visit 2). Following 6?months ibandronate therapy, the values in all four domains of the OPSAT-Q (convenience, confidence with daily activities, overall satisfaction, side effects) as well as in the Composite Satisfaction Score were higher in visit 2 (p?相似文献   

Ventricular response to isometric and isotonic exercise. Echocardiographic assessment

The effects of supine isometric handgrip and graded isotonic bicycle ergometer exercise on left ventricular performance were studied echocardiographically in 20 normal subjects, aged 18 to 36. Measurements of the left ventricular minor axis diameter were taken from recordings performed at rest, during each form of exercise, and during recovery. At the completion of isometric exercise, the pressure-rate product increased significantly. There was no significant change in percentage of fractional shortening (%deltaD), while there was a small but significant fall in peak velocity of circumferential fibre shortening (peak Vcf). Isotonic exercise resulted in a significant increase in %deltaD and peak Vcf. The pressure-rate product also increased and showed a positive correlation with peak Vcf. Isotonic exercise produced a much greater stimulus to left ventricular contractility than isometric exercise and may be a useful means of detecting latent left ventricular dysfunction echocardiographically.     

Some immediate hemodynamic consequences of closure of atrial septal defects of the secundum type

The circumclusion method for surgical closure of atrial septal defects (ASDs) of the secundum type makes it possible, during surgery, to close and reopen the defect as desired. In each of 23 patients the following statistically significant pressure and flow changes were found when the ASD was closed: increasing mean pressures in the ascending aorta (from 74 to 87 mm Hg), left atrium (from 10 to 18 mm Hg), and right pulmonary artery (from 20 to 24 mm Hg); increasing mean flows in the ascending aorta (from 84 to 111 ml/min/kg); decreasing mean pressures in the right atrium (from 9.0 to 7.7 mm Hg); and decreasing mean flows in the right pulmonary artery (from 78 to 46 ml/min/kg). Surprisingly, no correlation between shunt size determined before and during surgery was found. However, in the calculation of the intraoperative shunt, several factors might have contributed to an erroneous result. In 17 patients a right heart catheterization was performed in the third to thirteenth postoperative month and the following statistically significant changes from the intraoperative results with closed ASD were found: The intraoperative mean pressure in the left atrium (18 mm Hg) decreased to 7.3 mm Hg after surgery (pulmonary wedge pressure), the pulmonary arterial pressure decreased from 23 to 13 mm Hg, and the right atrial pressure from 8.2 to 1.6 mm Hg.     

Increased concentration of the fast-acting plasminogen activator inhibitor in plasma associated with familial venous thrombosis

We have earlier demonstrated that in a family with a tendency to recurrent venous thrombosis the release of tissue plasminogen activator (t-PA) activity in blood after stimulation was abnormally low. This observation could be related either to an impaired release of t-PA into the blood stream or to a masking of the released t-PA by a high concentration of PA inhibitor(s). In order to distinguish between these two possibilities the family was reinvestigated using various newer techniques, including an ELISA for t-PA, an assay for quantitation of the fast-acting PA inhibitor and SDS polyacrylamide gel electrophoresis followed by fibrin-enzymography. Hereby the family members were demonstrated to have a high concentration in plasma of the PA inhibitor. After stimulation the release of t-PA into the blood was normal, the t-PA activity, however, was immediately inactivated by complex formation with the fast-acting PA inhibitor.     

Amount of self-reported illicit drug use compared to quantitative hair test results in community-recruited young drug users in Amsterdam

Aims To assess the dose–effect relationship between self‐reported drug intake and the concentration of drugs and/or their metabolites in hair and to examine factors that may mediate this relationship. Design and setting A cohort study among young drug users (YDU) in Amsterdam, the Netherlands, which began in July 2000. At intake, YDU were asked to report their average drug intake over a 2‐month period. A hair sample was taken and then analysed for cocaine, benzoylecgonine (BE), morphine, 6‐monoacetylmorphine and methadone. Weighted least‐squares regression analysis was used to model hair‐test results as a function of reported drug use. Participants Subjects were 95 YDU (using cocaine, heroin, methadone and/or amphetamines at least 3 days/week) aged 18–30 residing in Amsterdam in 2000–2001. Findings Of the 95 YDU, one‐third were women; mean age was almost 26; 30% had black hair, 33% blond hair and 37% brown hair. Cocaine use was reported by 92%, heroin by 75% and methadone by 64% of participants. All hair samples contained one or more drugs. Crude correlation coefficients between reported drug doses and drug concentrations in hair ranged between 0.45 and 0.59. The multivariate regression analysis showed that, for one or more types of drug, black‐haired people, women and non‐western European people had relatively high drug concentrations in hair (significant slope effects). The corresponding multivariate correlation coefficients ranged between 0.63 and 0.87. Conclusions Hair testing can be used to quantify drug use in epidemiological studies, given that factors such as hair colour and sex are taken into account.     

The relationship between body dysmorphic disorder symptoms and self‐construals

Background: Cognitive models of body dysmorphic disorder (BDD) suggest that beliefs and evaluations related to self‐concept are central to the maintenance of the disorder, but such beliefs have received little empirical attention. This study examined the relative importance of contingent self‐worth and self‐ambivalence to BDD symptoms in comparison to their importance to obsessive–compulsive disorder and social phobia symptoms. Method: The sample comprised 194 non‐clinical participants (female, N = 148; males, N = 46) with a mean age of 24.70 years (standard deviation = 9.34). Participants were asked to complete a battery of self‐report questionnaires. Results: While significant relationships were found between the self‐beliefs and symptoms of all three disorders, some specificity was found in the relationships. Conclusions: Self‐worth based upon appearance was most important in BDD, while contingent self‐worth based on the approval of others was important in social phobia. Self‐ambivalence was associated with each disorder. Implications and limitations are discussed.