Unaltered insulin sensitivity during calcium channel blockade with amlodipine

Summary The sensitivity of peripheral tissues to insulin is of pathophysiological, therapeutic and possibly also of prognostic relevance. Calcium channel blockers are widely used in the treatment of cardiovascular disorders that are commonly associated with decreased insulin sensitivity (S_I). To evaluate the effects of calcium channel blokkade on S_I, glucose homoeostasis and lipid profiles, studies were made of S_I (determined by the Minimal Model Method of Bergman), basal glucose and insulin levels, serum total triglyceride (Tg) and lipoprotein cholesterol (C) fractions and certain other variables in 38 healthy young men (24 y) during placebo and after 3 weeks of calcium channel blockade with amlodipine 5 mg once daily. Measurements were made after 3 days on a standard diet (2200 kcal · day^–1, 45% carbohydrates, 40% fat and 15% proteins) and after an overnight fast. Compared to placebo, amlodipine decreased supine systolic blood pressure (P<0.01). Heart rate, body weight and 24 h urinary sodium excretion were unaltered, and so were fasting plasma glucose (placebo vs amlodipine: 4.86 vs 4.83 mmol·1^–1, respectively) and insulin levels (7.7 vs 7.9 U·ml^–1), S_I (10.5 vs 9.6·10^–4 × min^–1 pro U·ml^–1), serum total Tg, C and lipoprotein C fractions.The findings demonstrate unchanged insulin sensitivity and secretion, as well as lipoprotein regulation, during maintenance administration of 5 mg amlodipine daily to healthy young men.This work was supported in part by the Swiss National Science Foundation     

Role of prothrombin 19911 A>G polymorphism,blood group and male gender in patients with venous thromboembolism: Results of a German cohort study

Journal of Thrombosis and Thrombolysis - The role of the A&gt;G polymorphism at position 19911 in the prothrombin gene (factor [F] 2 at rs3136516) as a risk factor for venous thromboembolism...     

mGluR5 and GABAA receptor‐specific parametric PET atlas construction—PET/MR data processing pipeline,validation, and application

The glutamate and γ‐aminobutyric acid neuroreceptor subtypes mGluR₅ and GABA_A are hypothesized to be involved in the development of a variety of psychiatric diseases. However, detailed information relating to their in vivo distribution is generally unavailable. Maps of such distributions could potentially aid clinical studies by providing a reference for the normal distribution of neuroreceptors and may also be useful as covariates in advanced functional magnetic resonance imaging (MR) studies. In this study, we propose a comprehensive processing pipeline for the construction of standard space, in vivo distributions of non‐displaceable binding potential (BP _ND), and total distribution volume (V _T) based on simultaneously acquired bolus‐infusion positron emission tomography (PET) and MR data. The pipeline was applied to [¹¹C]ABP688‐PET/MR (13 healthy male non‐smokers, 26.6 ± 7.0 years) and [¹¹C]Flumazenil‐PET/MR (10 healthy males, 25.8 ± 3.0 years) data. Activity concentration templates, as well as V _T and BP _ND atlases of mGluR₅ and GABA_A, were generated from these data. The maps were validated by assessing the percent error δ from warped space to native space in a selection of brain regions. We verified that the average δ_ABP = 3.0 ± 1.0% and δ_FMZ = 3.8 ± 1.4% were lower than the expected variabilities σ of the tracers (σ_ABP = 4.0%–16.0%, σ_FMZ = 3.9%–9.5%). An evaluation of PET‐to‐PET registrations based on the new maps showed higher registration accuracy compared to registrations based on the commonly used [¹⁵O]H₂O‐template distributed with SPM12. Thus, we conclude that the resulting maps can be used for further research and the proposed pipeline is a viable tool for the construction of standardized PET data distributions.     

Emotional but not physical maltreatment is independently related to psychopathology in subjects with various degrees of social anxiety: a web-based Internet survey

ABSTRACT: BACKGROUND: Previous studies reported that social phobia is associated with a history of child maltreatment. However, most of these studies focused on physical and sexual maltreatment whilst little is known about the specific impact of emotional abuse and neglect on social anxiety. We examined the association between emotional maltreatment, including parental emotional maltreatment as well as emotional peer victimization, and social anxiety symptoms in subjects with various degrees of social anxiety. METHODS: The study was conducted as a web-based Internet survey of participants (N = 995) who had social anxiety symptoms falling within the high range, and including many respondents who had scores in the clinical range. The assessment included measures of child maltreatment, emotional peer victimization, social anxiety symptoms and general psychopathology. RESULTS: Regression and mediation analyses revealed that parental emotional maltreatment and emotional peer victimization were independently related to social anxiety and mediated the impact of physical and sexual maltreatment. Subjects with a history of childhood emotional maltreatment showed higher rates of psychopathology than subjects with a history of physical maltreatment. CONCLUSIONS: Although our findings are limited by the use of an Internet survey and retrospective self-report measures, data indicated that social anxiety symptoms are mainly predicted by emotional rather than physical or sexual types of victimization.     

Prognostic significance of cytokine modulation in non-small cell lung cancer

Increased production of immunosuppressive interleukin-10 (IL-10) by non-small cell lung cancer (NSCLC) and increased serum IL-10 concentrations in NSCLC-patients have recently been correlated to reduced survival. We earlier demonstrated suppression of IL-2 secretion in whole blood cell cultures of NSCLC-patients. We now analyzed the influence of IL-2 secretion on survival in NSCLC-patients and the influence of IL-10 on IL-2 secretion. The correlation of the IL-2 producing ability of whole blood cells in response to PHA in 90 NSCLC-patients at the time of diagnosis to survival was calculated by Crit-level, the Kaplan-Meier method and the log-rank test. With a cut-off value of IL-2 production of 1,100 pg/ml by whole blood cells the difference in survival was significant with a p-value of 0.014. In the group with high and low IL-2, median survival was 14.1 and 9.7 months, respectively. In the subgroup of 33 surgically-treated patients the difference in survival was significant with a p-value of 0.011. In 14 patients with surgical resection of the tumor and high IL-2 at diagnosis and 19 patients with surgical resection, but low IL-2 at diagnosis, median survival was 86.2 and 11.3 months, respectively. Secretion of IL-2 in whole blood cell cultures from healthy individuals was inhibited in a dose-dependent manner upon addition of IL-10. Taken together, suppression of IL-2 secretion has prognostic significance for survival of NSCLC-patients and may be mediated by tumor-derived IL-10.     

Negative and positive childhood experiences across developmental periods in psychiatric patients with different diagnoses – an explorative study

Background  

A high frequency of childhood abuse has often been reported in adult psychiatric patients. The present survey explores the relationship between psychiatric diagnoses and positive and negative life events during childhood and adulthood in psychiatric samples.     

Posttraumatic Stress Disorder in patients with traumatic brain injury

Background  

Severe traumatic stressors such as war, rape, or life-threatening accidents can result in a debilitating psychopathological development conceptualised as Posttraumatic Stress Disorder (PTSD). Pathological memory formation during an alarm response may set the precondition for PTSD to occur. If true, a lack of memory formation by extended unconsciousness in the course of the traumatic experience should preclude PTSD.