Acute Encephalopathy with Unilateral Cortical-Subcortical Lesions in Two Unrelated Kindreds Treated with Glucocorticoids Prenatally for Congenital Adrenal Hyperplasia due to 21-Hydroxylase Deficiency: Established Facts and Novel Insight

Background: Prenatal glucocorticoid (GC) treatment of the female fetus with 21-hydroxylase deficiency (21-OHD) may prevent genital virilization and androgen effects on the brain, but prenatal GC therapy is controversial because of possible adverse effects on fetal programming, the cardiovascular system and the brain. Case Reports: We report 2 patients with congenital adrenal hyperplasia (CAH) due to 21-OHD who were treated prenatally with dexamethasone, suffered from an acute encephalopathy and showed focal and multifocal cortical and subcortical diffusion restrictions in early MRI and signs of permanent alterations in the follow-up neuroimaging studies. Both patients recovered from the acute episode. Whereas the first patient recovered without neurological sequelae the second patient showed hemianopsia and spastic hemiplegia in the neurological follow-up examination. Conclusion: These are 2 children with CAH, both treated prenatally with high doses of dexamethasone to prevent virilization. The question arises whether prenatal high-dose GC treatment in patients with CAH might represent a risk factor for brain lesions in later life. Adverse effects/events should be reported systematically in patients undergoing prenatal GC treatment and long-term follow-up studies involving risk factors for cerebrovascular disease should be performed.

Semaphorins guide PerPlexeD endothelial cells

Abrogation of the endothelial cell-specific semaphorin receptor PlexinD1 in zebrafish and mouse reveals semaphorin functions selectively affecting the cardiovascular system. Neuropilins team up with PlexinD1 to form a novel endothelial receptor complex for class 3 semaphorins.

Effects of growth hormone (GH) replacement therapy on low-density lipoprotein apolipoprotein B100 kinetics in adult patients with GH deficiency: a stable isotope study

GH replacement therapy has been shown to improve the dyslipidemic condition in a substantial proportion of patients with adult GH deficiency. The mechanisms are not yet fully elucidated. Low-density lipoprotein (LDL) apolipoprotein B100 (apoB) formation and catabolism are important determinants of plasma cholesterol concentrations. This study examined the effect of GH replacement therapy on LDL apoB metabolism using a stable isotope turnover technique. LDL apoB kinetics was determined in 13 adult patients with GH deficiency before and after 3 months GH/placebo treatment in a randomized, double-blind, placebo-controlled study. LDL apoB (13)C-leucine enrichment was determined by isotope-ratio mass spectrometry. Plasma volume was assessed by standardized radionuclide dilution technique. GH replacement therapy significantly decreased LDL cholesterol, LDL apoB concentrations, and LDL apoB pool size compared with placebo. Compared with baseline, GH replacement therapy resulted in a significant increase in plasma volume and fractional catabolic rate, whereas LDL formation rate remained unchanged. LDL lipid content did not significantly change after GH and placebo. This study suggests that short-term GH replacement therapy decreases the LDL apoB pool by increasing removal of LDL particles without changing LDL composition or LDL apoB production rate. In addition, it is possible that the beneficial effects of GH on the cardiovascular system contribute to these findings.

Energy beverages: content and safety.

Exercise is making a resurgence in many countries, given its benefits for fitness as well as prevention of obesity. This trend has spawned many supplements that purport to aid performance, muscle growth, and recovery. Initially, sports drinks were developed to provide electrolyte and carbohydrate replacement. Subsequently, energy beverages (EBs) containing stimulants and additives have appeared in most gyms and grocery stores and are being used increasingly by "weekend warriors" and those seeking an edge in an endurance event. Long-term exposure to the various components of EBs may result in significant alterations in the cardiovascular system, and the safety of EBs has not been fully established. For this review, we searched the MEDLINE and EMBASE databases from 1976 through May 2010, using the following keywords: energy beverage, energy drink, power drink, exercise, caffeine, red bull, bitter orange, glucose, ginseng, guarana, and taurine. Evidence regarding the effects of EBs is summarized, and practical recommendations are made to help in answering the patient who asks, "Is it safe for me to drink an energy beverage when I exercise?"

Essentials of forensic post-mortem MR imaging in adults

Post-mortem MR (PMMR) imaging is a powerful diagnostic tool with a wide scope in forensic radiology. In the past 20 years, PMMR has been used as both an adjunct and an alternative to autopsy. The role of PMMR in forensic death investigations largely depends on the rules and habits of local jurisdictions, availability of experts, financial resources, and individual case circumstances. PMMR images are affected by post-mortem changes, including position-dependent sedimentation, variable body temperature and decomposition. Investigators must be familiar with the appearance of normal findings on PMMR to distinguish them from disease or injury. Coronal whole-body images provide a comprehensive overview. Notably, short tau inversion–recovery (STIR) images enable investigators to screen for pathological fluid accumulation, to which we refer as “forensic sentinel sign”. If scan time is short, subsequent PMMR imaging may be focussed on regions with a positive forensic sentinel sign. PMMR offers excellent anatomical detail and is especially useful to visualize pathologies of the brain, heart, subcutaneous fat tissue and abdominal organs. PMMR may also be used to document skeletal injury. Cardiovascular imaging is a core area of PMMR imaging and growing evidence indicates that PMMR is able to detect ischaemic injury at an earlier stage than traditional autopsy and routine histology. The aim of this review is to present an overview of normal findings on forensic PMMR, provide general advice on the application of PMMR and summarise the current literature on PMMR imaging of the head and neck, cardiovascular system, abdomen and musculoskeletal system.

Estrogen induces nitric oxide production via nitric oxide synthase activation in endothelial cells.

INTRODUCTION 17β-estradiol (E2) has been found to induce vasodilation in the cardiovascular system and at physiological levels, resulting in prevention of cerebral vasospasm following subarachnoid hemorrhage (SAH) in animal models. The goal of this study was to analyze the cellular mechanism of nitric oxide (NO) production and its relation to E2, in vitro in brain and peripheral endothelial cells. METHODS Human umbilical endothelial cells (HUVEC) and brain endothelial cells (bEnd.3) were treated with estradiol (E2, 0.1, 10, 100, and 1,000 nM), and supernatant was collected at 0, 5, 15, 30, 60, and 120 min for nitric oxide metabolome (nitrite, NO₂) measurements. Cells were also treated with E2 in the presence of 1400W, a potent eNOS inhibitor, and ICI, an antagonist of estradiol receptors (ERs). Effects of E2 on eNOS protein expression were assessed with Western blot analysis. RESULTS E2 significantly increased NO2 levels irrespective of its concentration in both cell lines by 35 % and 42 % (p < 0.05). The addition of an E2 antagonist, ICI (10 μM), prevented the E2-induced increases in NO2 levels (11 % p > 0.05). The combination of E2 (10 nM) and a NOS inhibitor (1400W, 5 μM) inhibited NO2 increases in addition (4 %, p > 0.05). E2 induced increases in eNOS protein levels and phosphorylated eNOS (eNOS(p)). CONCLUSIONS This study indicates that E2 induces NO level increases in cerebral and peripheral endothelial cells in vitro via eNOS activation and through E2 receptor-mediated mechanisms. Further in vivo studies are warranted to evaluate the therapeutic value of estrogen for the treatment of SAH-induced vasospasm.

Improved bioassay for the detection of porcine tumor necrosis factor using a homologous cell line: PK(15)

Close similarities of various physiological parameters makes the pig one of the preferred animal models for the study of human diseases, especially those involving the cardiovascular system. Unfortunately, the use of pig models to study diseases such as viral hemorrhagic fevers and endotoxic shock syndrome have been hampered by the lack of the necessary immunological tools to measure important immunoregulatory cytokines such as tumor necrosis factor (TNF). Here we describe a TNF-bioassay which is based on the porcine kidney cell line PK(15). Compared to the widely used murine fibroblastoid cell line L929, the PK(15) cell line displays a 100-1000-fold higher sensitivity for porcine TNF-alpha, a higher sensitivity for human TNF-alpha, and a slightly lower sensitivity for murine TNF-alpha. Using a PK(15) bioassay we can detect recombinant TNF-alpha as well as cytotoxic activity in the supernatants of lipopolysaccharide (LPS)-activated porcine monocytes at high dilutions. This suggests that the sensitivity of the test should permit the detection of TNF in biological specimens such as pig serum.

[Air pollution and asthma in childhood].

Exposure to outdoor air pollutants and passive tobacco smoke are common but avoidable worldwide risk factors for morbidity and mortality of individuals. In addition to well-known effects of pollutants on the cardiovascular system and the development of cancer, in recent years the association between air pollution and respiratory morbidity has become increasingly apparent. Not only in adults, but also in children with asthma and in healthy children a clear harmful effect of exposure towards air pollutants has been demonstrated in many studies. Among others increased pollution has been shown to result in more frequent and more severe respiratory symptoms, more frequent exacerbations, higher need for asthma medication, poorer lung function and increased visits to the emergency department and more frequent hospitalisations. While these associations are well established, the available data on the role of air pollution in the development of asthma seems less clear. Some studies have shown that increased exposure towards tobacco smoke and air pollution leads to an increase in asthma incidence and prevalence; others were not able to confirm those findings. Possible reasons for this discrepancy are different definitions of the outcome asthma, different methods for exposure estimation and differences in the populations studied with differing underlying genetic backgrounds. Regardless of this inconsistency, several mechanisms have already been identified linking air pollution with asthma development. Among these are impaired lung growth and development, immunological changes, genetic or epigenetic effects or increased predisposition for allergic sensitisation. What the exact interactions are and which asthmatic phenotypes will be influenced most by pollutants will be shown by future studies. This knowledge will then be helpful in exploring possible preventive measures for the individual and to help policy makers in deciding upon most appropriate regulations on a population level.