Gender, hyperandrogenism and vitamin D deficiency related functional and morphological alterations of rat cerebral arteries

Hyperandrogenism is a risk factor of cerebrovascular diseases as androgens can alter markedly the regulation of cerebrovascular tone. We examined the combined impact of androgen excess and vitamin D deficiency (VDD), a common co-morbidity in hyperandrogenic disorders, on remodeling and testosterone-induced vascular responses of anterior cerebral arteries (ACA) in order to evaluate the interplay between androgens and VDD in the cerebral vasculature. Male and female Wistar rats were either fed with vitamin D deficient or vitamin D supplemented diet. Half of the female animals from both groups received transdermal testosterone treatment. After 8 weeks, vessel lumen, wall thickness and testosterone-induced vascular tone of isolated ACA were determined using pressure microangiometry and histological examination. Androgen receptor protein expression in the wall of cerebral arteries was examined using immunohistochemistry. In female rats only combined VDD and testosterone treatment decreased the lumen and increased the wall thickness of ACA. In males, however VDD by itself was able to decrease the lumen and increase the wall thickness. Vascular reactivity showed similar alterations: in females, testosterone constricted the ACA only after combined VDD and hyperandrogenism, whereas in males VDD resulted in increased testosterone-induced contractions in spite of decreased androgen receptor expression. In conclusion, a marked interplay between hyperandrogenism and VDD results in inward remodeling and enhanced testosterone-induced constrictions of cerebral arteries, which might compromise the cerebral circulation and thus, increase the risk of stroke in the long term. In addition, the early cerebrovascular manifestation of VDD appears to require androgen excess and thus, depends on gender

Recombinant human activated protein C attenuates cardiovascular and microcirculatory dysfunction in acute lung injury and septic shock

Introduction: This prospective, randomized, controlled, experimental animal study looks at the effects of recombinant human activated protein C (rhAPC) on global hemodynamics and microcirculation in ovine acute lung injury (ALI) and septic shock, resulting from smoke inhalation injury

Baseline Characteristics and Disease Phenotype In Inflammatory Bowel Disease Results of A Paediatric IBD Cohort.

BACKGROUND AND AIMS Predicting short-term relapses and long-term prognosis is of outmost importance in paediatric inflammatory bowel disease. Our aim was to investigate the short-term disease outcome and medication during the first year in a paediatric incident cohort from Hungary. In addition, association laboratory markers and disease activity indices with short-term disease outcome and medication were analysed. METHODS From January 1, 2008 to December 31, 2010 demographic data and clinical characteristics of newly diagnosed paediatric inflammatory bowel disease patients younger than 18 years of age were prospectively recorded. RESULTS A total of 420 patients were identified [Crohn's disease: 266; ulcerative colitis 124]. Initially, 48% (124/256) of Crohn's disease patients had moderate to severe disease (PCDAI>31), and this rate decreased to 2.1% at one-year follow-up. Proportion of ulcerative colitis patients with moderate to severe disease (PUCAI>35) at diagnosis declined from 57.5% (69/120) to 6.8% at one-year follow-up. Terminal ileal involvement correlated with higher initial CRP (p = 0.021) and initial PCDAI (p = 0.026). In ulcerative colitis, elevated CRP (p = 0.002) was associated with disease extension. CRP and PCDAI at diagnosis were associated with the need for immunomodulators at one year in children with Crohn's disease. Initial CRP was also associated with the need for immunomodulators in patients with ulcerative colitis at one-year follow-up. CONCLUSIONS At diagnosis half of the patients with inflammatory bowel disease had moderate to severe disease and this rate decreased to less than 10% after one year. Initial CRP and PCDAI were related to the need for aggressive therapy in Crohn's disease

Reduced Estradiol-Induced Vasodilation and Poly-(ADP-Ribose) Polymerase (PARP) Activity in the Aortas of Rats with Experimental Polycystic Ovary Syndrome (PCOS)

Polycystic ovary syndrome (PCOS) is a complex endocrine disorder characterized by hyperandrogenism and insulin resistance, both of which have been connected to atherosclerosis. Indeed, an increased risk of clinical manifestations of arterial vascular diseases has been described in PCOS. On the other hand endothelial dysfunction can be detected early on, before atherosclerosis develops. Thus we assumed that vascular dysfunction is also related directly to the hormonal imbalance rather than to its metabolic consequences. To detect early functional changes, we applied a novel rodent model of PCOS: rats were either sham operated or hyperandrogenism was achieved by implanting subcutaneous pellets of dihydrotestosterone (DHT). After ten weeks, myograph measurements were performed on isolated aortic rings. Previously we described an increased contractility to norepinephrine (NE). Here we found a reduced immediate relaxation to estradiol treatment in pre-contracted aortic rings from hyperandrogenic rats. Although the administration of vitamin D3 along with DHT reduced responsiveness to NE, it did not restore relaxation to estradiol. Poly-(ADP-ribose) polymerase (PARP) activity was assessed by poly-ADP-ribose immunostaining. Increased PAR staining in ovaries and circulating leukocytes from DHT rats showed enhanced DNA damage, which was reduced by concomitant vitamin D3 treatment. Surprisingly, PAR staining was reduced in both the endothelium and vascular smooth muscle cells of the aorta rings from hyperandrogenic rats. Thus in the early phase of PCOS, vascular tone is already shifted towards vasoconstriction, characterized by reduced vasorelaxation and vascular dysfunction is concomitant with altered PARP activity. Based on our findings, PARP inhibitors might have a future perspective in restoring metabolic disorders in PCOS

A pilot study of early onset obsessive-compulsive disorder: Symptom dimensions and association analysis with polymorphisms of the serotonin transporter gene

Our aim was to introduce more homogenous phenotypes for studying genetic variations in the clinically heterogeneous obsessive compulsive disorder (OCD) beside classical case-control analysis. Symptoms were assessed with Children's Yale-Brown Obsessive Compulsive Scale (CY-BOCS), and principle component analysis of the lifetime symptom categories yielded four factors (Cleaning, Obsessive, Compulsive, Sexual). The comparison of serotonin transporter linked polymorphic region (5-HTTLPR) in 102 OCD patients and 223 controls showed an increased L-allele frequency but no difference was observed when rs25531 was included. Intronic variants of the serotonin transporter gene did not show association with either OCD, nor with the obtained factors. © 201

Incidence Rates and Disease Course of Pediatric IBD in Western Hungary Between 1977 and 2011

BACKGROUND: Limited data are available on paediatric inflammatory bowel diseases in Eastern Europe. Our aim was to analyse disease characteristics in the population-based Veszprem province database between 1977 and 2011. METHODS: 187 (10.5%, ulcerative colitis/Crohn's disease/undetermined colitis: 88/95/4) out of 1565 incident patients were diagnosed with a paediatric onset in this population-based prospective inception cohort. RESULTS: The incidence of Crohn's disease and ulcerative colitis increased from 0 and 0.7 in 1977-1981 to 7.2 and 5.2 in 2007-2011 per 100,000 person years. Ileocolonic location (45%) and inflammatory disease behaviour (61%) were most frequent in Crohn's disease, while azathioprine use was frequent (66%) and surgical resection rates were high (33% at 5 years) in cases with paediatric onset. In ulcerative colitis, 34% of patients were diagnosed with extensive disease, with high rates of disease extension (26% and 41% at 5 and 10 years), fulminant episodes (19.3%) and systemic steroid use (52.3%). The cumulative rate of colectomy was low (6.9%). CONCLUSIONS: The incidence of paediatric inflammatory bowel diseases has rapidly increased in the last three decades in Western Hungary. Ileocolonic disease and a need for azathioprine were characteristic in paediatric Crohn's disease, while paediatric onset ulcerative colitis was characterised by extensive disease and disease extension, while the need for colectomy was low

Crohn-beteg gyermekek infliximabkezelésének kezdeti tapasztalatai hazánkban [Analysis of infliximab treated pediatric patients with Crohn disease in Hungary]

Infliximab, the chimeric antibody to tumor necrosis factor-alpha, is indicated for medically refractory pediatric Crohn disease. Aim of our study was to examine the efficacy and side effects of infliximab therapy in Hungarian pediatric patients with Crohn disease since the authorisation of medicine for children to 31.12.2008. 23 children with refractory Crohn disease received infliximab during this period. Induction therapy with 5 mg/kg infliximab at weeks 0, 2, and 6 was introduced. 18 patients (81.8%) achieved clinical response, and 13 patients (59.1%) were in remission at the 6th week of the observation period. The evaluation was based on data of 22 children. Fistula closure rate was 70% at the at the 6th week. Two patients had acute infusion reaction, one had severe anaphilactic reaction after infliximab infusion. Chronic side effects were also observed in three cases. In our study infliximab induction therapy was effective in most pediatric patients with therapy refractory Crohn disease