The first trimester of pregnancy is characterized by continuous proliferation, invasion and differentiation of cytotrophoblasts. These processes are precisely controlled both, in space and time by molecules such as endothelin-1 (ET-1). ET-1 is expressed in human first trimester trophoblast and is known to stimulate cytotrophoblast proliferation through endothelin A and B receptor subtypes (ETA and ETB), and cytotrophoblast invasion through ETB. However, temporal changes of the ET system during the first trimester of pregnancy have not been previously studied. This study tested the hypothesis that ET-1 release, ETA and ETB expression are increased towards the end of the first trimester of pregnancy (weeks 10-12 vs. weeks 6-9), resulting in increased cytotrophoblast proliferation and invasion. Tissue samples were obtained from 17 surgical pregnancy interruptions (week 6-9: n=9; week 10-12: n=8). After cytotrophoblast isolation, the invasive and proliferative phenotypes were immune-separated by an α6-integrin antibody. Both proliferative and invasive cytotrophoblasts were cultured separately on plastic or Matrigel for 24 h. ET-1 release into the culture medium of both cytotrophoblast subtypes was measured by radioimmunoassay. ETA and ETB mRNA expression was measured by RT-PCR, and the ET-1 effect on cytotrophoblast proliferation and invasion was determined using proliferation and invasion assays, respectively. ET-1 release increased from early to late first trimester of pregnancy in both proliferative (1.8-4.5 fold) and invasive cytotrophoblasts (9.3-28 fold), especially when cultured on Matrigel. This was paralleled by less ETB mRNA on invasive cytotrophoblasts independent of the time period in first trimester, whereas ETA expression was similar on proliferative an invasive cytotrophoblasts. Proliferation and invasion of cytotrophoblasts under control conditions decreased from early to late first trimester. The ET-1/ET-receptor system changes between weeks 6-9 and 10-12 in pregnancy. Our data suggest an autocrine and endocrine ET-1 effect, which is stronger in late than in early first trimester of pregnancy paralleled by different stimulatory effects on trophoblast invasion and proliferation. In general, this suggests time as an additional effector of the critical processes governing placental development in the first trimester of human pregnancy., A. Majali-Martinez, S. Barth, U. Lang, G. Desoye, M. Cervar-Zivkovic., and Seznam literatury
Glucose tolerance, serum insulin, insulin receptors in epididymal fat tissue, circulating total cholesterol and triglyceride concentrations as well as serum prolactin were studied in obese and lean spontaneously hypertensive rats (SHR) of both sexes. Obese animals displayed insulin resistance and elevated insulin and triglyceride concentrations. Moreover, in obese rats the increased mass of epididymal fat tissue was accompanied with decreased capacity of high affinity binding sites of insulin receptors in the tissue plasma membranes. Terguride treatment lowered prolactin serum levels which was accompanied by ameliorated insulin sensitivity in obese animals of both sexes. In addition, terguride treatment decreased serum insulin and triglyceride concentrations in obese females and at the same time enhanced the affinity of high affinity insulin binding sites. Our results show that obesity in SHR is associated with a decreased capacity of insulin receptors and that prolactin may play a role in obesity-induced insulin resistance, particularly in female rats., V. Golda +, M. Ficková, L. Pinterová, J. Jurčovičová, L. Macho, Š. Zórad., and Obsahuje bibliografii
Autism spectrum disorders (ASD) are neurodevelopmental conditions characterized by impairment in social communication and presence of stereotyped/restricted behaviors. Children with ASD very often demonstrate co-morbid psychiatric problems, problems known to be affected by testosterone in neurotypical populations. However, there are few reports investigating relationships between testosterone and psychiatric conditions in children with ASD. The aim of this study was to determine the relationship between plasmatic levels of testosterone and behavioral/emotional problems in pre-pubertal boys with ASD. The study sample consisted of 31 pre-pubertal boys (ages 3-10) with ASD. Parents completed the Nisonger Child Behavior Rating Form (NCBRF) to assess specific behavioral/emotional problems as observed in the previous 2 months. Plasmatic testosterone levels were determined in boys according to standardized procedures. It was found that there were positive correlations between testosterone levels and the conduct problems subscale (p=0.034, rs=0.382) of NCBRF and also between testosterone levels and the hyperactive subscale (p=0.025, rs=0.402) of NCBRF. Findings in this study are in line with research conducted in the neurotypical population. This is the first large study investigating testosterone and emotional/behavioral problems in ASD and warrants further research in this field in order to clarify the etiopathogenesis of psychiatric co-morbidities and improve their treatment., A. Pivovarciova, J. Durdiakova, S. Hnilicova, D. Filcikova, D. Ostatnikova., and Obsahuje bibliografii
The extent to which sex differences in cardiac function may be attributed to the direct myocardial influence of testosterone is unclear. In this study the effects of gonadal testosterone withdrawal (GDX) and replacement (GDX+T) in rats, on cardiomyocyte shortening and intracellular Ca2+ handling was investigated (0.5 Hz, 25 oC). At all extracellular [Ca2+] tested (0.5-2.0 mM), the Ca2+ transient amplitude was significantly reduced (by ~ 50 %) in myocytes of GDX rats two weeks post- gonadectomy. The time course of Ca2+ transient decay was significantly prolonged in GDX myocytes (tau, 455±80 ms) compared with intact (279±23 ms) and GDX+T (277±19 ms). Maximum shortening of GDX myocytes was markedly reduced (by more than 60 %) and relaxation significantly delayed (by more than 35 %) compared with intact and GDX+T groups. Thus testosterone replacement completely reversed the cardiomyocyte hypocontractility induced by gonadectomy. These results provide direct evidence for a role of testosterone in regulating functional Ca2+ handling and contractility in the heart., C. L. Curl ... [et al.]., and Obsahuje seznam literatury
Chronic allograft nephropathy (CAN) represents a frequent and irreversible cause of long-term renal graft loss. TGF- β 1 is a key profibrogenic cytokine associated with CAN pathogenesis. Because of clinical diagnostic inaccuracy, protocol biopsy has been suggested to be a beneficial method for early CAN detection. Protocol core biopsy was carried out in 67 consecutive cyclosporine-based immunosuppression-treated kidney transplant recipients with stable renal function 12 months after renal transplantation. Biopsy specimens were analyzed morphologically according to Banff-97' criteria and immunohistologically for TGF- β 1 staining. The data obtained were correlated with plasma TGF- β 1 levels and clinical data. CAN (grade I-III) was found in 51 patients (76 %). CAN grade I was found to be the most frequent one (44 %). A normal finding within the graft was made in only 12 patients (18 %). Clinically silent acute rejection Banff IA was present in 4 patients (6 %). In 8 patients (12 %) with CAN, borderline changes were present. We found a significant correlation between CAN grade and creatinine clearance, as measured by the Cockroft-Gault formula (p<0.01) as well as body mass index (p<0.01). There was a significant correlation between chronic vasculopathy (Banff cv) and creatinine clearance, and between the degree of TGF- β 1 staining and chronic vasculopathy (p<0.01). There were no relations between morphological findings and TGF- β 1 plasma levels, cyclosporine levels, plasma lipids, HLA- mismatches, panel reactive antibodies (PRA), proteinuria, and the donor's age. In conclusion, CAN is a frequent finding in protocol kidney graft biopsies 12 months after transplantation. TGF- β 1 tissue expression is linked with chronic vasculopathy., O. Viklický, I. Matl, L. Voska, R. Böhmová, M. Jarešová, J. Lácha, A. Lodererová, I. Stříž, V. Teplan, Š. Vítko., and Obsahuje bibliografii