Atrial fibrillation (AF) is the most frequent arrhythmia found in clinical practice. In recent studies, a decrease in the development or recurrence of AF was found in hypertensive patients treated with angiotensin-converting enzyme inhibitors or angiotensin receptor-blocking agents. Hypertension is related to an increased wall tension in the atria, resulting in increased stretch of the individual myocyte, which is one of the major stimuli for the remodeling process. In the present study, we used a model of cultured atrial neonatal rat cardiomyocytes under conditions of stretch to provide insight into the mechanisms of the preventive effect of the angiotensin receptor-blocking agent losartan against AF on a molecular level. Stretch significantly increased protein-to-DNA ratio and atrial natriuretic factor mRNA expression, indicating hypertrophy. Expression of genes encoding for the inward rectifier K(+) current (I(K1)), Kir 2.1, and Kir 2.3, as well as the gene encoding for the ultrarapid delayed rectifier K(+) current (I(Kur)), Kv 1.5, was significantly increased. In contrast, mRNA expression of Kv 4.2 was significantly reduced in stretched myocytes. Alterations of gene expression correlated with the corresponding current densities: I(K1) and I(Kur) densities were significantly increased in stretched myocytes, whereas transient outward K(+) current (I(to)) density was reduced. These alterations resulted in a significant abbreviation of the action potential duration. Losartan (1 microM) prevented stretch-induced increases in the protein-to-DNA ratio and atrial natriuretic peptide mRNA expression in stretched myocytes. Concomitantly, losartan attenuated stretch-induced alterations in I(K1), I(Kur), and I(to) density and gene expression. This prevented the stretch-induced abbreviation of action potential duration. Prevention of stretch-induced electrical remodeling might contribute to the clinical effects of losartan against AF.

The aim of this study was to determine the prevalence of autoimmune thyroid disease and the risk of miscarriage in autoimmune thyroid antibody (ATA)-positive women. Eight hundred seventy-six subjects completed the study, and 12.3% were thyroid antibody-positive (4.5% tested positive for both thyroid peroxidase antibody [TPO-Ab] and thyroglobulin autoantibody [Tg-Ab], 4.79% were TPO-Ab-positive only, and 3.1% were Tg-Ab-positive only). Fifty percent of the ATA-positive women and 14.1% of the ATA-negative group had a history of spontaneous abortion. Forty-eight of the ATA-positive women developed postpartum autoimmune thyroid dysfunction (PATD). Of these, 50% had hypothyroidism alone, 31.3% had transient hyperthyroidism followed by hypothyroidism, and 18.8% had transient thyrotoxicosis alone. Of the 48 PATD subjects, 12.5% developed persistent hypothyroidism. None of the ATA-negative women developed any form of thyroid dysfunction. The thyroid-stimulating hormone (TSH) levels in the ATA-positive group were significantly higher than those in the ATA-negative group, and only the ATA-positive women with a history of abortion had significantly higher TSH and lower free thyroxine (FT4) concentrations than the other subgroups. The results revealed a 5.5% prevalence rate for PATD in the study population. In addition to TPO-Ab, Tg-Ab is a useful marker for autoimmune thyroiditis.

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Pressure overload is the major stimulus for cardiac hypertrophy. Accumulating evidence suggests an important role for calcium-induced activation of calcineurin in mediating hypertrophic signaling. Hypertrophy is an important risk factor for cardiovascular morbidity and mortality. We therefore employed an in vitro mechanical stretch model of cultured neonatal cardiomyocytes to evaluate proposed mechanisms of calcium-induced calcineurin activation in terms of inhibition of calcineurin activity and hypertrophy. The protein/DNA ratio and ANP gene expression were used as markers for stretch-induced hypertrophy. Stretch increased the calcineurin activity, MCIP1 gene expression and DNA binding of NFATc as well as the protein/DNA ratio and ANP mRNA in a significant manner. The specific inhibitor of calcineurin, cyclosporin A, inhibited the stretch-induced increase in calcineurin activity, MCIP1 gene expression and hypertrophy. The L-type Ca²⁺ channel blocker nifedipine and a blocker of the Na⁺/H⁺ exchanger (cariporide) both suppressed stretch-dependent enhanced calcineurin activity and hypertrophy. Also application of a blocker of the Na⁺/Ca²⁺ exchanger (KB-R7943) was effective in preventing calcineurin activation and increases in the protein/DNA ratio. Inhibition of capacitative Ca²⁺ entry with SKF 96365 was also sufficient to abrogate calcineurin activation and hypertrophy. The blocker of stretch-activated ion channels, streptomycin, was without effect on stretch-induced hypertrophy and calcineurin activity. The present work suggests that of the proposed mechanisms for the calcium-induced activation of calcineurin (L-type Ca²⁺ channels, capacitative Ca²⁺ entry, Na⁺/H⁺ exchanger, Na⁺/Ca²⁺ exchanger and stretch-activated channels) all but stretch-activated channels are possible targets for the inhibition of hypertrophy.

The biomechanical environment to which cells are exposed is important to their normal growth, development, interaction, and function. Accordingly, there has been much interest in studying the role of biomechanical forces in cell biology and pathophysiology. This has led to the introduction and even commercialization of many experimental devices. Many of the early devices were limited by the heterogeneity of deformation of cells cultivated in different locations of the culture plate membranes and were also attached with complicated technical/electronic efforts resulting in a restriction of the reproducibility of these devices. The objective of this study was to design and build a simple device to allow the application of dose-dependent homogeneous equibiaxial static stretch to cells cultured on flexible silicone membranes to investigate biological and biomedical questions. In addition, cultured neonatal rat atrial cardiomyocytes were stretched with the proposed device with different strain gradients. For the first time with this study we could demonstrate that stretch up to 21% caused dose-dependent changes in biological markers such as the calcineurin activity, modulatory calcineurin-interacting protein-1, voltage-gated potassium channel isoform 4.2, and voltage-gated K(+) channel-interacting proteins-2 gene expression and transient outward potassium current densities but not the protein-to-DNA ratio and atrial natriuretic peptide mRNA. With both markers mentioned last, dose-dependent stretch alterations could only be achieved with stretch up to 13%. The simple and low-cost device presented here might be applied to a wide range of experimental settings in different fields of research.

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We report the radiologic presentations of two cases of peritoneal-pelvic tuberculosis. The initial interpretation based on the adnexal masses, ascites, omental and peritoneal thickening, and elevated serum CA-125 levels led to an erroneous preliminary diagnosis of disseminated ovarian cancer. In both patients, histologic examination showed tuberculosis. The clinical and radiologic findings resolved significantly after several months of multidrug antituberculosis treatment.

Subthreshold electrical stimulation (SES) has been shown to induce an improvement of angiogenesis in ischemic and nonischemic skeletal muscles, mediated by increased VEGF expression. VEGF plays a key role in physiological and pathological angiogenesis. Cardiomyocytes possess the ability to synthesize and secrete VEGF. Thus, we thought to investigate the effect of SES on VEGF regulation in cultured neonatal rat ventricular myocytes (NRVMs), in the aim to reveal new techniques for therapeutic angiogenesis in ischemic heart disease. Cell cultures of NRVMs were electrically stimulated with field strengths below the myocyte depolarization threshold (0.5 V/cm with 1 ms bipolar impulse duration). Frequencies ranging from 5 Hz up to 25, 50, and 99 Hz were applied over a period of 48 h. The expression of VEGF and its receptor KDR was determined with Western blot and ELISA. To reveal the biological activity of the secreted VEGF amount, cultured human coronary artery endothelial cells (HCAECs) were treated with the cell culture supernatant of NRVMs exposed to SES. A dominant effect of SES was observed at 25 Hz. Within this particular frequency the VEGF protein amount in the cytoplasm as well as in the cell culture supernatant increased significantly. In parallel, the protein expression of the KDR receptor decreased in a significant manner. Moreover, cell culture supernatant of NRVMs exposed to SES augmented the growth of HCAECs. Cardiomyocytes respond to SES with an increase in biologically active VEGF expression that promotes cell proliferation of HCAECs. This mechanism may provide new approaches to develop therapeutic angiogenesis in the ischemic heart.