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Background and Purpose: Omecamtiv mecarbil (OM) is a novel cardiac myosin activator drug for inotropic support in systolic heart failure. Here we have assessed the concentration-dependent mechanical effects of OM in permeabilized cardiomyocyte-sized preparations and single skeletal muscle fibres of Wistar-Kyoto rats under isometric conditions.Experimental Approaches: Ca2+ -dependent active force production (Factive ), its Ca2+ sensitivity (pCa50 ), the kinetic characteristics of Ca2+ -regulated activation and relaxation, and Ca2+ -independent passive force (Fpassive ) were monitored in Triton X-100-skinned preparations with and without OM (3nM-10 μM).Key Results: In permeabilized cardiomyocytes, OM increased the Ca2+ sensitivity of force production (ΔpCa50 : 0.11 or 0.34 at 0.1 or 1 μM respectively). The concentration-response relationship of the Ca2+ sensitization was bell-shaped, with maximal effects at 0.3-1 μM OM (EC50 : 0.08 ± 0.01 μM). The kinetics of force development and relaxation slowed progressively with increasing OM concentration. Moreover, OM increased Fpassive in the cardiomyocytes with an apparent EC50 value of 0.26 ± 0.11 μM. OM-evoked effects in the diaphragm muscle fibres with intrinsically slow kinetics were largely similar to those in cardiomyocytes, while they were less apparent in muscle fibres with fast kinetics.Conclusions and Implications: OM acted as a Ca2+ -sensitizing agent with a downstream mechanism of action in both cardiomyocytes and diaphragm muscle fibres. The mechanism of action of OM is connected to slowed activation-relaxation kinetics and at higher OM concentrations increased Fpassive production. [ABSTRACT FROM AUTHOR]

Aims Myeloperoxidase ( MPO) catalyses the formation of a wide variety of oxidants, including hypochlorous acid ( HOCl), and contributes to cardiovascular disease progression. We hypothesized that during its action MPO evokes substantial vasomotor responses. Methods Following exposure to MPO (1.92 mU mL−1) in the presence of increasing concentrations of hydrogen peroxide (H2O2), changes in arteriolar diameter of isolated gracilis skeletal muscle arterioles ( SMAs) and coronary arterioles ( CAs) and in the isometric force in basilar arteries ( BAs) of the rat were monitored. Results Myeloperoxidase increased vascular tone to different degrees in CAs, SMAs and BAs. The mechanism of increased vasoconstriction was studied in detail in SMAs. MPO-evoked vasoconstrictions were prevented by the MPO inhibitor 4-aminobenzhydrazide (50 μ m), by endothelium removal in the SMAs. Surprisingly, the HOCl scavenger L-methionine (100 μ m), the thromboxane A2 ( TXA2) antagonist SQ-29548 (1 μ m) or the non-specific cyclooxygenase ( COX) antagonist indomethacin (1 μ m) converted the MPO-evoked vasoconstrictions to pronounced vasodilations in SMAs, not seen in the presence of H2O2. In contrast to noradrenaline-induced vasoconstrictions, the MPO-evoked vasoconstrictions were not accompanied by significant increases in arteriolar [Ca2+] levels in SMAs. Conclusion These data showed that H2O2-derived HOCl to be a potent vasoconstrictor upon MPO application. HOCl activated the COX pathway, causing the synthesis and release of a TXA2-like substance to increase the Ca2+ sensitivity of the contractile apparatus in vascular smooth muscle cells and thereby to augment H2O2-evoked vasoconstrictions. Nevertheless, inhibition of the HOCl- COX- TXA2 pathway unmasked the effects of additional MPO-derived radicals with a marked vasodilatory potential in SMAs. [ABSTRACT FROM AUTHOR]

BACKGROUND AND PURPOSE The transient receptor potential vanilloid 1 (TRPV1) plays a role in the activation of sensory neurons by various painful stimuli and is a therapeutic target. However, functional TRPV1 that affect microvascular diameter are also expressed in peripheral arteries and we attempted to characterize this receptor. EXPERIMENTAL APPROACH Sensory TRPV1 activation was measured in rats by use of an eye wiping assay. Arteriolar TRPV1-mediated smooth muscle specific responses (arteriolar diameter, changes in intracellular Ca2+) were determined in isolated, pressurized skeletal muscle arterioles obtained from the rat and wild-type or TRPV1−/− mice and in canine isolated smooth muscle cells. The vascular pharmacology of the TRPV1 agonists (potency, efficacy, kinetics of action and receptor desensitization) was determined in rat isolated skeletal muscle arteries. KEY RESULTS Capsaicin evoked a constrictor response in isolated arteries similar to that mediated by noradrenaline, this was absent in arteries from TRPV1 knockout mice and competitively inhibited by TRPV1 antagonist AMG9810. Capsaicin increased intracellular Ca2+ in the arteriolar wall and in isolated smooth muscle cells. The TRPV1 agonists evoked similar vascular constrictions (MSK-195 and JYL-79) or were without effect (resiniferatoxin and JYL-273), although all increased the number of responses (sensory activation) in the eye wiping assay. Maximal doses of all agonists induced complete desensitization (tachyphylaxis) of arteriolar TRPV1 (with the exception of capsaicin). Responses to the partial agonist JYL-1511 suggested 10% TRPV1 activation is sufficient to evoke vascular tachyphylaxis without sensory activation. CONCLUSIONS AND IMPLICATIONS Arteriolar TRPV1 have different pharmacological properties from those located on sensory neurons in the rat. [ABSTRACT FROM AUTHOR]

1. Urbanized habitats differ from natural ones in several ecological features, including climate, food availability, strength of predation and competition. Although the effects of urbanization on avian community composition are well known, there is much less information about how individual birds are affected by these human-generated habitat differences. 2. In this study we investigated the relationships between the morphological characteristics and the degree of habitat urbanization in house sparrows, Passer domesticus (Linne 1758) . We collected data for more than 1000 non-breeding adult birds in Hungary between 1997 and 2006, from seven sites including farmlands, suburban areas and city centres. 3. We found that the body mass, tarsus length and body condition of free-living sparrows differed among the sites: birds in more urbanized habitats were consistently smaller and in worse condition than birds in more rural habitats. A composite measure of habitat urbanization (based on building density, road density and vegetation cover) explained over 75% of variance between sites in the studied traits, after we controlled for the effects of sex, year, season and time of capture. 4. The difference in body mass between rural and urban sparrows was significant when birds were kept in aviaries under identical conditions, with constant ad libitum food availability. It is therefore unlikely that the reduced body size and condition of urban sparrows are a consequence of reduced access to food for adults (e.g. due to strong competition), or their short-term responses to high food predictability (e.g. by strategic mass regulation). 5. We suggest that habitat differences in nestling development or adaptive divergence of sparrow populations due to distinct environmental conditions (such as differing predation pressure) may account for the differences along the urbanization gradient. [ABSTRACT FROM AUTHOR]

Objective: To assess the outcomes of bilateral hypogastric (internal iliac) ligation performed to control intractable pelvic hemorrhage and avoid hysterectomy.Methods: A review of indications and outcomes for 117 cases of bilateral hypogastric artery ligation over 15 years (1990-2004).Results: Apart from a slight lesion to the hypogastric vein, no complications were observed. Hemorrhage was effectively controlled in all 37 obstetric cases. In 13 of these cases, the uterus was preserved even when there was cervical pregnancy, placenta previa, placental abruption, uterine atony, and uterine rupture, and 4 women were delivered of mature infants. Hemorrhage was effectively controlled in 41 of 80 gynecologic cases. Prophylactic reduction of pelvic blood flow was the indication for the procedure in 39 cases, 5 of whom involving Jehovah's Witnesses adverse to blood transfusion. The uterus was preserved in only a few of the 41 controlled cases, but one woman (so far) was delivered of a mature infant.Conclusion: Hypogastric artery ligation was found to be indicated if (1) life-threatening pelvic hemorrhage could not be controlled by conservative methods; (2) prophylactic reduction of pelvic blood flow was needed to prevent anticipated hemorrhage; and (3) preservation of reproductive function was desired. The procedure was found to be safe and usually effective and should be taught during obstetric and gynecologic training. [ABSTRACT FROM AUTHOR]

The value of ultrasound examinations depends heavily on the preparation of the personnel carrying out the examination and the technical capabilities of the equipment they use. Only well-organized regional or national programs are able to provide high level, cost-effective care based on certification of quality. Such certification must include the training of professionals, the definition of competence levels, accreditation of laboratories and the establishment of professional protocols. Together, these factors can guarantee the standard of care and provide legal protection for practitioners. It is worth carrying out routine screening in each pregnancy because the majority of abnormalities occur in pregnancies with low risk. Abnormalities detected on screening cases and the examination of high risk groups should be referred to higher level centers. Here, appropriate technical background and qualified personnel are present to provide cost-effective care. At the same time, necessary invasive interventions can also be performed. A minimum of three screening tests should be performed during pregnancy. The first should be performed at the fetal age of 10–14 weeks to detect abnormalities and pathological conditions in early pregnancy. The second one has to be performed between the fetal ages of 18 and 22 weeks to assess detailed fetal anatomy and rate of development. The third should be performed between the fetal age of 30 and 34 weeks to assess fetal anatomy, rate of development, placentation and circulation. It is worth considering a fourth screening at approximately 36–38 weeks to assess the intrauterine condition of the fetus and determine the appropriate method of delivery. Finally, besides improving the standard of living, education, and hygienic conditions in developing countries, developed countries also have to help improve the standard of pregnancy care. Within this context, the dissemination of diagnostic ultrasound must be given special emphasis. [Copyright &y& Elsevier]

Presents a case of an unusual form of iniencephaly in the first trimester of pregnancy. Characteristic features of iniencephaly; Exhibition of extreme lordosis; Importance of prenatal diagnosis to prevent developmental abnormalities.

Reports on a newborn infant who is heterozygous for factor V Leiden mutation and who developed renal vein and inferior vena cava thrombosis. Implications of adrenal haemorrhage and renal vein thrombosis; Medical history of the infant.

An abstract of the study "The Levosimendan Metabolite OR-1896 Elicits Vasodilation by Activating the KATP and BKCa Channels in Isolated Arterioles of the Rat," by N. Erdei et al. is presented.

An abstract of the study "Possible molecular determinants of altered myocardial function during oxidative stress," by Z. Hertelendi and colleagues, is presented.

As previous sequential and structural analyses showed its conserved homology to members of the galectin superfamily, Placental Protein 13 (PP13) was designated galectin-13. Similarly to eosinophil Charcot Leyden Crystal protein / galectin-10, its weak lysophospholipase activity was proved. Sugar binding assays revealed that residues widely expressed in placenta had the strongest binding affinity to PP13, which expression was found to be restricted to placenta. With regard to its strong labeling of the syncythiotrophoblasts’ brush border membrane as well as its co-localization and specific binding to annexin II, PP13 was assumed to be externalized to the cell surface like other galectins. In a comparative study we found, that in the 3rd trimester, expression of PP13 was significantly reduced in preeclamptic (n = 20) and HELLP syndrome (n = 5) placentas compared to gestational age matched healthy samples (n = 25). In the same pathologic cases, maternal PP13 serum levels were also lower than in controls. Recently, PP13 was also successfully tested as a new 1st and 2nd trimester placental marker for the prediction of preeclampsia and IUGR. With regard to these results, PP13 may have special immunobiological function at the lining of the common feto-maternal blood-paces. The possible clinical importance of PP13 in pathological pregnancies with immunological background have to be emphasized. [ABSTRACT FROM AUTHOR]

An abstract of the article "Calpain-I Sensitive Proteins of the Human Myocardium," by J. Barta and colleagues is presented.

An abstract of the study "Peroxinitrite induced mechanical alterations of the actin-myosin interaction in isolated human myocardial cells," by A. Borbély et al, is presented.

[Ca[sup 2+]][sub i]-dependent modulation of the action potential has been studied in Fura-2 dialysed ventricular myocytes of the rabbit using the whole-cell current-clamp method. Fifteen consecutive action potentials (AP[sub 1]–AP[sub 15]) and [Ca[sup 2+]][sub i] transients were elicited at a frequency of 0.2 Hz. A single, brief application of caffeine (during AP[sub 9]) first enhanced and thereafter attenuated the [Ca[sup 2+]][sub i] transients accompanying AP[sub 9] and AP[sub 10]–AP[sub 12], respectively. This approach provided direct comparison between time courses of action potentials: during the initial steady state (e.g. AP[sub 8]) and when Ca[sup 2+] release from the sarcoplasmic reticulum was increased by caffeine (AP[sub 9]) or decreased by depletion (AP[sub 10]). The increase in [Ca[sup 2+]][sub i] facilitated repolarization and decreased action potential duration. However, action potentials at reduced Ca[sup 2+] release (AP[sub 10]) had longer duration than during steady state. The caffeine-induced changes in L-type Ca[sup 2+] current (I[sub Ca,L]), during voltage-clamp conditions partially explained the effects of caffeine on action potentials. When I[sub Ca,L] was blocked by 500 μmol L[sup –1] Cd[sup 2+], enhanced [Ca[sup 2+]][sub i] transients revealed an extra current component which was outward at +10 mV and inward at the resting membrane potential (most probably the transient inward current). In the presence of Cd[sup 2+], however, AP[sub 8] and AP[sub 10] had identical time courses, suggesting that I[sub Ca,L] alone was responsible for the lengthening of AP[sub 10]. Alterations in the transmembrane Na[sup +] gradient resulted in changes of the steady state action potential durations (AP[sub 8]) consistently with the expected modulation of the Na[sup +]–Ca[sup 2+] exchange current. However, the contribution of this current to the [Ca[sup 2+]][sub i]-dependent behaviour of action potential plateau could not... [ABSTRACT FROM AUTHOR]

In this study, we aimed to determine the contribution of peroxynitrite-dependent sulfhydryl group (SH) oxidation to the contractile dysfunction in permeabilized left ventricular human cardiomyocytes using a comparative approach with the SH-oxidant 2,2'-dithiodipyridine (DTDP). Additionally, different antioxidants: dithiothreitol (DTT), reduced glutathione (GSH) or N-acetyl-L-cysteine (NAC) were employed to test reversibility. Maximal isometric active force production (F(o)) and the maximal turnover rate of the cross-bridge cycle (k(tr,max)) illustrated cardiomyocyte mechanics. SH oxidation was monitored by a semi-quantitative Ellman's assay and by SH-specific protein biotinylation. Both peroxynitrite and DTDP diminished F(o) in a concentration-dependent manner (EC(50,peroxynitrite) = 49 microM; EC(50,DTDP) = 2.75 mM). However, k(tr,max) was decreased only by 2.5-mM DTDP, but not by 50 microM peroxynitrite. The diminution of F(o) to zero by DTDP was paralleled by the complete elimination of the free SH groups, while the peroxynitrite-induced maximal reduction in free SH groups was only to 58 +/- 6% of the control (100%). The diminutions in F(o) and free SH groups evoked by 2.5-mM DTDP were completely reverted by DTT. In contrast, DTT induced only a partial restoration in F(o) (DeltaF(o,): approximately 13%; P < 0.05) despite full reversion in protein SH content after 50 microM peroxynitrite. Although, NAC or DTT were equally effective on F(o) after peroxynitrite exposures, NAC or GSH did not restore F(o) or k(tr,max) after DTDP treatments. Our results revealed that the peroxynitrite-evoked cardiomyocyte dysfunction has a small, but significant component resulting from reversible SH oxidation, and thereby illustrated the potential benefit of antioxidants during cardiac pathologies with excess peroxynitrite production.

Problem: Galectin-1 can regulate immune responses upon infection and inflammation. We determined galectin-1 expression in the chorioamniotic membranes and its changes during histological chorioamnionitis., Method of Study: Chorioamniotic membranes were obtained from women with normal pregnancy (n = 5) and from patients with pre-term pre-labor rupture of the membranes (PPROM) with (n = 8) and without histological chorioamnionitis (n = 8). Galectin-1 mRNA and protein were localized by in situ hybridization and immunohistochemistry. Galectin-1 mRNA expression was also determined by quantitative reverse transcriptase polymerase chain reaction., Results: Galectin-1 mRNA and protein were detected in the amniotic epithelium, chorioamniotic fibroblasts/myofibroblasts and macrophages, chorionic trophoblasts, and decidual stromal cells. In patients with PPROM, galectin-1 mRNA expression in the fetal membranes was higher (2.07-fold, P = 0.002) in those with chorioamnionitis than in those without. Moreover, chorioamionitis was associated with a strong galectin-1 immunostaining in amniotic epithelium, chorioamniotic mesodermal cells, and apoptotic bodies., Conclusion: Chorioamnionitis is associated with an increased galectin-1 mRNA expression and strong immunoreactivity of the chorioamniotic membranes; thus, galectin-1 may be involved in the regulation of the inflammatory responses to chorioamniotic infection.

Problem: Mannose-binding lectin (MBL) is a pattern-recognition receptor that activates complement and modulates inflammation. Homozygosity for the most common allele of the MBL2 gene that is associated with high MBL serum concentrations is more prevalent among patients with pre-eclampsia. The objective of this study was to determine maternal plasma MBL concentrations in normal pregnant women and patients with pre-eclampsia., Method of Study: This cross-sectional study included normal pregnant women (n = 187) and patients with pre-eclampsia (n = 99). Maternal plasma MBL concentrations were determined by ELISA., Results: Women with pre-eclampsia had a higher median maternal plasma MBL concentration than normal pregnant women. MBL concentration distribution curves were three-modal, the subintervals in normal pregnancy were low (< 143.7), intermediate (143.7-1898.9) and high (> 1898.9 ng/mL). The proportion of normal pregnant women was larger in the low subinterval, while the proportion of patients with preeclampsia was larger in the high subinterval (P = 0.02). Normal pregnant women in the high subinterval had a larger rate of placental underperfusion than those in the low and intermediate subintervals (P = 0.02)., Conclusions: The median maternal plasma MBL concentration is elevated in patients with pre-eclampsia and a larger proportion of these patients are in the high subinterval than normal pregnant women, suggesting that this component of the innate immune system is involved in the mechanisms of disease in pre-eclampsia.

Problem: This prospective study was aimed to evaluate whether non-invasive clinical and serologic parameters of tubal disease are predictive for subsequent spontaneous conception and pregnancy outcome after first episode of ectopic pregnancy (EP)., Method of Study: Overall, 144 women aged <35 years were enrolled. Outcome of subsequent spontaneous conception was analyzed after 3 years and compared with clinical parameters and antibody responses to Chlamydia trachomatis and epitopes of the 60-kDa chlamydial heat shock protein (CHSP-60)., Results: Antibody response to a conserved epitope of CHSP-60 (amino acids, aa 260-277) was independently correlated with both decreased spontaneous conception and term delivery rates (adjusted odds ratios, OR: 3.6 and 5.4, respectively)., Conclusion: Presence of circulating antibodies to a conserved epitope of the CHSP-60 is associated with a lower spontaneous conception rate, and increased likelihood of adverse pregnancy outcome in women treated by salpingectomy for first episode of EP.

This is a review of cases of perinatally diagnosed congenital diaphragmatic hernia (CDH) with associated malformations with regard to time of diagnosis, side of hernia, associated malformations, and outcome. The authors analyzed the data of CDH cases with associated malformations from records of the I. Department of Obstetrics and Gynecology, Semmelweis University Faculty of Medicine, Budapest, between July 1, 1990 and June 30, 2005. The observed period was analyzed in two parts. The pre- and postnatal examinations verified CDH in 100 cases, 71% of which were associated with other malformations. In 52% (37/71) CDH was diagnosed before the 24th week of gestation. The rate of early diagnosed cases doubled in the second period. Ten percent (7/71) of cases were verified postnatally. Between 1990 and 1997, the percentage of right-sided hernia was 6% (2/34) while in the second period it was 19% (7/37). The association with cardiovascular, chest, and craniofacial anomalies doubled in the second period, while association of central nervous system anomalies halved. Chromosome anomalies were verified in four cases. Pregnancy was terminated in 53% (34/64) and 13% (4/30) of newborn infants survived the perinatal period. Intrauterine or intrapartum death occurred in 8% (5/64) of cases. The prevalence of cardiovascular, pulmonary, and craniofacial anomalies doubled, while that of central nervous system malformations decreased. The prevalence of other associated malformations has not changed significantly between the two periods. The improvement of technical facilities and accumulated experience make it possible to identify a higher number of associated malformations before the 24th week of gestation.

Under physiological conditions, calcium-dependent ([Ca2+]i-dependent) Cl- currents (ICl(Ca)) have been suggested to participate in the repolarizing processes. In this paper, the possible contribution of ICl(Ca) to transient inward currents and, hence to arrhythmias, has been studied in myocytes from the working myocardium and from the conductive system. Single atrial, ventricular and Purkinje cells, isolated enzymatically from rabbit heart, have been studied under whole-cell voltage-clamp and were internally perfused with the fluorescent Ca2+ indicator, fura-2 (100 microM). Ca2+ release from the sarcoplasmic reticulum was either induced by external application of caffeine or occurred spontaneously in Ca(2+)-overloaded cells. Membrane currents accompanying Ca2+ transients showed linear current-voltage characteristics between -60 and +80 mV as evidenced from fast voltage ramps. When intra- and extracellular Cl- concentrations were kept symmetrical in the absence of the Na(+)-Ca2+ exchange mechanism, transient currents had a reversal potential close to 0 mV. Reduction of external Cl- concentration shifted this reversal potential towards the new Cl- equilibrium potential. Neither the time course of the transient currents nor the shift in their reversal potentials was significantly affected by the presence of Na+. Approximately 90% of this current was blocked by the application of the Cl- channel blocker, anthracene-9-carboxylic acid (0.5 mM) at +80 mV. It is concluded, that [Ca2+]i-activated transient membrane currents in atrial, ventricular and Purkinje cells of rabbit heart are mainly due to the activation of a [Ca2+]i-dependent Cl- current.

Data on Turner Syndrome from four sources were analysed for possible associations with several aetiological factors. Two classes of liveborn propositae were included, those with a non-mosaic 45, X karyotype (XO) and those with an isochromosome of the long arm of the X (iso-X). The numbers were 288 and 84 respectively and constitute the largest series of such cases to be analysed to date. For the XO's, an analysis using the liveborn full sibs of propositae as controls (method of Carothers et al. 1978) confirmed earlier studies in finding no positive association with parental age or birth order, and even suggested a small negative association. There were no significant differences between the mean parental ages of those cases shown by Xg grouping to have received a maternal X chromosome and those of the remainder. Among the iso-X's there was an exceptionally high proportion (17.5%) of parents with an age difference (paternal-maternal) of 10 or more years, raising the possibility of a paternal age effect. This agrees with earlier studies but conflicts with the finding of a negligible tendency for affected individuals to be born later within their sibships. The apparent discrepancy may be due to the relative insensitivity of the latter method to small parental age effects in samples of this size. For the XO's there were no detectable seasonal variations in the month of birth, but for the iso-X's there was a significant excess of births in the first 6 months of the year. Reviewing the conflicting evidence from the literature on seasonal variations in chromosomal aberrations, we urge caution in interpreting these results. In agreement with earlier studies, the incidence of twins among both XO's and iso-X's was higher than the population average, but the numbers were too small for statistical significance. There was no evidence for any alteration in the sex ratio among the liveborn sibs of either class.