Comparison of diurnal variations, gestational age and gender related differences in fetal heart rate (FHR) parameters between appropriate-for-gestational-age (AGA) and small-for-gestational-age (SGA) fetuses in the home environment

Objective To assess the influence of gender, time of the day and gestational age on fetal heart rate (FHR) parameters between appropriate-for-gestational-age (AGA) and small-for-gestational age (SGA) fetuses using a portable fetal ECG monitor employed in the home setting. Methods We analysed and compared the antenatal FHR data collected in the home setting on 61 healthy pregnant women with singleton pregnancies from 24 weeks gestation. Of the 61 women, 31 had SGA fetuses (estimated fetal weight below the tenth gestational centile) and 30 were pregnant with AGA fetuses. FHR recordings were collected for up to 20 h. Two 90 min intervals were deliberately chosen retrospectively with respect to signal recording quality, one during day-time and one at night-time for comparison. Results Overall, success rate of the fetal abdominal ECG in the AGA fetuses was 75.7% compared to 48.6% in the SGA group. Based on randomly selected episodes of heart rate traces where recording quality exceeded 80% we were able to show a marginal difference between day and night-time recordings in AGA vs. SGA fetuses beyond 32 weeks of gestation. A selection bias in terms of covering different representation periods of fetal behavioural states cannot be excluded. In contrast to previous studies, we neither controlled maternal diet and activity nor measured maternal blood hormone and heart rate as all mothers were monitored in the home environment. Conclusion Based on clinically unremarkable, but statistically significant differences in the FHR parameters between the AGA and SGA group we suggest that further studies with large sample size are required to assess the clinical value of antenatal fetal ECG monitoring

Therapeutic efficacy of TBC3711 in monocrotaline-induced pulmonary hypertension

Background: Endothelin-1 signalling plays an important role in pathogenesis of pulmonary hypertension. Although different endothelin-A receptor antagonists are developed, a novel therapeutic option to cure the disease is still needed. This study aims to investigate the therapeutic efficacy of the selective endothelin-A receptor antagonist TBC3711 in monocrotaline-induced pulmonary hypertension in rats. Methods: Monocrotaline-injected male Sprague-Dawley rats were randomized and treated orally from day 21 to 35 either with TBC3711 (Dose: 30 mg/kg body weight/day) or placebo. Echocardiographic measurements of different hemodynamic and right-heart hypertrophy parameters were performed. After day 35, rats were sacrificed for invasive hemodynamic and right-heart hypertrophy measurements. Additionally, histologic assessment of pulmonary vascular and right-heart remodelling was performed. Results: The novel endothelin-A receptor antagonist TBC3711 significantly attenuated monocrotaline-induced pulmonary hypertension, as evident from improved hemodynamics and right-heart hypertrophy in comparison with placebo group. In addition, muscularization and medial wall thickness of distal pulmonary vessels were ameliorated. The histologic evaluation of the right ventricle showed a significant reduction in fibrosis and cardiomyocyte size, suggesting an improvement in right-heart remodelling. Conclusion: The results of this study suggest that the selective endothelin-A receptor antagonist TBC3711 demonstrates therapeutic benefit in rats with established pulmonary hypertension, thus representing a useful therapeutic approach for treatment of pulmonary hypertension

Sepsid even-skipped enhancers are functionally conserved in Drosophila despite lack of sequence conservation

10.1371/journal.pgen.1000106PLoS Genetics46

Brain-Derived Neurotrophic Factor Ameliorates Brain Stem Cardiovascular Dysregulation during Experimental Temporal Lobe Status Epilepticus

Background: Status epilepticus (SE) is an acute, prolonged epileptic crisis with a mortality rate of 20–30%; the underlying mechanism is not completely understood. We assessed the hypothesis that brain stem cardiovascular dysregulation occurs during SE because of oxidative stress in rostral ventrolateral medulla (RVLM), a key nucleus of the baroreflex loop; to be ameliorated by brain-derived neurotrophic factor (BDNF) via an antioxidant action. Methodology/Principal Findings: In a clinically relevant experimental model of temporal lobe SE (TLSE) using Sprague-Dawley rats, sustained hippocampal seizure activity was accompanied by progressive hypotension that was preceded by a reduction in baroreflex-mediated sympathetic vasomotor tone; heart rate and baroreflex-mediated cardiac responses remained unaltered. Biochemical experiments further showed concurrent augmentation of superoxide anion, phosphorylated p47 phox subunit of NADPH oxidase and mRNA or protein levels of BDNF, tropomyosin receptor kinase B (TrkB), angiotensin AT1 receptor subtype (AT1R), nitric oxide synthase II (NOS II) or peroxynitrite in RVLM. Whereas pretreatment by microinjection bilaterally into RVLM of a superoxide dismutase mimetic (tempol), a specific antagonist of NADPH oxidase (apocynin) or an AT1R antagonist (losartan) blunted significantly the augmented superoxide anion or phosphorylated p47 phox subunit in RVLM, hypotension and the reduced baroreflex-mediated sympathetic vasomotor tone during experimental TLSE, pretreatment with a recombinant human TrkB-Fc fusion protein or an antisense bdn

The Drosophila speciation factor HMR localizes to genomic insulator sites

Hybrid incompatibility between Drosophila melanogaster and D. simulans is caused by a lethal interaction of the proteins encoded by the Hmr and Lhr genes. In D. melanogaster the loss of HMR results in mitotic defects, an increase in transcription of transposable elements and a deregulation of heterochromatic genes. To better understand the molecular mechanisms that mediate HMR's function, we measured genome-wide localization of HMR in D. melanogaster tissue culture cells by chromatin immunoprecipitation. Interestingly, we find HMR localizing to genomic insulator sites that can be classified into two groups. One group belongs to gypsy insulators and another one borders HP1a bound regions at active genes. The transcription of the latter group genes is strongly affected in larvae and ovaries of Hmr mutant flies. Our data suggest a novel link between HMR and insulator proteins, a finding that implicates a potential role for genome organization in the formation of species

Synthesis of PEGylated lactose analogs for inhibition studies on T.cruzi trans-sialidase

Trypanosoma cruzi, the agent of Chagas disease, expresses a unique enzyme, the trans-sialidase (TcTS) involved in the transfer of sialic acid from host glycoconjugates to mucins of the parasite. The enzyme is shed to the medium and may affect the immune system of the host. We have previously described that lactose derivatives effectively inhibited the transfer of sialic acid to N-acetyllactosamine. Lactitol also prevented the apoptosis caused by the TcTS, although it is rapidly eliminated from the circulatory system. In this paper we report covalent conjugation of polyethylene glycol (PEG) with lactose, lactobionolactone and benzyl β-D-galactopyranosyl-(1→6)-2-amino-2- deoxy-α-D-glucopyranoside (1) with the hope to improve the bioavailability, though retaining their inhibitory properties. Different conjugation methods have been used and the behavior of the PEGylated products in the TcTS reaction was studied.Fil: Giorgi, María Eugenia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Centro de Investigaciones en Hidratos de Carbono. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Centro de Investigaciones en Hidratos de Carbono; ArgentinaFil: Ratier, Laura. Universidad Nacional de San Martín; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Agusti, Rosalia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Centro de Investigaciones en Hidratos de Carbono. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Centro de Investigaciones en Hidratos de Carbono; ArgentinaFil: Frasch, Alberto Carlos C.. Universidad Nacional de San Martín; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Muchnik, Rosa. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Centro de Investigaciones en Hidratos de Carbono. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Centro de Investigaciones en Hidratos de Carbono; Argentin