The Pharmacology and Therapeutic Utility of Sodium Hydroselenide

Metabolically active gasotransmitters (nitric oxide, carbon monoxide and hydrogen sulfide) are important signalling molecules that show therapeutic utility in oxidative pathologies. The reduced form of selenium, hydrogen selenide (HSe⁻/H₂Se), shares some characteristics with these molecules. The simple selenide salt, sodium hydroselenide (NaHSe) showed significant metabolic activity, dose-dependently decreasing ex vivo O₂ consumption (rat soleus muscle, liver) and transiently inhibiting mitochondrial cytochrome C oxidase (liver, heart). Pharmacological manipulation of selenoprotein expression in HepG2 human hepatocytes revealed that the oxidation status of selenium impacts on protein expression; reduced selenide (NaHSe) increased, whereas (oxidized) sodium selenite decreased the abundance of two ubiquitous selenoproteins. An inhibitor of endogenous sulfide production (DL-propargylglycine; PAG) also reduced selenoprotein expression; this was reversed by exogenous NaHSe, but not sodium hydrosulfide (NaHS). NaHSe also conferred cytoprotection against an oxidative challenge (H₂O₂), and this was associated with an increase in mitochondrial membrane potential. Anesthetized Wistar rats receiving intravenous NaHSe exhibited significant bradycardia, metabolic acidosis and hyperlactataemia. In summary, NaHSe modulates metabolism by inhibition of cytochrome C oxidase. Modification of selenoprotein expression revealed the importance of oxidation status of selenium therapies, with implications for current clinical practice. The utility of NaHSe as a research tool and putative therapeutic is discussed.     

Lactate, lactate/pyruvate ratio and catecholamine interrelations in cord blood at delivery in complicated pregnancies

Fucosyltransferases are the enzymes transferring fucose from GDP-Fuc to Gal in an alpha1,2-linkage and to GlcNAc in alpha1,3-, alpha1,4-, or alpha1,6-linkages. Since all fucosyltransferases utilize the same nucleotide sugar, their specificity will probably reside in the recognition of the acceptor and in the type of linkage formed. A search of nucleotide and protein databases yielded more than 30 sequences of fucosyltransferases originating from mammals, chicken, nematode, and bacteria. On the basis of protein sequence similarities, these enzymes can be classified into four distinct families: (1) the alpha-2-fucosyltransferases, (2) the alpha-3-fucosyltransferases, (3) the mammalian alpha-6-fucosyltransferases, and (4) the bacterial alpha-6-fucosyltransferases. Nevertheless, using the sensitive hydrophobic cluster analysis (HCA) method, conserved structural features as well as a consensus peptide motif have been clearly identified in the catalytic domains of all alpha-2 and alpha-6-fucosyltranferases, from prokaryotic and eukaryotic origin, that allowed the grouping of these enzymes into one superfamily. In addition, a few amino acids were found strictly conserved in this family, and two of these residues have been reported to be essential for enzyme activity for a human alpha-2-fucosyltransferase. The alpha-3-fucosyltransferases constitute a distinct family as they lack the consensus peptide, but some regions display similarities with the alpha-2 and alpha-6-fucosyltranferases. All these observations strongly suggest that the fucosyltransferases share some common structural and catalytic features.     

Genital Group B Streptococcus carriage in the antenatal period: its role in prom and preterm labour

The authors report a case of pleural fibroma discovered during an examination for thoracic pains in a 65 year old woman. Histochemical studies were positive with vimentin and negative with KL1 antibodies and compatible with the most recent hypotheses concerning the purely fibroblastic origin of these tumours.     

Immunolocalization and protein expression of the alpha subunit of the large-conductance calcium-activated potassium channel in human myometrium

Large-conductance calcium-activated potassium (BKCa) channels play an important role in the control of myometrial excitability. The aim of the present study was to determine the localization and protein expression of the alpha subunit of BKCa channels in the pregnant and parturient human uterus. An anti-alpha BKCa channel monoclonal antibody (anti-alpha(995-1113)) was used to localize and quantitate immunoreactive BKCa channel protein in myometrium of singleton term pregnant women undergoing either elective (n=26) or emergency Caesarean section following the onset of spontaneous labour (n=25). Data are presented as medians (interquartile range). Differences between groups were analysed using the Mann-Whitney U test. Immunohistochemistry studies localized the alpha subunit of the BKCa channel to the plasma membrane and the cytosol of myometrial cells with similar reaction end product in pregnant women who were or were not undergoing labour. Expression of this subunit, observed as a 125 kDa band in western blots, was significantly higher in pregnant women who were not undergoing labour (30.6% (20.3, 43.9)) than in those who were undergoing labour (15.7% (11.3, 22.4); P<0.01). Reduced BKCa alpha subunit expression in pregnant women during labour may underlie the initiation of uterine contractility during parturition.     

Electrical characteristics of AlGaN/GaN HEMTs on 4-in diameter sapphire substrate

AlGaN/GaN high-electron-mobility transistors (HEMTs) were fabricated and the uniformity of dc properties were studied for the first time on 4-in diameter sapphire substrate. A quarter of 4-in diameter AlGaN/GaN epitaxial wafer was used for the uniformity studies of HEMTs. The observed average maximum drain current density, extrinsic transconductance and threshold voltage values for HEMTs were 515 mA/mm, 197 mS/mm, and -2.30 V with standard deviations 9.34%, 4.82%, and 6.52%, respectively. The uniformity of Hall mobility across the 4-in wafer was 1322 cm/sup 2//Vs with a standard deviation of 4.27%. The uniformity of sheet resistance across 4-in diameter wafer, measured using Hall Effect was 575 /spl Omega//sq. with a standard deviation 9.01%. The uniformity of HEMTs dc properties are in good correlation with the electrical characteristics of AlGaN/GaN heterostructures, which was obtained from the Hall Effect and capacitance-voltage (C-V) measurements.     

Coagulation activation, fibrinolysis and inhibitors in neonates

OBJECTIVES: To update information on endogenous retroviral sequences and discuss their role in systemic autoimmune disease. DATA SOURCES: Articles retrieved after MEDLINE search and personal communications and cooperation with the Institute of Virology. DATA SYNTHESIS: There are 2 modes of pathogenetic mechanisms through which endogenous retroviral sequences could cause systemic autoimmune disease: expression of endogenous retroviral gene products sharing antigenic determinants with cellular proteins; and activation or destruction of cellular genes as a consequence of insertional mutagenesis. Both mechanisms have been demonstrated in vitro and in vivo in animal models. CONCLUSION: Investigations on endogenous retroviral sequences in humans may offer new insights into the pathogenesis of autoimmune disease.     

Incidence of chromosomal abnormalities in 153 pregnancies with ultrasound detected fetal abnormalities

We report a caroticocavernous fistula (CCF) treated by an endovascular procedure in a young woman with Ehlers-Danlos syndrome type IV, with severe bilateral carotid and vertebral artery dysplasia. The CCF, which appeared after minor trauma, was successfully occluded by a detachable balloon introduced into the venous side by an arterial approach. Six previously published cases are reviewed, five successfully treated. The difficulties and risks of the endovascular procedure due to the vascular changes, are emphasised. The possibility of the venous approach is discussed.     

Temperature dependent microwave performance of AlGaN/GaN high-electron-mobility transistors on high-resistivity silicon substrate

The influence of temperature (− 50 °C to + 200 °C) was studied on the DC and microwave characteristics of AlGaN/GaN high-electron-mobility transistors (HEMTs) on high resistivity Si substrate for the first time. The AlGaN/GaN HEMTs exhibited a current-gain cut-off frequency (f_T) of 11.8 GHz and maximum frequency of oscillation (f_max) of 27.5 GHz. When compared to room temperature values, about 4% and 10% increase in f_T and f_max and 23% and 39.5% decrease in f_T and f_max were observed when measured at − 50 °C and 200 °C, respectively. The improvement of I_D, g_mf_T, and f_max at − 50 °C is due to the enhancement of 2DEG mobility and effective electron velocity. The anomalous drain current reduction in the I-V curves were observed at low voltage region at the temperature ≤ 10 °C but disappeared when the temperature reached ≥ 25 °C. A positive threshold voltage (V_th) shift was observed from − 50 °C to 200 °C. The positive shift of V_th is due to the occurrence of trapping effects in the devices. The drain leakage current decreases with activation energies of 0.028 eV and 0.068 eV. This decrease of leakage current with the increase of temperature is due to the shallow acceptor initiated impact ionization.     

High Microwave-Noise Performance of AlGaN/GaN MISHEMTs on Silicon With Gate Insulator Grown by ALD

High microwave-noise performance is realized in AlGaN/GaN metal–insulator semiconductor high-electron mobility transistors (MISHEMTs) on high-resistivity silicon substrate using atomic-layer-deposited (ALD) $hbox{Al}_{2}hbox{O}_{3}$ as gate insulator. The ALD $hbox{Al}_{2}hbox{O}_{3}/hbox{AlGaN/GaN}$ MISHEMT with a 0.25- $muhbox{m}$ gate length shows excellent microwave small signal and noise performance. A high current-gain cutoff frequency $f_{T}$ of 40 GHz and maximum oscillation frequency $f_{max}$ of 76 GHz were achieved. At 10 GHz, the device exhibits low minimum-noise figure $(hbox{NF}_{min})$ of 1.0 dB together with high associate gain $(G_{a})$ of 10.5 dB and low equivalent noise resistance $(R_{n})$ of 29.2 $Omega$. This is believed to be the first report of a 0.25-$muhbox{m}$ gate-length GaN MISHEMT on silicon with such microwave-noise performance. These results indicate that the AlGaN/GaN MISHEMT with ALD $hbox{Al}_{2}hbox{O}_{3}$ gate insulator on high-resistivity Si substrate is suitable for microwave low-noise applications.