Pregnancy augments nitric oxide-dependent dilator response to acetylcholine in the human uterine artery

The influence of pregnancy on the dilator effects of acetylcholine in the isolated human uterine artery was investigated. Acetylcholine (0.1 nM to 0.1 microM) produced concentration- and endothelium-dependent relaxation of norepinephrine (3 microM)-induced contraction. The relaxation was greater in arteries from pregnant patients (P arteries) than from non-pregnant patients (NP arteries). The maximal relaxation was 53.5+/-3.4% (n=21) in P arteries and 23.5+/-2.5% (n=35) in NP arteries. In both P and NP arteries the cholinergic relaxation was increased in the presence of superoxide dismutase and greatly reduced in the presence of the nitric oxide synthase inhibitors, NG-mono-methyl L-arginine (L-NMMA) and L-nitro-arginine-methylester (L-NAME). The effect of these nitric oxide synthase inhibitors was reversed by L- arginine. We conclude that pregnancy enhances acetylcholine-induced nitric oxide synthesis and release in the human uterine artery.      

Murine model (Galns(tm(C76S)slu)) of MPS IVA with missense mutation at the active site cysteine conserved among sulfatase proteins

Mucopolysaccharidosis IVA (MPS IVA) is an autosomal recessive disorder caused by deficiency of N-acetylgalactosamine-6-sulfate sulfatase (GALNS), required for degradation of keratan sulfate and chondroitin-6-sulfate. In order to study the effects of a missense mutation in the active site cysteine in the GALNS gene that is conserved in all mammalian sulfatases, we produced a p.C76S (an active site replacement) knock-in mouse by replacing the Cys76 with Ser in the endogenous murine Galns by targeted mutagenesis. Homozygous Galns(tm(C76S)slu) mice had no detectable GALNS enzyme activity. At age of 2-4 months, lysosomal storage was present primarily within reticuloendothelial cells such as Kupffer cells and spleen sinusoidal lining cells. Vacuolar change was present in glomerular visceral epithelial cells and was not present in hepatocytes or renal tubular cells. In the brain, hippocampal and neocortical neurons and meningeal cells showed lysosomal storage. Radiographs revealed no change in the skeletal bones of mice up to 12 months old. Thus, the Galns(tm(C76S)slu) mice had visceral storage of GAGs in organs but lacked the skeletal features of human MPS IVA. In contrast to a previously reported transgenic model (Galns(tm(hC79S.mC76S)slu)), in which the inactive human GALNS transgene was overexpressed, no reduction in other sulfatases was observed. In addition, the Galns(tm(C76S)slu) mice displayed milder storage. We conclude that the milder phenotype is characteristic of isolated GALNS deficiency while the more severe phenotype reflected in the Galns(tm(hC79S.mC76S)slu) mice was due to deficiency of other sulfatases caused by oversaturation of the sulfate modifying enzyme by the inactive human gene product.     

Genome analysis linking recent European and African influenza (H5N1) viruses

To better understand the ecology and epidemiology of the highly pathogenic avian influenza virus in its transcontinental spread, we sequenced and analyzed the complete genomes of 36 recent influenza A (H5N1) viruses collected from birds in Europe, northern Africa, and southeastern Asia. These sequences, among the first complete genomes of influenza (H5N1) viruses outside Asia, clearly depict the lineages now infecting wild and domestic birds in Europe and Africa and show the relationships among these isolates and other strains affecting both birds and humans. The isolates fall into 3 distinct lineages, 1 of which contains all known non-Asian isolates. This new Euro-African lineage, which was the cause of several recent (2006) fatal human infections in Egypt and Iraq, has been introduced at least 3 times into the European-African region and has split into 3 distinct, independently evolving sublineages. One isolate provides evidence that 2 of these sublineages have recently reassorted.     

The role of vitamin D in protecting type 1 diabetes mellitus

The relationship between autoimmune diabetes or type 1 diabetes mellitus and vitamin D has been reported in the literature. Many factors, environmental and genetic, have been known, as risk factors, to cause both type 1 diabetes and vitamin D deficiency. Vitamin D treatment has improved or prevented type 1 diabetes mellitus in animals and humans. Vitamin D also has been known to protect from autoimmune diseases in animal models. Therefore, it would be interesting to review the role of vitamin D in type 1 diabetes mellitus.     

A case of dengue‐related osteonecrosis of the maxillary dentoalveolar bone

Dengue is a mosquito transmitted flaviviral infection which can give rise to severe haemorrhage (dengue haemorrhagic fever) and with capillary leakage induces hypovolaemic shock (dengue shock syndrome). Although dengue symptoms and complications have been known for many decades, there has only been one documented case of osteonecrosis of the maxilla which was treated by excision of the necrotic bone. In this case of dengue infection, extensive maxillary osteonecrosis and minimal root resorption appeared to follow factitious injury with a toothpick but resolved with non‐surgical management.     

Triple phase boundary and power density enhancement in PEMFCs of a Pt/C electrode with double catalyst layers

Exploring efficient approaches to design electrodes for proton exchange membrane fuel cells (PEMFCs) is of great advantage to overcome the current limitations of the standard platinum supported carbon (Pt/C) catalyst. Herein, a Pt/C electrode consisting of double catalyst layers (DCL) with low Pt loading of around 0.130 mg_Pt cm⁻² is prepared using spray and electrophoresis (EPD) methods. The DCL electrode demonstrated a higher electrochemical surface area (ECSA-52.5 m² g_Pt⁻¹) and smaller internal resistance (133 Ω) as compared to single catalyst layer (SCL) sprayed (37.1 m² g_Pt⁻¹ and 184 Ω) or EPD (42.4 m² g_Pt⁻¹ and 170 Ω) electrodes. In addition, the corresponding DCL membrane electrode assembly (MEA), which consists of a Pt/C DCL electrode at the anode side and a Pt/C sprayed electrode at the cathode side, also showed improved PEMFC performance as compared to others. Specifically, the DCL MEA generated the highest power density of 4.9 W mg_Pt⁻¹, whereas, the SCL MEAs only produced 3.1 and 3.8 W mg_Pt⁻¹, respectively. The superior utilization of the Pt catalysts into the DCL MEA can originate from the enrichment of the triple phase boundary (TPB) presented on the Pt/C DCL electrode, which can strongly promote the adsorbed hydrogen intermediates'' removal from the anode side, thus improving the overall PEMFC performance.

Pt/C double catalyst layers (DCL), serving as an anodic electrode, have been utilized in a PEMFC application for the first time.     

Congenital afibrinogenemia: identification and expression of a missense mutation in FGB impairing fibrinogen secretion

Congenital afibrinogenemia is a rare autosomal recessive disorder characterized by complete absence of detectable fibrinogen. We previously identified the first causative mutations for this disease: a homozygous deletion of approximately 11 kb of the fibrinogen alpha-chain gene (FGA). Subsequent studies revealed that the great majority of afibrinogenemia mutations are localized in FGA, but mutations were also found in FGG and FGB. Apart from 3 missense mutations identified in the C-terminal portion of FGB, all fibrinogen gene mutations responsible for afibrinogenemia are null. In this study, a young boy with afibrinogenemia was found to be a compound heterozygote for 2 mutations in FGB: an N-terminal nonsense mutation W47X (exon 2) and a missense mutation (G444S, exon 8). Coexpression of the FGB G444S mutant cDNA in combination with wild-type FGA and FGG cDNAs demonstrated that fibrinogen molecules containing the mutant beta chain are able to assemble but are not secreted into the media, confirming the pathogenic nature of the identified mutation.