Involvement of ADAM10 in axonal outgrowth and myelination of the peripheral nerve

The disintegrin and metalloproteinase 10 (ADAM10) is a membrane‐anchored metalloproteinase with both proteolytic and disintegrin characteristics. Here, we investigate the expression, regulation, and functional role of ADAM10 in axonal outgrowth and myelination of the peripheral nerve. Expression pattern analysis of 11 ADAM family members in co‐cultures of rat dorsal root ganglia (DRG) neurons and Schwann cells (SCs) demonstrated the most pronounced mRNA expression for ADAM10. In further studies, ADAM10 was found to be consistently upregulated in DRG‐SC co‐cultures before the induction of myelination. Neurons as well as SCs widely expressed ADAM10 at the protein level. In neurons, the expression of ADAM10 was exclusively limited to the axons before the induction of myelination. Inhibition of ADAM10 activity by the hydroxamate‐based inhibitors GI254023X and GW280264X resulted in a significant decrease in the mean axonal length. These data suggest that ADAM10 represents a prerequisite for myelination, although its activity is not required during the process of myelination itself as demonstrated by expression analysis of myelin protein zero (P0) and Sudan black staining. Hence, during the process of myelin formation, ADAM10 is highly upregulated and appears to be critically involved in axonal outgrowth that is a requirement for myelination in the peripheral nerve. © 2009 Wiley‐Liss, Inc.     

Silver nanoparticles production by two soil isolated bacteria,Bacillus thuringiensis and Enterobacter cloacae,and assessment of their cytotoxicity and wound healing effect in rats

Production of silver nanoparticles by Bacillus thuringiensis and Enterobacter cloacae was performed and confirmed through UV–visible spectrophotometry, transmission electron microscopy (TEM), and x‐ray diffraction (XRD) analyses. The 3‐(4,5‐dimethylthiazol‐2‐yl)?2,5‐diphenyltetrazolium bromide (MTT) assay using mouse fibroblast cell line NIH‐3T3 D4 was carried out and IC_50s of AgNPs were obtained. The nontoxic dose of each AgNPs solution was selected for wound healing assay. Thirty‐two rats were divided into four groups; two were used as the controls and two were treated by AgNPs that were produced by two bacterial strains. Results revealed that the produced AgNPs were amorphous, spherical in shapes, and had sizes under 100 nm. Histological analysis showed that AgNPs had better wound healing efficacy than the control groups. In conclusion, when the biologically produced AgNPs were used in vivo, they induced the epithelization, formation of the collagen bundles and fibroplasia and reduced the duration of completion of the epithelization and the angiogenesis.     

Androgen receptor gene and sex-specific Alzheimer's disease

Women are at a 2-fold risk of developing late-onset Alzheimer's disease (AD) (onset at 65 years of age or older) compared with men. During perimenopausal years, women undergo hormonal changes that are accompanied by metabolic, cardiovascular, and inflammatory changes. These all together have been suggested as risk factors for late-onset AD. However, not all perimenopausal women develop AD; we hypothesize that certain genetic factors might underlie the increased susceptibility for developing AD in postmenopausal women. We investigated the Androgen Receptor gene (AR) in a clinical cohort of male and female AD patients and normal control subjects by sequencing all coding exons and evaluating the length and distribution of the CAG repeat in exon 1. We could not establish a correlation between the repeat length, sex, and the disease status, nor did we identify possible pathogenic variants. AR is located on the X chromosome; to assess its role in AD, X-inactivation patterns will need to be studied to directly correlate the actual expressed repeat length to a possible sex-specific phenotypic effect.     

A Randomized Clinical Trial of Insulin Glargine and Aspart,Compared to NPH and Regular Insulin in Children with Type 1 Diabetes Mellitus

Objective

Appropriate treatment of patients with Type 1 diabetes mellitus (T1DM) is necessary to avoid further complications. This study was performed to compare the efficacy of insulin Glargine and Aspart with NPH insulin and regular insulin regimen in a group of children with T1DM.

Methods

Forty patients with T1DM were enrolled in this study. During run-in, all subjects were treated with conventional therapy consisting of twice-daily NPH and thrice-daily regular. Following randomization, 20 subjects received Glargine and Aspart and 20 subjects received NPH and Regular insulin.

Findings

Mean HbA1c was 8.8% and 8.6% at first and 8.4% and 8.2% at the end of study for subjects randomized initially to Glargine and Aspart and for those randomized to NPH and Regular, respectively (P>0.05). Mean fasting blood glucose (FBS) of the subjects randomized initially to Glargine and Aspart was 217±101 mg/dL, with no significant difference to 196±75 mg/dL for those randomized to NPH and Regular (P=0.48). This was also true at the end of the study. The difference in total cholesterol and triglyceride between the two groups in the beginning of study and at the end did not show any significance.

Conclusion

The current study showed no significant difference in glycemic control [Glycated hemoglobin (HbA1c) and FBS] and lipid profile (total cholesterol and triglyceride) between two regimes.     

Oral Nitrate Reductase Activity and Erosive Gastro-esophageal Reflux Disease: A Nitrate Hypothesis for GERD Pathogenesis

Background  

Despite the rich literature on GERD, its cause and reason for increased prevalence remain obscure. Currently accepted mechanisms leave many questions unanswered. Nitrite chemistry at the GEJ is well described for carcinogenesis. Recent epidemiological and animal data have linked nitrates to GERD. “Nitrate reductase” of oral bacteria converts nitrates to nitrites. We hypothesized that nitrate reductase activity is higher in patients with erosive GERD, delivering more nitrite at the gastroesophageal-junction for a given nitrate intake.