Matrix Metalloproteinase-1 and -9 in Human Placenta during Spontaneous Vaginal Delivery and Caesarean Sectioning in Preterm Pregnancy

Preterm birth is a major public health problem in terms of loss of life, long-term and short term disabilities worldwide. The process of parturition (both term and preterm) involves intensive remodelling of the extracellular matrix (ECM) in the placenta and fetal membranes by matrix metalloproteinases (MMPs). Our previous studies show reduced docosahexaenoic acid (DHA) in women delivering preterm. Further omega 3 fatty acids are reported to regulate MMP levels. This study was undertaken to examine the placental levels of MMPs and their association with placental DHA levels in women delivering preterm. The levels of MMP-1 and MMP-9 in 74 women delivering preterm (52 by spontaneous vaginal delivery and 22 by caesarean sectioning) and 75 women delivering at term (59 by spontaneous vaginal delivery and 16 by caesarean sectioning) were determined by enzyme-linked immunosorbent assay (ELISA) and their association with placental DHA was studied. Placental MMP-1 levels were higher (p<0.05) in women delivering preterm (both by spontaneous vaginal delivery and caesarean sectioning) as compared to those delivering at term. In contrast, placental MMP-9 levels in preterm pregnancies was higher (p<0.05) in women with spontaneous vaginal delivery while lower (p<0.05) in women delivering by caesarean sectioning. Low placental DHA was associated with higher placental MMP-9 levels. Our study suggests a differential effect of mode of delivery on the levels of MMPs from placenta. Further this study suggests a negative association of DHA and the levels of MMP-9 in human placenta although the mechanisms need further study

Characterization of the Influenza A H5N1 Viruses of the 2008-09 Outbreaks in India Reveals a Third Introduction and Possible Endemicity

Widespread infection of highly pathogenic avian influenza A H5N1 was reported from backyard and commercial poultry in West Bengal (WB), an eastern state of India in early 2008. Infection gradually spread to Tripura, Assam and Sikkim, the northeastern states, with 70 outbreaks reported between January 2008 and May 2009. Whole genome sequence analysis of three isolates from WB, one isolate from Tripura along with the analysis of hemagglutinin (HA) and neuraminidase (NA) genes of 17 other isolates was performed during this study. In the HA gene phylogenetic tree, all the 2008-09 Indian isolates belonged to EMA3 sublineage of clade 2.2. The closest phylogenetic relationship was found to be with the 2007-09 isolates from Bangladesh and not with the earlier 2006 and 2007 Indian isolates implying a third introduction into the country. The receptor-binding pocket of HA1 of two isolates from WB showed S221P mutation, one of the markers predicted to be associated with human receptor specificity. Two substitutions E119A (2 isolates of WB) and N294S (2 other isolates of WB) known to confer resistance to NA inhibitors were observed in the active site of neuraminidase. Several additional mutations were observed within the 2008-09 Indian isolates indicating genetic diversification. Overall, the study is indicative of a possible endemicity in the eastern and northeastern parts of the country, demanding active surveillance specifically in view of the critical mutations that have been observed in the influenza A H5N1 viruses

The Role of Alliums and Their Sulfur and Selenium Constituents in Cancer Prevention

Garlic and its sulfur and selenium-containing components are widely known for their cancer preventive activities primarily in preclinical in vitro and in vivo model systems. Most of our common foods including garlic contain very low levels of selenium compounds relative to those of sulfur. Humans consume a substantial portion of their dietary sulfur and selenium in organic forms. Selenium-enriched foods such as garlic, broccoli and wheat are more effective chemopreventive agents than the corresponding regular dietary items. Naturally occurring and synthetic organoselenium compounds are superior cancer chemopreventive agents compared to their corresponding sulfur analogs. Mechanistic studies demonstrate that sulfur and selenium compounds are capable of cell growth inhibition, cell cycle arrest, induction of apoptosis, alterations of phase I and phase II enzyme activities, and histone deacetylase (HDAC) inhibition. The fact that organosulfur and organoselenium compounds can target multiple pathways suggests that these agents can be used directly as chemopreventive and/or therapeutic agents or in combination with other medicinal compounds. The effect of these agents on the aforementioned parameters varies depending on the dose and form (structure) and whether cells are normal or transformed. Whether the protective effects observed in animals and in cell cultures can be applicable to humans remain to be determined. Thus, studies using genomic, proteomic, and metabolomic techniques in well designed small-scale clinical trials are needed to unequivocally evaluate the potential of allium vegetable constituents on biomarkers of risk for specific cancers prior to entering into long-term expensive phase III clinical chemoprevention trials