A comparative study of circulating plasma lipid components and superoxide dismutase activity in pre and postmenopausal women

Background: Menopause is associated with increased oxidative stress and decreased antioxidative activity in females which leads to increased risk of cardiovascular and many other diseases. The objective was to compare the lipid profiles and superoxide dismutase (SOD) activity of pre and postmenopausal women in an attempt to establish the fact that menopause is associated with increased oxidative stress.Methods: A hospital based cross-sectional study was done at the department of obstetrics and gynaecology and biochemistry, Shri Mahant Indiresh Hospital, Dehradun, India. Out of total of 120 women, 60 women were in premenopausal group aged between 30-45 years and 60 women of 55-70 years of age group in post menopause status. Assessment of lipid profile was done by an automated chemistry analyzer (Vitors 5, I FS) and SOD activity was measured by colorimetric activity kit. Statistical analysis was done by Standard Microsoft Excel software.Results: Mean serum SOD level in premenopausal women was 4.80±1.73 U/ml and in postmenopausal was 1.35±0.58 U/ml. This variation was found to be extremely significant (p <0.0001). Changes in lipid components in pre and postmenopausal women showed that total cholesterol and triglycerides levels were higher in postmenopausal than premenopausal participants. These variations were also significant (p = 0.0003). Levels of HDL-C were lower in postmenopausal women than pre-menopausal group with a mean±SD of 51.5±12.20 mg/dl and 54.05±14.03mg/dl respectively.Conclusions: Findings of this study corroborate the hypothesis that gradual loss of ovarian function is associated with a decrease in antioxidant status. Menopause also leads to changes in lipid components, which can predispose women to cardiovascular diseases

A Laminin G-EGF-Laminin G Module in Neurexin IV Is Essential for the Apico-Lateral Localization of Contactin and Organization of Septate Junctions

Septate junctions (SJs) display a unique ultrastructural morphology with ladder-like electron densities that are conserved through evolution. Genetic and molecular analyses have identified a highly conserved core complex of SJ proteins consisting of three cell adhesion molecules Neurexin IV, Contactin, and Neuroglian, which interact with the cytoskeletal FERM domain protein Coracle. How these individual proteins interact to form the septal arrays that create the paracellular barrier is poorly understood. Here, we show that point mutations that map to specific domains of neurexin IV lead to formation of fewer septae and disorganization of SJs. Consistent with these observations, our in vivo domain deletion analyses identified the first Laminin G-EGF-Laminin G module in the extracellular region of Neurexin IV as necessary for the localization of and association with Contactin. Neurexin IV protein that is devoid of its cytoplasmic region is able to create septae, but fails to form a full complement of SJs. These data provide the first in vivo evidence that specific domains in Neurexin IV are required for protein-protein interactions and organization of SJs. Given the molecular conservation of SJ proteins across species, our studies may provide insights into how vertebrate axo-glial SJs are organized in myelinated axons

SARS-CoV-2 B.1.617.2 Delta variant replication and immune evasion

Abstract: The B.1.617.2 (Delta) variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first identified in the state of Maharashtra in late 2020 and spread throughout India, outcompeting pre-existing lineages including B.1.617.1 (Kappa) and B.1.1.7 (Alpha)1. In vitro, B.1.617.2 is sixfold less sensitive to serum neutralizing antibodies from recovered individuals, and eightfold less sensitive to vaccine-elicited antibodies, compared with wild-type Wuhan-1 bearing D614G. Serum neutralizing titres against B.1.617.2 were lower in ChAdOx1 vaccinees than in BNT162b2 vaccinees. B.1.617.2 spike pseudotyped viruses exhibited compromised sensitivity to monoclonal antibodies to the receptor-binding domain and the amino-terminal domain. B.1.617.2 demonstrated higher replication efficiency than B.1.1.7 in both airway organoid and human airway epithelial systems, associated with B.1.617.2 spike being in a predominantly cleaved state compared with B.1.1.7 spike. The B.1.617.2 spike protein was able to mediate highly efficient syncytium formation that was less sensitive to inhibition by neutralizing antibody, compared with that of wild-type spike. We also observed that B.1.617.2 had higher replication and spike-mediated entry than B.1.617.1, potentially explaining the B.1.617.2 dominance. In an analysis of more than 130 SARS-CoV-2-infected health care workers across three centres in India during a period of mixed lineage circulation, we observed reduced ChAdOx1 vaccine effectiveness against B.1.617.2 relative to non-B.1.617.2, with the caveat of possible residual confounding. Compromised vaccine efficacy against the highly fit and immune-evasive B.1.617.2 Delta variant warrants continued infection control measures in the post-vaccination era

Primary Ampullary Adenosquamous Carcinoma: Report of Two Cases

Introduction: Adenosquamous carcinoma of the ampulla of Vater is a rare neoplasm with its clinicopathological profile limited to a few case reports. Here we report clinical profile, morphology and outcome of two cases of this rare entity. Case report: Case 1 was a 57 year old male who presented with features of obstructive jaundice; Case 2 was a 55 year old female with complaints of pain abdomen. Imaging studies suggested a pre-emptive diagnosis if periampullary malignancy for which both patients underwent Whipple’s pancreaticoduodenectomy. Histopathological examination revealed an ampullary malignancy with variable proportions of adenocarcinoma and squamous cell carcinoma. Case 2 also showed concurrent region lymph node metastasis. Case 1was alive at 15months follow up with no recurrence/metastasis while case 2 survived for only 10 days post surgery. Conclusion: Adenosquamous carcinoma occurring at the ampulla of Vater is a rare event with less than 15 cases documented in the English literature so far. It is an aggressive tumour and is associated with a dismal prognosis. Here we add two more cases to the literature for better understanding of the clinicopathological profile, prognostic indicators and clinical outcome of this rare neoplasm

Design, synthesis, characterization, photophysical and pH chemosensor studies of novel 2,4,6-trisubstituted pyridines

<p>For the application in organic electronics as well as pH meters, a series of novel 2,4,6-trisubstituted pyridines have been synthesized by the reaction of substituted aromatic aldehydes and substituted 3-acetylcoumarin with ammonium acetate. The structures of all the new compounds were characterized by IR, NMR, and GC–MS analysis. The important photo physical prerequisites for organoelectronic such as optical absorption and thermal stability were determined for the synthesized molecules. Optical properties were studied by UV–visible absorption and fluorescence spectroscopy. Optical band gaps of the 2,4,6-trisubstituted pyridines were found to be around 3.01–3.06 eV as calculated from their onset absorption edge. The pH-dependent changes in the fluorescence intensity suggest that 2,4,6-trisubstituted pyridines are useful applicants in intracellular pH meters.</p

A comparative study of circulating plasma lipid components and superoxide dismutase activity in pre and postmenopausal women

Background: Menopause is associated with increased oxidative stress and decreased antioxidative activity in females which leads to increased risk of cardiovascular and many other diseases. The objective was to compare the lipid profiles and superoxide dismutase (SOD) activity of pre and postmenopausal women in an attempt to establish the fact that menopause is associated with increased oxidative stress.Methods: A hospital based cross-sectional study was done at the department of obstetrics and gynaecology and biochemistry, Shri Mahant Indiresh Hospital, Dehradun, India. Out of total of 120 women, 60 women were in premenopausal group aged between 30-45 years and 60 women of 55-70 years of age group in post menopause status. Assessment of lipid profile was done by an automated chemistry analyzer (Vitors 5, I FS) and SOD activity was measured by colorimetric activity kit. Statistical analysis was done by Standard Microsoft Excel software.Results: Mean serum SOD level in premenopausal women was 4.80±1.73 U/ml and in postmenopausal was 1.35±0.58 U/ml. This variation was found to be extremely significant (p &lt;0.0001). Changes in lipid components in pre and postmenopausal women showed that total cholesterol and triglycerides levels were higher in postmenopausal than premenopausal participants. These variations were also significant (p = 0.0003). Levels of HDL-C were lower in postmenopausal women than pre-menopausal group with a mean±SD of 51.5±12.20 mg/dl and 54.05±14.03mg/dl respectively.Conclusions: Findings of this study corroborate the hypothesis that gradual loss of ovarian function is associated with a decrease in antioxidant status. Menopause also leads to changes in lipid components, which can predispose women to cardiovascular diseases

Effect of roscovitine on developmental competence of small follicle-derived buffalo oocytes

Background & objectives: The lower recovery of competent oocytes in buffalo species limits the commercialization of in vitro embryo production technology in field condition. In this context, pre-maturation of small follicle (SF)-derived oocytes with meiotic inhibition may be a promising alternative to obtain more number of competent oocytes. Thus, the present study was conducted with an objective to enhance the developmental potential of less competent SF-derived buffalo oocytes. Methods: All the visible follicles (used for aspiration) from buffalo ovaries were divided into two categories: large follicle (LF) (follicles having diameter ≥6 mm) and SF (follicles of diameter <6 mm). The competence of LF and SF oocytes was observed in terms of brilliant cresyl blue (BCB) staining, cleavage rate, blastocyst rate and relative gene expression of oocyte and blastocyst competence markers. Thereafter, less competent SF oocytes were treated with 0, 12.5, 25, 50 and 100 mM doses of roscovitine (cyclin-dependent kinase inhibitor) to enhance their developmental potential. Results: Based on parameters studied, LF oocytes were found to be more competent than SF oocytes. Pre-maturation incubation of SF oocytes with roscovitine reversibly arrested oocyte maturation for 24 h to ensure the proper maturation of less competent oocytes. A significantly higher number of BCB-positive oocytes were noted in roscovitine-treated group than SF group. Cleavage and blastocyst rates were also higher in roscovitine-treated group. The relative messenger RNA expression of oocyte (GDF9, BMP15, GREM1, EGFR, PTGS2 and HAS2) as well as blastocyst (INF-τ, GLUT1 and POU5F1) competence markers was significantly greater in roscovitine-treated group relative to SF group. Again, on comparison with LF group, these parameters depicted a lower value in the treatment group. Interpretation & conclusions: The findings of this study has revealed that pre-maturation incubation of SF-derived oocytes with 25 μM roscovitine can improve its developmental competence and thus can be utilized to get maximum number of competent oocytes for better commercialization of in vitro embryo production technology in buffalo