HIV gp120 Binds to Mannose Receptor on Vaginal Epithelial Cells and Induces Production of Matrix Metalloproteinases

BACKGROUND: During sexual transmission of HIV in women, the virus breaches the multi-layered CD4 negative stratified squamous epithelial barrier of the vagina, to infect the sub-epithelial CD4 positive immune cells. However the mechanisms by which HIV gains entry into the sub-epithelial zone is hitherto unknown. We have previously reported human mannose receptor (hMR) as a CD4 independent receptor playing a role in HIV transmission on human spermatozoa. The current study was undertaken to investigate the expression of hMR in vaginal epithelial cells, its HIV gp120 binding potential, affinity constants and the induction of matrix metalloproteinases (MMPs) downstream of HIV gp120 binding to hMR. PRINCIPAL FINDINGS: Human vaginal epithelial cells and the immortalized vaginal epithelial cell line Vk2/E6E7 were used in this study. hMR mRNA and protein were expressed in vaginal epithelial cells and cell line, with a molecular weight of 155 kDa. HIV gp120 bound to vaginal proteins with high affinity, (Kd = 1.2±0.2 nM for vaginal cells, 1.4±0.2 nM for cell line) and the hMR antagonist mannan dose dependently inhibited this binding. Both HIV gp120 binding and hMR exhibited identical patterns of localization in the epithelial cells by immunofluorescence. HIV gp120 bound to immunopurified hMR and affinity constants were 2.9±0.4 nM and 3.2±0.6 nM for vaginal cells and Vk2/E6E7 cell line respectively. HIV gp120 induced an increase in MMP-9 mRNA expression and activity by zymography, which could be inhibited by an anti-hMR antibody. CONCLUSION: hMR expressed by vaginal epithelial cells has high affinity for HIV gp120 and this binding induces production of MMPs. We propose that the induction of MMPs in response to HIV gp120 may lead to degradation of tight junction proteins and the extracellular matrix proteins in the vaginal epithelium and basement membrane, leading to weakening of the epithelial barrier; thereby facilitating transport of HIV across the vaginal epithelium

Lifestyle, dietary and treatment adherence pattern of uncontrolled diabetics in coastal Karnataka, India

Background: Diabetes Mellitus shows a rising trend in India, driven by a combination of factors like sedentary lifestyle, unhealthy diet and tobacco use. The cornerstone for interventions to reduce this is lifestyle modification. Aim & Objective: This study aims to determine lifestyle behaviours among uncontrolled diabetics in rural South India. Settings and Design: This is a pilot study conducted as part of a community trial which enrolled uncontrolled diabetics (Glycosylated haemoglobin, HbA1C of 7% or more) selected from baseline survey of 2 RBS readings. Methods and Material: The sociodemographic details, lifestyle habits and treatment adherence of eligible participants were recorded with a validated questionnaire. Statistical analysis used: Data was compared among 2 groups of poor glycaemic control using Chi square test. Results: There was no significant association of age or gender with HbA1C levels. Majority were non-smokers, non-alcoholics and did not exercise. Higher proportions of those with hospital admissions, longer duration of disease and less frequent check-ups had poor control; but these were not statistically significant. Dietary control was inadequate. However, there were no significant association of dietary habits with poor control. Conclusions: Although overall adherence to medication and follow up was satisfactory, lifestyle modification is not being sufficiently followed

Clinical experience with the use of Fluorescence In Situ Hybridization on uncultured cells for prenatal diagnosis.

The aim of the study was to prospectively evaluate the usefulness and limitations of Fluorescence In Situ Hybridization (FISH) on uncultured cells for prenatal diagnosis of numeric aneuploidies of chromosomes 13, 18, 21, X and Y. Hundred prospectively selected pregnant women that were at high risk of giving birth to an abnormal child were offered prenatal diagnosis by FISH after appropriate counseling. Fetal tissue was obtained by chorionic villus sampling (n=26), amniocentesis (n=62) and or fetal blood sampling (n=12) and processed for FISH using commercial probes. Six cases were excluded initially owing to maternal blood contamination or inadequate sample. FISH results were available in 98% of cases, in 2% of cases there was FISH failure. Of the remaining 92 cases, chromosome aneuploidy was detected in eleven cases. FISH was found extremely valuable in cases presenting with fetal abnormalities detected on ultrasonography and also for rapid screening of aneuploidies in cases of abnormal triple marker test. But as the diagnosis is limited to only a small number of chromosomes, appropriate evaluation of the cases with counseling regarding the limitations of FISH is mandatory before offering this test for prenatal diagnosis

Acute and chronic effects of aspirin on hematological parameters and hepatic ferritin expression in mice

OBJECTIVE: To examine the acute and chronic effects of aspirin on peripheral blood and bone marrow counts and hepatic ferritin expression in mice. MATERIAL AND METHODS: Adult male albino mice were orally administered aspirin at a dose of 600 mg/kg thrice daily for 7 days or 150 mg/kg once daily for 6/7 days up to 25 weeks. At the end of the experiment the red and white blood cell counts, hemoglobin, and packed cell volume were estimated. Bone marrow films were studied to estimate the rate of erythropoiesis and leucopoiesis. Expression of liver ferritin was tested by immunohistochemistry. RESULTS: Acute or chronic doses of aspirin reduced the RBC count, hemoglobin and other red cell indices as compared to controls. The WBC counts were higher in the treated animals as compared to the untreated animals. Both the treatment regimens appeared to suppress the rate of erythropoiesis in the marrow, while the rate of leucopoiesis appeared to increase in the marrow of the treated animals. Aspirin treatment did not significantly affect the expression of ferritin in the liver. CONCLUSION: Aspirin in either acute or chronic doses induces anemia associated with leucocytosis in mice; the anemia does not seem to be induced due to alterations in iron metabolism. The drug appears to use multiple targets which affect red cell production and maturation processes

Pregnancy outcomes, Newborn complications and Maternal-Fetal Transmission of SARS-CoV-2 in women with COVID-19: A systematic review of 441 cases

ABSTRACTObjectiveThe aim of this systematic review was to examine the maternal and fetal outcomes in pregnant women with COVID-19 and also assess the incidence of maternal-fetal transmission of SARS CO-V-2 infection.Data sourcesWe searched PUMBED. Medline, Embase, MedRxiv and bioRxiv databases upto 3rdMay 2020 utilizing combinations of word variants for “coronavirus” or “COVID-19” or “severe acute respiratory syndrome” or “SARS-COV-2” and “pregnancy”. We also included data from preprint articles.Study eligibility criteriaOriginal case reports and case series on pregnant women with diagnosis of SARS-CoV-2 infection.Study appraisal and synthesis methodsWe included 50 studies reporting the information on 441 pregnant women and 391 neonates. The primary outcome measures were maternal health characteristics and adverse pregnancy outcomes, neonatal outcomes and SARS-CoV-2 infection in neonates was extracted. Treatments given to pregnant women with COVID-19 were also recorded.ResultsOut of 441 women affected by COVID-19 in pregnancy, 387 women have delivered. There are nine maternal deaths reported. In pregnant women with COVID-19, the most common symptoms were fever (56%), cough (43%), myalgia (19%), dyspnea (18%) and diarrhea (6%). Pneumonia was diagnosed by CT scan imaging in 96 % of COVID-19 pregnant women. Pregnancy complications included delivery by cesarean section (80%), preterm labor (26%), fetal distress (8%) and premature rupture of membranes (9%). Six still births (2%) are reported. The most common co-morbidities associated with pregnant women with COVID-19 were hypertensive disorders (10%), diabetes (9%), placental disorders (2%), co-infections (3%), scarred uterus (3%) and hypothyroidism (3%). Amongst the neonates of COVID-19 mothers, preterm birth (25%), respiratory distress syndrome (8%), pneumonia (8%) were reported. There were four neonatal deaths reported. Vertical transmission rate of SARS-CoV-2 is estimated to be 8%.ConclusionIn pregnant women with COVID-19, hypertensive disorders and diabetes are common comorbidities and there is a risk of preterm delivery and maternal death. Amongst the neonates born to mothers with COVID-19, respiratory distress syndrome and pneumonia are common occurrence. There are reports of still births and neonatal deaths. There is an evidence of vertical transmission of SARS-CoV-2 infection in women with COVID-19.</jats:sec

A systematic review on Multisystem Inflammatory Syndrome in Children (MIS-C) with COVID-19: Development of a scoring system for clinical diagnosis

AbstractBackgroundThere is growing evidence of Multisystem Inflammatory Syndrome in Children (MIS-C) resembling Kawasaki disease in children infected with SARS-CoV-2. The review was undertaken to evaluate the case definition, the spectrum of clinical presentations and current management practices in children with COVID-19 presenting with or without MIS-C.MethodsThe individual patient data from 119 studies accounting for 333 children were analyzed. We devised a scoring system as per WHO criteria to classify the patients as MIS-C or without MIS-C. A score of 3 was given for the presence of fever (&gt;24h) and a score of 1 for lab-confirmed diagnosis of SARS-CoV-2. Additionally, a score of 1 was given for a) rash or conjunctivitis or muco-cutaneous inflammation signs, b) hypotension or shock, c) diarrhea, vomiting or abdominal pain, d) features of myocardial dysfunction as determined by abnormal eco-cardiography or elevated Troponin or N-terminal pro B-type Natriuretic Peptide (NT-proBNP), e) evidence of coagulopathy as evidenced by elevated levels of prothrombin time PT, partial thromboplastin time PTT or D-dimer, f) laboratory evidence of inflammation as determined by elevated erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP) or procalcitonin. A negative score of (−3) was given when there was a diagnosis of sepsis, staphylococcal or streptococcal shock syndrome. Based on these criteria, a minimum score of 6 was essential to classify the child as MIS-C.ResultsBased on this score, 18% (52/289) of cases were identified to be MIS-C. A greater proportion of children with MIS-C had cardiac involvement (MIS-C 80% vs Non-MIS-C 20%) and gastrointestinal involvement (MIS-C 71% vs Non-MIS-C 12%). Lymphopenia was commonly reported in MIS-C (MIS-C 54.2% vs Non-MIS-C 29.7%). In addition to routine inflammatory markers, significantly greater proportion of children with MIS-C had elevated Ferritin, LDH, Fibrinogen and IL-6. Children with MIS-C were less likely to have respiratory symptoms like cough (MIS-C 25% vs Non-MIS-C 75%) and rhinorrhea (MIS-C 4% vs Non-MIS-C 22.8%). A greater proportion of children with MIS-C required intensive care and aggressive treatment; and mortality rates were also higher in MIS-C group (MIS-C 10% vs Non-MIS-C 1%).ConclusionThe children with COVID-19 having cardiac and/or gastrointestinal involvement are more likely to develop MIS-C. The children with MIS-C have higher mortality rates. The scoring system developed herein will aid clinicians in patient diagnosis and timely management.</jats:sec