Prevalence of bacterial vaginosis among reproductive age group women in a tertiary care centre

Background: Vaginal discharge in reproductive age poses a serious problem in the developing countries. Bacterial vaginosis also known as non-specific vaginitis is the most common cause of vaginal infections, detecting the organism at an early stage and initiating a proper treatment is very difficult in our country due to lack of awareness and proper follow-up. The disease manifests in the form of vaginal discharge with or without itching. It has a strong association with preterm labor, preterm premature rupture of membranes and low birth weight in pregnancy. The objective of this study was to find out the prevalence of bacterial vaginosis among the reproductive age group women, in a tertiary care centre.Methods: A cross sectional study was conducted among 150 women of the reproductive age group in the department of obstetrics and gynaecology Sree Mookambika Institute of Medical Sciences over a period of one month October 2018 the diagnosis was made with history and nugents scoring system.Results: Out of the total 150 women enrolled in the study 74 had positive results, 50% of them were of the age group 26-30.Conclusions: The study shows us the high prevalence of bacterial vaginosis

Mechanisms of Action of Metformin as an Anti-cancer Agent

Cancer is the second leading cause of death worldwide and epidemiological studies suggest the association of diabetes mellitus with an enhanced risk for multiple cancers. Metformin (1,1-dimethylbiguanide hydrochloride) is the most widely prescribed anti-diabetic drug. However, in addition to its anti-diabetic activity metformin exhibits antineoplastic effects by inhibiting development of tumors and also by inhibiting tumor growth, survival and metastasis. Specificity protein (Sp) transcription factors (TFs) belong to the Sp/Kruppel-like family of transcription factors (KLFs). Sp1 and other Sp proteins are overexpressed in many tumors and regulate the expression of genes essential for cancer cell proliferation, growth, angiogenesis, and survival. Based on the reported metformin-induced activities in cancer cells and tumors, we hypothesize that the anti-neoplastic effect of metformin is due, in part, to downregulation of Sp transcription factors in cancer cells. Treatment of pancreatic cancer cells with metformin inhibited cell proliferation, induced apoptosis and also downregulated Sp1, Sp3 and Sp4 proteins and several prooncogenic Sp-regulated genes. Metformin also decreased microRNA-27a and induced the Sp repressor, ZBTB10, and disruption of miR-27a:ZBTB10 interaction by metformin was mediated by MAPK phosphatases 1 and 5 (MKP1 & MKP5). Furthermore, we also demonstrated that treatment with metformin or downregulation of Sp TFs by RNA interference (RNAi) inhibited two major pro-oncogenic pathways in pancreatic cancer cells, namely insulin-like growth factor receptor (IGF-1R) mediated mTOR signaling and epidermal growth factor (EGFR)-dependent activation of RAS. Knockdown of IGF-1R and EGFR inhibited mTOR signaling and RAS activity respectively. Metformin also inhibited pancreatic tumor growth and downregulated Sp and Sp regulated genes in tumors in an orthotopic model. We also investigated the antineoplastic effect of metformin in breast cancer cells. The effects of metformin in breast cancer cells were comparable to those observed in pancreatic cancer cells. In addition, metformin also decreased expression of ErbB2 in breast cancer cells overexpressing this oncogene. Treatment with metformin or downregulation of Sp TFs by RNAi decreased expression of ErbB2, YY1 and mTOR signaling. Results of this study have unraveled an important mechanism of action of metformin in cancer cells which will facilitate the design of clinical applications of metformin in various combination drug therapies

Aspirin Inhibits Colon Cancer Cell and Tumor Growth and Downregulates Specificity Protein (Sp) Transcription Factors

Acetylsalicylic acid (aspirin) is highly effective for treating colon cancer patients postdiagnosis; however, the mechanisms of action of aspirin in colon cancer are not well defined. Aspirin and its major metabolite sodium salicylate induced apoptosis and decreased colon cancer cell growth and the sodium salt of aspirin also inhibited tumor growth in an athymic nude mouse xenograft model. Colon cancer cell growth inhibition was accompanied by downregulation of Sp1, Sp3 and Sp4 proteins and decreased expression of Sp-regulated gene products including bcl-2, survivin, VEGF, VEGFR1, cyclin D1, c-MET and p65 (NFκB). Moreover, we also showed by RNA interference that β-catenin, an important target of aspirin in some studies, is an Sp-regulated gene. Aspirin induced nuclear caspase-dependent cleavage of Sp1, Sp3 and Sp4 proteins and this response was related to sequestration of zinc ions since addition of zinc sulfate blocked aspirin-mediated apoptosis and repression of Sp proteins. The results demonstrate an important underlying mechanism of action of aspirin as an anticancer agent and, based on the rapid metabolism of aspirin to salicylate in humans and the high salicylate/aspirin ratios in serum, it is likely that the anticancer activity of aspirin is also due to the salicylate metabolite

Interferon Tau Alleviates Obesity-Induced Adipose Tissue Inflammation and Insulin Resistance by Regulating Macrophage Polarization

Chronic adipose tissue inflammation is a hallmark of obesity-induced insulin resistance and anti-inflammatory agents can benefit patients with obesity-associated syndromes. Currently available type I interferons for therapeutic immunomodulation are accompanied by high cytotoxicity and therefore in this study we have examined anti-inflammatory effects of interferon tau (IFNT), a member of the type I interferon family with low cellular toxicity even at high doses. Using a diet-induced obesity mouse model, we observed enhanced insulin sensitivity in obese mice administered IFNT compared to control mice, which was accompanied by a significant decrease in secretion of proinflammatory cytokines and elevated anti-inflammatory macrophages (M2) in adipose tissue. Further investigations revealed that IFNT is a potent regulator of macrophage activation that favors anti-inflammatory responses as evidenced by activation of associated surface antigens, production of anti-inflammatory cytokines, and activation of selective cell signaling pathways. Thus, our study demonstrates, for the first time, that IFNT can significantly mitigate obesity-associated systemic insulin resistance and tissue inflammation by controlling macrophage polarization, and thus IFNT can be a novel bio-therapeutic agent for treating obesity-associated syndromes and type 2 diabetes

Taila Dāha (Cauterization with Oil) an innovative approach in pilonidal sinus

Pilonidal sinus is a chronic inflammatory track in mid gluteal cleft usually associated with hairs with an incidence rate of twenty six per one lakh population. It is more prevalently seen in the natal cleft of hairy middle aged obese, males. Such type of non-healing tracts may be considered as Nāḍivraṇa (Sinuses) and can either be treated by the conventional Kṣārasūtra (medicated seton) therapy or contemporary treatment methods. Irrespective of whatsoever management protocol adopted, it inevitably needs long term hospitalisation and is associated with complications. A case of a 28 year old male patient, presenting with pain (within tolerable limits) in the natal cleft and frequent occurrence of a pustule which burst out spontaneously on and off, diagnosed as pilonidal sinus (nāḍi vraṇa) was treated with excision of tract and Tailadāha (thermal cauterization with hot oil) with a combination of yaṣṭimadhu taila and powdered Copper Sulphate (CuSO4). Good haemostasis and uneventful wound healing with a minimally invasive and cost effective treatment was the outcome of study. This study represents an innovative treatment modality in pilonidal sinus

Lack of association of mirSNP rs11174811 in AVPR1A gene with arterial blood pressure and hypertension in South Indian population

Epigenetic regulation of arterial blood pressure mediated through mirSNPs in renin–angiotensin aldosterone system (RAAS) genes is a less explored hypothesis. Recently, the mirSNP rs11174811 in the 3’UTR of the AVPR1A gene was associated with higher arterial blood pressure in a large study population from the Study of Myocardial Infarctions Leiden (SMILE). The aim of the present study was to replicate the association of mirSNP rs11174811 with blood pressure outcomes and hypertension in a south Indian population. Four hundred and fifteen hypertensive cases and 416 normotensive controls were genotyped using a 5’ nuclease allelic discrimination assay. Logistic regression was used to test the association of mirSNP rs11174811 with the hypertension phenotype. Censored normal regression was used to test the association of the polymorphism with continuous blood pressure outcomes such as systolic and diastolic blood pressure. The mirSNP rs11174811 did not show any significant association with hypertension. The adjusted odds ratio was 1.02, with 95% CI of 0.72 to 1.45 (p = 0.909). The mean systolic and diastolic blood pressure values were not significantly different across the three genotypic groups, between hypertensives and normotensives, or when stratified by gender. Despite having a similar minor allele frequency (MAF) of 14.5% compared with the SMILE cohort, our results did not support an association of the mirSNP rs11174811 with the hypertension phenotype or with continuous blood pressure outcomes in the south Indian population

Menthol in Electronic Cigarettes: A Contributor to Respiratory Disease?

Menthol is widely used in tobacco products. This study compared the effects of menthol on human bronchial epithelium using submerged cultures, a VITROCELL® cloud chamber that provides air liquid interface (ALI) exposure without solvents or heating, and a Cultex ALI system that delivers aerosol equivalent to that inhaled during vaping. In submerged culture, menthol significantly increased calcium influx and mitochondrial reactive oxygen species (ROS) via the TRPM8 receptor, responses that were inhibited by a TRPM8 antagonist. VITROCELL® cloud chamber exposure of BEAS-2B monolayers increased mitochondrial protein oxidation, expression of the antioxidant enzyme SOD2, activation of NF-κB, and secretion of inflammatory cytokines (IL-6 and IL-8). Proteomics data collected following ALI exposure of 3D EpiAirway tissue in the Cultex showed upregulation of NRF-2-mediated oxidative stress, oxidative phosphorylation, and IL-8 signaling. Across the three platforms, menthol adversely effected human bronchial epithelium in a manner that could lead to respiratory disease

Aspirin decreases expressions of Sp1, Sp3, Sp4 and Sp-regulated gene products in colon cancer cells.

<p>Downregulation of Sp proteins in RKO and SW480 (A) and HT29 and HCT116 (B) and Sp-regulated gene products in RKO and SW480 (C) and HT29 and HCT116 (D) cells. Cells were treated with 5 or 10 mM aspirin for 24 or 48 hr, and whole cell lysates were analyzed by western blot analysis as described in the <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0048208#s3" target="_blank">Experimental Procedures</a>. Results are typical of duplicate experiments. (E) Aspirin decreases reporter gene activity. Cells were transfected with pSp1For4, pSp3For5, pVEGF and pSurvivin and treated with DMSO or aspirin (5 or 10 mM). Luciferase activity was determined as described in the <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0048208#s3" target="_blank">Experimental Procedures</a>. Results are expressed as means ± SE (3 replicates) and significant (p<0.05) inhibition is indicated (*).</p