Expression of EZH2 and H3K27me3 predicts tumor biology of urothelial carcinoma

Background: Enhancer of zeste homolog 2 (EZH2) is one of the major epigenetic modifiers involved in the transcriptional repression of target genes through trimethylation of H3K27 (lysine 27 residue of histone H3). Deregulated expression of both EZH2 and H3K27me3 has been implicated in the biological behavior and prognostic outcome of various malignancies. Aim: To assess the role of EZH2 and H3K27me3 in the carcinogenesis of urothelial carcinoma of urinary bladder. Materials and Methods: One hundred fifty consecutive urothelial carcinoma cases of urinary bladder (54.7% high-grade) were included in this study. Immunohistochemical analysis for EZH2 and H3K27me3 was performed on whole tissue sections. A multiplication score obtained by multiplying staining intensity and proportion of positively stained neoplastic cells was used for assessment. Results: EZH2 showed a significant correlation with the tumor grade and lamina propria invasion (p < 0.001). The cases with high EZH2 expression showed a significantly high proliferative index (Mean- 32.7%; p < 0.001). In contrast, negative and low expression of H3K27me3 was significantly more common in high-grade cases (p = 0.006). The expression of H3K27me3 was significantly associated with lamina propria (p = 0.01) and deep muscle invasion (p = 0.007). EZH2 showed a significantly higher expression in the high-grade invasive areas as compared to the high-grade non-invasive areas of the same tumor (p = 0.03). Conclusions: This study establishes an important role of the key epigenetic regulators EZH2 and H3K27me3 in the pathobiology of urothelial carcinomas. Strong expression of EZH2 and weak expression of H3K27me3 are associated with higher grade, proliferative index and invasive behavior.

Effect of aluminium on lipid profile and atherogenic index in prepubertal and young adult female rats: A pilot study

Objectives: Exposure of aluminium (Al) to mankind is inescapable, and its dyslipidaemic impact is a possible contributing factor to health hazards like cardiovascular diseases. The health effects due to the metalloestrogenic property of the metal need imperative consideration. The current experimental work was undertaken to explore Al-induced dyslipidaemia due to its metalloestrogenic property. Materials and Methods: To fulfil this objective, prepubertal (PP) and young adult (YA) female Wistar rats were intraperitoneally administered to two doses of Al [5 and 10 mg/Kg body weight (BW)] once daily for 2 weeks. After the completion of the acute exposure protocol, plasma and hepatic tissue lipid profiles were estimated. Analysis of variance was carried out by the Kruskal–Wallis test and the differences between the groups were analysed by Mann–Whitney U post hoc test Results: Increased triglyceride, total cholesterol, low-density lipoprotein (LDL) cholesterol and very-LDL cholesterol in plasma were found in YAs treated with both doses of Al in a dose-dependent manner. Similar changes were not present in PP female rats. Decreased levels of lipid levels were observed in the case of hepatic lipid profile. Conclusion: The study ushers light towards the dyslipidaemic alterations in experimental female rats after acute Al exposure. Impacts of Al on the growth and organosomatic index during the vital developmental days were significantly decided by the pubertal status of the female rats. The results of this study indicate the impact of puberty on the Al-induced modifications in lipid profile parameters and cardiovascular risk factors.

Preparation and Characterization of Chitosan Nanocomposite Films in Different Solvent and its Antimicrobial Activity.

In this present research programme,chitosan nanocomposites were prepared by using C 30B which is an organomodified nanoclay by solvent casting method and were characterized by FTIR, XRD and SEM. Different chitosan films like acetate, formate, citrate, lactate and ascorbate were also prepared by taking different types of solvent like acetic acid, formic acid, citric acid, lactic acid and ascorbic acid respectively. The properties like thickness, density and transparency of those films were studied. The antimicrobial activity of those films were also investigated against various food borne pathogens like S.aureus, B.cereus, S.typhimurium and E.coli and it was found that all chitosan citrate films showed higher inhibitory activity against all the types of pathogens.

In Vitro α-Amylase Inhibition and Antioxidant potential of Chloroform Fraction of Hydroalcoholic Extract Obtained from Hyptis Suaveolens.

The plant Hyptis is an effective medicinal herb and a well known medicinal plant in herbal world. The present study was aimed to investigate the α-amylase inhibition and antioxidant activities of chloroform fraction of H. suaveolens. Chloroform fraction of H. suaveolens was screened for α-amylase inhibition activity by 3, 5- dinitrosalicylic acid (DNSA) method respectively. and antioxidant activity was evaluated by 1,1-diphenyl-2- picryl-hydrazile (DPPH) free radical scavenging, Super oxide radical Scavenging, nitric oxide (NO) radical scavenging, and 2.2’-azinobis-3-ethylbenzothiazole-6-sulfonic acid (ABTS) radical scavenging assays. The chloroform fraction of H. suaveolens showed effective α-amylase inhibition activity (IC50 57.34μg/ml). Chloroform fraction demonstrated significant antioxidant activity in all the in vitro antioxidant models. Moreover, the chloroform fraction was found to be extremely effective in scavenging DPPH (IC50 57.51 μg/ml) while compared to super oxide (IC50 61.36 μg/ml), NO (IC5076.3 μg/ml) and ABTS radical (IC50 93.16 μg/ml) scavenging activity. In conclusion, from the results of present study it is established that antioxidant and alphaamylase inhibitory activity of chloroform fraction of H. suaveolens may contribute in its earlier observed antidiabetic potential.

Chitosan–sodium alginate nanocomposites blended with cloisite 30B as a novel drug delivery system for anticancer drug curcumin.

In the present research program, polymer nanocomposites have been used as the drug carrier for delivery systems of anticancer drug. Chitosan (CS) and sodium alginate (ALG) with different ratios were blended with different wt% of Cloisite 30B solution by solvent evaporation method. Cloisite 30B was incorporated in the formulation as a matrix material component which also plays the role of a co-emulsifier in the nanocomposite preparation. Curcumin with different concentrations were loaded with CS-ALG/ C 30B nanocomposites for studying the in-vitro drug delivery systems. Morphology and structure characterization of nanocomposites were investigated by X-Ray Diffraction (XRD), Scanning Electron Microscope (SEM) and Fourier Transmission Infra Red Spectroscopy (FTIR) respectively. The drug release was studied by changing time, pH and drug concentrations. The kinetics of the drug release was studied in order to ascertain the type of release mechanism. Based on the diffusion as well as the kinetics, the mechanism of the drug release from the composite matrix has been reported.

Prevalence and distribution of dental anomalies in 500 Indian school children.

Objective: Developmental disturbances of teeth contribute to dental problems encountered in general practice. These are a group of disorders where prevention is not possible, with the exception of environmental enamel hypoplasia. Surveys done on various populations have found prevalence of dental anomalies to be 5.46%. Knowledge of common dental anomalies when available can be a useful tool for forensic dentistry. Since such epidemiological data is not available for the Jodhpur population in Rajasthan, this study was conducted to determine the prevalence of developmental dental anomalies in 500 school going children. Methodology & Result: A total of 500 school children (290 male & 210 female) of age ranging between 6 - 15 years were examined clinically for developmental anomalies of teeth. Prevalence of Peg lateral, supernumerary teeth & Talon’s cusp was 0.4%, 0.6% & 0.2% respectively while 18.8% showed fluorosis induced enamel hypoplasia.

Oral manifestations associated with human immunodeficiency virus infection in 200 Indian patients..

Objective: To determine the pattern and prevalence of oral lesions in HIV infected 200 costal Andhra Pradesh patients. Patients and methods: the study population comprised 200 consecutive HIV seropositive patients presented to regional ART center at Andhra Pradesh, India. The oral lesions were diagnosed based on clinical appearance and were entered in to the database for analysis. Results: 30-39 yrs age group was most commonly affected and 87% of the patients had acquired infection via heterosexual contact. Oral lesions were seen in 66% of the patients. Gingivitis (36.7% males & 33.9% females) was the most common lesion followed by candidiasis (21% males & 26.4% females), periodontitis (6.8% males & 7.5% females), pigmentation (36.7% males & 33.9% females), ulcers (2.7% males & 0% females) and leukoplakia (1.3% males & 0% females). Conclusion: The pattern of oral lesions associated with HIV infection was not markedly different form those reported in the literature, the prevalence of each type of lesion differ slightly.

Cobalt chromium stent with antiproliferative for restenosis trial in India (COSTAR I).

BACKGROUND: The CoStar stent is a novel cobalt chromium stent designed specifically for drug delivery. The COSTAR I trial represents the first-in-man study of the CoStar Paclitaxel-Eluting Coronary Stent System evaluating three dose release formulations of paclitaxel in a bioresorbable polymer matrix in the treatment of de novo coronary lesions. METHODS: The COSTAR I Trial was a prospective, multi-center registry enrolling 87 patients in four Indian centers for treatment of up to two de novo lesions = 25 mm in length in a reference vessel 2.5-3.5 mm in diameter. Three dose release formulations were studied: 30 microg eluted over 10 days bidirectionally (Group 1, n =10), 10 microg eluted over 30 days abluminally (Group 2, n=40) and 3 microg eluted over 30 days abluminally (Group 3, n = 37). RESULTS: Demographics and lesion characteristics were similar between the groups and treatment in all three groups included small caliber vessels (RVD 2.45 +/- 0.30 - 2.57 +/- 0.36 mm). The primary endpoint of in-stent late loss at four months was lowest in Group 2 (0.43 +/- 0.43 mm) compared to Group 1 and Group 3 (0.51 +/- 7 mn; 0.74 mm and 1.07 +/- 0.65 mm respectively). In-segment late loss followed similar trends, being lowest in Group 2 (0.24 +/- 0.39 mm) compared to Groups 1 and 3 (0.52 +/- 0.66 mm and 0.76 +/- 0.57 mm respectively). Group 2 demonstrated better angiographic out-comes at 12 months with in-stent late loss of 0.55 +/- 0.38 mm when compared to Groups 1 and 3 (0.90 +/- 0.76 mm and 0.74 +/- 0.55 mm respectively). Cumulative binary restenosis rates at twelve months were 1.9%, 35.7% and 39.1% in Groups 2, 1 and 3 respectively. Clinical outcomes trended similarly with cumulative MACE rates at twelve months being lowest at 7.5% in Group 2 as compared to 20% in Group 1 and 21.6% in Group 3 respectively. CONCLUSIONS: In this first-in-man feasibility trial, angiographic and clinical results seen with the extended release formulation at a higher dose (10 microg/30 days) demonstrate the feasibility of the CoStar stent platform in the treatment of native coronary lesions. It also demonstrates the importance of drug dose and release kinetics.

Biochemical toxicity study on rat brain upon co-exposure to aluminium and ethanol.

Aluminium and alcohol are well known neuro toxins. Co-exposure of these neuro toxins has been studied in rats. Alcohol exposure significantly affected the aluminium content, protein content, acid phosphatase activity, alkaline phosphatase activity, alanine aminotransferase activity, glutathione-S-transferase activity, and glucose 6-phosphate dehy-drogenase activity of brain. Aluminium exposure, on the other hand, contributed significantly only in the alterations of aluminium content, acid phosphatase activity, and aspartate aminotransf erase activity of brain of rats in the present study. The interaction of both aluminium intoxication and alcohol exposure is significant only in the case of acid phosphatase and glutathione-S-transferase activities of brain. Therefore, from the observations of the present investigation, it can be suggested that the general neurotoxic-ity produced by aluminium is not modified by alcohol. However, the aluminium load and oxidative stress, caused by aluminium exposure, may be influenced by alcohol co-exposure.

Sub acute and chronic meningitis in children--an immunological study of cerebrospinal fluid.

Cerebrospinal fluid (CSF) from 274 cases of subacute to chronic meningitis in age groups from 3 months to 12 years were analysed for the presence of antibody response to mycobacterial and cysticercal antigens by enzyme linked immunosorbent assay (ELISA). Simultaneously other correlative parameters such as CSF cell cytology by cytospin studies, mycobacterial antigens of Lipoarabinomannan (LAM) type (a polysaccharide antigen) by reverse passive haemagglutination assay (RPHA) CSF C-reactive protein (CRP) by latex agglutination and microbial cultures for mycobacterium tuberculosis and fungi were carried out. Antimycobacterial antibody was present in 35.4% of the cases. In 57.66% of the cases there was no demonstrable immune response to either mycobacterial or cysticercal antigens. However, it was interesting to note that 5.47% of the cases revealed the presence of anticysticercal antibody in the CSF. The mycobacterial antigen (LAM polysaccharide antigen) was found in 72.6% of the cases. There was no evidence of carcinomatous or cryptococcal meningitis. This study stresses the role of multimodal diagnostic tests on CSF for investigating cases of chronic and subacute meningitis irrespective of leading clues such as tuberculosis.