Triple-negative breast cancers with expression of glucocorticoid receptor in immune cells show better prognosis.

Background: Glucocorticoid receptor (GR) is shown to have variable frequency of expression in invasive tumors of the breast. Investigation of additional nuclear receptors like GR in receptor negative tumors like triple negative breast cancer (TNBC) may have prognostic and therapeutic significance. Methods: Expression of GR was evaluated by immunohistochemistry in 175 tumors of invasive breast cancer with long term follow up. GR Expression was separately evaluated in invasive tumor cells, stromal cells and tumor infiltrating lymphocytes (TIL's). Staining pattern was categorised as positive when more than 1% of the cells stained in each subpopulation of cells. Disease free survival was analysed between GR positive and negative status by Kaplan Meier analysis. Results: Of the 175 tumors, 121 (70%) were ER positive, 53 (30%) were ER negative and 29% (51) were triple negative. 74% (130/175) tumors showed expression of GR in invasive tumor cells while (84%) 147/175 had expression in TIL's. No significant difference in distribution of GR was noted between ER positive and ER negative tumors (78% vs 66%, p-0.1). Of the TNBC's 54% (28/51) and 70% (36/51) showed expression of GR in invasive tumor and TIL's respectively. Overall, GR positive tumors had significant better survival than GR negative tumors (mean survival time of 85 vs 59 months respectively, p-0.04) Contrary to the reports that GR expression in TIL's are associated with immunosuppressive activity in model systems, TNBC's with increased expression of GR in immune cells were associated with better survival (Mean survival time 74 vs 41 months, log rank test- p-0.03). TNBC tumors which were GR negative had higher lymph node metastases (p-0.04) and none of the other clinical features like age, menopausal state, tumor size and grade were different between GR positive and negative tumors within TNBC. Conclusions: Glucocorticoids (GC) are often used to alleviate the adverse symptoms during chemotherapy. Determining the GR status is of importance due to the pro cell survival effect of the glucocorticoids mediated through GR during chemotherapy. Though GC mediated effects on chemotherapy are controversial, our results indicate favourable effects in TNBC.

A prospective study to compare the clinical efficacy of Tolvaptan with 3% hypertonic saline solution in hospitalized patients having hyponatremia.

OBJECTIVE: Hyponatremia is one of the most common electrolyte abnormalities in hospitalized patients. The treatment of hyponatremia is controversial as rapid correction of serum sodium can give rise to neurologic disorder and at the same time if not corrected timely, it can lead to brain damage. The aim of this study was to compare the efficacy of Tolvaptan with 3% hypertonic saline solution for the management of hyponatremia in hospitalized patients. METHODS: In this prospective observational study, data of 60 hospitalized patients having hyponatremia from February 2013 to July 2013 were collected and analyzed. Patients either received oral Tolvaptan or intravenous infusion of 3% hypertonic saline solution. The serum sodium concentration before administration of treatment and 24 h and 48 h after the administration of the drugs were recorded and analyzed. Data were analyzed using GraphPad Software, by Student's paired t-test and one-way analysis of Variance (ANOVA). FINDINGS: Tolvaptan and 3% hypertonic saline solution had significant effects in raising serum sodium level in hyponatremic patients at both 24 h and 48 h (P < 0.0001). This increase was about 8.030 ± 0.6507 mEq/L and 12.33 ± 0.6489 mEq/L for 3% hypertonic saline and about 5.111 ± 0.6616 mEq/L and 10.11 ± 0.6230 mEq/L for Tolvaptan, after 24 h and 48 h, respectively. CONCLUSION: Both drugs had significant effects in raising serum sodium level in hyponatremic patients; however administration of 3% hypertonic saline solution had a slightly superior efficacy in raising the serum sodium concentration at both 24 h and 48 h periods in Hyponatremic patients compared with oral Tolvaptan.

Design, statistical optimisation, characterisation and pharmacodynamic studies on Pioglitazone hydrochloride floating microparticles.

The purpose of this study was to develop floating microparticles containing Pioglitazone HCl, for controlled release and perform pharmacodynamic studies. The FTIR and DSC studies revealed that there is no interaction between drug and excipients used. The 2(2) factorial design was employed to evaluate the effect of drug: polymer (total) and Eudragit RS 100: Eudragit RL 100. The floating microparticles were prepared by solvent evaporation technique. The predicted and actual values of drug release at 1 h, 8 h and drug entrapment were 38.307%, 77.76%, 84.25% and 38.712%, 76.237% and 84.62%, respectively. XRD and SEM studies showed reduced crystallinity of drug and spherical microparticles. Buoyancy studies revealed good floating of particles for 12 h. Pharmacodynamic studies showed significant reduction in blood glucose levels in male New Zealand rabbits. The results demonstrate the feasibility of the factorial design in successfully developing floating microparticles of Pioglitazone HCl for controlled release.

Desarrollo y caracterización de comprimidos bucodispersables de antibiótico / Development and characterization of antibiotic orodispersible tablets

The goal of this project is to formulate oro-dispersible tablet of Azithromycin that is intended to disintegrate rapidly into the oral cavity and form a stabilized dispersion. A direct compression method was failed to formulate dispersible tablet of Azithromycin so wet granulation method was used. In preliminary study different superdisintegrant croscarmellose sodium (CCS), sodium starch glycolate (SSG) and crospovidone (CPVP) were evaluated for weight variation, content uniformity, hardness, disintegration time, and friability of tablets. In all the formulations water was used as a binding agent to attain hardness. Avicel was used as diluents. Aspartame was used as a sweetening agent. Magnesium stearate and Aerosil were used as lubricant and glidant respectively. FT-IR studies were utilized to obtain the compatibility of the drug and excipients. The simplex lattice design was utilized using amount of intragranular concentration of superdisintegrants, sodium starch glycolate(A), cros-carmellose sodium(B) and crospovidone(C) were selected as independent variable. The Hardness (R1), Disintegration time (R2), Friability (R3) and Wetting time (R4) were selected as dependent variables. A total of 11 formulations with 4 replicas was obtained and optimized. From response surface plot of disintegration time, wetting time, friability and hardness it was found that lower disintegration time of tablets could be obtained when C and B are kept at optimum level. Stability study of final batch showed no significant changes in tablet properties(AU)

El objetivo de este proyecto es la formulación de comprimidos bucodispersables de azitromicina que se desintegren rápidamente en la cavidad bucal y formen una dispersión estable. La formulación de comprimidos dispersables de azitromicina no se pudo realizar con el método de compresión directo, por lo que se usó el método de granulación húmeda. En un estudio preliminar, se evaluó el efecto de diferentes superdisgregantes, como croscarmelosa de sodio (CSS), glicolato sódico de almidón (SSG) y crospovidona, en la variación de peso, uniformidad, dureza, tiempo de disgregación y friabilidad de los comprimidos. En todas las formulaciones, se usó agua como agente aglutinante para conseguir dureza. Se usó Avicel como agente disolvente y aspartamo como agente edulcorante. Estearato de magnesio y Aerosil se usaron como lubricante y deslizante, respectivamente. Se usaron estudios FT-IR para obtener la compatibilidad de los fármacos y los excipientes. El diseño de celosía simple se aplicó usando distintas cantidades de concentraciones intragranulares de superdisgregantes. Se seleccionaron, como variables independientes, el glicolato sódico de almidón (A), la croscarmelosa de sodio (B) y la crospovidona (C). Como variables dependientes, se eligieron la dureza (R1), el tiempo de desintegración (R2), la friabilidad (R3) y el tiempo de humectación (R4). Se obtuvieron y se optimizaron un total de 11 formulaciones con 4 réplicas. Según la gráfica de la superficie de respuesta del tiempo de disgregación, el tiempo de humectación, la friabilidad y la dureza, se observó que se podía obtener un tiempo de disgregación más bajo cuando C y B se mantenían en un nivel óptimo. El estudio de estabilidad del último grupo no mostró cambios significativos en las propiedades de los comprimidos(AU)

Antiviral properties of the seed extract of an Indian medicinal plant, Pongamia pinnata, Linn., against herpes simplex viruses: in-vitro studies on Vero cells.

Pongamia pinnata, Linn., an Indian medicinal plant used in the Ayurvedha and Siddha traditional medicine systems, for treatment of clinical lesions of skin and genitalia, was evaluated for antiviral properties against herpes simplex virus type-1 (HSV-1) and type-2 (HSV-2) by in-vitro studies in Vero cells. A crude aqueous seed extract of P. pinnata completely inhibited the growth of HSV-1 and HSV-2 at concentrations of 1 and 20 mg/ml (w/v), respectively, as shown by complete absence of cytopathic effect.