SYNTHESIS AND IN VITRO ANTIMICROBIAL EVALUATION OF PIPERAZINE SUBSTITUTED QUINAZOLINE-BASED THIOUREA/THIAZOLIDINONE/CHALCONE HYBRIDS.

In frames of the search for new biological entities to fight against recent drug-resistant microbial strains, we report a library of quinazoline-based thiourea/4-thiazolidinone/chalcone hybrids. The newly synthesized compounds were studied for efficacy against several bacteria (Staphylococcus aureus, Bacillus cereus, Pseudomonas aeruginosa, and Klebsiella pneumoniae) and fungi (Candida albicans and Aspergillus clavatus) using the broth dilution technique. From the biological evaluation, (E)-3-(3,4-dimethoxyphenyl)-1-(4-((4-(4-ethylpiperazin-1-yl)quinazolin-2-yl)amino)phenyl)prop-2-en-1-one was found to be the most active analogue (microbial inhibition concentration 3.12 µg/mL) to inhibit the bacterial growth. The rest of the compounds showed equipotent efficacy (3.12-12.5 µg/mL) as compared to the standard. Final compounds were characterized by FT-IR, 1H NMR, 13C NMR, mass spectroscopy, and elemental analysis.

Bioadhesive films containing fluconazole for mucocutaneous candidiasis.

Fluconazole is a broad spectrum antifungal agent that has been extensively applied for the management of oral, pharyngeal and cutaneous candidiasis. Fluconazole has a high volume of distribution (0.55-0.65 l/kg) and has systemic toxicity due to high drug-drug interaction. The present study focuses on the formulation of bioadhesive film as a controlled release carrier for fluconazole. The formulation was intended to provide localized delivery of fluconazole exclusively at the site of infection, thereby reducing its total dose and hence, dose-related toxicities. Bioadhesive films were prepared by solvent casting method using sodium alginate and polyvinyl alcohol alone as well as in various combinations. Prepared films were evaluated for physical characteristics like, weight and content uniformity, film thickness, swelling index, microenvironment pH and folding endurance. In vitro drug release, in vitro and ex vivo residence time, bioadhesive strength and skin irritation were also studied. Accelerated stability study was conducted on the optimized formulation as per ICH guidelines. Weight of all the films were not more than 20 mg. Thickness of the films ranged between 0.09 to 0.15 mm whereas swelling indices showed a high extent of variation. Films composed of polyvinyl alcohol alone provided a swelling index of 6%. Bioadhesive strength was found to be more than 18 g. Microenvironment pH was near to 7.0 for most of the formulations. Ex vivo residence time of optimized batch was more than 5 h and it provided controlled drug release up to 8 h. As revealed in FT-IR and DSC studies, drug was found to be compatible with the excipients used in this study.

Development and validation of simultaneous spectrophotometric methods for drotaverine hydrochloride and aceclofenac from tablet dosage form.

Two simple spectrophotometric methods have been developed for simultaneous estimation of drotaverine hydrochloride and aceclofenac from tablet dosage form. Method I is a simultaneous equation method (Vierodt's method), wavelengths selected are 306.5 and 276 nm. Method II is the absorbance ratio method (Q-Analysis), which employs 298.5 nm as λ(1) and 276 nm as λ(2) (λmax of AF) for formation of equations. Both the methods were found to be linear between the range of 8-32 µg/ml for drotaverine and 10-40 µg/ml for aceclofenac. The accuracy and precision were determined and found to comply with ICH guidelines. Both the methods showed good reproducibility and recovery with % RSD in the desired range. The methods were found to be rapid, specific, precise and accurate and can be successfully applied for the routine analysis of drotaverine and aceclofenac in their combined tablet dosage form.

A method for content uniformity determination of atenolol and losartan potassium in combined tablet dosage form.

A simple, accurate, rapid, specific and reproducible UV spectrophotometric method was developed for estimation of content uniformity of atenolol and losartan potassium in its combined tablet dosage form. The method involves formation and solving the simultaneous equation using 226.4 and 254 nm as two wavelengths for atenolol and losartan, respectively. Developed method was employed to determine the atenolol and losartan content in ten individual tablet units of five market formulations. Methanol was used as solvent. The method was validated. From the results, it was concluded that all brands are within the content uniformity limit, 85-115%.

An autopsy study of maternal mortality: a tertiary healthcare perspective.

BACKGROUND: An audit of autopsies of maternal deaths is important for the establishment of accurate cause of maternal deaths and to determine the contribution of various etiologies responsible in a given community. AIM: To study the causes of maternal deaths as determined by a pathological autopsy. SETTINGS AND DESIGN: A retrospective study of all the cases of maternal deaths that underwent a pathological autopsy in a tertiary healthcare center from January 1998 to December 2006. MATERIALS AND METHODS: The autopsy records with clinical notes were retrieved; gross and histopathology specimens and slides were studied to establish the accurate cause of maternal deaths. The variables like age (years), stay in the hospital, gravidity, trimester of pregnancy and method of delivery were used to classify and analyze the data from the autopsies. The causes of maternal deaths were divided in to direct and indirect; each being classified into subgroups based on the most evident pathology on autopsy. RESULTS: The Maternal Mortality Rate (MMR) over a nine-year period (1998-2006) was 827/100000 live births (471 maternal deaths against 56944 live births). An autopsy was performed in 277 cases (58.8%). In the autopsy group, the most common causes of maternal mortality were pre-ecclampsia/ecclampsia (40 of 277, 14.44%) and hemorrhage (32 of 277; 11.55%); However, indirect causes like infectious diseases (27 of 277; 9.75%) and cardiac (27 of 277; 9.75%) disease also contributed to maternal deaths. CONCLUSION: Indirect causes like rheumatic heart disease and infections like tuberculosis, malaria or leptospirosis and nutritional anemia are still major causes of maternal mortality in developing countries like India. Intensive efforts need to be taken in these areas to reduce the maternal mortality in developing countries like India.

A review on plant-derived natural products and their analogs with anti-tumor activity.

Traditional medicines, including Chinese herbal formulations, can serve as the source of potential new drugs, and initial research focuses on the isolation of bioactive lead compound(s). The development of novel plant-derived natural products and their analogs for anticancer activity details efforts to synthesize new derivatives based on bioactivity- and mechanism of action-directed isolation and characterization coupled with rational drug design - based modification. Also, the anticancer activity of certain natural products and their analogs can be enhanced by synthesizing new derivatives based on active pharmacophore models; drug resistance and solubility and metabolic limitations can be overcome by appropriate molecular modifications; and new biological properties or mechanisms of action can be added by combining other functional groups or molecules. Preclinical screening for in vitro human cell line panels and selected in vivo xenograft testing then identifies the most promising drug development targets.

Von Hippel-Lindau disease with multiple malignant renal tumors: the importance of genetic testing.

We present an adult man who, while being evaluated for gross hematuria, was found to have polycystic kidneys and multiple bilateral renal cell carcinomas. Further evaluation and the presence of a significant family history of cancer suggested the diagnosis of von Hippel-Lindau disease. Through the aid of genetic testing, this unusual diagnosis was confirmed and led to the identification of other family members with the von Hippel-Lindau gene. Patients with von Hippel-Lindau disease have an increased incidence of malignant carcinomas and the syndrome can mimic the presentation of other cystic diseases of the kidney. Early diagnosis and genetic screening of family members is essential to improve the prognosis and survival of those affected.

Effect of oral zinc sulphate on serum lipids and lipoproteins in human subjects.

A controlled study was undertaken to evaluate the hypolipidemic effect of zinc. Ten stabilized patients of ischaemic heart disease (IHD) were given 200 mg of zinc sulphate orally thrice a day for one month (Test group). Ten other patients were given a placebo (Control group). Serum cholesterol, triglycerides, alpha-lipoproteins and beta-lipoproteins were measured before and after the treatment period. Test group showed a significant decrease in serum cholesterol and beta-lipoproteins, a significant increase in alpha-lipoproteins and no significant change in triglycerides. Control group showed no significant change in any parameter. These results show the potential value of zinc sulphate in the treatment of hyperlipidemia and IHD.