Reverse transcriptase drug resistance mutations in HIV-1 subtype C infected patients on ART in Karonga District, Malawi.

BACKGROUND: Drug resistance testing before initiation of, or during, antiretroviral therapy (ART) is not routinely performed in resource-limited settings. High levels of viral resistance circulating within the population will have impact on treatment programs by increasing the chances of transmission of resistant strains and treatment failure. Here, we investigate Drug Resistance Mutations (DRMs) from blood samples obtained at regular intervals from patients on ART (Baseline-22 months) in Karonga District, Malawi. One hundred and forty nine reverse transcriptase (RT) consensus sequences were obtained via nested PCR and automated sequencing from blood samples collected at three-month intervals from 75 HIV-1 subtype C infected individuals in the ART programme. RESULTS: Fifteen individuals showed DRMs, and in ten individuals DRMs were seen from baseline samples (reported to be ART naïve). Three individuals in whom no DRMs were observed at baseline showed the emergence of DRMs during ART exposure. Four individuals who did show DRMs at baseline showed additional DRMs at subsequent time points, while two individuals showed evidence of DRMs at baseline and either no DRMs, or different DRMs, at later timepoints. Three individuals had immune failure but none appeared to be failing clinically. CONCLUSION: Despite the presence of DRMs to drugs included in the current regimen in some individuals, and immune failure in three, no signs of clinical failure were seen during this study. This cohort will continue to be monitored as part of the Karonga Prevention Study so that the long-term impact of these mutations can be assessed. Documenting proviral population is also important in monitoring the emergence of drug resistance as selective pressure provided by ART compromises the current plasma population, archived viruses can re-emerge

A cross sectional study of behavioral problems of secondary school children and related socio-demographic factors

Background: School-going children form an important vulnerable segment of the nation’s population. Children in the school-going age group of 5 to 16 years constitute a total of 30% of the total population. School age is a dynamic period of physical growth and development, when the child undergoes rapid mental, emotional, and social changes. Therefore, school-going children are susceptible groups for psychiatric disorders especially behavioural problems. The present research was carried out with an objective to study the behavioural problems of secondary school children and its relation to the various socio-demographic and socio-economic factors.Methods: This cross sectional observational study was conducted on 304 secondary school children studying in 8th and 9th standard in the regarding socio-demographic profile and Strength and difficulties questionnaire. The analysis was done using Microsoft Excel and SPSS software.Results: In this study, the prevalence of abnormal behavioral according to self-rated SDQ was found to be 1.6% while prevalence of borderline abnormal behavior was 11.2% and majority 87.2% of study subjects were normal having no behavioral problem. The combined borderline and abnormal behavioral problems were more prevalent in the age group of 12-13year (64.1%) and 13-14 years (30.8%), also more prevalent among girls (69.2%) compared to boys (30.8%). The prevalence of behavioral problems was higher among students studying in 9th standard (74.4%, 29/39) and studying in Hindi medium (61.5%). The incidence was found to be more in students who belongs to nuclear families (79.5%) and also was more among those who were first born compared to middle born and last born children. Majority of fathers were working as semiskilled (41.4%) and skilled (32.9%) workers, among the father’s alcohol users (45.06%) were high compared to the tobacco users (31.9%).Conclusions: Socio-demographic factors and occupation of father and alcohol consumption among them was found to be significantly associated with the behavioural problems of the study subjects

Ultrasound enhances lipase-catalyzed synthesis of poly (ethylene glutarate)

The present work explores the best conditions for the enzymatic synthesis of poly (ethylene glutarate) for the first time. The start-up materials are the liquids; diethyl glutarate and ethylene glycol diacetate, without the need of addition of extra solvent. The reactions are catalyzed by lipase B from Candida antarctica immobilized on glycidyl methacrylate-ter-divinylbenzene-ter-ethylene glycol dimethacrylate at 40 °C during 18 h in water bath with mechanical stirring or 1 h in ultrasonic bath followed by 6 h in vacuum in both the cases for evaporation of ethyl acetate. The application of ultrasound significantly intensified the polyesterification reaction with reduction of the processing time from 24 to 7 h. The same degree of polymerization was obtained for the same enzyme loading in less time of reaction when using the ultrasound treatment. The degree of polymerization for long-term polyesterification was improved approximately 8-fold due to the presence of sonication during the reaction. The highest degree of polymerization achieved was 31, with a monomer conversion of 96.77%. The ultrasound treatment demonstrated to be an effective green approach to intensify the polyesterification reaction with enhanced initial kinetics and high degree of polymerization.This study was supported by Portuguese Foundation for Science and Technology (FCT) under the scope of the strategic funding of UID/BIO/04469/2013 unit and COMPETE 2020 (POCI-01-0145-FEDER-006684). The work was also supported by Bioprocess and Bionanotechnology Research Group (BBRG) of Minho University and the Post Graduate Funding Program of Jiangnan University for Overseas Study. All authors also acknowledge the funding of Department of Science and Technology and Portuguese Science Foundation under the Indo-Portuguese collaborative program

AN EXHAUSTIVE REVIEW ON EMERGING DRUG TARGETS OF TUBERCULOSIS WITH SPECIAL EMPHASIS ON CELL WALL SYNTHESIS

Tuberculosis (TB) is one of the top 10 causes of mortality and morbidity. Worldwide, yet, it has been over 60 years since a novel drug was introduced in market to treat the disease exclusively. Increased number of drug resistant TB cases has prompted the search for novel potent anti-TB drug. Mycobacterial cell wall has unique structure which provides integrity to the cell. The future development of new potent anti-TB drug targets is associated with the synthesis of various cell wall constituents; the structural and genetic information about mycobacterial cell wall envelope is now available. In the present review, we have focused on prospective drug targets that can be optimum triumph for successful drug candidate

THERMOSENSITIVE IN SITU GEL OF TINIDAZOLE IN TREATMENT OF BACTERIAL VAGINOSIS: FORMULATION AND EVALUATION

Bacterial Vaginosis (BV) is the leading cause of vaginal discharge. Because of its big surface area, wealthy blood supply, avoidance of the first-pass effect and high permeability to many drugs, the vagina offers a promising location for local impact as well as systemic drug delivery. In situ gels give several benefits, such as ease of administration in the respective body cavities, elevated spreadability at certain temperatures, reduced administration frequency, improved patient compliance and comfort compared to standard dosage forms. Tinidazole (TNZ) can give effective treatment over the BV. In situ gel of TNZ containing polaxomer 407 and HPMC E100 or carbopol 941NF was optimized on the basis of various evaluation parameters. Gelation temperature (Tgel) and pH of all batches was found in range of 36.6 to 38.0 ºC and 4.20 to 5.03, viscosity was found in range of 1100-2050 cps at 25ºC and 4800-6530 cps at 37ºC. The Spredability was found in range of 16-20 cm. From these evaluation parameters we selected best combination for the mucoadhesive property, antimicrobial study, in vitro drug release and for HET CAM irritation study. The optimized formulation gives satisfactory results. In this study we also compare the performance of two mucoadhesive polymer. Based on maximum desirability and cost effectiveness, in situ vaginal gel containing 20% polaxomer and 0.5% HPMC E100 could be considered as a highly promising treatment for bacterial vaginosis

Evaluation of lipid lowering ability of atorvastatin and ezetimibe combination as compared with atorvastatin monotherapy

Background: Many patients on statin therapy do not achieve recommended LDL cholesterol goals. They require either high dose statin regimen or combination of statins with other lipid modifying agents. Ezetimibe is a novel drug when added to statins, will provide additional reduction in LDL-C level.Methods: Total 100 patients with CHD or hypertension and having serum LDL-C levels of ≥100 mg/dl were enrolled for the study and were randomly allocated to two groups. Baseline investigations done. Patients from Group I received Atorvastatin (10mg) per day orally and patients from group II received combination of Atorvastatin (10mg) and Ezetimibe (10mg) per day orally. Study treatment was started on the day of randomization and continued for 12 weeks and follow up visits were scheduled at 4, 8, and 12 weeks. During each follow up investigations repeated and patients were interviewed and examined for occurrence of any adverse effect.Results: There was greater reduction in levels of LDL-C, Total cholesterol and serum triglycerides in patients treated with Atorvastatin plus Ezetimibe combination as compared to those patients treated with Atorvastatin alone. This difference in percentage reduction in LDL-C, Total cholesterol and serum triglycerides levels in two groups was highly significant at 4, 8 and 12 weeks (p100mg/dl as it significantly lowers the LDL-C along with total cholesterol and triglycerides