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

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

Comparison of artesunate and quinine in the treatment of severe falciparum malaria: a randomized control trial

Background: Severe malaria is a medical emergency that required prompt clinical assessment and management. Very few studies underwent to evaluate the best possible treatment for severe malaria.Methods: This is a prospective, randomized, open-labeled, study to evaluate the efficacy and safety of artesunate compared with quinine. Totally, 50 patients were included in each group. Patients above 18 years, peripheral smear positive and fulfilling the WHO criteria were included. The endpoint of the study was fever clearance time (FCT), parasite clearance time (PCT) and coma resolution time (CRT), and the adverse effect if any were compared for safety analysis.Results: FCT and PCT were much less with artesunate (29.64 and 39.72 hrs) as compared to quinine (51.12 and 55.20 hrs). CRT was less with quinine (25.80 hrs) than artesunate (42 hrs). The incidence of adverse effects such as hypoglycemia and QT prolongation are significant with quinine compared to artesunate.Conclusions: Artesunate is a better alternative for severe malaria with minimal side effects

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

STABILITY INDICATING RP-HPLC-PDA METHOD FOR DETERMINATION OF ABIRATERONE ACETATE AND CHARACTERIZATION OF ITS BASE CATALYZED DEGRADATION PRODUCT BY LC-MS

Objective: The present work describes stability indicating (SI) RP-HPLC-PDA method for determination of abiraterone acetate (ABA) and characterization of its base catalyzed degradation product by LC-MS.Methods: The separation was achieved by using column Kromasil C18 (250 mm × 4.6 mm, 4.0 µ) using acetonitrile (ACN): ammonium acetate buffer 10 mM, pH adjusted to 3.5 with acetic acid (AA) in the ratio of 10:90 % v/v as eluent. The Mobile phase flow rate was 0.6 ml/min and data integration was achieved at 235 nm.Results: The retention time of ABA was 5.4±0.01 min. Linearity was found to be in the range of 5–30 μg/ml. The limit of detection and quantitation were 0.25 μg/ml and 0.75 μg/ml respectively, and percentage recovery of ABA was found to be 99.52 to 100.13 %. Mass spectral data of base degraded product of ABA shows a prominent molecular ion peak at m/z-391.5. Major fragmentation leads to formation of 10–Methyl 2,3,4,7,8,9,10,11,12,13,14,15-dodecanhydro-1H cyclopenta (α)phenanthren-3-ol as a degradant (D2) at m/z-257.81, due to corresponding loss of C8H12ON. All the analytical validation parameters were determined and found in the limit as per ICH guidelines.Conclusion: The results of the various validation studies showed that the LC method is fast, specific, accurate, reproducible, possessed significant linearity and precision. The drug was found to be stable under all the stress conditions except basic stress. Thus developed method reported first time is novel with a very short run time of 6 min.Â

Evaluation of losartan plus hydrochlorothiazide combination therapy against amlodipine monotherapy in patients of hypertension

Background: Microalbuminuria has been shown to predict cardiovascular disease (CVD) in patients with hypertension. Recently the FDC of losartan and hydrochlorothiazide (HCTZ) has been reported to be effective for achieving a target BP level and also improvement in cardiovascular prognosis. The present study was conducted to compare effect of losartan plus hydrochlorothiazide combination therapy and high dose amlodipine monotherapy on blood pressure and microalbuminuria.Methods: Total 184 patients with hypertension were randomly allocated to two groups. The patients in group 1 received Amlodipine 5 mg orally for first 4 weeks. The  patients  from  group  2  received  losartan  50  mg  orally  for  first  4  weeks. Patients  in  group  1  were  titrated  to  amlodipine  10  mg  orally  for next 4 weeks. The patients in group 2 were titrated to FDC of losartan (50 mg) plus HCTZ (12.5 mg) for next 4 weeks. Follow–up visits were scheduled at 4 weeks and 8 weeks. Pulse rate, sSBP and sDBP were estimated at each follow–up. Microalbuminuria was estimated at 8 weeks.Results: There was no significant difference in mean change in sSBP, sDBP and pulse rate between two treatment groups (p>0.05). There was greater reduction in microalbuminuria in group 2 patients (p<0.0001). The adverse effects such as flushing and lower extremity oedema were significantly more in amlodipine group (p<0.05).Conclusions: Losartan plus HCTZ has similar effect on BP, better safety profile and superior effect on microalbuminuria level  reduction

Cross-sectional descriptive observational study of RT PCR proven category C H1N1 patients at tertiary care centre from January 2015- December 2015

Background: The onset of winter of 2014-2015 saw an alarming spurt in influenza A (H1N1) pdm 09 leading to a significant mortality. H1N1 primarily affects the very young, elderly, pregnancy and those patients with comorbidities. But the epidemiologic hallmark of pandemic influenza is its "pandemic signature " meaning most early mortalities are among young healthy adults.Methods: To study clinical profile, premorbid conditions and radiological features of Category C H1N1 proven by RTPCR retrospectively from hospital records from Jan 2015 to Dec 2015 at Tertiary Care Centre.Results: Total 108 cases RT PCR proven category C H1N1 studied from hospital records. 43 were males and 65 females. The mean age group was 50 years for males and 40 for females. Common symptoms were fever, cough, dyspnoea with pre-morbid illness like hypertension, diabetes mellitus, pregnancy, cancer and immune compromised with pulmonary tuberculosis. Radiologically there was lower zone involvement common in live patients and reticulonodular was common in death cases.Conclusions: In current study young to middle age group was commonly affected. Pre-morbid conditions, more than two risk factors and late referral were the most common findings in death cases

Callus induction from various explants of French bean (Phaseolus vulgaris L.)

Callus cultures were studied in white seed induced mutant obtained from Phaseolus vulgarisL., cv. varunto help establish a suitable protocol for a prospective in vitro program. Callus cultures were initiated from the axillary leaves, axillary shoots, node, internode, and root segments.The initiation and growth of callus were evaluated on MS medium with 3% sucrose, 0.4% agar, 1.5 mg.l-1BAP, and three levels of IAA. The highest callus relative growth was obtained on medium with 0.5 mg.l-1IAA and 1.5 mg.l-1BAP