Synthesis of S‐thiomethyl DMSA and S‐thiomethyl ECD,radiolabelling with technetium‐99m and biological evaluation

Protection of the thiolate function of dimercaptosuccinic acid (DMSA) and ethylenedi‐l ‐cysteine diethyl ester (ECD) by S‐thiomethylation allowed automatic deprotection during technetium‐99m (^99mTc) radiolabelling by direct reduction with stannous chloride dihydrate. Protection of the free thiolate group increased the stability of the ligands as well as deprotection during complexation, which resulted in the desired radiopharmaceuticals. The complexes obtained from the protected ligands were chromatographically (HPLC) and biologically compared with the corresponding ^99mTc complexes of the unprotected ligands. The results suggest that the aforementioned method of protection by S‐thiomethylation could be utilized for the development of single‐vial DMSA and ECD kit. Copyright © 2012 John Wiley & Sons, Ltd.     

Development of a discriminating in vitro dissolution method for a poorly soluble NO-donating selective cyclooxygenase-2 inhibitor

A discriminating dissolution method using a USP apparatus 2 dissolution tester was developed for a nitric oxide donating selective COX-2 inhibitor to support phase I and II formulation development, clinical supplies release and stability testing of an immediate release oral tablet. The BCS class II compound showed very low aqueous solubility and required the use of surfactant-containing (sodium lauryl sulfate (SLS)) dissolution medium in order to achieve an appropriate release profile. The dissolution method utilized 900 mL of 2% SLS (w/v). Samples were withdrawn at five specified time-points over 60 min, at a paddle speed of 75 rpm. Analysis of samples was performed using a validated HPLC method. Despite the use of high levels of SLS, the ability to discriminate variations in physical properties such as drug particle size, granule particle size and tablet compression force was demonstrated. In order to confirm the relationship between these physical parameters and the tablet in vivo release profile, oral dosing of the formulations in fasted beagle dogs was performed to determine if the changes observed in the dissolution profiles were biorelevant. The results of the dissolution and corresponding in vivo experiments helped identify the critical processing parameters likely to influence product bioavailability.     

Risk for Infection with Highly Pathogenic Avian Influenza Virus (H5N1) in Backyard Chickens, Bangladesh

To evaluate risk factors for infection with highly pathogenic avian influenza A virus (H5N1) in backyard chickens in Bangladesh, we conducted a matched case–control study. We enrolled 25 case farms (cases March–November 2007) and 75 control farms (June–November 2007). We used a questionnaire to collect farm data, which were analyzed by matched-pair analysis and multivariate conditional logistic regression. Factors independently associated were offering slaughter remnants of purchased chickens to backyard chickens (odds ratio [OR] 13.29, 95% confidence interval [CI] 1.34–131.98, p = 0.027), having a nearby water body (OR 5.27, 95% CI 1.24–22.34, p = 0.024), and having contact with pigeons (OR 4.47, 95% CI 1.14–17.50, p = 0.032). Separating chickens and ducks at night was protective (OR 0.06, 95% CI 0.01–0.45, p = 0.006). Reducing these risks and taking protective measures might reduce the risk for influenza (H5N1) infection in backyard chickens.     

Evaluation of oleoresin capsicum of Capsicum frutescenes var. Nagahari containing various percentages of capsaicinoids following inhalation as an active ingredient for tear gas munitions

Comparative efficacy as peripheral sensory irritant, oral and inhalation exposure studies were carried out on oleoresin capsicum (OC) of Capsicum frutescence var. Nagahari containing various percentages of capsaicinoids and two synthetic isomers of capsaicin in Swiss albino male mouse model to come up with a suitable active ingredient from natural source for tear gas munitions. The compounds screened were OC having varying percentages of capsaicinoids (20, 40 and 80%, respectively) and synthetic isomers (E and Z) of capsaicin (8-methyl-N-vanillyl-6-nonenamide). Mice were exposed to pyrotechnically generated smoke of the compounds in an all glass static exposure chamber for 15?min to determine acute inhalation toxicity (LC(50)) and quantitative sensory irritation potential (RD(50)). Acute oral median lethal dose (LD(50)) was also evaluated. Safety index of tear gas (SITG), a ratio of lethal concentration 50% (LC(50)) and the concentration which depresses respiration by 50% (RD(50)) due to peripheral sensory irritation is also proposed. The compound having highest SITG is considered as the most suitable to be used for tear gas munitions. The study revealed that oleoresin capsicum containing 40% capsaicinoids had the highest SITG among the compounds studied. The oral dosage versus mortality pattern of some compoundsdid not follow a true dose-response curve (DRC); however, following inhalation, all the compounds followed DRC. It was concluded that oleoresin capsicum (40% capsaicinoids) may be considered as the most suitable and environmental friendly compound from natural source to be used as an active ingredient for tear gas munitions.     

Antiproliferative, cytotoxic and apoptogenic activity of Indian toad (Bufo melanostictus, Schneider) skin extract on U937 and K562 cells.

The antiproliferative, cytotoxic and apoptogenic activities of Bufo melanostictus (Indian common toad) skin extract (TSE) on U937 and K562 leukemic cell line has been investigated. TSE significantly (P<0.001) reduced the time-dependent cell proliferation and decreased MTT values in U937 and K562 cells. TSE (IC50 doses) suppressed the proliferating cell nuclear antigen expression in both the cells. It was demonstrated that, TSE (IC50 doses) primarily arrested the U937 and K562 cells at G1 phase of the cell cycle. Confocal microscopy showed the altered fragmented nuclei and apoptotic bodies formation in TSE (IC50 doses) treated U937 and K562 cells. Membrane blebbing, cell surface shrinkage and perforation were observed through scanning electron microscope. TSE-induced DNA fragmentation in U937 and K562 cells was reflected in single-cell gel electrophoresis. TSE significantly (P<0.001) increase the length-width ratio of DNA mass as compared to control in comet assay. The flow cytometric analysis of annexin-V binding to the cancer cells further supported the apoptotogenic activity of TSE. The effect of TSE on normal human peripheral blood mononuclear cells viability and cytotoxicity was studied in culture and found to be less cytotoxic than on the U937 and K562 cells. The findings from the present study suggested that TSE might possess potent antineoplastic agent having antiproliferative, cytotoxic and apoptogenic activity against U937 and K562 myeloid leukemic cells.     

Five minutes' field study on each Indian hockey player in a coaching camp

Peak expiratory flow rate (PEFR) was measured using portable Wright's peak flow meter on 21 male hockey players of Indian national hockey team probables attending a zonal coaching camp. The mean PEFR was observed to be 580.95 +/- 43.34 1/minute. The PEFR in hockey players were higher than those recorded in inter-university 'kabaddi', basketball players and football goalkeepers. All the group of players had shown higher mean PEFR than those of age matched healthy Indian males.     

Simple anthropometry and peak expiratory flow rate in elite South Asian athletes.

The athletes (n = 40) of South Asian Federation (SAF) Games were examined each taking a very short time. The athletes were runners (short distance, long distance and marathon), jumpers and throwers who were persuaded for the purpose. The throwers and the jumpers respectively comprised the oldest and youngest group of athletes in the study. The throwers were observed to be the tallest (mean height 179.96 +/- 1.49 cm) and heaviest (mean weight 92.27 +/- 3.81), whereas the long distance runners were of short height (mean value 162.80 +/- 2.61 cm) and light weight (mean value 50.41 +/- 2.58 kg). The highest mean values of PEFR (lit/min) were noted among the throwers (596.60 +/- 27.53) followed by marathon (590.0 +/- 32.18) and long distance runners (588.0 +/- 27.35). The lower values of PEFR were noted among the short distance runners (528.60 +/- 15.83) and jumpers (525.70 +/- 22.60). The PEFR values, when arranged according to height, were noted to be insignificantly increasing with the increase in age. The overall values of height, weight and PEFR were all found to be higher in these elite sportsmen when compared with their non-sportsman Indian counterparts.     

Ocular side effects of systemic steroid therapy in renal transplant patients

Sixty-one renal transplant patients were studied for ocular complications of steroid therapy. Twenty patients (32.8%) were found to have posterior subcapsular cataract. Three patients (4.9%) had ocular hypertension. There was no significant correlation between cataract formation and the total dose of steroids, number of rejection episodes, or the period of hemodialysis. HLA-A9 was present in noncataract patients to a greater extent, a statistically significant (P less than .05) finding not reported before to our knowledge.