Repurposing — a ray of hope in tackling extensively drug resistance in tuberculosis

Tuberculosis (TB) remains a serious concern more than two decades on from when the World Health Organization declared it a global health emergency. The alarming rise of antibiotic resistance in Mycobacterium tuberculosis, the etiological agent of TB, has made it exceedingly difficult to control the disease with the existing portfolio of anti-TB chemotherapy. The development of effective drugs with novel mechanism(s) of action is thus of paramount importance to tackle drug resistance. The development of novel chemical entities requires more than 10 years of research, requiring high-risk investment to become commercially available. Repurposing pre-existing drugs offers a solution to circumvent this mammoth investment in time and funds. In this context, several drugs with known safety and toxicity profiles have been evaluated against the TB pathogen and found to be efficacious against its different physiological states. As the endogenous targets of these drugs in the TB bacillus are most likely to be novel, there is minimal chance of cross-resistance with front-line anti-TB drugs. Also, reports that some of these drugs may potentially have multiple targets means that the possibility of the development of resistance against them is minimal. Thus repurposing existing molecules offers immense promise to tackle extensively drug-resistant TB infections

Evaluation of cytogenic damage in the form of micronuclei in oral exfoliated buccal cells in tobacco users

Background: Variety of substances such as tobacco, UV radiation, infrared rays, X-radiations, and chemicals on oral induction results in chromosomal aberrations and production of micronucleus (MN). Among them, tobacco-specific nitrosamines are potent mutagenic agents causing oral cancer. Objective: The objective of the study is to compare the genotoxicity in buccal mucosal cells, i.e. the MN count of all groups and to find the incidence of micronucleated cells (MNCs) in accordance to duration and frequency of tobacco usage and timing of contact of tobacco in the oral mucosa. Materials and Methods: Individuals without any oral diseases were divided into 3 groups having 25 in each group: smoking, chewing, and control. Smears were made from buccal exfoliated cells and stained with DNA-specific Feulgen stain. Frequency on MNC per 500 cells was assessed with one-way ANOVA and Tukey HSD multiple comparisons test and mean rank with Kruskal–Wallis test. Results: The mean micronucleus MN revealed that chewers had 8.00, smokers had 7.20 and controls had 0.4. The ANOVA test for mean frequency of micronucleated cell MNC revealed High significance (<0.001) for between groups comparison. The mean rank by Kruskal Wallis test revealed the MNC increases as the duration and frequency of habit increases. An increase in MNC in accordance to time of contact with buccal mucosa increases as the duration and time increases. Conclusion: Estimation of MN serve as an indicator of genetic damage and points that tobacco in chewing form induce genotoxic effect. This is studied in an easily accessible tissue- buccal mucosa in a non invasive manner

<span style="font-size:11.0pt;font-family: "Times New Roman";mso-fareast-font-family:"Times New Roman";mso-bidi-font-family: Mangal;mso-ansi-language:EN-GB;mso-fareast-language:EN-US;mso-bidi-language: HI" lang="EN-GB">Selection of nutrients for polygalacturonase production by <i style="mso-bidi-font-style:normal">Aspergillus awamori</i> MTCC 9166 using Plackett-Burman design</span>

502-507Selection of the best nutrients is one of the most critical stage in media optimization for polygalacturonase production. Plackett-Burman design was used to screen various pectin substrates, nitrogen sources and mineral nutrients for polygalacturonase production by Aspergillus awamori MTCC 9166. Fifteen different pectin sources like crude pectin, polygalacturonic acid, orange peel, citrus peel, jackfruit peel, etc. were selected for polygalacturonase production using 16 experimental design of Plackett-Burman. Similarly, eleven nitrogen sources like yeast extract, tryptone, casein hydrolysate, sodium nitrate, ammonium chloride, etc. and eleven mineral nutrients like NaCl, MgSO4, KH2PO4, CaCl2, etc. were screened for polygalacturonase production using 12 experimental design of Plackett-Burman. The enzyme production was studied for 5 d, where the maximum production was observed on 3rd d and so this data was analyzed using Indostat software to obtain regression coefficients and t-values. Based on these values significant nutrients like seven pectin sources (orange peel, jack fruit rind, apple peel, pine apple peel, mango peel, banana peel & tomato pulp), four nitrogen sources (urea, yeast extract, casein hydrolysate & potassium nitrate) and four mineral nutrients (NaCl, KH2PO4, CaCl2 & KH2PO4) were selected for second level screening of efficient nutrients for polygalacturonase production using 16 experimental design of Plackett-Burman. Orange peel as pectin source, casein hydrolysate as nitrogen source and NaCl showed maximum enzyme production and so were selected for further quantitative optimization

Fibrocalculous pancreatic diabetes: long-term survival analysis

Objective: To determine the long-term survival and causes of death in fibrocalculous pancreatic diabetes, a form of diabetes secondary to tropical chronic pancreatitis. Research design and methods: A cohort of 370 patients with fibrocalculous pancreatic diabetes were analyzed with respect to survival time from the date of occurrence of the first symptom of the disease as well as after the onset of diabetes. The cause of death was analyzed in the patients who died. Cumulative survival rates were calculated by the actuarial method, and life table graphs were plotted by mathematical calculations. Results: Long-term survival of patients with fibrocalculous pancreatic diabetes is much better today than that described 30 years ago. About 80% of patients were alive 35 years after the first episode of abdominal pain. The median survival time after the diagnosis of diabetes was 25 years. These figures, however, are still considerably lower than the life expectancy of the age- and sex-matched general population. Diabetic nephropathy was the main cause of death. Pancreatic cancer and other chronic pancreatitis-related causes as well as malnutrition and infections were also important contributors to mortality. Conclusions: The overall prognosis for patients with fibrocalculous pancreatic diabetes appears to have improved possibly because of earlier diagnosis, better management of diabetes, and improved nutrition

Optimization of fermentation conditions for production of glycopeptide antibiotic vancomycin by Amycolatopsis orientalis

Glycopeptides produced by Streptomyces species are the drugs used against β-lactam drug-resistant staphylococcal infections, and vancomycin is important among them. Increased prevalence of resistant strains increased the usage of vancomycin worldwide and also promoted attempts for indigenous production. The optimum process conditions pH, temperature, inoculum size, agitation, and aeration for vancomycin production by Amycolatopsis orientalis were evaluated, statistically analyzed, and the response surface curves were constructed. The optimum process conditions were a pH of 7.6, a temperature of 29°C, an inoculum size of 4.5%, an agitation of 255 rpm, and an aeration of less than 1:10 medium-to-air ratio