Process development and immunogenicity studies on a serogroup 'X' Meningococcal polysaccharide conjugate vaccine.

Meningococcal group X (MenX) is responsible for recent outbreaks of meningitis reported in sub-Saharan region of Africa. Although protective vaccines are available for meningitis, they are not effective against MenX. An efficacious, monovalent conjugate vaccine was designed against MenX and a fed-batch fermentation process was developed. The MenX polysaccharide (PS) was purified and yield estimated to be 15-fold higher than the reported elsewhere. Structure of MenX polysaccharide was confirmed by (1)H, (13)C NMR spectroscopy analysis. Molecular weight of PS was found to be 310 kDa using HPLC-SEC coupled to refractive index (RI) detector. The MenX-Tetanus toxoid (TT) monovalent conjugate proved to be highly immunogenic in mice, and the bactericidal titers of MenX-TT conjugate were 10-fold higher than native PS. Increasing the dose of MenX-TT conjugate from 0.5 µg to 1.0 µg induced an 8-fold higher antibody titer as well as serum bactericidal titer. The current work suggests that the MenX-TT conjugate is a candidate vaccine against meningitis caused by Meningococcal group X strains.

Evaluation of the Prevalence and Risk Factors of Drug-Related Problems in Hypertension and Type 2 Diabetes Mellitus Patients at a Tertiary Care Hospital: A Cross-Sectional Study.

Background Drug-related problems (DRPs) potentially interfere with the desired treatment goals which may lead to increased healthcare costs, morbidity, and mortality. Despite the negative consequences of DRPs, there is a lack of comprehensive research on their prevalence and risk factors, particularly in chronic diseases such as hypertension and type 2 diabetes mellitus (DM). This study aims to evaluate the prevalence and contributing factors of DRPs among hypertension, type 2 DM, and hypertension with type 2 DM in the outpatient general medicine department. Methodology A hospital-based, prospective, observational study was conducted over three months. DRPs were classified using the Helper-Strand classification. The potential risk factors contributing to DRPs were assessed using binary and multinomial logistic regression methods. A p-value <0.05 was considered statistically significant. Results Among the 236 study participants, DRPs were more prevalent in males, and the mean age of the participants was 51.73 ± 9.47 years. DRPs were found in 76% of the study participants, and the mean number of DRPs per patient was 1.16 ± 0.45. Among the identified DRPs, suboptimal therapeutic goals (33%) were the most frequently observed, followed by ineffective drugs (32%), medication non-adherence (23%), and drug-drug interaction (5%). Therapeutic duplication and overdose were less commonly encountered as DRPs. The presence of comorbidity (adjusted odds ratio (AOR) = 5.77), and smoking (AOR = 21.07) were found to be significant risk factors (p < 0.05) contributing to DRPs. Conclusions DRPs are more prevalent in hypertension, type 2 DM, and hypertension with type 2 DM. Age range (40-60 years), comorbidity, and smoking were found to be associated with a higher incidence of DRPs. The implementation of a multidisciplinary team approach involving clinical pharmacists and physicians can effectively identify the prevalence and determine the associated risk factors of DRPs and subsequently may help employ targeted interventions to mitigate the development of DRPs.

Computational studies on N-phenyl pyrrole derivatives as MmpL3 inhibitors in Mycobacterium tuberculosis.

The fight against tuberculosis (TB) is a time immemorial one and the emergence of new drug resistant strains of Mycobacterium tuberculosis keeps throwing new challenges to the scientific community immersed in finding mechanisms to control this dreaded disease. Computer aided drug designing (CADD) is one of the several approaches that can assist in identifying the potent actives against Mycobacterium. In this work, a series of 109 known Mycobacterial membrane proteins large 3 (MmpL3) inhibitors were pooled and atom based 3D QSAR analysis was performed to understand the structural features essential for inhibitory activity against the MmpL3, known to be a key player in transporting substances critical for cell wall integrity of Mycobacterium. The data set employed was randomly split into training set and test set molecules. The training set of 74 molecules was used to derive CoMFA and CoMSIA models that were statistically reliable (CoMFA: q2loo = 0.53; r2ncv = 0.93 and CoMSIA: q2loo = 0.60; r2ncv = 0.93). The derived models also exhibited good external predictive ability (CoMFA: r2pred = 0.78 and CoMSIA: r2pred = 0.79). The results are quite encouraging and information derived from these analyses was applied to design new molecules. The designed molecule showed appreciable predicted activity values and reasonably good ADMET profile. The strategy used in designing new molecules can be pursued in the hunt for new chemical entities targeting MmpL3, expanding the existing arsenal against TB.

Oral health related knowledge, attitude and practices among the primary health care workers of a district in India.

AIM: To assess the knowledge, attitude, and practices of the primary health care workers in our country. MATERIALS AND METHODS: Data was gathered by means of a closed-ended questionnaire form. A total of 30 primary health centers (PHCs) and 60 subcenters (SCs) were included in the study. Frequency distribution was used together with Chi-square tests and analysis of variance (ANOVA) in this study. A P value of < 0.05 was considered significant. RESULTS: Only 40% of the primary health care workers knew that dental caries is multifactorial, majority of them could not identify the symptoms of gum diseases, a meager number of the primary health care workers (28%) knew about the oral health aspects of a pregnant lady, and with the exception of doctors, the other health care workers were not sure of the etiology of oral cancer. CONCLUSION: About one-tenth of the primary care workers had high knowledge regarding oral health, only one-tenth of them had highly favorable oral health attitudes, and 9% of them had highly favorable oral health practices.

Antimicrobial activity of some pentacyclic triterpenes and their synthesized 3-O-lipophilic chains.

The major metabolites of Diopsyros melanoxylon viz. amyrins and ursolic acid and their lipophilic 3-O-fatty acid ester chains (C12-C18), which are synthesized now under mild esterification conditions in excellent yields (80-95%), were evaluated for their antimicrobial activity against a series of Gram positive and Gram negative bacteria. Significantly these compounds were found to exhibit potent activity against Gram negative bacteria Pseudomonas syringae (ATCC #13457) and fairly good activity against Gram positive bacteria, Bacillus sphaericus (ATCC #14577) and Bacillus subtilis (ATCC #6051).