Psychobiotics for Mitigation of Neuro-Degenerative Diseases: Recent Advancements.

Ageing is inevitable and poses a universal challenge for all living organisms, including humans. The human body experiences rapid cell division and metabolism until approximately 25 years of age, after which the accumulation of metabolic by-products and cellular damage leads to age-related diseases. Neurodegenerative diseases are of concern due to their irreversible nature, lack of effective treatment, and impact on society and the economy. Researchers are interested in finding drugs that can effectively alleviate ageing and age-related diseases without side-effects. Psychobiotics are a novel class of probiotic organisms and prebiotic interventions that confer mental health benefits to the host when taken appropriately. Psychobiotic strains affect functions related to the central nervous system (CNS) and behaviors mediated by the Gut-Brain-Axis (GBA) through various pathways. There is an increasing interest in researchers of these microbial-based psychopharmaceuticals. Psychobiotics have been reported to reduce neuronal ageing, inflammation, oxidative stress, and cortisol levels; increase synaptic plasticity and levels of neurotransmitters and antioxidants. The present review focuses on the manifestation of elderly neurodegenerative and mental disorders, particularly Alzheimer's disease (AD), Parkinson's disease (PD), and depression, and the current status of their potential alleviation through psychobiotic interventions, highlighting their possible mechanisms of action.

Purification and characterization of a broad spectrum bacteriocin produced by a selected Lactococcus lactis strain 63 isolated from Indian dairy products.

Lactococcus lactis subsp. lactis strain 63 was isolated from Indian dairy products, produced a bacteriocin with broad spectrum inhibition against several of food pathogens like Listeria monocytogenes and Bacillus cereus as well as Gram negative bacteria viz., E. coli, Yersinia, Citrobacter, Proteus, Enterobacter, Klebsiella and Serratia strains. Bacteriocin production was higher in GM-17 and MRS as compared to TYGE broth and enriched skim milk broth and reached the maximum level during the early stationary phase. The bacteriocin was purified by performing ammonium sulfate precipitation. The bacteriocin was able to survive 90 °C/10 min but not 100 °C/10 min. Complete inactivation of bacteriocin was observed after autoclaving. The bacteriocin maintained its activity over a wide range of pH (3-9). The antimicrobial compound produced by the isolate 63, was sensitive to papain, pepsin, trypsin and amylase but was resistant to detergents like SDS and urea. Tween 20, Tween-80 as well as Triton X-100 enhanced its activity. Since the treatment with proteolytic enzymes resulted in loss of activity, this shows that the proteinaceous nature of the antimicrobial substance. Tentative molecular weight of the bacteriocin was found to be between 3.5 and 5 kDa by Tricine SDS-PAGE. Finally, we confirmed the presence of gene for nisin, and the sequence thus obtained, was identical to the sequences previously described for nisin Z. Lactococcus lactis subsp. lactis 63 or its bacteriocin, which has a wide inhibitory spectrum, has the potential for use as a starter or protective culture in the manufacture of fermented products.

Lurasidone Induced Thrombocytopenia: Is it a Signal of Drug Induced Myelosuppression?

The U.S. Food and Drug Administration (FDA) has approved a supplemental new drug application Lurasidone (Latuda, Sunovion Pharmaceuticals), an atypical antipsychotic, for the treatment of schizophrenia in adolescents 13-17 years of age. Lurasidone was previously indicated in the U.S. for the treatment of adults with schizophrenia and major depressive episodes with bipolar I disorder as monotherapy. We present a case of a 29-year-old male patient who was hospitalized with thrombocytopenia (WHO grade-3 toxicity) (unlabeled) along with extrapyramidal disorder, gastritis, and hyperprolactinemia within 2-3 months of initiation of tablet lurasidone 80 mg/day (Lurasid, Intas Pharmaceuticals) in bipolar depression. Dechallenge was found to be positive in three reactions except hyperprolactinemia (outcome unknown) during hospital stay. The terms anemia and leukopenia are well labeled/listed with the drug literatures of lurasidone. Thus, this case presents a strong probability of lurasidone to cause myelosuppression/bone marrow depression.

Impact of regulatory spin of pioglitazone on prescription of antidiabetic drugs among physicians in India: A multicentre questionnaire-based observational study.

Background & objectives: Pioglitazone was suspended for manufacture and sale by the Indian drug regulator in June 2013 due to its association with urinary bladder carcinoma, which was revoked within a short period (July 2013). The present questionnaire-based nationwide study was conducted to assess its impact on prescribing behaviour of physicians in India. Methods: Between December 2013 and March 2014, a validated questionnaire was administered to physicians practicing diabetes across 25 centres in India. Seven hundred and forty questionnaires fulfilling the minimum quality criteria were included in the final analysis. Results: Four hundred and sixteen (56.2%) physicians prescribed pioglitazone. Of these, 281 used it in less than the recommended dose of 15 mg/day. Most physicians (94.3%) were aware of recent regulatory events. However, only 333 (44.8%) changed their prescribing pattern. Seventeen of the 416 (4.1%) physicians who prescribed pioglitazone admitted having come across at least one type 2 diabetes mellitus patient (T2DM) who had urinary bladder carcinoma, and of these 13 said that it was in patients who took pioglitazone for a duration of more than two years. Only 7.8 per cent of physicians (n=58) categorically advocated banning pioglitazone, and the rest opined for its continuation or generating more evidence before decision could be taken regarding its use in T2DM. Interpretation & conclusions: Majority of the physicians though were aware of the regulatory changes with regard to pioglitazone, but their prescribing patterns were not changed for this drug. However, it was being used at lower than the recommended dose. There is a need for generating more evidence through improved pharmacovigilance activities and large-scale population-based prospective studies regarding the safety issues of pioglitazone, so as to make effectual risk-benefit analysis for its continual use in T2DM.

A study of knowledge, attitudes, and practice of dental doctors about adverse drug reaction reporting in a teaching hospital in India.

OBJECTIVE: The aim was to investigate the knowledge, attitudes, and practice of dental doctors about adverse drug reaction (ADR) reporting. MATERIALS AND METHODS: In a cross-sectional study, questionnaire was administered to 95 dental doctors working in a teaching dental hospital attached to a medical college with an ADR monitoring center (AMC). STATISTICAL ANALYSIS USED: Descriptive statistics were used to analyze responses. The association of knowledge and attitude with respect to position of dentists was analyzed with Chi-square test. RESULTS: The response rate and spontaneous reporting rate was found to be 61.0% and 13.7%, respectively. Important factors contributing to under reporting of ADRs include lack of awareness about AMC in the institute (81.0%) and pharmacovigilance program (72.4%), complacency (67.2%), lack of training to identify ADRs (65.5%), fear factor (63.7%), lethargy (58.6%), lack of risk perception of over the counter product related ADR (39.6%), inadequate risk perception of nonallopathic and herbal medicines (31%), indifference (27.5%) and concern that report may be wrong (27.5%). No significant difference in knowledge and attitudes of doctors with respect to position was found except for reporting of ADRs of newly marketed drugs and serious reactions to established product (P < 0.05). CONCLUSION: The deficiencies in knowledge and attitudes appear to be the underlying factor for under reporting by dental practitioners. It should be addressed urgently in order to increase spontaneous reporting by them.

Knowledge, attitudes, and practice of doctors to adverse drug reaction reporting in a teaching hospital in India: An observational study.

BACKGROUND: Underreporting of spontaneous adverse drug reaction (ADR) is a threat to pharmacovigilance. Various factors related with the knowledge and attitudes are responsible for underreporting of ADRs. AIMS: The study was aimed at investigating the knowledge and attitudes of doctors to ADR reporting. MATERIALS AND METHODS: It was a questionnaire-based cross-sectional study. One hundred and eight questionnaires were administered to doctors working in a teaching hospital with an ADR monitoring center. STATISTICAL ANALYSIS USED: The descriptive statistics were used for responses to evaluate the knowledge and attitudes toward ADR reporting. Pearson's Chi-square test was used to observe the association of knowledge and attitude with experience and position. RESULTS: The response rate was 62.9%. Spontaneous reporting rate was found to be 19.1%. The major factors found to be responsible for underreporting of ADR include inadequate risk perception about newly marketed drugs (77.9%), fear factor (73.5%), diffidence (67.7%), lack of clarity of information on ADR form about reporting (52.9%), lethargy (42.7%), insufficient training to identify ADRs (41.2%), lack of awareness about existence of pharmacovigilance program (30.9%) and ADR monitoring center in the institute (19.1%), and inadequate risk perception of over-the-counter (OTC) product (20.6%) and herbal medicines (13.2%). Experience and position did not influence the knowledge and attitudes of doctors. CONCLUSION: The deficiencies in knowledge and attitudes require urgent attention not only to improve the rate of spontaneous reporting, but also for enhanced safety of the patients and society at large.