Outcome of tuberculous meningitis in children aged 9 months to 12 years at the end of intensive phase of treatment.

BACKGROUND: Tuberculous meningitis (TBM) is associated with high morbidity and mortality. Most of the literature focuses on outcomes at the end of therapy when it may be too late for intervention to improve the outcomes. So, the present study addresses outcomes by the end of intensive course of therapy. METHODS: It was a prospective cohort observational study that enrolled 80 patients with TBM between 9 months and 12 years of age. Participants were classified into Definite, Probable and Possible TBM using Marais criteria. Survival/Mortality was evaluated at the end of hospital stay. Demographic, clinical, cerebrospinal fluid and radiological parameters were evaluated for predictors of morbidity and mortality. Standardized tools were used to assess possible impairments in different domains at the end of intensive phase of treatment, namely Gross Motor Functional Classification System for motor functional ability, Pediatric-Mini Mental score examination (MMSE), Blantyre Coma Scale (BCS) score and Vineland Social Maturity Scale (VSMS) for cognitive outcome, Auditory Brainstem Evoked Responses for hearing outcome and using Teller's/Snellen's visual acuity charts to assess visual impairment. RESULTS: A high Mortality rate of 42.5% was seen in the enrolled patients. Out of the total 80 patients, 20% recovered completely while 36.25% survived with disability (morbidity). Motor, Hearing, Cognitive and Vision impairment was present in 33.3%, 4%, 33.3% and 48.9% of the survivors respectively. On multivariate regression, raised intracranial tension and stage III disease were significantly associated with mortality. Morbidity was significantly associated with Stage III disease on multivariate analysis. CONCLUSIONS: Despite advances in treatment, Tuberculous meningitis is associated with high burden of deaths and devastating neurological sequelae. Timely diagnosis and intervention of neurological impairments is needed to improve the outcome of TBM in survivors.

QSAR Studies and Scaffold Optimization of Predicted Novel ACC 2 Inhibitors to treat Metabolic Syndrome.

BACKGROUND: Metabolic syndrome is one of the major non-communicable global health hazards of the modern world owing to its amplifying prevalence. Acetyl coenzyme-A carboxylase 2 (ACC 2) is one of the most crucial enzymes involved in the manifestation of this disease because of its regulatory role in fatty acid metabolism. OBJECTIVE: To find novel potent ACC 2 inhibitors as therapeutic potential leads for combating metabolic syndrome. METHODS: In the present study, a two-dimensional quantitative structure-activity relationship (2D QSAR) approach was executed on biologically relevant thiazolyl phenyl ether derivatives as ACC 2 inhibitors for structural optimization. The physiochemical descriptors were calculated and thus a correlation was derived between the observed and predicted activity by the regression equation. The significant descriptors i.e. log P (Whole Molecule) and Number of H-bond Donors (Substituent 1) obtained under study were considered for the design of new compounds and their predicted biological activity was calculated from the regression equation of the developed model. The compounds were further validated by docking studies with the prepared ACC 2 receptor. RESULTS: The most promising predicted leads with the absence of an H-bond donor group at the substituted phenyl ether moiety yet increased overall lipophilicity exhibited excellent amino acid binding affinity with the receptor and showed predicted inhibitory activity of 0.0025 µM and 0.0027 µM. The newly designed compounds were checked for their novelty. Lipinski's rule of five was applied to check their druggability and no violation of this rule was observed. CONCLUSION: The compounds designed in the present study have tremendous potential to yield orally active ACC 2 inhibitors to treat metabolic syndrome.

Metabolic Syndrome: The Constellation of Co-morbidities, A Global Threat.

BACKGROUND: Metabolic syndrome, also referred to as Syndrome X or obesity syndrome is a cluster of diseases prevalent worldwide in both developed and developing countries. According to WHO, it is referred to as a pathological condition wherein multiple disorders are manifested in the same individual. These include hypertension, hyperglycemia, dyslipidemia and abdominal obesity. AIMS: Metabolic syndrome is one of the most serious non-communicable health hazards that have gained pivotal importance in the present scenario. The increasing prevalence affecting around 25 % of the world populace, mainly attributes to the acceptance of western culture, i.e. the intake of highcalorie food along with a substantial decrease in manual labor and adoption of sedentary lifestyles. Therefore, its timely prevention and management are the dire need in the present scenario. METHODS: For successful accomplishment of the present review, an exhaustive analysis was performed utilizing a pool of previous related literature. The terms used during the search included 'metabolic syndrome, prevalence, etiology, current pharmacotherapy for metabolic syndrome, etc. PUBMED, Medline and SCOPUS were explored for the study of abstracts, research and review papers in the quest for related data. The articles were downloaded and utilized for a meta-analysis study approach. CONCLUSION: In this review, an attempt was made to apprehend and summarize the epidemiology and treatment strategies for metabolic syndrome with a better understanding of its pathogenesis. It was postulated that an early diagnostic approach and subsequent line of treatment is required to prevent the deterioration of an individual's health and life.

Chitinases: Therapeutic Scaffolds for Allergy and Inflammation.

BACKGROUND: Chitinases are the evolutionary conserved glycosidic enzymes that are characterized by their ability to cleave the naturally abundant polysaccharide chitin. The potential role of chitinases has been identified in the manifestation of various allergies and inflammatory diseases. In recent years, chitinases inhibitors are emerging as an alluring area of interest for the researchers and scientists and there is a dire need for the development of potential and safe chitinase antagonists for the prophylaxis and treatment of several diseases. OBJECTIVE: The present review expedites the role of chitinases and their inhibitors in inflammation and related disorders. METHODS: At first, an exhaustive survey of literature and various patents available related to chitinases were carried out. Useful information on chitinases and their inhibitor was gathered from the authentic scientific databases namely SCOPUS, EMBASE, PUBMED, GOOGLE SCHOLAR, MEDLINE, EMBASE, EBSCO, WEB OF SCIENCE, etc. This information was further analyzed and compiled up to prepare the framework of the review article. The search strategy was conducted by using queries with key terms " chitin", "chitinase", "chitotrisidase", "acidic mammalian chitinase", "chitinase inhibitors", "asthma" and "chitinases associated inflammatory disorders", etc. The patents were searched using the key terms "chitinases and uses thereof", "chitinase inhibitors", "chitin-chitinase associated pathological disorders" etc. from www.google.com/patents, www.freepatentsonline.com, and www.scopus.com. RESULTS: The present review provides a vision for apprehending human chitinases and their participation in several diseases. The patents available also signify the extended role and effectiveness of chitinase inhibitors in the prevention and treatment of various diseases viz. asthma, acute and chronic inflammatory diseases, autoimmune diseases, dental diseases, neurologic diseases, metabolic diseases, liver diseases, polycystic ovary syndrome, endometriosis, and cancer. In this regard, extensive pre-clinical and clinical investigations are required to develop some novel, potent and selective drug molecules for the treatment of various inflammatory diseases, allergies and cancers in the foreseeable future. CONCLUSION: In conclusion, chitinases can be used as potential biomarkers in prognosis and diagnosis of several inflammatory diseases and allergies and the design of novel chitinase inhibitors may act as key and rational scaffolds in designing some novel therapeutic agents in the treatment of variety of inflammatory diseases.