Monoamine oxidase A inhibition by fluoxetine: an in vitro and in vivo study

Monoamine oxidase A (MAO-A) inhibition was investigated both in vitro and in vivo in rat brains by using the radioligand, 18F-fluoroclorgyline (N-[3-(2',4'-dichlorophenoxy)-2-18F-fluoropropyl]-N-methylpropa rgylamine). In vitro binding affinities of six compounds, clorgyline, Ro 41-1049, deprenyl, fluoxetine, norfluoxetine and citalopram, were studied. Fluoxetine and norfluoxetine showed in vitro affinities of 36.5 and 68 microM for MAO-A, respectively. Fluoxetine and norfluoxetine also significantly inhibited (more than 20%) the binding of the radioligand in vivo while citalopram and deprenyl showed very poor affinities in vitro for MAO-A and had no effect in vivo. The in vivo effects of the various drugs were directly comparable to their in vitro affinities for binding to MAO-A as seen in the correlation plot of percent control in vivo binding of 18F-fluoroclorgyline and binding affinity, -log IC50 (R2 = 0.979). An acute dose of 20 mg/kg of fluoxetine inhibited binding of 18F-fluoroclorgyline by more than 20%, while lower doses had some significant effects. These results provide evidence on the in vitro and in vivo inhibition of monoamine oxidase A by fluoxetine.     

The voluntary community health movement in India: A strengths,weaknesses, opportunities,and threats (SWOT) analysis

There has been a prolific growth of voluntary organizations in India since independence in 1947. One of the major areas of this growth has been in the field of community health. The purpose of this article is to historically trace the voluntary movement in community health in India, analyze the current status, and predict future trends of voluntary efforts. A review of the literature in the form of a Strengths, Weaknesses, Opportunities, and Threats (SWOT) analysis was the method of this study. Some of the key trends which emerged as the priority areas for progress and for strengthening voluntary organizations in the future were enhancing linkages between health and development; building upon collective force; greater utilization of participatory training; establishing egalitarian and effectual linkages for decision making at the international level; developing self-reliant community-based models; and the need for attaining holistic empowerment at individual, organizational, and community levels through duty consciousness as opposed to merely asking for rights.The authors would like to express gratitude to Voluntary Health Association of India for sharing the necessary documents and to Dr. Rick Petosa for valuable editorial comments.     

Complete inversion of the urinary bladder through a vesicovaginal fistula

This is the case of an Indian woman who was hospitalized after a diagnosis of chronic inversion of the uterus with a vesicovaginal fistula. She suffered from urinary incontinence for 40 years, the condition having developed following a difficult labor. Ultimately, she proved to have a complete inversion of the bladder through a vesicovaginal fistula.     

Interpreting the improved outcome of patients with central nervous system metastases managed in clinical trials compared with standard hospital practice*

The aims were to determine the median survival and prognostic factors of patients with central nervous system (CNS) metastases managed with whole‐brain radiation therapy (WBRT), and to explore selection criteria in recently published clinical trials using aggressive interventions in CNS metastases. A retrospective audit was performed on patients managed with WBRT for CNS metastases. Potential prognostic factors were recorded and analysed for their association with survival duration. The proportion of patients with these factors was also compared with those of patients managed under three recently reported studies investigating aggressive interventions, such as radiosurgery and chemotherapy for CNS metastases. Seventy‐three patients were treated with WBRT for cerebral metastases over a 12‐month period. The median survival of the population was 3.4 months (95% confidence interval: 2.7–4.1), with 6‐ and 12‐month survival rates of 30 and 18%, respectively. Significant prognostic factors for prolonged median survival were Eastern Cooperative Oncology Group status 0–2 (P = 0.015), Medical Research Council neurological functional status 0–1 (P = 0.006), and Recursive Partitioning Analysis Class 2 versus Class 3 (P = 0.020). On multivariate analysis, younger patient age (P = 0.02) and better performance status (P < 0.01) were associated with improved outcome. When comparing these characteristics with selected published studies, our study cohort demonstrated a higher proportion of patients with poor performance status, a greater number of metastases per patient and a higher incidence of extracranial disease. This reflects the selected nature of patients in these published studies. Central nervous system metastases confer a poor prognosis and, for the majority of patients, aggressive interventions are unlikely to improve survival. The use of potentially toxic and expensive treatments should be reserved for those few in whom these studies have shown a potential benefit.     

Candida biofilm resistance.

Device-related infections in most nosocomial diseases can be traced to the formation of biofilms (microbial communities encased within polysaccharide-rich extracellular matrix) by pathogens on surfaces of these devices. Candida species are the most common fungi isolated from these infections, and biofilms formed by these fungal organisms are associated with drastically enhanced resistance against most antimicrobial agents. This enhanced resistance contributes to the persistence of this fungus despite antifungal therapy. Candida biofilms exhibit enhanced resistance against most antifungal agents, except echinocandins and lipid formulations of AmB. The expression of drug efflux pumps during the early phase of biofilm formation and alterations in membrane sterol composition contribute to resistance of these biofilms against azoles. Metabolic dormancy and ECM do not appear to contribute to resistance, although in a mixed-species biofilm, ECM does retard the diffusion of drugs across biofilm. These multifactorial mechanisms of resistance in fungal biofilms constitute a broad-spectrum defense that is effective against many types of antifungal agents, and represent a common theme present across microbial biofilms.     

Effects of Exercise Intervention Program on Bone Mineral Accretion in Children and Adolescents with Cystic Fibrosis: A Randomized Controlled Trial

Indian Journal of Pediatrics - To evaluate effect of one year exercise intervention program on bone mineral accrual in children and adolescent with cystic fibrosis (CF). Fifty-two CF children (mean...     

Label-free metabolic imaging of non-alcoholic-fatty-liver-disease (NAFLD) liver by volumetric dynamic optical coherence tomography

Label-free metabolic imaging of non-alcoholic fatty liver disease (NAFLD) mouse liver is demonstrated ex vivo by dynamic optical coherence tomography (OCT). The NAFLD mouse is a methionine choline-deficient (MCD)-diet model, and two mice fed the MCD diet for 1 and 2 weeks are involved in addition to a normal-diet mouse. The dynamic OCT is based on repeating raster scan and logarithmic intensity variance (LIV) analysis that enables volumetric metabolic imaging with a standard-speed (50,000 A-lines/s) OCT system. Metabolic domains associated with lipid droplet accumulation and inflammation are clearly visualized three-dimensionally. Particularly, the normal-diet liver exhibits highly metabolic vessel-like structures of peri-vascular hepatic zones. The 1-week MCD-diet liver shows ring-shaped highly metabolic structures formed with lipid droplets. The 2-week MCD-diet liver exhibits fragmented vessel-like structures associated with inflammation. These results imply that volumetric LIV imaging is useful for visualizing and assessing NAFLD abnormalities.     

Sequential radiation changes in cytology of vaginal smears in carcinoma of cervix uteri during radiotherapy

The study deals with acute/immediate radiation changes in 2020 sequential vaginal smears in 101 patients of carcinoma of the cervix uteri, 97 were of squamous cell carcinoma and 4 of adenocarcinoma. The smears were collected after 12-14 days, 15-24 days and 25 days to 6 weeks following radiotherapy. The pretreatment vaginal smears were collected and examined for percentage of cancer cells. Subsequent smears were studied for radiation changes in benign and malignant cells, such as cell size, vacuolation of cytoplasm, multinucleation and nuclear changes, etc. A gradual and linear decline in cancer cells was observed until the end of therapy; 41.6% of patients had less than 10% cancer cells within 12-14 days of therapy, 63.4% of patients between 15 and 24 days and 74.6% after 25 days to 6 weeks following radiation. Eighty three percent of the patients attained zero level at the end of therapy.