Effects of ascorbic acid and alpha-tocopherol on arsenic-induced oxidative stress

Arsenic is an ubiquitous element in the environment causing oxidative burst in the exposed individuals leading to tissue damage. Antioxidants have long been known to reduce the free radical-mediated oxidative stress. Therefore, the present study was designed to determine whether supplementation of alpha-tocopherol (400 mg/kg body weight) and ascorbic acid (200 mg/kg body weight) to arsenic-intoxicated rats (100 ppm in drinking water) for 30 days affords protection against the oxidative stress caused by the metalloid. The arsenic-treated rats showed elevated levels of lipid peroxide, decreased levels of non-enzymatic antioxidants and activities of enzymatic antioxidants. Administration of alpha-tocopherol and ascorbic acid to arsenic-exposed rats showed a decrease in the level of lipid peroxidation (LPO) and enhanced levels of total sulfhydryls, reduced glutathione, ascorbic acid and alpha-tocopherol and so do the activities of superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase and glucose-6-phosphate dehydrogenase to near normal. These findings suggest that alpha-tocopherol and ascorbic acid prevent LPO and protect the antioxidant system in arsenic-intoxicated rats.     

Limited genetic diversity of Candida albicans in fecal flora of healthy volunteers and inpatients: a proposed basis for strain homogeneity in clinical isolates

Molecular analysis of Candida albicans isolates from individual patients often yields a single strain at multiple sites. Whether this strain-limitation is due to virulence factors favoring the invasive strain or to lack of genetic diversity in the gastrointestinal reservoir is uncertain. We elected to study C. albicans genotypes in the fecal flora among healthy volunteers and inpatients. Self-obtained stool swabs or stool samples were cultured on inhibitory mold agar. From each subject with C. albicans, nine colonies were randomly selected, individually propagated, and typed utilizing random amplified polymorphic DNA. Colonies were considered identical (all bands matched), related variants (one to three unique bands), or distinct strains (more than three unique bands). Analysis showed a single clone in 33/43 (76.7%) volunteers and 6/18 (33.3%) inpatients (P = 0.018), two to four related variants in eight (18.6%) volunteers and 10 (55.6%) inpatients, and two distinct strains in two volunteers (4.6%) and two inpatients (11.1%). Strain variation was more common in females (33.5 versus 5.6%; P = 0.04) and tended to increase with age (r = 0.245, P = 0.06). These findings illustrate that most healthy subjects harbor a single strain of C. albicans in the fecal flora. This strain may undergo genetic evolution leading to minor clonal variations. The mechanisms for strain selection, maintenance and possible evolution remain to be delineated.     

Randomized trial of influenza vaccine with granulocyte-macrophage colony-stimulating factor or placebo in cancer patients.

PURPOSE: To determine whether granulocyte-macrophage colony-stimulating factor (GM-CSF) would improve response to influenza vaccination in cancer patients. PATIENTS AND METHODS: In a randomized, patient-blinded, placebo-controlled trial carried out in 1997 to 2000, 133 patients were stratified into five groups of treatment and disease. Single doses of standard split trivalent influenza vaccine and either placebo or 250 micro g of GM-CSF were administered at the same time. Hemagglutination inhibition assay titers were measured before and 4 weeks after vaccination. RESULTS: Standard analyses, which define response as at least a four-fold increase in titers, detect no effect of GM-CSF for any of the three influenza subtypes in the trivalent vaccines (P >or=.12). Analysis that includes the magnitude of the change in titers and combines responses of the subtypes suggests that the placebo group had the greater response (P =.051), thus indicating that GM-CSF does not improve response. Ancillary analyses show that response declines both with increasing age and with higher initial titers. The fraction of patients with at least a four-fold increase in titers was 0.36 (95% confidence interval, 0.29 to 0.42) CONCLUSION: A single 250- micro g dose of GM-CSF administered with the influenza vaccine does not improve response to vaccination. Response in cancer patients is low and declines as age and initial titer increase.     

Induction of potent Th1-type immune responses from a novel DNA vaccine for West Nile virus New York isolate (WNV-NY1999)

West Nile virus (WNV) is a vectorborne pathogen that induces brain inflammation and death. Recently, confirmed cases of infection and deaths have occurred in the United States Mid-Atlantic region. In this study, a DNA vaccine encoding the WNV capsid protein was constructed, and the in vivo immune responses generated were investigated in DNA vaccine-immunized mice. Antigen-specific humoral and cellular immune responses were observed, including a potent induction of antigen-specific Th1 and cytotoxic T lymphocyte responses. Strong induction of Th1-type immune responses included high levels of antigen-specific elaboration of the Th1-type cytokines interferon-gamma and interleukin-2 and beta-chemokines RANTES (regulated upon activation, normal T cell-expressed and secreted) and macrophage inflammatory protein-1beta. Dramatic infiltration of CD4 and CD8 T cells and macrophages also was observed at the muscle injection site. These results support the potential utility of this method as a tool for developing immunization strategies for WNV and other emerging pathogens.     

Pharmacokinetics of gemcitabine and 2',2'-difluorodeoxyuridine in a patient with ascites

Gemcitabine (dFdC) is a prodrug that undergoes metabolism by cytidine deaminase to form an inactive metabolite, 2',2'-difluorodeoxyuridine (dFdU). The pharmacokinetics of dFdC and dFdU have been studied; however, their disposition has never been evaluated in a patient with ascites. A patient with pancreatic cancer and malignant ascites was treated with dFdC 1,500 mg/m2 over 150 minutes weekly for 3 weeks, repeated every 4 weeks. Serial plasma and ascites samples were obtained on weeks 1 and 2 of cycle 2. High-pressure liquid chromatography was used to quantify dFdC and dFdU in plasma and ascites. The systemic dispositions of dFdC and dFdU were similar to those reported in patients without ascites. The concentration of dFdC in ascites approached 1 mg/ml. Ascitic fluid did not serve as a depot for dFdC, and the agent's concentration in ascites approached that at which its phosphorylation is saturated.     

Tuberculous meningitis

Summary In a five-year-period, 288 cases of tuberculous meningitis were seen in in the R.M. & T.M.C. hospitals, Thanjavur, Tamilnadu. 87 children died. Of 215 cases discharged as relieved, only 117 cases were followed up. The period of follow up varied from 6 months to over 3 years. 41 children were followed up for more than 1 year. 47 children were found to have residual sequelae. The most frequent sequelae were mental retardation, seizures, generalised rigidity and spastic hemiplegia. From the Department of Pediatrics, Thanjavur Medical College, Thanjavur, Tamilnadu