Homomeric alpha 1 glycine receptors were expressed in Xenopus laevis oocytes, and the two-electrode voltage-clamp technique was used to measure glycine-mediated currents in the presence of combinations of zinc with ethanol, pentanol or isoflurane. The combined effects of zinc plus ethanol were greater than
the sum of the effects produced by either compound alone. However, this was not seen when zinc was combined with either pentanol or isoflurane. Chelation of zinc by tricine decreased the effects of sub-maximal, but not maximal, selleck chemical concentrations of glycine, and diminished the magnitude of ethanol enhancement observed. These findings suggest a zinc/ethanol interaction at the alpha 1 GlyR that results in the enhancement of the effects of ethanol action on GlyR function. (C) 2009 Elsevier Ltd. All rights reserved.”
“Background Oral cholera vaccines consisting of killed whole cells have been available for many years, but they have not been used extensively in
populations with endemic disease. An inexpensive, locally produced oral killed-whole-cell vaccine has been used in high-risk areas in Vietnam. To expand the use of this vaccine, it was modified to comply with WHO standards. We assessed the efficacy and safety of this modified vaccine AZD6094 in a population with endemic cholera.
Methods In this double-blind trial, 107 774 non-pregnant residents of Kolkata, India, aged 1 year
or older, were cluster-randomised by dwelling Methocarbamol to receive two doses of either modified killed-whole-cell cholera vaccine (n=52212; 1966 clusters) or heat-killed Escherichia coli K12 placebo (n=55 562; 1967 clusters), both delivered orally. Randomisation was done by computer-generated sequence in blocks of four. The primary endpoint was prevention of episodes of culture-confirmed Vibrio cholerae 01 diarrhoea severe enough for the patient to seek treatment in a health-care facility. We undertook an interim, per-protocol analysis at 2 years of follow-up that included individuals who received two completely ingested doses of vaccine or placebo. We assessed first episodes of cholera that occurred between 14 days and 730 days after receipt of the second dose. This study is registered with ClinicalTrials.gov, number NCT00289224.
Findings 31932 participants assigned to vaccine (1721 clusters) and 34 968 assigned to placebo (1757 clusters) received two doses of study treatment. There were 20 episodes of cholera in the vaccine group and 68 episodes in the placebo group (protective efficacy 67%; one-tailed 99% CI, lower bound 35%, p<0.0001). The vaccine protected individuals in age-groups 1.0-4.9 years, 5.0-14.9 years, and 15 years and older, and protective efficacy did not differ significantly between age-groups (p=0.28). We recorded no vaccine-related serious adverse events.