In Vivo Confocal Microscopy Use in Endotheliitis.
Chemically pure dithiocarbamates, thiuramsulphides and ethylene-bis-dithiocarbamates display a well-marked antidiuretic action. They materially reduce diuresis, natri- and kaliuresis in rats (1/5 LD(50) per 1 kg into the stomach) and in dogs (sodium N, N-diethyl-dithiocarbamate-into renal artery). Without changing the tubular reabsorption DEDTC inhibits the glomerular filtration of the dogs' kidneys. Furosemide (lasix) prevents the development of the an antidiuletic anidiuretic effect and reduction of the sodium and potassium excretion provoked in rats with DEDTC, zinc N, N', N"-tetraethylthiuram-disulphide and ethylene-bis-dithiocarbamate. Furosemide is recommended for the treatment of acute poisonings with dithiocarbaminic acid derivatives.
To test the suggestion that chlorpropamide-alcohol flushing (CPAF) resembles the disulfiram effect and might be mediated by acetaldehyde, the initial metabolite of alcohol, blood concentrations of acetaldehyde were measured after a drink of alcohol in controls and diabetics positive and negative for CPAF. The CPAF-positive diabetics had significantly greater blood acetaldehyde concentrations after alcohol than the CPAF-negative diabetics both with a single dose of chlorpropamide and after two weeks' chlorpropamide treatment. Concentrations in the CPAF-positive group after chlorpropamide were also significantly greater than after a placebo tablet. There was also a clear separation in the increase in facial temperature after two weeks of chlorpropamide between the CPAF-positive and CPAF-negative groups (although there was some overlap after a single tablet). There was no difference in plasma chlorpropamide or alcohol concentrations between CPAF-positive and CPAF-negative diabetics. These findings show that CPAF is distinct from alcohol flushing and that the acetaldehyde concentration in the blood provides an objective measure of CPAF. The difference between flushing and non-flushing diabetics cannot be accounted for by differences in blood concentrations of chlorpropamide or alcohol.
A double-blind, placebo-controlled study in eight healthy male volunteers was conducted to study possible disulfiram-type reactions and hypoprothrombinemia associated with cefotetan administration. Three doses of cefotetan (2 g) or of placebo were administered at 12-h intervals. Ethanol (0.5 g/kg of total body weight) was ingested 1 h after the third dose. Blood ethanol, serum acetaldehyde, and prothrombin times were measured throughout the study. Heart rate, blood pressure, and clinical signs as well as symptoms suggestive of a disulfiram-type reaction were also noted. Five of eight volunteers that received cefotetan showed significant flushing. A significant increase in heart rate also was noted. No change in mean arterial pressure was observed during the cefotetan phase, and no one experienced nausea or vomiting. No statistical differences were observed between phases with respect to ethanol area under the time-concentration curve, elimination rate, or serum acetaldehyde concentrations. A slight but statistically significant increase in prothrombin time also was observed with cefotetan. This study suggests that patients receiving cefotetan might be at risk to develop disulfiram-type reactions and hypoprothrombinemia.
Oral treatment of rats with tetramethylthiuram disulphide (TMTDS), 0.1% mixed in the food (corresponding to 20--30 mumol daily) for one week, increased the brain levels of endogenous copper and zinc to 120% and 170%, respectively, of the control levels. Mice injected with HgCl2 (2.5 mumol/kg) were used to study further the effect of DDC (diethyldithiocarbamate), disulfiram, TMTDS or CS2 on heavy metal distribution. The brain levels of Hg were significantly increased in mice given DDC or TMTDS. Disulfiram and CS2 increased the brain levels marginally. Pregnant rats exposed to HgCl2 (0.5 mumol/kg) were also included in the studies. Treatment with DDC (0.5 mmol/kg) immediately after the mercury injection, increased the maternal brain concentration of mercury considerably, as measured after 24 and 78 h. The kidney levels were also increased. In the foetuses, the brain and liver levels were transiently increased after treatment with diethyldithiocarbamate. The observations support the hypothesis that the neurotoxicity of diethyldithiocarbamate and other thiocarbamates may be related to changes in heavy metal metabolism.
In a crossover randomized study, participants received threat and neutral messages during two cue exposure sessions. The threat condition consisted of leading the patients to believe they had ingested 500 mg of disulfiram and the neutral condition of informing them that they had ingested a placebo, while in both condition they received the same placebo.
[Formula: see text] levels in the retinas of OLETF rats were significantly higher than in LETO rats, and the [Formula: see text] levels in the retinas of 60-week-old OLETF rats increased with increasing Glu. CCO activity in the retinas of OLETF rats showed no significant difference from that in LETO rats; however, ATP levels in the retinas of OLETF rats were significantly lower than those in LETO rats. The oral administration of aminoguanidine or disulfiram, an iNOS inhibitor, attenuated the decrease in ATP levels in the retinas of 60-week-old OELTF rats.