The toxicological effects of pure dietary adenine base in the rat.

Ethylenebisdithiocarbamate of manganese (maneb) and zinc (zineb) and their degradation and metabolic product, ethylenethiourea (ETU), have produced similar teratogenic anomalies in rats. The mode of teratogenicity of maneb, deduced from the protective effects of zinc acetate following their simultaneous administration, has been attributed to its ability to chelate zinc. Whether ETU has a similar mode of action was investigated. Mated females from five control groups were fed a standard diet for the entire period of pregnancy. Dams in five other groups were fed the standard diet to which 0.0444% zinc (as zinc acetate) was added during the period from the 11th to the 14th day of pregnancy. On the 13th day of pregnancy, control dams and those given supplemental zinc were not treated, treated with distilled water, or with 80, 120, or 160 mg/kg ETU sc. A necropsy was performed on some dams 3 hr postinjection and concentrations of zinc were measured in the conceptus and maternal serum. The remaining dams were sacrificed and a necropsy performed on the 22nd day of gestation and their fetuses were examined for external, visceral, or skeletal anomalies. Zinc acetate was ineffective in reducing ETU-induced malformations, and concentrations of zinc in the conceptus and maternal serum were not affected by feeding zinc acetate or injecting ETU.     

The adsorption of quinine and quinidine to activated charcoal with and without magnesium sulfate

The effect of magnesium sulfate on the in vitro adsorption of quinine and quinidine to activated charcoal (AC) was studied. Solutions of quinine and quinidine were prepared at concentrations of 5 and 10 micrograms/ml and at simulated toxic concentrations of 62.5, 125 and 250 micrograms/ml in distilled water. Drug-charcoal slurries were vortex mixed, centrifuged and analysed for free drug in the supernatant. Quinine had adsorption capacities of 78.2 to 100% with 12.5 or 50 mg AC; 12.5 or 50 mg AC adsorbed 29.5-87.2% of the quinidine. Quinine (250 micrograms/ml) had adsorption capacities of 0.0, 21.1, 52.4, 78.3 or 93.8% to 12.5, 50, 125, 250 or 500 mg AC, respectively. There was a corresponding increase quinine and quinidine adsorption at increasing concentrations of AC. The adsorption of quinine and quinidine seemed dose dependent. Magnesium sulfate (7.5 mg/ml) enhanced the adsorption of quinine to AC, but increased the amount of AC required for quinidine-charcoal adsorption.     

Detachment of ribosomes of rough endoplasmic reticulum by NADPH and reduced glutathione (GSH)

NADPH, an endogenous, naturally occurring compound was found to be positive in the stripping of ribosomes from rough endoplasmic reticulum (RER) test (degranulation) for carcinogens using the hepatocellular postmitochondrial (PMS) system. However, glutathione (GSH) another naturally occurring compound was negative in the hepatocellular PMS system in contrast to GSH which was previously reported as being positive in the mutagenicity test using kidney PMS but negative using liver PMS. Akintonwa has classified degranulation into three types, viz, DIA, DIB, and DII (D.A.A. Akintonwa, Ecotoxicol. Environ. Saf. 9, 53-63 (1985]. Most carcinogens fall into DIA and DIB types. NADPH was of DIA type in the mouse and of DII in the female rat PMS systems. NADPH was consistently negative in the male rat PMS system.     

Polysorbate 80 and E-Ferol toxicity

The relatively recent introduction and use of an intravenous form of a vitamin E preparation (E-Ferol) has been associated with the development of an unusual syndrome and fatalities among low birth weight (less than 1,500 g), premature infants in neonatal intensive care units. We have observed an inhibitory effect by this vitamin E preparation on the in vitro response of human lymphocytes to phytohemagglutinin (PHA). E-Ferol suppressed the expected response to low doses of PHA. However, this suppression was not due to the alpha-tocopherol acetate (vitamin E) component, because alpha-tocopherol acetate by itself was not inhibitory; in fact, it often enhanced the PHA response. Because a mixture of polysorbate 80 and polysorbate 20 is used as a carrier in E-Ferol, these components were also tested and were found to be responsible for the suppression, especially the polysorbate 80. Concurrent with this suppression of PHA-induced mitogenesis was a decrease in the percentage of T11 lymphocytes.     

Continuous-infusion flumazenil in the management of chlordiazepoxide toxicity

Flumazenil is indicated for reversal of sedation from benzodiazepines administered during therapeutic or diagnostic procedures and during induction or maintenance of general anesthesia, as well as for benzodiazepine overdose. Bolus doses of flumazenil are usually adequate to achieve reversal; however, when medical conditions may lead to a prolonged half-life of the benzodiazepine involved, continuous infusion may be warranted. A 67-year-old man with chlordiazepoxide toxicity required a 9-day infusion of flumazenil to prevent resedation and respiratory insufficiency; he initially was admitted to the hospital for alcohol detoxification. Concomitant medical conditions and the metabolism characteristics of each benzodiazepine must dictate the agent of choice. When measures are required to ensure adequate recovery of a patient's respiratory function and mental awareness, such as in patients with benzodiazepine toxicity, consideration of continuous-infusion flumazenil is warranted.