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Biomedical subjects

S I Baskin

Publications and source records attributed to S I Baskin.

At least 73 records · Page 4Linked to original sources
PubMed1973

The effects of diphenylhydantoin and potassium on the biological activity of ouabain in the guinea-pig heart.

1. Diphenylhydantoin (DPH) and potassium significantly prevent ouabain intoxication without preventing the inotropic effects of ouabain in the guinea-pig isolated heart.2. The antiarrhythmic effect of DPH and K on ouabain-induced toxicity appears to be related to their ability to reduce ouabain accumulation by the myocardium and thereby prevent the intracellular Na and K changes which lead to the arrhythmic state.

Animals↗
PubMedDate not supplied

Temperature effects in cyanolysis using elemental sulfur.

As part of our studies directed at new treatments for cyanide poisoning we examined the effect of temperature on both the non-catalyzed and the albumin-catalyzed reactions of cyanide with a colloidal suspension of elemental sulfur (CSES). Using saturated sulfur solutions prepared in two solvents, pyridine (PY) and methyl cellosolve (MC), the reactions were studied at 15.0, 25.0, 30.0 and 37.5 degrees C. For all the cyanolysis reactions (non-catalyzed and albumin-catalyzed) there is an enhancement of reaction rate when the organic solvent for the sulfur is MC. Irrespective of the solvent for the CSES, the non-catalyzed reactions gave linear Arrhenius plots (PY, correlation coefficient = 0.998; MC, correlation coefficient = 0.997). In each case the entropy of activation was positive (14.1 cal K-1 mol-1 for PY and 56.4 cal K-1 mol-1 for MC). In contrast with these results the albumin-catalyzed reactions generated non-linear Arrhenius plots and negative entropies of activation. Non-linear plots were observed with the three albumins studied: human serum albumin, heat-shock bovine serum albumin and fatty acid-free bovine serum albumin. The non-linear plots are the result of a more complex reaction sequence than a simple cyanolysis reaction.

Colloids↗
PubMedDate not supplied

In vitro and in vivo comparison of sulfur donors as antidotes to acute cyanide intoxication.

Antidotes for cyanide (CN) intoxication include the use of sulfane sulfur donors (SSDs), such as thiosulfate, which increase the conversion of CN to thiocyanate by the enzyme rhodanese. To develop pretreatments that might be useful against CN, SSDs with greater lipophilicity than thiosulfate were synthesized and assessed. The ability of SSDs to protect mice against 2LD50 of sodium cyanide (NaCN) administered either 15 or 60 min following administration of an SSD was assessed. To study the mechanism of action of the SSD, the candidate compounds were examined in vitro for their effect on rhodanese and 3-mercaptopyruvate sulfurtransferase (MST) activity under increasing SSD concentrations. Tests were conducted on nine candidate SSDs: ICD1021 (3-hydroxypyridin-2-yl N-[(N-methyl-3-aminopropyl)]-2-aminoethyl disulfide dihydrochloride), ICD1022, (3-hydroxypyridin-2-yl N-[(N-methyl-3-aminopropyl)]-2-aminoethyl disulfide trihydrochloride), ICD1584 (diethyl tetrasulfide), ICD1585 (diallyl tetrasulfide), ICD1587 (diisopropyl tetrasulfide); ICD1738 (N-(3-aminopropyl)-2-aminoethyl 2-oxopropyl disulfide dihydrochloride), ICD1816 (3,3'-tetrathiobis-N-acctyl-L-alanine), ICD2214 (2-aminoethyl 4-methoxyphenyl disulfide hydrochloride) and ICD2467 (bis(4-methoxyphenyl) disulfide). These tests demonstrated that altering the chemical substituent of the longer chain sulfide modified the ability of the candidate SSD to protect against CN toxicity. At least two of the SSDs at selected doses provided 100% protection against 2LD50 of NaCN, normally an LD99. All compounds were evaluated using locomotor activity as a measure of potential adverse behavioral effects. Positive hypoactivity relationships were found with several disulfides but none was found with ICD1584, a tetrasulfide. Separate studies suggest that the chemical reaction of potassium cyanide (KCN) and cystine forms the toxic metabolite 2-iminothiazolidine-4-carboxylic acid. An alternative detoxification pathway, one not primarily involving the sulfur transferases. may be important in pretreatment for CN intoxication. Although studies to elucidate the precise mechanisms are needed. it is clear that these newly synthesized compounds provide a new rationale for anti-CN drugs, with fewer side-effects than the methemoglobin formers.

Animals↗
PubMedDate not supplied

Is chlordiazepoxide the rational choice among benzodiazepines?

Diazepam is frequently the subject of review by various agencies and institutions charged with determining whether or not to substitute another, more economical drug--in most instances, chlordiazepoxide. A review of the comparative literature has shown that, on clinical and pharmacokinetic grounds, chlordiazepoxide is not the drug of choice for all clinical indications recommended for the benzodiazepines as a class, particularly for use as an antianxiety agent. There is evidence that the antianxiety effect of chlordiazepoxide is related to the appearance of its two active metabolites, which may explain the observed delay in its onset of action. When chlordiazepoxide's reduced clearance in the elderly and in patients with liver disease is considered along with its limited range of indications, substitution of diazepam with chlordiazepoxide is clearly not reasonable. Diazepam and lorazepam are preferred choices in acute anxiety because they are themselves active anxiolytics. Oxazepam is recommended in alcoholic cirrhotics because its plasma clearance does not seem to be significantly affected by liver disease. Diazepam is recommended for chronic anxiety because of the rapid onset of action of diazepam itself and the smooth transition to the nondrug state via its longer-acting active metabolite.

Adult↗
PubMedDate not supplied

Topical anesthetic-induced methemoglobinemia and sulfhemoglobinemia in macaques: a comparison of benzocaine and lidocaine.

Benzocaine (BNZ) and lidocaine (LC) are commonly used topical (spray) anesthetics approved for use in humans. Benzocaine has structural similarities to methemoglobin (MHb)-forming drugs that are current candidates for cyanide prophylaxis, while LC has been reported to increase MHb in man. In this study, we compared MHb and sulfhemoglobin (SHb) production in three groups of Macaques (Chinese rhesus and Indian rhesus (Macaca mulatta) and pig-tailed macaques (Macaca nemestrina)) after exposure to BNZ and LC. Formation of SHb, unlike MHb, is not thought to be reversible and therefore is considered to be of greater toxic significance. Both MHb and SHb levels were measured periodically on a CO-Oximeter. All rhesus macaques (n = 8) were administered an intratracheal/intranasal) dose of 56 mg (low dose) or 280 mg (high dose) of BNZ or 40 mg of LC in a randomized cross-over design (all animals received all three treatments). Pig-tailed macaques (n = 6) were given an intranasal dose of 56 mg of BNZ and 40 mg of LC. As no differences in the peak MHb or time to peak (mean +/- SD) were observed among the three macaque subspecies, the data were pooled. Lidocaine did not cause MHb or SHb formation above baseline in any monkey. In contrast, all monkeys (n = 14) had a significant elevation in peak MHb formation after 56 mg of BNZ, which ranged from 4.0% to 19.4% with an average of 8.6 +/- 4.0% (mean +/- SD), with peak MHb levels reached at 30 min.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Intranasal↗
PubMedDate not supplied

Correlation of platelet taurine levels with thyroid function.

Changes in neurotransmitter or neuromodular activity and levels have been thought to be responsible for some of the behavioral characteristics observed in patients with thyroid disease. To investigate these relationships, taurine, a proposed inhibitory neurotransmitter or modulator, was measured in platelets, which may serve as biochemical model for synaptosomes. Blood of euthyroid, hypothyroid and hyperthyroid patients was collected. Thyroxine was determined by RIA. Platelets were separated using differential centrifugation techniques. The taurine in platelets was separated by ion exchange chromatography and was assayed spectrophotometrically as a product produced by coupling with dinitrofluorobenzene. In hypothyroid, untreated hyperthyroid and euthyroid individuals, taurine/platelet and number of platelets/ml of blood were inversely related. In propranolol-treated hyperthyroid patients, such a relation was not found. Following initial treatment with either antithyroid drugs (i.e. methimazole or propylthiouracil) and/or propranolol, taurine/platelet returned to euthyroid levels while plasma thyroxine levels remained elevated. These data implicate a relationship between taurine in platelets and the thyroid state in man.

Blood Platelets↗