Search PubMed⌕ Search

Biomedical subjects

S D Cohen

Publications and source records attributed to S D Cohen.

At least 73 records · Page 4Linked to original sources
PubMed1985

Antagonism of cyanide poisoning by chlorpromazine and sodium thiosulfate.

Anti-cyanide action by sodium thiosulfate (ST) was enhanced by prior administration of chlorpromazine (CPZ). However, CPZ (alone) provided no protection against cyanide lethality. To investigate the possibility that CPZ enhances thiocyanate formation in ST-pretreated mice, the effects of CPZ on rhodanese activity and the time course of plasma thiocyanate concentrations were investigated. CPZ did not alter hepatic rhodanese kinetics nor did it enhance plasma thiocyanate concentrations in ST-pretreated mice. The effect of CPZ and ST on the time course of cytochrome oxidase inhibition and recovery, in vivo, was also investigated. At 4 mg KCN/kg, maximal inhibition of brain (40%) and heart (60%) cytochrome oxidase occurred 10 to 20 min post-challenge in control and CPZ-pretreated mice, while no inhibition occurred in ST- and CPZ/ST-pretreated mice. Twenty milligrams KCN/kg caused 100% lethality in control and CPZ-pretreated mice and 6/25 and 4/20 deaths were observed in ST- and CPZ/ST-pretreated mice, respectively. No significant inhibition of brain, heart, and liver cytochrome oxidase activities was observed in surviving ST- and CPZ/ST-pretreated mice challenged with 20 mg KCN/kg. Control and CPZ-pretreated mice died within 5 min of KCN challenge and had almost the same degree of inhibition of brain (35 and 29%, respectively) and heart (60 and 55%, respectively) cytochrome oxidase as did similarly pretreated mice 5 min after challenge with a nonlethal cyanide dose (4 mg/kg). Our results suggest that CPZ does not enhance the formation of thiocyanate in ST-pretreated mice. In addition, the similar degree of cytochrome oxidase inhibition noted after both lethal and nonlethal KCN treatments raises questions as to the ultimate target in cyanide-induced lethality.

Analysis of Variance↗
PubMed1985

Comparative sensitivity of bovine and rodent acetylcholinesterase to in vitro inhibition by organophosphate insecticides.

Biochemical studies were conducted to compare the in vitro sensitivities of bovine and rodent brain and erythrocyte cholinesterases to inhibition by Dyfonate-oxon, paraoxon, and malaoxon. This comparison was done to determine if the reported greater sensitivity of cattle to Dyfonate might be explained by a greater sensitivity of the target enzyme, acetylcholinesterase, in cattle to inhibition by Dyfonate's toxic metabolite, Dyfonate-oxon. Studies were conducted with brain homogenates and lysed erythrocytes obtained from cows and from male and female rats. Additional studies were conducted with a commercially available sample of purified bovine erythrocyte acetylcholinesterase (ACHE). In all cases, the concentrations of organophosphates required to produce 50% inhibition (IC50) of enzyme activity were determined. Cow brain ACHE was 1.7 to 3.8 times more resistant to inhibition by Dyfonate-oxon, paraoxon, and malaoxon than was brain ACHE from male or female rats. For both species, paraoxon was 1.2 to 1.6 times more potent than Dyfonate-oxon and 3.8 to 6.9 times more potent than malaoxon. The bimolecular reaction rate constants (ki) were also determined for inhibition of brain ACHE of cows and male rats by the three organophosphates. In general, the ki data were in agreement with the IC50 data indicating that cow brain ACHE was less sensitive than rat brain ACHE to inhibition. Additional IC50 studies were conducted with lysed erythrocytes from cows and from male and female rats. Both quantitative and qualitative differences between species and among the organophosphates were in excellent agreement with the results of the brain ACHE studies. Also, in related studies with purified bovine erythrocyte ACHE, there was excellent agreement with the results of tests involving ACHE inhibition in erythrocyte lysates. This study demonstrated that, as an inhibitor of ACHE in vitro, Dyfonate-oxon was equal to or slightly lower in potency than paraoxon and more potent than malaoxon. In addition, the study demonstrated that, in general, ACHE from brain or erythrocytes of cows was less sensitive to in vitro inhibition by organophosphates than was that from male or female rats. Thus, the apparent greater susceptibility of cows to Dyfonate, in vivo, cannot be explained on the basis of an unusual target enzyme (ACHE) sensitivity to inhibition by Dyfonate-oxon.

Acetylcholinesterase↗
PubMed1984

Mechanisms of toxicological interactions involving organophosphate insecticides.

Administration of apparently nontoxic doses of organophosphorus compounds can greatly alter the toxicity of other compounds. These might include other organophosphates, as well as other drug or nondrug xenobiotics. Mechanisms of toxicologic interactions are discussed. Emphasis is placed upon organophosphate inhibition of noncritical tissue esterases and alterations in the metabolism and toxicity of selected ester and amide containing xenobiotics.

Acetaminophen↗
PubMed1984

Parathion-induced suppression of humoral immunity in inbred mice.

Numbers of IgM plaque-forming cells (PFC) were reduced by 65% in C57Bl/6 mice given parathion 2 days after immunization with sheep red blood cells (SRBC). The immunosuppressive dose (16 mg/kg, p.o.) caused signs of cholinergic poisoning and 20% mortality. Survivors appeared to have recovered fully from the cholinergic crisis at the time of immunologic assay. However, these animals had reduced tissue cholinesterase (ChE) activities and decreased numbers of nucleated spleen cells. Immunosuppression was apparent on day 4 but not on day 3 or days 5-8 of the primary IgM response. Reduction of serum hemagglutinin titers coincided with reduction of the number of splenic PFC. A lower dose of insecticide (4 mg/kg, p.o.) did not produce signs of poisoning and was not immunosuppressive. The number of 8-day IgG PFC was reduced by 45% when parathion (16 mg/kg, p.o.) was given 6 days after immunization, but not when parathion was given 2 days after immunization. The data suggest that cholinergic stimulation and/or the associated toxic chemical stress may be involved in parathion-induced immunosuppression.

Animals↗
PubMed1984

Two-year follow-up of agoraphobics after exposure and imipramine.

Forty-five agoraphobic out-patients were randomly assigned to treatment with imipramine or placebo, and also to brief therapist-aided exposure or relaxation. All patients did systematic self-exposure homework and recorded this in a diary. Forty of these patients were followed-up two years later with self-ratings and ratings by interviewers blind to their treatment conditions. About two-thirds of the patients remained improved or much improved in their phobias, with no significant difference between any of the four treatment conditions. Spontaneous panics also remained improved. The absence of an imipramine effect may reflect the lack of initial dysphoria (anxiety-depression) in this sample compared with other studies where drug-effects have been found. The post-treatment superiority (evident at week 28) of patients who had therapist-aided exposure was no longer present at the two-year follow-up; the others had caught up, presumably because of their self-exposure homework.

Adult↗
PubMed1983

The effects of organophosphate-induced cholinergic stimulation on the antibody response to sheep erythrocytes in inbred mice.

In a previous study, we demonstrated that parathion suppressed both the primary IgM and IgG response to sheep erythrocytes (SRC) in inbred and outbred mice (G. P. Casale, S. D. Cohen, and R. A. DiCapua, 1982, toxicologist 2, 94). Suppression occurred after a dosage which produced cholinergic effects but was absent after a lower dosage which did not produce cholinergic signs. This information suggested that immunosuppression might be mediated indirectly as a result of toxic chemical stress. The present study evaluated the relationship between the anticholinesterase action of parathion, malathion, and dichlorvos (DDVP) and their effects on the primary humoral response to SRC. Male C57Bl/6 mice were given a single dose of parathion (16 mg/kg, po), malathion (720 mg/kg, po), or DDVP (120 mg/kg, po) 2 days after immunization with SRC. Two days later, tissues were removed for cholinesterase (CHE) assay and enumeration of splenic antibody-forming cells (PFC). All three compounds produced moderate to severe cholinergic poisoning. DDVP produced cholinergic signs beginning 1/2 hr after dosing and lasting 1/2 to 1 hr. This profile was associated with a rapid but transient inhibition of brain CHE activity. In contrast, malathion and parathion produced prolonged cholinergic poisoning (4 to 7 hr) and prolonged suppression of brain CHE activity. All three compounds suppressed the primary IgM response. However, when they were given as multiple lower doses, none of the compounds suppressed the primary IgG response. These latter treatments produced no cholinergic signs. The cholinomimetic agent, arecoline (65 mg/kg, ip) produced a short-lived cholinergic crisis but no IgM suppression. Sustained-release arecoline produced prolonged cholinergic poisoning (3 to 5 hr) and reduced the number of IgM PFC to 50% of control. These results demonstrated that organophosphate-induced immunosuppression was associated with severe cholinergic stimulation. The immunosuppression may result from direct action of acetylcholine upon the immune system or it may be secondary to the toxic chemical stress associated with cholinergic poisoning.

Animals↗
PubMed1982

Effects of dexamethasone on antigen expression and virus production in avian sarcoma virus-transformed cells.

We studied the effects of dexamethasone on virus production and antigen expression in avian retrovirus-infected chick embryo fibroblast (CEF) cells. The presence of specific receptors for this hormone in both normal and infected CEF cells could only be demonstrated using cultures that were at or near confluence. Dexamethasone, while not toxic to the cells, exerted a growth-retarding influence when employed at concentrations of 10(-8) or 10(-9) M. These same concentrations of hormone were inhibitory to virus production, elaboration of plasminogen activator activity, and antigen expression as determined in a sensitized lymphocyte stimulation assay. In contrast, infected cells that had been treated with hormone displayed enhanced reactivity in a specific immunofluorescence test.

Alpharetrovirus↗
PubMed1981

Plasminogen activator is an apparent lymphocyte mitogen.

Culture fluids of avian sarcoma virus (ASV)-transformed but not normal chicken embryo cells frequently elicited a mitogenic response in normal avian and murine lymphocytes. We examined the possibility that plasminogen activator (PA) might be responsible for the observed mitogenic effect. PA activity, present in culture medium, was correlated positively with lymphocyte mitogenic capacity. Treatment of cells with phorbol myristate acetate, which elevates PA levels, increased mitogenesis. Similar treatment with dexamethasone, which inhibits PA biosynthesis and/or secretion, reduced lymphocyte mitogenic activity. Addition to culture fluids of either benzamidine or diisopropylfluorophosphate, both specific PA inhibitors, blocked lymphocyte proliferative responsiveness to culture fluids. In contrast, neither epsilon-amino-caproic acid nor trasylol, which inhibits plasmin esterase activity but not PA, abrogated lymphocyte responsiveness. Furthermore, purified urokinase, an enzyme of similar substrate specificity to PA, had lymphocyte stimulatory activity. These results strongly suggest that PA can function as a lymphocyte mitogen.

Animals↗
PubMed1977

DDVP (dichlorvos) detoxification by binding and interactions with DDT, dieldrin, and malaoxon.

Binding to tissue carboxylesterases has been suggested as an important mechanism of detoxification for several organophosphates. In this study DDVP, malaoxon, and paraoxon were inactivated, in vitro, by mouse liver under assay conditions that were consistent with a binding mechanism of inactivation. Binding of the three organophosphates was inhibited in livers of mice pretreated, 18 hr before sacrifice, with TOTP (triorthotolyl phosphate, 125 mg/kg, ip). Previous studies have shown that similar TOTP treatment enhanced the toxicity of malaoxon and paraoxon but did not alter the toxicity of DDVP. Both DDT (50 mg/kg, ip, given 4, 3.5, and 2.5 days before sacrifice) and dieldrin (16 mg/kg, po, given 4 days before sacrifice) increased liver/body weight ratios and decreased the duration of pentobarbital-induced loss of righting ability. Dieldrin increased liver carboxylesterase activity and liver binding of malaoxon and paraoxon but not of DDVP. In contrast, DDT did not increase liver carboxylesterase activity nor did it increase binding of malaoxon or paraoxon. Yet DDT pretreatment increased mouse liver binding of DDVP. Neither DDT nor dieldrin pretreatments altered the toxicity of subsequently administered DDVP. These results support the hypothesis that carboxylesterase binding does not represent an important mechanism for DDVP detoxification in the mouse. In other experiments, in vitro inactivation of malaoxon by binding was inhibited in livers of mice given DDVP (30 mg/kg, ip) 30 min before sacrifice. Similar DDVP pretreatment potentiated the anticholinesterase action of malaoxon (10 mg/kg, ip). Thus, even though DDVP toxicity was not altered by DDT- or dieldrin-induced changes in organophosphate binding, DDVP inhibited malaoxon binding and increased malaoxon toxicity.

Animals↗