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S H Pollock

Publications and source records attributed to S H Pollock.

34 records · Page 2Linked to original sources
PubMed1975

Effects of subchronic steroid therapy on vitamin E-deficient rats (38480).

Experiments were carried out to determine the effectiveness of steroid therapy in vitamin E-deficiency, as measured by autohemolysis of isolated RBC's body weight gain, serum creatine phosphokinase activity, and stabilization or labilization of isolated hepatic lysosomes. Results of such experiments would indicate whether triamcinolone acetonide could supplant vitamin E in vitamin E-deficiency states via its ability to stablize various membranes. Autohemolysis induced by vitamin E-deficiency could not be prevented by daily administration of triamcinolone. Daily dosages of 0.1 and 0.4 mg/kg (ip) triamcinolone given concomitantly with replacement vitamin E (at sufficient dosages to reverse the autohemolysis) resulted in an increased autohemolysis. No changes in lysosomal membrane fragility were noted when hepatic lysosomes were obtained from vitamin E-deficient rats with triamcinolone resulted in a greater attenuation of body-weight gain. Creatine phosphokinase levels were not augmented in vitamin E-deficient rats. Vitamin E-deficient rats supplemented with vitamin E and treated with triamcinolone, manifested an increase in creatine, phosphokinase. It was therefore concluded that although triamcinolone and vitamin E possess a common ability to stablize membranes and proteins, their mechanisms must be different since triamcinolone could not substitute for vitamin E in a deficiency state. Indeed, triamcinolone was found to be more toxic in the absence of vitamin E.

Acid Phosphatase↗
PubMedDate not supplied

Effects of phenyl-2-aminoethyl sulfide, a novel dopamine-beta-hydroxylase substrate, on the cardiovascular system of the anesthetized dog.

In previous work we have established that phenyl-2-aminoethyl sulfide (PAES) is a novel substrate for dopamine-beta-hydroxylase (DBH) which is stereospecifically oxygenated by the enzyme to the corresponding sulfoxide, (S)-phenyl-2-aminoethyl sulfoxide (PAESO). We now report that PAES possesses very little, if any, direct adrenergic agonist activity, but exhibits indirect sympathomimetic activity at relatively high doses (approximately 4 mg/kg). This assertion, that PAES is a new indirect sympathomimetic, is supported by our finding that pretreatment with cocaine completely abolishes the sympathomimetic activity of PAES. Furthermore, the effects of PAES are diminished with consecutive administration. In addition to its indirect sympathomimetic activity, we have also observed that PAES infusion almost completely blocks the reflex response elicited by hydralazine, a direct vasodilator. In contrast, we have found that PAESO possesses neither direct nor indirect sympathomimetic activity at doses as high as 6 mg/kg. Since PAES should be readily converted in vivo into PAESO, the implications of these findings in terms of potential antihypertensive action of PAES are discussed.

Animals↗
PubMedDate not supplied

Pharmacokinetic analysis of cyclosporine in adjuvant arthritic rats.

Cyclosporine A (CsA) has been shown to be effective in patients with rheumatoid arthritis and to prevent the development and improve the symptoms of adjuvant-induced arthritis in rats. Since abnormal drug disposition has been reported in inflammatory conditions, we have evaluated the pharmacokinetics of CsA in this animal model of arthritis. We found a statistically significant decrease in the rate of disappearance of blood concentrations of CsA following iv administration to arthritic rats. The plasma half-life of CsA increased with a corresponding decrease in total body clearance. The volume of distribution remained unchanged. This abnormality in CsA kinetics was not observed in these animals until 10 days after adjuvant injection. The administration of CsA (15 mg/kg ip) twice daily to arthritic rats for 8 days produced a 39.8% and 49.5% inhibition of swelling in the right and left hindpaw, respectively. There was also a 63.5% decrease in the arthrogram score. Trough levels of CsA in arthritic animals were initially higher than in controls during this treatment but returned to control values after 8 days of dosing, suggesting reversal of abnormal disposition with improvement of the disease. The addition of indomethacin to the dosing regimen resulted in a significant increase in trough levels of CsA, indicating a drug interaction between these two compounds. Possible mechanisms responsible for these observations with CsA are discussed.

Animals↗
PubMedDate not supplied

Cyclosporine-cimetidine interaction.

Cyclosporine (CsA) is used to prevent rejection of transplanted organs. It is extensively metabolized in the liver by the mixed function oxidase enzyme system by demethylation and hydroxylation. Since cimetidine is a widely prescribed H2 antagonist drug which is known to inhibit the P-450 enzyme system, we studied the effect of chronic treatment with cimetidine on CsA by determining the disposition of CsA (15 mg/kg, iv), prior to and after chronic treatment with cimetidine (60 mg/kg, po), for 5 days. CsA was determined by an HPLC procedure. The clearance (Cl) of CsA was significantly reduced following treatment with cimetidine when compared to the Cl value obtained in the control group (15.46 versus 10.36 ml/min/kg). There were no significant changes in the volume of distribution of CsA, one reason being that cimetidine and cyclosporine bind to different proteins. From the results obtained, we conclude that since cimetidine is an inhibitor of the mixed function oxidase system enzyme system, it inhibits the metabolism of CsA.

Animals↗
PubMedDate not supplied

Cyclosporine-phenytoin interaction.

Cyclosporine (CsA), an immunosuppressant, is used widely to prevent rejection of transplanted organs. It is extensively metabolized in the liver by hydroxylation and demethylation. Since phenytoin is used extensively post-transplant as an anti-convulsant, we studied the effect of chronic treatment with phenytoin on CsA by determining the disposition of CsA, prior to and after chronic treatment with phenytoin (30 mg/kg, po) for 5 days. CsA was analyzed by HPLC. The clearance (CL) of CsA was significantly enhanced following treatment with phenytoin when compared to the CL values obtained pretreatment (15.46 +/- 0.76 vs. 25.3 +/- 3.11 ml/min/kg). There were no significant changes in the volume of distribution of CsA. From the above data, we conclude that phenytoin probably induces the metabolism of CsA.

Animals↗
PubMedDate not supplied

An investigation of the adrenergic uptake specificity of phenyl-2-aminoethyl sulfides.

In earlier work we have demonstrated that a novel series of phenylethylamine analogs (phenyl-2-aminoethyl sulfides) cause a potent antihypertensive effect in spontaneously hypertensive rats. In addition, we have shown in vitro that these compounds are facile substrates for dopamine beta-hydroxylase, the terminal enzyme of norepinephrine synthesis. While the mechanism of action of these derivatives is as yet hypothetical, we have proposed that, if they are capable of gaining entrance into adrenergic nerve endings and neurotransmitter storage vesicles, these compounds may reduce norepinephrine synthesis by competing with dopamine for oxygenation. In this report, we present results of preliminary studies designed to examine this hypothetical mechanism of action. We find that all derivatives of this series are classical indirect-acting sympathomimetics whose initial cardiovascular activity is blocked by cocaine. These results suggest that compounds of this type gain entrance to adrenergic neurons via the normal norepinephrine uptake mechanism on adrenergic nerve endings. We also present data which demonstrate that the methylated derivative was not only the most potent indirect-acting sympathomimetic, but also the only derivative capable of producing a marked tachyphylaxis. In addition, we find these compounds affect a specific pool of intraneuronal norepinephrine, distinct from that affected by tyramine, a well-known indirect-acting sympathomimetic agent.

Anesthesia↗
PubMedDate not supplied

Preliminary characterization of enzymes for reduction of naloxone and naltrexone in rabbit and chicken liver.

The enzyme systems involved in the reduction of the narcotic antagonists, naloxone and naltrexone, were studied from the liver of chicken and rabbit. These secies were chosen because the relative amounts of diastereoisomeric products formed by enzymatic reduction between these species are so different; naloxone and naltrexone are converted in the chicken to 6alpha-naloxol and 6alpha-naltrexol, respectively, and in the rabbit to 6beta-naloxol and 6beta-naltrexol, respectively. In the present study, the enzymes for carrying out this reduction were found to require NADPH and to occur in the soluble fraction of liver homogenates. These enzymes were precipitated at 60-70% ammonium sulfate saturation for the chicken and at 50-60% for the rabbit. Differential sensitivity to inhibitors could be shown. For example, the rabbit enzyme was more sensitive to inhibition by morphine than was the chicken enzyme. The reverse order of sensitivity was seen with ketamine. These differences in properties between the chicken and rabbit liver enzymes indicate that the alpha- and beta-hydroxy product stereoselectivity arises from two different enzymes carrying out the reduction.

Animals↗