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Biomedical subjects

S W May

Publications and source records attributed to S W May.

71 records · Page 4Linked to original sources
PubMed1975

Structural effects on the reactivity of substrates and inhibitors in the epoxidation system of Pseudomonas oleovorans.

The epoxidation reaction catalyzed by an enzyme system of Pseudomonas oleovorans exhibits a substrate specificity different from that expected on the basis of chemical reactivity in non-enzymatic epoxidation reactions. Cyclic and internal olefins, aromatic compounds and styrene are not epoxidated. The reactivity of straight chain diolefins is maximal for octadiene and falls off rapidly as the carbon chain is shortened, but decreases only slightly as the chain is lengthened. In contrast, methyl group hydroxylation is less sensitive to decreasing chain length. As a consequence, propylene and 1-butene are hydroxylated but not epoxidated by this enzyme system. With the substrate 1-decene, which is capable of undergoing both epoxidation and hydroxylation, the former reaction predominates. Methyl imidoesters were found to be inhibitors of enzymatic epoxidation, and the potency of a homologous series of imidoester inhibitors was examined. The results parallel the substrate specificity patterns observed, and support the conclusion that the mode of substrate binding severely moderates the inherent chemical reactivity of the activated oxygen in this system. The effect of the bifunctional imidoester, dimethyladipimidate, was also examined and the results compared with those obtained in other investigations.

Alcohols↗
PubMed1974

Inactivated Venezuelan equine encephalomyelitis vaccine prepared from attenuated (TC-83 strain) virus.

Formalin-inactivated Venezuelan equine encephalomyelitis vaccine was prepared from virus propagated in rolling-bottle cultures of chicken embryo cells. The attenuated, TC-83 strain of virus was propagated in these cultures with a maintenance medium consisting of serum-free medium 199 containing 0.25% human serum albumin and antibiotics. By adjustment of maintenance medium volume (100 to 300 ml) and multiplicity of inoculum (0.04 to 0.00004), high-titered yields of virus were obtained with minimal cell destruction at convenient harvest times, viz, 18 to 24 h postinoculation. Inactivation of virus at 37 C was complete between 8 to 10 h with 0.05% Formalin and within 6 to 8 h with 0.1% Formalin. Antigen extinction potency tests in mice indicated that potent vaccines could be produced at both Formalin concentrations and, furthermore, that potency was not adversely affected by inactivation periods of up to 96 h.

Animals↗
PubMed1973

Formalin-inactivated Venezuelan equine encephalomyelitis (Trinidad strain) vaccine produced in rolling-bottle cultures of chicken embryo cells.

Formalin-inactivated Venezuelan equine encephalomyelitis vaccine was prepared from virus grown in rolling-bottle cultures of chicken embryo cells. Trinidad strain virus was propagated in these cultures with a maintenance medium consisting of serum-free medium 199 containing 0.25% human serum albumin (USP) and antibiotics. Manipulation of multiplicity of inoculum (0.06 to 0.00006) and maintenance medium volume (100 to 300 ml) resulted in high-titered virus yields and only moderate cell destruction when fluids from infected cultures were harvested at 18 to 24 hr. The virus was inactivated at 37 C by 0.05% Formalin within 8 to 10 hr and with 0.1% Formalin within 6 to 8 hr. Single dose, antigen extinction tests in mice performed with 30 small-scale vaccine lots showed excellent potency at either Formalin concentration with inactivation periods ranging from 24 to 96 hr.

Animals↗
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

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↗