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Biomedical subjects

S Spector

Publications and source records attributed to S Spector.

At least 145 records · Page 8Linked to original sources
PubMed1978

Increased vascular collagen biosynthesis by hypertension and reversal by antihypertensive drugs.

Collagen synthesis was increased in aortas, mesenteric arteries, cerebral microvessels, pial artery, basilar artery and decreased in the heart of rats made hypertensive with deoxycorticosterone acetate-salt or the spontaneously hypertensive animal. The markers of collagen biosynthesis that were elevated were prolyl hydroxylase, prolyl hydroxylase-related antigen, total collagen content and the incorporation of labelled proline into total protein and into collagen. The antihypertensive drugs reserpine and chlorthiazide could both prevent the increase or reduce the increase in collagen synthesis.

Animals↗
PubMed1978

Studies on the monoamine oxidase and catechol-O-methyltransferase of the rat cerebral microvessels.

The rat cerebral microvessels were isolated and assayed both for monoamine oxidase (MAO) and catechol-o-methyltransferase (COMT) activities. Cerebral microvessels and brain filtrate were found to contain both forms (A & B) of MAO. On a per mg protein basis, the cerebral microvessels contained the greatest activity of MAO and COMT than that of brain filtrate and mesenteric artery. Chemical sympathectomy using 6-hydroxydopamine neither decreased total MAO activity, nor the A form of the enzyme, nor did it have any effect on COMT activity in the brain microvessels. These results suggest that COMT and both forms of MAO in the rat brain microvessels are extraneuronal in origin.

Animals↗
PubMed1978

Disposition of clonidine in rats as determined by radioimmunoassay.

The disposition of the potent antihypertensive drug clonidine has been poorly understood through the lack of a convenient and sensitive assay. A radioimmunoassay for clonidine has been developed and is capable of detecting as little as 10 pg of clonidine. 2,6-Dichlorophenyl-guanidine, a known metabolite of clonidine, did not cross-react with the antiserum whereas another metabolite, 4-hydroxyclonidine, was as potent as clonidine in displacing labeled clonidine from the antibody. However, a simple solvent extraction step before the radioimmunoassay selectively extracted clonidine from a mixture of clonidine and 4-hydroxyclonidine in alkaline plasma and this procedure permitted a specific assay for clonidine. The plasma levels of clonidine in rats after the administration of a hypotensive dose (100 microgram/kg i.v.) were determined by radioimmunoassay and these data indicated that the disposition of clonidine conforms to an open two-compartment, pharmacokinetic model. Clonidine rapidly accumulated in the brain as shown by the attainment of peak concentrations within 2 min of i.v. injection.

Animals↗
PubMed1978

The potentiating effect of clorgyline and pyrogallol on the blood pressure responses to norepinephrine.

Intraventricular administration of norepinephrine (NE) into pentobarbital anesthetized rats elicits a pressor or a depressor effect depending on the dose injected: after a low dose, a depressor response is seen while after a high dose, a pressor response is observed. In the animal pretreated intraventricularly with clorgyline or pyrogallol, the hypotensive effect of a low dose of NE was reversed to a hypertensive effect, while the hypertensive effect of a high dose of NE was markedly potentiated. This result suggests that brain monoamine oxidase and catechol-o-methyltransferase can metabolize centrally released NE before it leaks into the peripheral circulation.

Animals↗
PubMed1977

Hypertension: increase of collagen biosynthesis in arteries but not in veins.

In two models of hypertension in rats, it was shown that collagen synthesis and deposition are increased in arteries where blood pressure is elevated. By contrast, there were no alterations in any of the markers of collagen synthesis in veins, where blood pressure was only slightly elevated. It would appear that the stimulus for vascular collagen synthesis is provided by a direct effect of the increased pressure on the arterial cells rather than by a humoral factor released into the general circulation.

Animals↗
PubMed1977

The effect of guanethidine and hydrochlorothiazide on blood pressure and vascular tyrosine hydroxylase activity in the spontaneously hypertensive rat.

The present study examined the effects of antihypertensive drugs (hydrochlorothiazide and guanethidine) on blood pressure and tyrosine hydroxylase (TH) activity in the spontaneously hypertensive rat (SHR). Hydrochlorothiazide (50 mg/kg X 4 days) lowered blood pressure in the SHR to a degree equivalent to that produced by reserpine (0.3 mg/kg X 3 days). However, while reserpine increased vascular and adrenal TH activity, hydrochlorothiazide had no effect. Guanethidine (30 mg/kg X 2 days) reduced blood pressure in the SHR and also depleted cardiac, vascular and adrenal gland catecholamines; However, guanethidine administration did not increase TH activity in the mesenteric vasculature or adrenal glands. These studies indicate that at equieffective blood pressure lowering doses, different antihypertensive drugs have different effects on TH activity in the SHR. Neither blood pressure reduction nor catecholamine depletion in peripheral tissues are sufficient prerequisties for increasing TH activity. The data support the suggestion, however, that amine depletion in the central nervous system or ganglia may be an important factor in the regulation of TH.

Adrenal Glands↗
PubMed1977

Pharmacologic response to pentobarbital in actively immunized mice.

Mice were placed on an immunization schedule known to result in the production of antibodies directed against a variety of barbiturates (antibody binding capacity = 2.71 pmole 3H-phenobarbital bound/ml undiluted serum). The pharmacologic response to barbiturate in these actively immunized mice and suitably treated controls was investigates using rotarod apparatus for monitoring CNS depression. It was found that the response to pentobarbital in actively immunized mice was decreased, as reflected by an increase in the time the mice remained on the rotarod and a shift of the dose--response curve to the right. The decreased pharmacologic response to pentobarbital was not the result of changes in levels of the hepatic drug metabolism components. Furthermore, the alteration of pharmacologic response in actively immunized mice was selective for barbiturate and did not modify the ataxia produced by administration of another depressant agent, ethanol.

Aminopyrine N-Demethylase↗
PubMed1977

Monoamine metabolism in human brain.

Norepinephrine (NE), dopamine (DA), tyrosine hydroxylase (TH), catechol-O-methyltransferase (COMT) and monoamine oxidase (MAO) levels were measured in human brain tissue obtained at autopsy from a series of 39 patients dying of various medical and accidental causes. The nine following brain areas were studied: globus pallidus, thalamus, hypothalamus, hippocampus, substantia nigra, floor of the fourth ventricle, orbital cortex, caudate nucleus, and mammillary bodies. Enzyme activity correlated positively with age in all brain areas for MAO (with both benzylamine and tryptamine substrates) but no consistent pattern of correlation was found for COMT and TH. Mean MAO activity was significantly higher in women than men. There is increased brain MAO activity during late childhood and adolescence. These data are consistent with previous evidence suggesting that age and sex are important determinants of amine metabolism in the human central nervous system.

Adolescent↗
PubMed1977

Inhibition of theophylline clearance by troleandomycin.

The effect of troleandomycin, a macrolide antibiotic, on theophylline elimination was examined in eight patients with chronic asthma. Clearance from serum was reduced by 50 +/- 6% (mean +/- SD) during administration of 250 mg troleandomycin four times daily. Reduction of clearance persisted to a lesser degree in one of these patients examined while receiving 250 mg troleandomycin daily. An increase in serum theophylline concentration can thus result from initiating troleandomycin in asthmatic patients receiving continuous treatment with theophylline. This may be at least a partial explanation for the apparent benefit of troleandomycin in chronic asthma and also suggests that possibility of inducing theophylline toxicity, including seizures, as was observed in one of the patients in this study.

Drug Interactions↗
PubMed1977

Reduction of blood pressure and vascular collagen in hypertensive rats by beta-aminopropionitrile.

beta-Aminopropionitrile, a specific inhibitor of lysyl oxidase prevented the rise in blood pressure induced by deoxycorticosterone-salt in rats. In addition, after the onset of hypertension, administration of beta-aminopropionitrile lowered the blood pressure. Concomitant with the lowering of blood pressure, there was a reduction in the more highly crosslinked form of vascular collagen. These findings would indicate that increases in vascular connective tissue are not only sequelae of hypertension, but may also contribute to the maintenance of elevated blood pressure.

Amino Acid Oxidoreductases↗
PubMed1977

Binding of the endogenous nonpeptide morphine-like compound to opiate receptors.

The endogenous central nervous tissue substance called MLC (morphine-like compound) is shown to bind to the opiate receptors of the mouse neuroblastoma X glioma hybrid cell line NG108-15. The interaction of MLC with these opiate receptors is noncooperative, as is the interaction of morphine, naloxone, and Leu-enkephalin with these receptors. A specific antibody to morphine will bind MLC but will not bind beta-endorphin, Leu-enkephalin, or Met-enkephalin. It would appear, therefore, that MLC can be considered to be a different type of endogenous ligand for the opiate receptor.

Animals↗
PubMed1977

Cerebrospinal fluid levels of d-tubocurarine in man.

Using radioimmunoassay, d-tubocurarine (dTc) was found in the cerebrospinal fluid (CSF) of man after intravenous injection. When dTc was administered in a single dose (0.3 mg/kg) to nine patients, small quantities, 3.5 +/- .26 ng/ml (mean +/- SE), appeared in the lumbar CSF within 5 minutes. The concentration of dTc (0.3 mg/kg) were given at 90 minute intervals. Concentration of dTc in the CSF remained constant for the next 25 minutes, but then began to increase with time to to 9.3 +/- 4.4 ng/ml 30 minutes after injection, 14.5 +/- 4.4 ng/ml at one hour, and 24.9 +/- 6.5 ng/ml at six hours. In another group of six patients, three doses of dTc (0.3 mg/kg) were given at 90-minute intervals. Concentration of dTc in the CSF increased after each injection. The quantities of dTc found in the CSF are unlikely to produce any pharmacologic or adverse effect (e.g., convulsion) in man.

Humans↗
PubMed1977

Brain and vascular monoamine oxidase activity in the deoxycorticosterone-salt hypertensive rat.

1 The role of monoamine oxidase (MAO) in the maintenance of deoxycorticosterone-sodium chloride (DOCA-salt) hypertension was investigated by assaying the MAO activity both in central as well as peripheral blood vessels and in brain tissue. 2 The results suggest that the activity of MAO in the DOCA-salt hypertensive rat is similar to the activity present in the normotensive rat.

Animals↗
PubMed1977

Radioimmunoassay of atropine in plasma.

Antibodies, against atropine, were produced in rabbits immunized with atropine conjugated to bovine serum albumin. The antisera possessed a high binding affinity and were quite specific. The sensitivity of the method allowed detection of 6.25 ng of atropine per ml of plasma in a 10-microliter specimen. The method does not require an extraction procedure and can be performed using very small volumes of plasma. Plasma concentration-time profiles were determined by this method in dogs after rapid i.v. administration of atropine. Atropine declined from plasma in a biexponential fashion, exhibiting a terminal half-life of approximately 2.1 hours.

Animals↗