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Biomedical subjects

M Karmazyn

Publications and source records attributed to M Karmazyn.

140 records · Page 8Linked to original sources
PubMed1978

Adenosine as a prostaglandin antagonist. Possible mechanism of the defect in combined immunodeficiency disease due to adenosine deaminase deficiency.

Adenosine inhibition of cell division in EB-virus-transformed human lymphocytes and in normal lymphocytes stimulated by phytohemagglutinin can be overcome by prostaglandin (PG) E2. Analysis of adenosine/PGE2 interactions in smooth muscle suggests that adenosine causes immuno-deficiency by blocking a PG-dependent calcium stage of lymphocyte activation.

Adenosine↗
PubMed1977

Adenosine as a natural prostaglandin antagonist in vascular smooth muscle.

Adenosine has actions on smooth muscle similar to those of prostaglandin (PG) antagonists. Like some PG antagonists it is a phosphodiesterase inhibitor and seems to interfere with calcium effects. It has agonist/antagonist interactions with theophylline, a PG antagonist. In rat mesenteric vascular smooth muscle adenosine blocked responses to noradrenaline which depend on release of intracellular calcium but not those to potassium ions which depend on calcium entry from extracellular fluid. Partial inhibition of endogenous PG synthesis by indomethacin enhanced the adenosine effect. In preparations in which vascular reactivity had been abolished by indomethacin and then partly restored by 1 or 5 ng/ml PG2, adenosine also inhibited responses to noradrenaline: the curve for the 5 ng/ml PG2 concentration was to the right of and parallel to the 1 ng/ml curve consistent with a competitive interaction between adenosine and PG2. Similar interactions between adenosine and PG2 were shown in human lymphocytes in which activation also depends on calcium release. These findings suggest how calcium-dependent metabolic responses may be controlled and indicate further reasons for caution in the interpretation of cyclic AMP experiments.

Adenosine↗
PubMed1977

Effects of propranolol on the responses of the rat stomach strip to prostaglandin E2.

Propranolol is a local anaesthetic, membrane-stabilizing drug as well as a beta blocker. 2 mug/ml is added to many PG bioassay systems in order to inhibit beta adrenergic effects. This concentration inhibited responses of the rat stomach strip to PGE2 concentrations below 5 x 10(-7)M but potentiated responses to higher PGE2 concentrations. In calcium-free buffer only the potentiation was seen. Propranolol may not be a suitable drug for use in PG bioassay systems.

Animals↗
PubMed1977

Myo-inositol in physiological concentrations stimulates production of prostaglandin-like material.

In physiological concentrations myo-inositol stimulated production of prostaglandin (PG)-like material in a rat mesenteric vascular bed preparation. There were five lines of evidence: 1. Inositol potentiated pressor responses to both norepinephrine and potassium in a manner similar to PGE2. 2. Inositol had no potentiating effect in preparations in which endogenous PG production was blocked by indomethacin. 3. Inositol caused no further potentiation in preparations already potentiated by arachidonic acid, the PG precursor. 4. The inhibitory effect of the PG antagonist chloroquine was reduced in an apparently competitive manner by inositol. 5. As indicated by rat stomach bioassay inositol caused a three fold rise in the outflow of PG-like material from the preparation.

Animals↗
PubMed1977

Dopamine enhances the action of prolactin on rat blood vessels. Implications for dopamine effects on plasma prolactin.

It has been claimed that dopamine enhances peripheral uptake of prolactin. Dopamine at 2.1 x 10(-9)M, a concentration which had no effect by itself, enhanced both the potentiation of rat mesenteric vascular reactivity caused by 50ng/ml ovine prolactin and the inhibition of reactivity caused by 500ng/ml prolactin. These observations are consistent with the proposal that dopamine can interact peripherally with prolactin.

Animals↗
PubMedDate not supplied

Reduced tolerance to reperfusion-associated injury in hearts from myopathic hamsters.

This study was done to evaluate the response of myopathic hearts from dystrophic hamsters to 30 minutes of ischemia followed by 30 minutes of reperfusion. Hearts from male and female normal animals recovered 77 +/- 6% and 64 +/- 5% of their contractile force respectively following reperfusion whereas only 34 +/- 8% (male) and 34 +/- 7% (female) recovery was seen in myopathic hearts (P less than 0.01). Substantial sustained contractures were observed during reperfusion in hearts from dystrophic animals irrespective of gender whereas none were seen with control hearts. Reperfusion produced a rapid release of CPK that peaked at 5 minutes (approximate coronary effluent concentration of 40 mU/ml) and remained elevated for the reperfusion duration. Peak CPK values for normal hearts were reached at 10 minutes following reperfusion, were significantly lower from the myopathic hearts and returned to near control levels at the end of the 30 minute reperfusion period. Reducing Ca2+ in the perfusion medium by up to 80% or perfusing the hearts with the Ca2+-channel blocker verapamil produced no beneficial effects. Changes in the above parameters produced by ischemia or heart rate alterations throughout the perfusion sequence were not different between normal and myopathic hearts. This study shows a sensitivity of myopathic hearts that is manifested during reperfusion. Possible mechanisms for this reduced tolerance are discussed.

Animals↗
PubMedDate not supplied

The relationships between cyclic AMP, calcium and prostaglandins as second messengers.

There is considerable dissatisfaction with present second messenger hypotheses involving cyclic nucleotides and calcium. The recent findings that methyl xanthines and adenosine are prostaglandin antagonists casts doubt on much of the evidence in favour of the cyclic AMP hypothesis. There is evidence that allosteric sites may modify the binding of calcium and cyclic nucleotides to key cellular regulators and that a range of substances including steroids, adenosine and prostaglandins may occupy those sites. This concept introduces much needed flexibility into the second messenger concept, allows many experiments to be reinterpreted and has major implications throughout the biomedical sciences.

Adenosine↗
PubMedDate not supplied

The roles of prostaglandins and calcium accumulation in muscular dystrophy.

There is good evidence that abnormal calcium accumulation may be a final common pathway of muscle degeneration in the muscular dystrophies. Prostaglandins are able to promote calcium entry into cells and excess prostaglandin activity coupled with a defect in intracellular calcium release could cause toxic accumulations of calcium in intracellular organelles such as mitochondria. Serotonin stimulates prostaglandin synthesis while tricyclic antidepressants inhibit calcium release from intracellular organelles thus possibly accounting for the models of muscular dystrophy reported using this combination. The prostaglandin/calcium hypothesis can account for the effects of vitamin E, steroids and local anaesthetic-like drugs in muscular dystrophy. Since many drugs already in clinical use for other purposes can be used to control prostaglandin synthesis or action this hypothesis has immediate potential clinical applications.

Animals↗
PubMedDate not supplied

Correlation between the effects of aspirin and dipyridamole on platelet function and prevention of intimal hyperplasia in autologous vein grafts.

Fifty-four adult mongrel dogs receiving a lipid-supplemented diet were used to determine the effects of aspirin and dipyridamole on vein graft intimal hyperplasia. Twenty-one animals received the diet alone, 17 animals received a combination of dipyridamole and aspirin, while a further 16 animals received dipyridamole. Segments of undistended external jugular vein were anastomosed to bilaterally-divided femoral arteries. The vein grafts were harvested at six weeks and intimal thickness was measured with a Zeiss computerized microscope. Serum cholesterol, prothrombin time, partial thromboplastin time and clotting time was measured before the diet and at two, four and six weeks after operation. Plasma thromboxane B2 (TXB2) and the metabolite of prostacyclin I2 (6-keto PGF1 alpha) were determined by radioimmunoassay before and four weeks following operation. A similar and significant increase in serum cholesterol was observed in all animals receiving lipid supplementation. Platelet counts were significantly decreased in those animals receiving a combination of aspirin and dipyridamole while all other hematological parameters remained unchanged. Plasma TXB2 and 6-keto PGF1 alpha were unaffected by dipyridamole but were significantly decreased in those animals receiving the combined drug regimen. Intimal thickness measured 59 +/- 6 micron at six weeks in the controls. Dipyridamole reduced intimal thickness to 26 +/- 2 micron while aspirin and dipyridamole decreased intimal thickness to 28 +/- 2 micron. The data indicate that dipyridamole was as effective in reducing smooth muscle cell proliferation as the combination of aspirin and dipyridamole. Furthermore, the data suggest that antiplatelet drug regimens may reduce intimal thickening in autologous vein grafts by a mechanism other than affecting the thromboxane:prostacyclin ratio.

6-Ketoprostaglandin F1 alpha↗