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Biomedical subjects

J C Stoclet

Publications and source records attributed to J C Stoclet.

At least 145 records · Page 8Linked to original sources
PubMed1984

Smooth muscle cell hypertrophy and hyperplasia in the thoracic aorta of spontaneously hypertensive rats.

Changes in the smooth muscle cell compartment (SMCC) of the media layer of the aorta were studied in spontaneously hypertensive (SHR) and in normotensive rats (WKY) of both sexes between 3 to 18 weeks of age. Up to 7 weeks of age, development of the SMCC occurred in males and females of the two strains both through a massive increase in cell number and in cell size. In SHR after 7 weeks of age, the development of the SMCC was due to a marked increase in cell size together with an increase in cell number. In contrast during the same period, the development of the SMCC in WKY was associated almost exclusively with an increase in cell size. It is concluded that the presence of a greater number of larger smooth muscle cells contributes to the hypertrophy of the arterial wall of hypertensive animals.

Aging↗
PubMed1984

Endothelial mediated inhibition of contraction and increase in cyclic GMP levels evoked by the alpha-adrenoceptor agonist B-HT 920 in rat isolated aorta.

In the presence of endothelium maximal contractions of rat aorta preparations evoked by B-HT 920 were about 10% of those evoked in the absence of endothelium. 6-Allyl-2-amino-5,6,7,8-tetrahydro-4H-thiazolo-(4,5-d)azepin dihydrochloride (B-HT 920, 0.1 microM to 0.1 mM) induced concentration-dependent contractions of rat aorta in the absence of endothelium. Maximal contractions were comparable in magnitude to those induced by noradrenaline. In the presence of endothelium but not in its absence B-HT 920 (0.1 mM) stimulated an increase in tissue cyclic GMP levels of about 2 fold. Levels of cyclic AMP were unaffected. Removal of endothelium reduced basal tissue levels of cyclic GMP. The guanylate cyclase inhibitor methylene blue (0.5 microM) potentiated B-HT 920-induced contractions in the presence of endothelium and inhibited increases in cyclic GMP. In the presence of endothelium 5,8,11,14-eicosatetraynoic acid (ETYA; 0.1 mM), an inhibitor of both lipoxygenase and cyclo-oxygenase systems, inhibited the B-HT 920-induced increase in cyclic GMP but did not potentiate B-HT 920-induced contractions. ETYA also antagonized B-HT 920-induced contractions in the absence of endothelium. It is concluded that endothelium continuously releases a product or products which influence the smooth muscle. Inhibition of B-HT 920-induced contractions in the presence of endothelium is associated with increased tissue levels of cyclic GMP.

5,8,11,14-Eicosatetraynoic Acid↗
PubMed1983

Tissue and substrate specificity of inhibition by alkoxy-aryl-lactams of platelet and arterial smooth muscle cyclic nucleotide phosphodiesterases relationship to pharmacological activity.

Alkoxy-aryl-lactams (cilostamide, AAL 05, ZK 62 711, Ro 20-1724) inhibit differently cAMP or cGMP phosphodiesterases from blood platelets or vascular smooth muscle. Cilostamide (IC50 0.23 microM) and AAL 05 (IC50 0.15 microM) are 100 times more potent towards platelet cAMP phosphodiesterase whereas ZK 62 711 (IC50 2 microM) and Ro 20-1724 (IC50 33 microM) inhibit more selectively the enzyme from aorta. The substrate specificity of the inhibitors is different in the two tissues: ZK 62 711 and cilostamide are respectively 345 and 290 times more potent as inhibitor of cAMP than cGMP phosphodiesterase from vascular smooth muscle (ZK 62 711) or platelets (cilostamide). M + B 22,948 selectively inhibits cGMP phosphodiesterase with an IC50 of 9 or 24 microM on platelet or aorta enzyme, respectively. In general, the potencies of spasmolytic and platelet inhibitor effects vary from one drug to the other with the potency of inhibition of phosphodiesterase from the corresponding tissue. These data suggest that phosphodiesterases from platelets are different from those of arterial smooth muscle.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1983

Immunomodulating effects of a short-term oral treatment with C 1821 in untreated cancer patients: a controlled study.

C 1821 is a purified glycoprotein extract from Klebsiella pneumoniae serotype 2 with a molecular weight of about 350,000. It enhances immune responses in animals when given orally and the oral route of administration is devoided of any toxicity even in humans. The present controlled trial showed that C 1821 given per os at the single daily dose of 4 mg for 14 days in untreated cancer patients (mostly lymphomas) significantly enhanced delayed cutaneous hypersensitivity to recall antigens using the Multitest system (7 antigens). It also increased basal levels of lymphocyte cAMP and particularly of cGMP which were decreased in these patients. When incubated in vitro with lymphocytes from either normal controls or patients, C 1821 showed a dose-dependent stimulation of cAMP synthesis which was more pronounced in patients than in controls.

Adult↗
PubMed1983

Alterations of peripheral blood lymphocyte cyclic AMP and cyclic GMP in untreated patients with hodgkin's disease.

Cyclic AMP and cyclic GMP are important regulatory agents of lymphocyte functions. Depressed T-lymphocyte functions are frequently associated with Hodgkin's disease and suppressor monocytes have been implicated in the pathogenesis of this defect. In the present study cAMP and cGMP resting levels were measured in lymphocytes from 18 untreated patients with Hodgkin's disease using a sensitive radioimmunoassay. A significant decrease of cAMP (P less than 0.001) and, to a lesser degree, of cGMP (P less than 0.01) was found in monocyte-depleted lymphocyte suspensions from the patients compared to controls. Studies of patient and control lymphocyte subpopulations showed in patients a clear deficit of cAMP in T-depleted lymphocytes, rather than in T cells, with a low cAMP/cGMP molar ratio in both subpopulations. From this data it is clear that factors other than prostaglandin-mediated suppression of monocyte origin are involved in the pathogenesis of the T-lymphocyte depression associated with Hodgkin's disease.

Adolescent↗
PubMed1982

Age-related decrease of in vitro isoproterenol-induced cyclic AMP accumulation in rat aorta.

Isoproterenol-induced accumulation of cyclic AMP was investigated in aorta rings from 7 to 18 weeks old rats. The effect of isoproterenol on cyclic AMP reached a maximum in 1 min. The concentration-effect curves showed a significant decrease of the maximal accumulation of cyclic AMP as a function of age, without any variation in the effective concentration range. These results parallel the previously reported decrease of beta-adrenergic relaxation of rat aorta with age.

Aging↗
PubMed1981

Parathyroid hormone effects on calcium metabolism in the rat are impaired by 5-ethyl-5'-(1-methylpropyl)-2-thiobarbiturate (inaktin).

The mechanism by which inaktin, a thiobarbiturate, promotes a moderate drop in serum calcium has been investigated. The effect was cancelled in hypocalcemic parathyroidectomized rats. On the other hand inaktin antagonized the serum calcium raising effects of parathyroid extract in these animals. In rats wit intact parathyroid glands inaktin caused a two-fold increase in urinary calcium excretion and a marked decrease in body and bone calcium turnover (measured with 45 Ca). These results support the view that inaktin impairs the parathyroid hormone effects on calcium metabolism.

Anesthetics↗
PubMed1980

Cyclic nucleotide phosphodiesterase in the aorta of spontaneously hypertensive rats : variation with age and effect of propranolol.

The activities of cyclic AMP- and cyclic GMP-phosphodiesterase were studied in the aorta (freed of the adventitia layer) of spontaneously hypertensive rats (SHRs). At the time of weaning (3 weeks of age) young SHRs were separated into two groups. One group was chronically treated with propranolol, 50 mg.kg-1 daily for 4 weeks (treated rats), with treatement beginning either at the time of weaning or at 15 weeks of age. The second group (non-treated SHRs) was used as control. In both groups we observed that the protein content per aorta but not the DNA content increased parallel to the organ weight. The enzyme activities were related to the DNA content of aorta. In non-treated SHRs, the phosphodiesterase activties increased with age, but there was a considerable lag of time between the marked increase in blood pressure that occured between 5 and 12 weeks of age and the increase in phosphodiesterase activity which started after 12 weeks of age. Prolonged propranolol treatment significantly decreased both blood pressure and enzyme activities when started at the time of weaning but had no effect when given to mature SHRs. Thus, the effects of propranolol on blood pressure and on phosphodiesterase activities were associated, whereas no correlation could be established between the age-dependent increases in blood pressure and in phosphodiesterase activities in aorta cells of the SHR.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1980

[Expression of results in studies of vascular biochemical components during the development of the SHR rat].

Hypertrophy and hyperplasia induced by age and hypertension as well as tissue heterogeneity makes it difficult to analyse biochemical datas obtained with rats thoracic aortas from rats of various age and blood pressure. In SHR, the thoracic aorta weight increases parallely to the body weight from the first week after birth onwards. Meanwhile the protein content of the organ increases parallely to the organ weight. However, though the DNA content increases markedly up to 7 weeks of age, one observes a much lower increase with age afterwards. It seemed to us that the aorta DNA content was more representative of the organ cell number. This led us to use express our biochemical data per mg of the organ DNA content. Moreover, it seems necessary to take in account the cell volume which increases as well with age and hypertension on the one hand, and to be able to distinguish the cellular content of the myocytes from the one of other cells types contained in the adventitia and the intima, on the other hand. For these purposes pure media layers are prepared by completely removing the adventitia and intima and single cell suspensions are obtained after total enzyme digestion of the medias.

Age Factors↗