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Biomedical subjects

J Fontaine

Publications and source records attributed to J Fontaine.

At least 91 records · Page 5Linked to original sources
PubMed1991

The form and function of the Leydig cells in hypophysectomized rams treated with pituitary extract when spermatogenesis is disrupted by heating the testes.

The morphology and in-vivo function of the Leydig cells were studied in rams when spermatogenesis had been disrupted by a single exposure of the testes 20 days earlier to a temperature of about 42 degrees C for 45 min. To avoid complications due to changed negative feedback from the testes to the pituitary with consequent changes in the degree of gonadotrophic stimulation, ten of the animals (five heated and five unheated) were surgically hypophysectomized when the testes were heated and then treated twice daily with pituitary extract. Six intact rams (three heated and three unheated) were also studied. The heat-affected testes were about half the size of the unheated testes, and blood plasma flow was closely related to testis weight. There were no differences in the testosterone concentrations in spermatic venous blood, testicular lymph or rete testis fluid, or in oestradiol in spermatic venous plasma from heated or unheated testes. Consequently, testosterone secretion by the heat-affected testes was markedly reduced, and the concentrations in jugular blood were also lower in the heat-affected rams than in controls. The volume of the interstitial tissue was less in absolute terms in the heat-affected rams, but it made up a greater fraction of the testes. The absolute volume of the blood plus lymph vessels, and their fraction of the interstitial tissue were lower in the heat-affected testes, although there was no effect on their volume as a fraction of the whole testis. The heat-affected testes of the hormone-treated rams had fewer Leydig cells, but each cell was larger; no equivalent difference was found in the intact rams. However, the dose of pituitary extract chosen was somewhat excessive, as there were higher than normal concentrations of FSH, LH and testosterone in jugular blood plasma, of testosterone and oestradiol in testicular venous blood plasma and of testosterone in rete testis fluid in the hormone-treated hypophysectomized rams. The testes of the unheated hypophysectomized rams increased in size by about 20% during treatment with pituitary extract, although testicular blood plasma flow was lower per unit weight of testis. The absolute volume of each Leydig cell and the total volume in absolute terms and as a fraction of the interstitial tissue was greater in the hormone-treated than in the untreated rams, but not the volume as a fraction of the whole testis. The total number of Leydig cells was higher in the hormone-treated unheated rams than in all the other rams taken together.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1991

Effects of chronic prednisolone administration on plasma copper in rats with adjuvant arthritis.

Copper metabolism is known to be significantly affected by inflammation or by glucocorticoid administration. We have previously demonstrated that acute prednisolone administration induces a moderate but sustained increase in plasma copper in healthy rats while it induces a more pronounced but shorter increase in rats with adjuvant arthritis. In the present study we have investigated the effects of chronic prednisolone administration (around 0.65 mg/kg daily in food) in both healthy rats and rats with adjuvant arthritis at various stages of the disease. In healthy rats, a slight but significant increase of 11% was observed in plasma copper after 3 weeks of treatment. This modification was no longer apparent after 5 weeks of treatment. In arthritic rats, plasma copper was, as expected, higher than in healthy rats and reached a maximum 3 weeks after adjuvant injection. In prednisolone-treated arthritic rats, there was a sustained decrease in plasma copper starting after 2 weeks of treatment which could be correlated with an improvement of the clinical and biochemical signs of inflammation. In conclusion, chronic prednisolone treatment only slightly increases plasma copper in healthy rats while in arthritic rats plasma copper is dependent on the severity of the disease which is improved by the treatment.

Administration, Oral↗
PubMed1990

Effects of in vivo SIN1 treatment on nitrovasodilator relaxation and on EDRF-mediated responses in rat aorta.

SIN1 (the active metabolite of molsidomine), nitroglycerin, and endothelium-derived relaxing factor (EDRF) produce vasodilation by activation of soluble guanylate cyclase. Therefore, prolonged exposure to SIN1 might affect not only the responses to SIN1 itself and to nitroglycerin but also to EDRF. In vivo treatment of rats consisted of subcutaneous injections of either SIN1 (60 mg/kg) for the treated group or placebo for the control group, twice daily for 3 days. Thoracic aortas from the treated group were threefold and sixfold less sensitive to nitroglycerin and SIN1, respectively. The endothelium-dependent relaxations to acetylcholine were, nevertheless, similar in both groups. Moreover, the concentration-response curves to phenylephrine, which are known to be modulated by the endothelium, were similar in both groups. In addition, incubation with methylene blue (10 microM for 30 min), which blocks the vasodilator action of EDRF, potentiated in the same way the contractions to this alpha-adrenergic agonist. The increase in resting tone induced by methylene blue incubation was also equivalent in the two groups. The present results show that SIN1 treatment for several days in rats is associated with slight tolerance development not only to SIN1 itself but also to nitroglycerin, while the endothelial function remains operative. We conclude that the mechanisms involved in the activation of guanylate cyclase by SIN1 and nitroglycerin are probably different than those of EDRF-mediated responses.

Animals↗
PubMed1990

Relaxation response to pinacidil and diazoxide in the mouse isolated distal colon.

Pinacidil and diazoxide induced concentration-related relaxations of the longitudinal muscle of the mouse distal colon. The relaxing effects of pinacidil and diazoxide were unaffected by tetraethylammonium, but were antagonized by tolbutamide and glibenclamide. Relaxations provoked by nifedipine were not counteracted by the two hypoglycaemic sulfonylureas. It is tempting to suggest that the relaxation response to pinacidil and diazoxide could reflect the ability of both compounds to interfere with membrane K+ channels sharing common pharmacological properties with the K+ATP channels recently described in other tissues.

Animals↗
PubMed1990

Hypoglycemic sulfonylureas antagonize the effects of cromakalim and pinacidil on 86Rb fluxes and contractile activity in the rat aorta.

Cromakalim, pinacidil and nitroprusside provoked concentration-dependent relaxations of K(+)-depolarized rat aortae. Glibenclamide, tolbutamide and to a lesser extent tetraethylammonium antagonized the vasorelaxant action of cromakalim and pinacidil. Cromakalim, pinacidil but not nitroprusside elicited a marked increase in 86Rb outflow from preloaded and perifused aortic rings. These increases in 86Rb outflow were inhibited in a concentration-dependent manner by glibenclamide and tetraethylammonium. Our data extend previous observations indicating the involvement of K+ channels in the vasorelaxant properties of cromakalim and pinacidil. Moreover, the present findings suggest that both compounds could interfere with a vascular type of ATP-sensitive K+ channels.

Animals↗
PubMed1989

Generation of extracellular ATP in blood and its mediated inhibition of host weight loss in tumor-bearing mice.

Intraperitoneal injections of adenosine 5'-monophosphate (AMP) or adenosine 5'-triphosphate (ATP), but not of adenosine, inorganic phosphate or pyrophosphate, were shown to inhibit tumor growth and host weight loss in tumor-bearing murine hosts. The inhibition of tumor growth and host weight loss did not exhibit a cause-effect relationship, though both were mediated through expansion of red blood cell (RBC) ATP pools which were promoted by administered adenine nucleotides. We then demonstrated that expansion of RBC ATP pools was preceded by expansion of liver ATP pools and that the adenosine precursor for this type of enhanced RBC ATP synthesis originated in the turnover of expanded liver ATP pools. Although adenosine, which is the primary catabolic product of ATP in the peritoneal cavity or the systemic circulation, was sufficient to yield an expansion of mouse liver ATP pools in vivo, external phosphate was required for the subsequent expansion of RBC ATP pools, which in turn produced elevated extracellular (blood plasma) ATP levels. The anticancer activities which correlate with the elevated blood plasma ATP concentrations are proposed to be the result of direct action of extracellular ATP on the tumor and host tissues.

Adenosine Triphosphate↗
PubMed1989

Galanin: Ca2+-dependent contractile effects on the isolated mouse distal colon.

Galanin provoked concentration-dependent contractions of the longitudinal muscle of the mouse distal colon. The responses were not affected by atropine, mepyramine, methysergide, phentolamine, timolol, naloxone or tetrodotoxin. In contrast, the contractile responses were reduced by nifedipine and in Ca2+-free medium. These observations indicate that the contractile effects of galanin on the mouse distal colon result from a direct activation of smooth muscle cells and that these effects are mainly dependent on an increase in Ca2+ inflow.

Animals↗
PubMed1989

Study of ridazolol on isolated canine and human coronary arteries.

Experiments were performed on isolated canine and human coronary arteries to study the alpha- and beta-adrenolytic properties of ridazolol. On canine coronary arteries precontracted with prostaglandin F2 alpha 2 microM and pretreated with phentolamine 1 microM, ridazolol competitively antagonized the isoproterenol-induced relaxations, with a pA2 value of 8.5 (7.8-9.1). Thereafter the alpha-adrenolytic activity of ridazolol was assessed on these same canine coronary vessels. Ridazolol activity was compared with that of prazosin on dose-response curves to norepinephrine in the presence of cocaine (30 microM) and propranolol (3 microM). Schild plots for both drugs gave straight lines, with slopes not different from unity. The pA2 value was 7.1 (6.8-7.3) for ridazolol and 8.1 (7.9-8.4) for prazosin. In another set of experiments the alpha-adrenolytic activity of ridazolol was compared on canine and human coronary arteries. A submaximal contraction with norepinephrine (10 microM) was first assessed in the presence of propranolol 3 microM. The addition of ridazolol 3 microM significantly decreased the norepinephrine (10 microM)-induced contractions of both preparations. However, the inhibition was more pronounced on canine coronary arteries. In conclusion, ridazolol is a potent beta-adrenergic antagonist with moderate alpha-adrenolytic activity. The weaker inhibition of the norepinephrine-induced contraction observed in human preparations suggests the presence of a heterogeneous population of postjunctional alpha adrenoceptors.

Adrenergic alpha-Antagonists↗
PubMed1989

Prognostic significance of the signal-averaged ECG depends on the time of recording in the postinfarction period.

Serial recordings of the signal-averaged ECG and the 24-hour ambulatory ECG were obtained from 156 patients with acute myocardial infarction up to 5 days (phase 1), 6 to 30 days (phase 2), and 31 to 60 days (phase 3) after the infarction. Left ventricular ejection fraction by radionuclide ventriculography was also determined in phase 2. The signal-averaged ECG was abnormal during one or more of the three phases in 51 patients (31%). In 35 of these patients (69%) the recording changed category between normal and abnormal with the highest prevalence of abnormal recording occurring during phase 2. Eight patients had ventricular tachycardia/ventricular fibrillation in the first 48 hours after myocardial infarction. The signal-averaged ECG was abnormal in only one of these patients. Twelve patients had late arrhythmic events during the first year of follow-up (four sudden deaths and eight instances of documented ventricular tachycardia or ventricular fibrillation). Nine of the 12 patients had an abnormal signal-averaged ECG in phase 2 and four of these nine had a normal recording in phase 1. Five patients had a transient abnormal signal-averaged ECG in phase 1, whereas six patients had an abnormal recording only in phase 3. None of these 11 patients had an arrhythmic event. Stepwise logistic regression showed that an abnormal signal-averaged ECG in phase 2 has the most significant relation to late arrhythmic events. Both an abnormal signal-averaged ECG and a left ventricular ejection fraction less than 40%, but not complex ventricular arrhythmias, were independent significant risk factors for late arrhythmic events.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1989

Anticancer activities of adenine nucleotides in mice are mediated through expansion of erythrocyte ATP pools.

ATP and AMP exhibit significant anticancer activities against established footpad CT26 colon adenocarcinoma in CB6F1 mice. Adenosine, inorganic phosphate, and inorganic pyrophosphate were without such effects under identical conditions. Daily intraperitoneal injections of adenine nucleotides in large volumes of saline, starting after the tumors became palpable, resulted in inhibition of tumor growth and a few "cures." The treatment was not toxic to the host as determined by changes in body weights. Weight loss observed in animals upon progression of the fast-growing CT26 tumors was slowed markedly in adenine nucleotide-treated mice. The inhibition of weight loss in tumor-bearing mice was shown to be neither the cause nor the effect of the inhibition of tumor growth. Intraperitoneal injections of AMP or ATP but not of adenosine yielded expansions of erythrocyte ATP pools in host animals. The expanded erythrocyte ATP pools are stable over a period of hours, while slowly releasing micromolar amounts of ATP into the blood plasma compartment, leading to several-fold increases in plasma (extracellular) ATP levels. Based on previous studies in which 1-5 microM extracellular ATP effectively inhibited the growth of a variety of tumor cells in several in vitro systems, it is suggested that similar levels of ATP in blood plasma account for the anticancer activities observed in a murine host.

Adenocarcinoma↗
PubMed1989

Comparison of responses to acetylcholine and serotonin on isolated canine and human coronary arteries.

Canine and human coronary arteries were studied in organ baths to compare the responses to acetylcholine and serotonin in the two species. The human coronary rings were isolated from seven patients without cardiac disease (mean age 15 years, range 7-20). In one set of experiments canine and human preparations were incubated with phentolamine, propranolol and ketanserin (all at 1 mumol.litre-1 concentration) and precontracted with prostaglandin F2 alpha (PGF2 alpha 1-2 mumol.litre-1). Acetylcholine (0.1-10 mumol.litre-1) and serotonin (0.1-100 mumol.litre-1) relaxed canine preparations dose dependently, the maximum responses (expressed as % of depression of PGF2 alpha response) being 84 (SEM 6)% (n = 9) and 51(5)% (n = 6) respectively. In the same experimental conditions, acetylcholine and serotonin failed to relax the human coronary rings (n = 11) while substance P and bradykinin induced relaxations of 72(4)% (n = 11) and 66(7)% (n = 11) of PGF2 alpha response respectively. In another set of experiments, dose-contraction curves were constructed for acetylcholine or serotonin (in presence of phentolamine and propranolol). On human rings with endothelium, methylene blue (10 mumol.litre-1), a non-specific inhibitor of endothelium derived relaxing factor (EDRF), potentiated these dose-contraction curves: markedly for serotonin, the EC50 decreasing from 1.2(0.2) to 0.22(0.08) mumol.litre-1 (n = 11, p less than 0.01) with a significant increase in the maximal response); and slightly for acetylcholine, EC50 decreasing from 0.84(0.11) to 0.40(0.13) mumol.litre-1 (n = 10, p less than 0.05) without significant change in the maximal response.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗
PubMed1989

Alterations of beta-adrenoceptor mediated relaxations of atherosclerotic human coronary arteries.

Preliminary investigations suggest that atherosclerosis attenuates the beta-adrenergic relaxations of human coronary arteries. However, this finding could not be related specifically to the beta-agonists and responses to non-adrenergic relaxants could be also decreased. Therefore segments of coronary arteries were isolated from 35 human hearts (aged 18-58 years) with various degrees of atherosclerosis. On rings precontracted with KCl (15 mM) concentration-response curves were constructed for isoproterenol and were compared with the responses to three other vasodilators: forskolin, nitroglycerin and SIN1 (the active metabolite of molsidomine). At the end of each experiment, the degree of atherosclerosis was scored by histological examination. Moderate (class II) and severe (class III) lesions of atherosclerosis significantly altered the maximal response to isoproterenol, which was decreased from 76 +/- 5% (of KCl-induced contraction) to 33 +/- 6% in class II and 22 +/- 5% in class III. Conversely, the maximal relaxations to forskolin, nitroglycerin and SIN1 were not significantly modified. However, in class III, there was a significant shift to the right of the dose-response curves to nitroglycerin and SIN1 (but not to forskolin). Thus our results show that atherosclerosis markedly attenuates the relaxations of human coronary smooth muscles to isoproterenol, and that this abnormality is not related to an alteration in the intrinsic capacity of the atherosclerotic vessel to relax.

Adult↗
PubMed1989

Contractile effects of substance P and other tachykinins on the mouse isolated distal colon.

1. Substance P (SP), physalaemin, eledoisin and kassinin induced concentration-related contractions of the longitudinal muscle of the mouse distal colon. The responses were not antagonized by atropine (1.5 x 10(-7) M), mepyramine (2.5 x 10(-7) M), methysergide (5 x 10(-7) M), timolol (10(-6) M), phentolamine (10(-6) M) or naloxone (4 x 10(-7) M). They were enhanced by tetrodotoxin (TTX, 1.5 x 10(-7) M). These observations indicate that the contractile responses to the tachykinins result from a direct activation of smooth muscle cells. 2. The contractile activity provoked by SP and physalaemin was inhibited by nifedipine (a Ca2+-entry blocker) and was abolished in Ca2+-free EGTA solution. Such data suggest that the myogenic effects of SP and physalaemin are mainly dependent on their ability to promote Ca2+ influx. 3. Eledoisin and kassinin evoked a contractile response in the absence of external Ca2+ and their myogenic activity was, to some extent, resistant to the inhibitory effect of nifedipine. This may indicate that an additional process, probably the release of an intracellularly bound Ca2+ store, participates in the mechanism by which eledoisin and kassinin contract the mouse distal colon. 4. After desensitization of the mouse distal colon to SP, the contractile activity provoked by SP or physalaemin was totally abolished whilst the responses evoked by eledoisin and kassinin were barely affected. These observations and other experimental findings indirectly support the assumption that the mouse distal colon could possess different tachykinin-binding sites.

Animals↗
PubMed1989

Atherosclerosis and responses of human isolated coronary arteries to endothelium-dependent and -independent vasodilators.

In canine and porcine coronary arteries, experimental atherosclerosis (induced by endothelial denudation followed by a high-cholesterol diet) potentiates the vasoconstrictor effects of histamine, serotonin, and ergonovine. In isolated human atherosclerotic coronary arteries, only hypersensitivity to histamine has been demonstrated. This discrepancy could be due to several factors. First, the atherosclerotic lesions in human vessels are different from those observed in the animal, since experimental atherosclerosis often corresponds only to the early stage of the disease in humans. Second, the human atherosclerotic coronary arteries were isolated mainly from patients with cardiac failure, a condition that alters the responses of coronary smooth muscle to vasoactive amines. With regard to endothelium-dependent vasodilators, marked attenuations of the relaxations to substance P, bradykinin, and the Ca2+ ionophore A23187 have been described in isolated human atherosclerotic arteries. Acetylcholine elicits variable responses in these preparations and even if the arteries are devoid of atherosclerotic lesions, it often fails to relax them. In addition to this endothelial dysfunction, severely atherosclerotic human coronary vessels exhibit a slightly decreased responsiveness to nitroglycerin and SIN-1 but not to forskolin. Another abnormality of the smooth muscle is a marked attenuated beta-adrenergic relaxation. Thus, atherosclerosis of human coronary vessels induces not only marked alterations in endothelium-dependent responses but also modifies the sensitivity to several endothelium-independent vasodilators.

Animals↗
PubMed1989

Comparison of effects of chronic inflammation and long-term prednisolone administration on zinc metabolism in rats.

It is well known that plasma zinc is depressed in animals following administration of endotoxin, endogenous pyrogen, interleukin-1, and glucocorticoids. The modification is related to an induction of liver metallothionein causing an accumulation of the element in this organ. The changes in zinc metabolism induced by adjuvant arthritis in rats evidenced a redistribution of body zinc with a rapid and sustained decrease in plasma zinc that occurred simultaneously with an increase in liver zinc levels, and slower modification in erythrocyte and femur zinc concentrations. These effects were compared to those induced by a long-term corticosteroid administration in healthy rats. Male Wistar rats received either a commercially available complete maintenance diet or the same diet enriched with prednisolone at a level providing 1 mg prednisolone/kg body weight. Groups of animals were sacrificed after 3 or 5 weeks' treatment. Ingested food quantity, total body weight, total serum proteins and serum albumin were similar in treated and control rats. No significant modifications in parameters of zinc status could be observed after 3 weeks of treatment. However after 5 weeks, plasma zinc was significantly lower in treated rats as compared to controls, but modifications in liver, erythrocyte and femur zinc did not reach statistical significance. Changes induced by long-term corticosteroid administration are therefore less intense than those due to the inflammatory process of adjuvant arthritis.

Adrenal Cortex Hormones↗
PubMed1988

Changes in zinc, copper and selenium status during adjuvant-induced arthritis in rats.

Trace elements such as zinc, copper and selenium are involved in the pathogenesis of inflammatory diseases. In order to obtain more information about the overall movements of these minerals during the evolution of an experimental chronic inflammatory process, trace element levels were determined in five body compartments of the rat at several time intervals after induction of adjuvant arthritis. Rapid and significant changes in plasma zinc and copper levels and in liver zinc levels were observed. These modifications occurred as early as those in biochemical parameters of inflammation such as serum fibrinogen and ceruloplasmin, and preceded the appearance of any clinical symptom of the disease. Inverse correlations were found between plasma zinc levels and these two biochemical indices. Other modifications in trace element levels were observed two weeks after disease induction, the most important being a considerable increase in liver copper levels. Although food intake of affected animals decreased with the progression of the disease, there was no evidence of depletion in zinc and copper levels over the study period. A redistribution of body zinc between different biological compartments (mainly plasma and liver) occurred simultaneously with an accumulation of copper in several organs. The decreasing selenium status of animals was not clearly related to the inflammatory process.

Animals↗
PubMed1988

Persistence of the response to SIN1 on isolated coronary arteries rendered tolerant to nitroglycerin in vitro or in vivo.

Experiments were performed on isolated canine and human coronary arteries to provide more insight into the mechanisms responsible for the vascular tolerance to nitroglycerin that is induced under in vitro or in vivo conditions. In vitro tolerance was produced after an incubation of coronary ring segments with nitroglycerin (10 microM for 30 min at physiological pH). After elevation of tone with KCl (15 mM), dose-response curves were constructed for nitroglycerin or SIN1 (3-morpholino-syndnonimin) on control and tolerant rings. On canine tolerant rings the dose-response curve for nitroglycerin-induced relaxations was significantly (p less than 0.001) shifted to the right, and 50% of the maximal relaxation (ED50) increased from 55 +/- 9 nM to 1.2 +/- 0.2 microM. Pretreatment of tolerant rings with N-acetylcysteine (NAC, 10 microM 10 min before KCl-induced contraction) partially restored the responsiveness to nitroglycerin, with ED50 reducing to 0.56 +/- 0.03 microM (p less than 0.02). On the other hand, the dose-response curves to SIN1 were not significantly altered. Similar results were obtained on human preparations. On isolated canine coronary rings rendered tolerant in vivo by subcutaneous injections of 15 mg/kg nitroglycerin (two times daily for 4 consecutive days), ED50 for nitroglycerin was 0.67 +/- 0.08 microM (p less than 0.001 versus control rings), and NAC again partially restored the responsiveness to nitroglycerin. As for the in vitro tolerance, the relaxations to SIN1 were not significantly altered on these canine rings rendered nitrate tolerant in vivo.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗