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Biomedical subjects

F Noël

Publications and source records attributed to F Noël.

At least 37 records · Page 2Linked to original sources

Increased reactivity to 5-hydroxytryptamine of portal veins from mice infected with Schistosoma mansoni.

In chronic severe infection with Schistosoma mansoni, portal hypertension accompanied by anatomical changes of the portal vasculature can develop as a consequence of granulomatous response to eggs. Mice infected unisexually with male worms were used in the present study in order to investigate a direct effect of worms on the reactivity of their host portal vein. A higher reactivity in the presence of 5-hydroxytryptamine (5-HT), but not in the presence of KCl 100 mM solution, was observed in portal vein from infected mice compared to healthy mice. It was characterized by an increase in the maximal contraction and sensitivity to 5-HT. Blockade of NO-synthase with N omega-nitro-L-arginine methyl ester (L-NAME) induced a small increase in 5-HT potency in the portal vein from non-infected mice, but did not change the amplitude of the contractions. In portal veins from infected mice, preincubation with L-NAME did not affect the reactivity to 5-HT. Histological analysis indicated endothelial damage, subendothelial fibrous plaques, and focal areas of inflammatory infiltrates in the adventitial layer. As a conclusion, these results show that unisexual infection of mice with male S. mansoni increased the reactivity of the portal vein to 5-HT which seems to be only partially related to an alteration in the endothelial production of nitric oxide.

Animals↗

Portal veins of mice infected with Schistosoma mansoni exhibit an increased reactivity to 5-hydroxytryptamine.

In chronic severe infection with Schistosoma mansoni, portal hypertension and related vascular alterations usually develop as a consequence of granulomatous response to eggs. In order to investigate a putative direct effect of worms on the reactivity of their host portal vein, mice infected only with male worms were used in the present study. An higher reactivity to 5-hydroxytryptamine (5-HT) characterized by an increase in the maximal contraction and sensitivity was observed in portal vein from infected mice compared to healthy mice. Blockade of NO-synthase with l-NAME induced a small increase in 5-HT potency in portal vein from non-infected mice without changing the amplitude of the contractions, whereas it did not alter the reactivity of veins from infected mice. The present results show that unisexual infection of mice with male S. mansoni increased the reactivity of the portal vein to 5-HT which seems to be partially related to an alteration in the nitric oxide release by endothelium.

Animals↗

Communication of risks: organization of a methylmercury campaign in the Cree communities of James Bay, Northern Quebec, Canada.

In the James Bay region of Canada, with the advent of extensive hydroelectric development, methylmercury contamination of fish has become a serious problem, having a direct impact on the Cree way of living. In 1982, the Cree Board of Health and Social Services of James Bay implemented a methylmercury exposure surveillance program in all Cree communities. Since that time, it has developed several educational tools on methylmercury contamination, including posters, pamphlets, and a video. In 1993 and 1994, Cree leaders, Community Health Representatives, medical staff, and other selected band members were consulted to identify the needs of the population regarding information on mercury. All questions and comments were listed, and a summary was sent to those consulted to double check the type of information required by the population. This led to the preparation of a brochure on mercury in a question and answer format, as well as creation of posters. The brochure and the posters were published in French, English and Cree and distributed in each community. A radio message was broadcast in all communities, and individual and group meetings were also held. Cree involvement in the mercury information program has been essential to its success.

Animals↗

Praziquantel has no direct effect on (Na(+)+K+)-ATPases and (Ca2(+)-Mg2+)ATPases of Schistosoma mansoni.

Therapeutic concentrations of praziquantel produce a rapid and intense contraction of the human flatworm Schistosoma mansoni. As an action on ATPases responsible for calcium homeostasis arises as a possible explanation for the molecular mechanism of this effect, we tested here the effect of praziquantel on different preparations from male adult worms that were previously characterized for their content in (Na(+)+K+)-ATPase and (Ca2(+)-Mg2+)ATPase activities from different origins. Concentrations as high as 100 microM praziquantel did not inhibit (Na(+)+K+)-ATPase from tegument and carcass nor (Ca2(+)-Mg2+)ATPase from heterogeneous (P1) and microsomal (P4) fractions. As 100 microM praziquantel was also without effect on calcium permeability of microsomal vesicles actively loaded with 45Ca2+, the present results discard three hypotheses recently raised for the mechanism of praziquantel-induced contraction of S. mansoni.

Animals↗

Formation of a highly stable complex between BN 50730 [tetrahydro-4,7,8,10 methyl-1(chloro-2 phenyl)-6 (methoxy-4 phenyl-carbamoyl)-9 pyrido [4',3'-4,5] thieno [3,2-f] triazolo-1,2,4 [4,3-a] diazepine-1,4] and the platelet-activating factor receptor in rabbit platelet membranes.

BN 50730 [tetrahydro-4,7,8,10 methyl-1(chloro-2 phenyl)-6 (methoxy-4 phenyl-carbamoyl)-9 pyrido [4',3'-4,5] thieno [3,2-f] triazolo-1,2,4 [4,3-alpha] diazepine-1,4], a novel platelet-activating factor (PAF) receptor antagonist with a hetrazepine structure, decreased the maximal number of binding sites (Bmax) of [3H]PAF in rabbit platelet membranes without altering its dissociation constant. Platelet aggregation induced by 1 microM PAF was prevented by preincubation with 1 microM BN 50730. The washing of the platelets preincubated with BN 50730 failed to revert its inhibitory effects. We conclude that BN 50730 acts as a non-competitive antagonist of the PAF receptor, due to the formation of a highly stable drug-receptor complex.

Animals↗

Evidence for the presence of two (Ca(2+)-Mg2+) ATPases with different sensitivities to thapsigargin and cyclopiazonic acid in the human flatworm Schistosoma mansoni.

The subcellular localization of the (Ca(2+)-Mg2+)ATPase activities present in heterogeneous (P1), nuclear (P2), mitochondrial (P3) and microsomal (P4) fractions obtained by differential centrifugation of Schistosoma mansoni homogenate was investigated. In the microsomal fraction (P4), the (Ca(2+)-Mg2+)ATPase activity was completely blocked by 3 microM thapsigargin, whereas in the more heterogeneous fraction (P1), about 20-30% of this activity was resistant to the drug. The same pattern of inhibition was observed using 20 microM cyclopiazonic acid. The distribution pattern of (Ca(2+)-Mg2+)ATPase activity among the four subcellular fractions (P1 > P4 > > P3 > P2) was completely different from that of [3H]-ouabain binding sites (P1 > or = P4 = P2 > or = P3). These results indicate that the (Ca(2+)-Mg2+)ATPase in S. mansoni is predominantly of the SERCA type (localized in the endoplasmic reticulum). However, there is another enzyme, present in lower proportion that could have a plasma membrane origin (PMCA type), because it is resistant to thapsigargin and cyclopiazonic acid and its inhibition by tamoxifen is antagonized by calmodulin.

Animals↗

Varying mercury exposure with varying food source in a James Bay Cree community.

James Bay Quebec Crees are exposed to methylmercury (MM) through fish consumption. Hair mercury concentrations were measured in women of child-bearing age and men and women 40 years of age and above in a small Cree community of James Bay (with traditionally low exposure to MM) before and after fishing expeditions to inland lakes where fish were contaminated with methylmercury. Median hair mercury concentrations in persons 40 years and above increased from 4.1 mg/kg to 9.9 mg/kg and the highest value from 17.4 to 47.2 mg/kg. A similar increase was seen after a second fishing expedition where the median hair concentration increased from 3.4 mg/kg to 7.2 mg/kg and the highest value from 17.7 to 49.9 mg/kg. Populations with traditionally low exposure to MM can become highly exposed with changes in sources or quantities of fish consumed.

Adolescent↗

Time course of the effect of praziquantel on Schistosoma mansoni attachment in vitro: comparison with its effects on worm length and motility.

We report herein that praziquantel inhibits the capacity of adult male Schistosoma mansoni to attach to the bottom of a glass dish and produces a diminution of worm length and motility, acting under a similar concentration and time dependency. After removal of 1 microM praziquantel from the medium, the worms progressively recuperated their initial length and motility without recovering their attachment capability. The absence of calcium or presence of 1 microM verapamil did not change the praziquantel-induced effect on worm attachment, causing only a transient decrease in worm length and motility. The present data indicate that the diminution of motility induced by praziquantel results from the progressive contraction of the longitudinal musculature of the worm. In contrast, the loss of attachment should not be causally related to the contraction of the worm since these two praziquantel-induced effects have distinct patterns of response under some experimental conditions.

Animals↗

Decrease in the ratio of high- to low-affinity isozymes of (Na+ +K+)-ATPase during the development of rat cardiac ventricles.

The ratio of (Na+ +K+)-ATPase (EC 3.6.1.3.)isoforms with high and low affinity for cardiac glycosides was studied in heart preparations from neonatal, 3-month and 6-month old Wistar rats. Biphasic ouabain inhibition curves of (Na+ +K+)-ATPase activity indicated that the relative contribution of the high-affinity process decreased from 34% at 9 days to 23% at 3 months and to 10% at 6 months. Scatchard plots for [3H]ouabain binding were curvilinear and indicated that the relative contribution of the high-affinity sites (Kd = 0.1-0.25 microM) decreased by about one-half between 3 months (19-24%, N = 2) and 6 months (9-11%, N = 2).

Age Factors↗

Chronic morphine administration causes region-specific increase of brain type VIII adenylyl cyclase mRNA.

The up-regulation of the cyclic AMP system and enhanced phosphorylation of protein substrates after either sudden interruption of chronic opioid treatment or antagonist administration has been proposed to account for the various behavioral responses observed during withdrawal. Using in situ hybridization histochemistry, we show here for the first time that type VIII adenylyl cyclase mRNA is selectively increased, as early as 12 h after morphine treatment in the locus coeruleus and the amygdala, two brain regions suggested to be important in morphine dependence expression. Moreover, the time course of morphine-induced changes in type VIII adenylyl cyclase mRNA in locus coeruleus is related to the incidence of jumping, the most important sign of morphine withdrawal in mice. In addition, the overexpression of type VIII adenylyl cyclase mRNA in thalamic nuclei could add to morphine tolerance. These findings offer a strong support, at the molecular level, for an altered regulation of the cyclic AMP system in opiate tolerance and dependence. The present measure relates only to type VIII adenylyl cyclase mRNA and similar tests with other cyclases are needed to explore fully this relationship.

Adenylyl Cyclases↗

Heterogeneity of ouabain binding sites in Schistosoma mansoni. First evidence for the presence of two (Na+ + K+)-ATPase isoforms in platyhelminths.

Binding experiments with [3H]ouabain were performed to investigate the presence of (Na+ + K+)-ATPase (EC3.6.1.3) isoforms in adult male Schistosoma mansoni, the trematode responsible for human schistosomiasis. Non-linear regression analysis of equilibrium experiments performed with homogenates in a Mg-Pi medium indicated the presence of about 10% (Bmax = 223 +/- 67 fmol/mg protein) high-affinity sites (KD = 0.285 +/- 0.045 microM) and 90% (Bmax = 2117 +/- 348 fmol/mg protein) sites with a 20-fold lower affinity (KD = 4.9 +/- 1.28 microM). This was confirmed by their-exponential decay of [3H]ouabain dissociation. Furthermore, determination of association and dissociation rate constants indicated that the two classes of binding sites differed by their dissociation rate constants for ouabain (k-1 = 0.0185 +/- 0.0019 min-1 and 0.0997 +/- 0.0528 min-1 for high- and low-affinity sites, respectively). Surprisingly, the association rate constant measured for ouabain binding to S. mansoni homogenate (0.038 microM-1.min-1) was lower (25- to 80-fold) than the one usually observed for mammalian enzymes. This is the first direct evidence for the existence of (Na+ + K+)-ATPase isoforms in platyhelminths, invertebrates of great importance from the phylogenetic point of view.

Animals↗

A (Ca(2+)-Mg2+)ATPase from Schistosoma mansoni is coupled to an active transport of calcium.

The (Ca(2+)-Mg2+)ATPase activity in microsomes of Schistosoma mansoni is fully inhibited by vanadate (I50 = 2.5 microM). 45Ca2+ is accumulated within microsomal vesicles in an ATP-dependent process that is enhanced 5-fold in the presence of 40 mM phosphate. Accumulated 45Ca2+ is rapidly released by 5 microM of the Ca2+ ionophore A23187 (t1/2 less than or equal to 6 s). (Ca(2+)-Mg2+)ATPase activity and Ca2+ uptake share the same subcellular distribution pattern and similar Ca2+ sensitivities (K0.5 = 0.39 microM and 0.15 microM, respectively). The substrate selectivity is high for both ATPase activity and Ca2+ transport. These results indicate the presence of an active transport of Ca2+ coupled to the (Ca(2+)-Mg2+)ATPase activity previously described in this parasite. A plasma membrane localization and physiological role in calcium homeostasis are suggested.

Animals↗

Distribution of alpha 1 and alpha 2 (Na+,K+)-ATPase isoforms between the junctional (t-tubular) and non-junctional sarcolemmal domains of rat ventricle.

The alpha 1 and alpha 2 (Na+,K+)-ATPase isoforms in microsomal fractions from adult rat ventricle could not be separated by density gradient centrifugation. Both isoforms were mainly recovered in low-density subfractions and their distribution pattern was superimposable to those of other typical plasma membrane constituents (5'-nucleotidase, muscarinic receptors) but differed from that of 1,4-dihydropyridine receptors, which were mainly associated with high-density subfractions. Thus, both (Na+,K+)-ATPase isoforms were present essentially in the non-junctional sarcolemmal domain, i.e. at the cell surface, while 1,4-dihydropyridine receptors (voltage-dependent calcium channels) seemed much more concentrated in the junctional domain, which is predominantly of t-tubular origin. Therefore, the high inotropic efficacy of low ouabain concentrations in rat ventricle cannot be explained on the basis of a preferential localization of the high-affinity receptors (alpha 2 isoform) in the vicinity of junctional structures. The difference in inotropic efficacy between high and low ouabain concentrations might be related to differences in stimulus response coupling associated with alpha 1 and alpha 2 isoforms, as suggested by the greater sensitivity of the effect of low concentrations to ethylisopropylamiloride, an inhibitor of Na(+)-H+ exchange.

5'-Nucleotidase↗