Biomedical subjects

J Fontaine

Publications and source records attributed to J Fontaine.

At least 55 records · Page 3Linked to original sources

PubMed1999

Reduction of the developmental competence of sheep oocytes by inhibition of LH pulses during the follicular phase with a GnRH antagonist.

A GnRH antagonist (Antarelix) treatment was used during the breeding season of Romanov ewes, to investigate whether LH pulses are required the day before the preovulatory surge for normal early embryo development in vivo (Expt 1) and in vitro (Expt 2). In Expt 1, at the onset of oestrus after removal of a fluorogestone acetate sponge, group A0.5 (n = 22) received a subcutaneous injection of 0.5 mg Antarelix, and ovulation was induced with an intravenous injection of 3 mg pig LH 24 h later. The control group (group C, n = 20) were untreated. All ewes were mated naturally at 36 and 48 h after oestrus and embryos were recovered 8 days after sponge removal. There were significant differences in the decrease in LH and in the increase in FSH concentration after Antarelix treatment between treated and control groups. The ovulation rate and embryo recovery rate were not significantly different between the two groups but the blastocyst rate was lower (P < 0.0001) in group A0.5 than in group C, with more unfertilized or degenerated oocytes in group A0.5 (69.2%). In Expt 2, 24 h after sponge removal, group A (n = 10) and group B (n = 10) received one subcutaneous injection of 0.5 mg Antarelix. The control group (group C, n = 10) was left untreated. LH pulsatility was re-established in group B with hourly intravenous injections of 5 micrograms ovine LH for 24 h. Oocytes were collected by flushing the oviducts 28 h after the LH surge, and were fertilized and cultured in vitro for 7 days. Ovulation and cleavage rates were not significantly different among the three groups but a higher rate of blastocysts (P < 0.01) was obtained after Antarelix treatment when LH pulsatility was re-established (group B). Oestradiol concentration was strongly depressed (P < 0.0003) after Antarelix treatment in group A, but was maintained after injection of LH pulses in group B, although at a lower value than before the preovulatory surge in the control group. In conclusion, inhibition of endogenous LH pulses 1 day before the preovulatory surge was not essential for ovulation and in vitro fertilization but was associated with a decrease in plasma oestradiol concentrations and inferior embryo development both in vivo and in vitro. When LH pulsatility was re-established, oestradiol concentrations increased and embryo development was restored.

Analysis of Variance↗

PubMed1998

Witnessing the evolution of transcription in mitochondria: the mitochondrial genome of the primitive brown alga Pylaiella littoralis (L.) Kjellm. Encodes a T7-like RNA polymerase.

A region of the mitochondrial genome of the primitive brown alga Pylaiella littoralis containing a plasmid-like insert which contains a transcribed T7-phage-type RNA polymerase gene is described. This is a first report of a phage-type RNA polymerase gene integrated in a mitochondrial genome. As the mitochondrial genome of this alga also contains sigma-70 proteobacterial promoter regions, i.e. traces of the ancestral alpha2betabeta'sigma-70 proteobacterial RNA polymerase, this genome witnesses two types of RNA polymerases. As such the mitochondrial genome of P. littoralis represents a unique stage in the evolution of transcription in mitochondria, which contrasts with that of the primitive protist Reclinomonas americana, which still retains the ancestral alpha2betabeta'sigma-70 proteobacterial RNA polymerase genes, and with animals, land plants and fungi, which use phage-type polymerases.

Chromosome Mapping↗

PubMed1998

Immunization of sheep against GnRH early in life: effects on gonadotropins, follicular growth and responsiveness of granulosa cells to FSH and IGF-I in two breeds of sheep with different prolificacy (Romanov and Ile-de-France).

The profile Romanov (R, ovulation rate = 3) and non-prolific Ile-de-France (IF, ovulation rate = 1) breeds were compared for their ovarian sensitivity to gonadotropins and IGF-I before puberty. For this purpose, the effects of in vivo immunization against GnRH on populations of ovarian follicles and in vitro sensitivity of granulosa cells to FSH and IGF-I were studied in prepuberal lambs from both breeds. Seventeen prepuberal lambs of each breed were actively immunized against GnRH between 3 wk and 6 mo of age. Relative to untreated lambs, FSH levels at 4, 5, and 6 mo of age were (respectively) 41%, 25% and 29% for IF, and 43%, 24%, and 36% for R lambs. In a first experiment, histological analysis of ovaries was performed. Immunization treatment decreased the number of small (100-390 microns in diameter) and large size follicles (< 1500 microns) in both breeds at 6 mo of age. In both breeds, gonadotropin (FSH-LH-hCG) treatment increased the number of large size follicles (< 1500 microns in diameter) and induced the formation of preovulatory follicles in immunized as well as untreated lambs. The ovulation rate was less in immunized animals, but it was not different between breeds. In a second experiment, the effects of FSH and IGF-I were studied on granulosa cells from follicles between 1000 and 2000 microns in diameter. In both breeds, IGF-I increased granulosa cell proliferation, but enhanced progesterone secretion was observed only in R lambs after FSH and IGF-I stimulation. Granulosa cell response to FSH treatment was lost by immunization, whereas response to IGF-I remained unchanged in both breeds. These results indicate that long-term immunization of prepuberal lambs against GnRH reduced systemic concentrations of FSH, follicular development, and response to gonadotropins in vivo, similarly in the prolific R and the non-prolific IF breed. However, granulosa cells from R lambs had higher steroidogenic capacities and were more responsive to FSH. In addition, these results suggest that IGF-I could play an important role in regulating growth of small follicles both in immunized and non-immunized lambs.

Animals↗

PubMed1998

Murine Schistosoma bovis infection: analysis of parasitic and immune parameters.

Humoral and cellular responses to Schistosoma bovis antigens have been evaluated over a period of 11 weeks in mice exposed to S. bovis cercariae and data analysed in the context of the parasitic parameters (worm and egg loads) recorded at days 30, 60 and 80 of the ongoing infection. Results revealed a decrease of worm burden, particularly marked for female worms, between day 60 and day 80 of infection suggesting a higher susceptibility of female schistosomes to attrition mechanisms. The B-cell response, studied by measuring the production of different isotypes, was directed against different stage specific antigens, with a predominance of IgG1 antibodies associated with a significant increase of IgA and IgE antibodies after egg deposition. The T-cell response, assessed after in vitro stimulation of splenocytes, showed a predominant production of Th-2 cytokines (IL-4, IL-5 and IL-10) occurring after egg laying. Interestingly in contrast to S. mansoni infection the Th-2 polarization did not seem to be exclusively triggered by egg-associated antigens since significant amounts of IL-10 were produced after stimulation with adult worm antigen preparation (SWAP) before the beginning of egg deposition.

Animals↗

PubMed1998

Relationship of impairment of schistosome 28-kilodalton glutathione S-transferase (GST) activity to expression of immunity to Schistosoma mattheei in calves vaccinated with recombinant Schistosoma bovis 28-kilodalton GST.

Sera from calves vaccinated with the recombinant Schistosoma bovis-derived 28-kDa glutathione S-transferase (28GST) and subsequently naturally or experimentally exposed to Schistosoma mattheei were studied for their content of specific immunoglobulin G (IgG) and IgA antibodies to recombinant S. bovis 28GST as well as for their capacity to inhibit the enzymatic activity of the antigen. The results were analyzed in regard to the presence (natural infection) or absence (experimental infection) of a protective effect(s) (reductions in worm burden, egg load, fecal egg counts, and excretion of viable eggs) toward S. mattheei challenge. Under such conditions, no differences in the IgG- and IgA-specific antibodies to recombinant S. bovis 28GST or in the ability to block the catalytic function of the antigen between the two groups were recorded. Nevertheless, correlation analysis between the specific antibody responses to recombinant S. bovis 28GST and the inhibition of GST activity suggested an association with IgG in experimentally infected vaccinated animals, while in naturally infected vaccinated calves, the inhibitory activity appeared to be linked to a greater degree with IgA. These results suggest that in contrast to schistosomiasis in humans, IgG antibodies in calves with schistosomiasis may exhibit inhibitory functions toward GST enzymatic activity or have a modulatory effect on IgA antibody properties. Furthermore, sera from animals immunized with recombinant S. bovis 28GST recognized the native S. mattheei 28GST and achieved comparable levels of inhibition of activity of recombinant S. bovis 28GST and S. matthei 28GST, indicating the presence of cross-reactive epitopes on these two molecules.

Animals↗

PubMed1998

Effects of two MMPI-2 validity scales on basic scale relations to external criteria.

Many clinicians have come to rely on the broad array of validity scales available on the MMPI and the MMPI-2. In this study, we evaluated the utility of 2 MMPI-2 validity scales, the K scale and VRIN scale, in a sample of 692 psychiatric inpatients. Specifically, the effects of the K-correction procedure and the exclusion of protocols based on VRIN scale elevations were examined on the relation between MMPI-2 basic clinical scales and external criteria including both self-report and clinician ratings of psychopathology. Results indicated that the K-correction procedure commonly used with the MMPI and MMPI-2 did not result in higher correlations with external criteria in comparison to non-K-corrected scores. In contrast, MMPI-2 protocols that produced VRIN T-score values > or = 80 generally produced lower correlations with patients self-reports and clinician ratings of psychopathology in comparison to protocols judged to be valid based on VRIN scale results.

Adult↗

PubMed1998

Anti-Müllerian hormone (AMH) secretion in prepubertal and adult rams.

The aim of the present analysis was to determine whether anti-Müllerian hormone concentrations in prepubertal plasma or adult rete testis fluid are related to the number or function of Sertoli cells in rams or to the presence of the FecB Booroola gene. Twenty rams from two Booroola crosses, differing in their testicular masses were analysed; in each cross, half of the animals were heterozygous carriers of the FecB gene. The data from rams, during prepuberty and at adulthood during the non-sexual season, were analysed by two-way ANOVA and residual correlations. In 4-week-old intact male lambs, the mean anti-Müllerian hormone plasma concentration was 15 ng ml-1, irrespective of cross, genotype or eCG stimulation; it was significantly negatively correlated with FSH (r = -0.51; P = 0.02; n = 19). In adults, anti-Müllerian hormone was not detectable in plasma and was 0.5 ng ml-1 in rete testis fluid, irrespective of cross or genotype. The total number of Sertoli cells per testis was not related to anti-Müllerian hormone concentration in lamb prepubertal plasma or in adult rete testis fluid. The concentration of anti-Müllerian hormone in adult rete testis fluid was significantly and negatively correlated with the daily production of leptotene primary spermatocytes per testis (r = -0.56; P = 0.02; n = 16). The mean oestrogen concentration in the adult testicular vein was 2 pg ml-1 and was correlated negatively with the rete testis fluid concentration of anti-Müllerian hormone (r = -0.60; P = 0.02; n = 15) and correlated positively with the daily production of leptotene primary spermatocytes per testis (r = 0.53; P < 0.05; n = 19). In conclusion, anti-Müllerian hormone secretion was not correlated with the total numbers of Sertoli cells per testis and cannot be used as a predictor of the number of Sertoli cells. Anti-Müllerian hormone secretions were not affected by the presence of FecB gene. However, anti-Müllerian hormone secretion could be considered to be inversely related to the daily production of primary spermatocytes by the testis.

Analysis of Variance↗

PubMed1998

Gonadotrophin storage patterns in the ewe during the oestrous cycle or after long-term treatment with a GnRH agonist.

The storage pattern of gonadotrophins in the ewe pituitary was investigated during the oestrous cycle and after desensitization to GnRH using long-term treatment with a GnRH agonist, buserelin. Oestrous cycles in ewes were synchronized with progestagen sponges. Animals were allocated to two experiments. In the first, ewes were killed 36 h (before the preovulatory surge, n = 4), 48 h (end of the preovulatory surge, n = 5), 72 h (post-ovulation, n = 4) and 240 h (luteal phase, n = 3) after sponge removal. In the second experiment, another progestagen sponge was inserted in ewes 84 h after removal of the first sponge. Four ewes were infused continuously with buserelin (50 micrograms/day) for 15 days before killing. A further four ewes received no buserelin (controls). Pituitaries were collected and processed for immunocytochemistry to detect monohormonal (LH or FSH) and multihormonal (LH/FSH) cells. The percentages of LH or FSH immunoreactive cells in the pituitary were lower at the end of the preovulatory surge (7.4 +/- 0.3% and 1.2 +/- 0.3% respectively) compared with the other stages (11.4 +/- 0.5% and 5.4 +/- 0.7% respectively). Analysis of dual immunostaining showed the existence of monohormonal cells for LH and multihormonal cells (LH/FSH). No monohormonal cell for FSH was detected except at the end of the preovulatory surge when a few monohormonal FSH cells appeared (0.1 +/- 0.01% of pituitary cells). The percentage of monohormonal LH cells in the pituitary gland was similar in all studied stages of the oestrous cycle, whereas the percentage of multihormonal cells was lower at the end of the surge. In agonist-treated ewes, the percentages of LH or FSH immunoreactive cells (5.3 +/- 0.5% and 1.5 +/- 0.8% respectively) were decreased compared with controls (9.4 +/- 1% and 7.5 +/- 1.1% respectively). Analysis of the double immunostaining revealed a few monohormonal FSH cells (0.2 +/- 0.01% of pituitary cells) in agonist-treated ewes but not in controls. The percentage of monohormonal LH cells in the pituitary gland increased from 1.9 +/- 0.2% in controls to 3.8 +/- 0.3% in agonist-treated ewes, whereas multihormonal cells dropped from 7.5 +/- 1.1% to 1.3 +/- 0.7%. Our data suggest, therefore, that multihormonal cells contribute to gonadotrophin secretion, either during the preovulatory surge of the oestrous cycle or during the 'flare-up' effect initially induced by a GnRH agonist. Moreover, the appearance of monohormonal FSH cells in some conditions reflects a differential regulation of LH and FSH.

Animals↗

PubMed1998

Setting up of an original computer-assisted methodology to characterize in vitro drug-induced anti-angiogenic effects.

The development of angiogenesis within a tumor brings on a sequence of extremely complex molecular events. We have developed a methodology which enables a wide set of biological parameters to be quantitatively determined in the field of anti-angiogenesis pharmacology. This methodology which includes a video cell tracking device, is unique because it offers the possibility of evaluating the specific influence of a given compound with potential anti-angiogenic properties on cell cycle kinetics, cell death, global cell line growth, and cell motility. We chose TNP-470, a synthetic analogue of fumagilin, to test our methodology on HUVEC cell lines taken from various human umbilical cord veins. The experiments carried out with TNP-470 did not confirm all the data reported in the literature. Our results show that i) TNP-470 could be considered as a cytotoxic agent; ii) this compound had an apparently marginal cytostatic effect; and iii) it did not increase the apoptosis level. Our methodology also revealed that the HUVEC cell lines are very heterogeneous in terms of different biological parameters. This highlights the problem of the reproductibility of the result.

Angiogenesis Inhibitors↗

PubMed1997

Prevention by selenium supplementation of cyclosporin-A-induced vascular toxicity.

OBJECTIVE: The aim was to determine whether selenium supplementation, an important component of glutathione peroxidase, might attenuate cyclosporin (Cx)-induced vascular toxicity. METHODS: Four groups of rats were treated in parallel: the first group was supplemented with selenium (sodium selenite, 0.5 mg.kg-1) orally (p.o.) for 5 weeks and the same dose of selenium plus Cx 20 mg.kg-1 (i.m.) during the 6th week; group 2 received Cx only (20 mg.kg-1 i.m. for 1 week); group 3 was supplemented with selenium (0.5 mg.kg-1 p.o., for 6 weeks) and group 4 served as control. Thoracic aortas isolated from these various groups were studied in organ baths. RESULTS: In comparison with the control group, selenium supplementation did not modify acetylcholine (Ach)- and nitroprusside-induced relaxations. In group 2, endothelium-dependent relaxations (Ach) were markedly impaired and endothelium-independent relaxations (nitroprusside) were shifted to the right; with selenium supplementation (group 1), the responses to Ach were partially restored whereas the rightward shift of the concentration-response curves to nitroprusside persisted. Incubation with superoxide dismutase (SOD, 150 IU.ml-1) or selenium (1 microgram.ml-1) (but not with selenium plus an inhibitor of the glutathione redox cycle) improved the relaxations to Ach in group 2. CONCLUSIONS: The vascular toxicity of Cx seems related to generation of oxygen-derived radicals promoting EDRF destruction and is attenuated by selenium supplementation.

Acetylcholine↗

PubMed1997

Expression of a Schistosoma mansoni 28-kilodalton glutathione S-transferase in the livers of transgenic mice and its effect on parasite infection.

Schistosomiasis is a debilitating tropical disease for which an effective vaccine is needed. A 28-kDa glutathione S-transferase from Schistosoma mansoni (Sm28GST) has been shown to induce protective immunity. Sm28GST possesses significant sequence identity to mammalian GST isoforms. In order to study self-reactivity in mice immunized with Sm28GST and the concomitant phenomena of immune tolerance and epitope suppression, as well as their consequences for the protective immunity induced by this vaccination, we developed transgenic (Tg) mice that express Sm28GST under the control of a part of the mouse transferrin gene promoter. A study of (P28)Tg mice showed that the expression of Sm28GST was strictly localized in pericentrolobular hepatocytes. No histological change, inflammatory infiltrates, or modification of seric L-aspartate: 2-oxoglutarate aminotransferase concentration was observed over an 18-month period, despite a cross-reactivity between Sm28GST and a mouse molecule of 30 kDa. The immunoglobulin G anti-Sm28GST response of (P28)Tg mice immunized with recombinant Sm28GST was lower (P < 0.001) than that observed in non-(P28)Tg littermates and inversely proportional of Sm28GST liver expression. The response of non-(P28)Tg mouse spleen cells to Sm28GST stimulation was greater (P < 0.01) than that observed with (P28)Tg mouse spleen cells. (P28)Tg mice infected with 40 S. mansoni furcocercariae harbored more worms (P < 0.05) than did non-(P28)Tg control mice. The increase in the level of infection in (P28)Tg mice was reflected in concomitant increases in the numbers of adult worms and schistosome eggs found in livers and intestines after whole-body perfusion at 56 days postinfection, but no relative increase in the fertility of individual female worms was observed. The results obtained argue for the involvement of Sm28GST in reducing levels of infection and support the view that this enzyme has a central role in the maintenance of parasite viability, at least during its migration through host tissues.

Animals↗

PubMed1997

Ramipril prevents endothelial dysfunction induced by oxidized low-density lipoproteins: a bradykinin-dependent mechanism.

We wished to determine whether the acute toxic effects of oxidized LDL are attenuated in aortas isolated from rats chronically treated with an angiotensin-converting enzyme (ACE) inhibitor. In aortic rings incubated with human oxidized LDL (300 microg/mL), the endothelium-dependent relaxations to acetylcholine were attenuated, but not those to A23187 and to nitroprusside. This toxic effect of oxidized LDL was completely prevented in preparations coincubated with oxidized LDL and the nitric oxide (NO) precursor L-arginine (0.3 mmol/L). In aortas isolated from rats orally treated for 6 weeks with 10 mg/kg ramipril (group 1) or 1 mg/kg ramipril (group 2), this toxic effect of oxidized LDL was also markedly attenuated. In contrast, in aortas isolated from rats cotreated with ramipril (10 mg/kg) for 6 weeks and subcutaneous injections of Hoe 140 (a B2 kinin antagonist), 500 microg/kg per day for the last 2 weeks (group 3) or from rats orally treated for 6 weeks with losartan (an AT1-type angiotensin II receptor antagonist), 20 mg/kg (group 4), the inhibitory effect of oxidized LDL on acetylcholine-induced relaxations was similar to that observed in the control group (group 5). Moreover, long-term treatment with ramipril increased relaxations to acetylcholine in groups 1 and 2 and also relaxations to A23187 and aortic cGMP content in group 1, suggesting an enhanced NO availability. Thus, the protective effect of long-term ACE inhibition against the acute vascular toxicity of oxidized LDL is bradykinin dependent and seems to involve a facilitation of NO release via endothelial B2 kinin receptors.

Acetylcholine↗

PubMed1997

Vasodilative properties of BPDZ 79, a new potassium channel opener, in isolated aorta.

AIM: To compare the effect of a novel potassium channel opener 3-(1',2',2'-trimethylpropyl)amine-4H-pyrido (2,3-e)-1,2,4-thiadiazine, 1-dioxide (BPDZ 79), with diazoxide on aorta. METHODS: Muscle tension of rat aorta was compared with adjacent aortic rings without endothelium. One ring was precontracted with KCl 80 mmol.L-1. Three rings were precontracted with KCl 80 mmol.L-1, and two of them were incubated with glibenclamide (0, 1, and 10 mumol.L-1). 86Rb outflow from rat aorta was measured in the presence of glibenclamide 10 mumol.L-1. RESULTS: BPDZ 79 and diazoxide provoked concentration-dependent and endothelium-independent relaxation of the vasoconstriction evoked by KCl 30 mmol.L-1, but not by 80 mmol.L-1. BPDZ 79 showed more potent vasorelaxation and 86Rb outflow than diazoxide. After incubation with glibenclamide (1 and 10 mumol.L-1), an inhibitor of the ATP-sensitive K+ channels, the relaxation induced by BPDZ 79 and diazoxide were decreased with the same pattern. CONCLUSION: BPDZ 79 is a potent vasodilator by opening potassium channels.

Animals↗

PubMed1996

3-and 4-substituted 4H-pyrido[4,3-e]-1,2,4-thiadiazine 1,1-dioxides as potassium channel openers: synthesis, pharmacological evaluation, and structure-activity relationships.

4-N-Substituted and -unsubstituted 3-alkyl- and 3-(alkylamino)-4H-pyrido[4,3-e]-1,2,4-thiadiazine 1,1-dioxides were synthesized and tested vs diazoxide and selected 3-alykl- and 3-(alkylamino)-7-chloro-4H-1,2,4-benzothiadiazine 1,1-dioxides as potassium channel openers on pancreatic and vascular tissues. Several 4-N-unsubstituted 3-(alkylamino)pyridothiadiazines and some 3-(alkylamino)-7-chlorobenzothiadiazines were found to be more potent than diazoxide for the inhibition of the insulin-releasing process. Moreover, the 3-(alkylamino)pyridothiadiazines appeared to be more selective for the pancreatic than for the vascular tissue. By means of the pharmacological results obtained on pancreatic B-cells, structure--activity relationships were deduced and a pharmacophoric model for the interaction of these drugs with their receptor site associated to the pancreatic K(ATP) channel was proposed. According to their selectivity for the B-cell (endocrine tissue) vs the vascular (smooth muscle tissue) ionic channel, selected 3-(alkylamino)-4H-pyrido[4,3-e]-1,2,4,-thiadiazine 1,1-dioxides may serve as pharmacological tools in studying the K(ATP) channels ("pancreatic-like" K(ATP) channels) in other tissues.

Animals↗

PubMed1996

Coronary vasomotor responses in cyclosporine-treated piglets.

Chronic treatment with cyclosporine A (Cx) seems to produce a decreased ability of the endothelium to secrete nitric oxide. However, its effect on the coronary arterial system remains controversial. Therefore, coronary arteries isolated from piglets treated by intramuscular injections of Cx (10 mg/kg/day, IM, for 22 days) were studied in organ baths and compared with those isolated from control animals (IM injections of the Cx solvent). Depolarization-induced contractions (KCl 120 mM) were similar in both groups, whereas the acetylcholine-induced contractions (percent of 120 mM KCl) were enhanced: The area under the curve (AUC) was 245 +/- 51 in the Cx group versus 110 +/- 15 in the control group (p < 0.05). Removal of the endothelium did not significantly modify the acetylcholine-induced contractions in both groups and, therefore, did not attenuate the enhanced responsiveness to acetylcholine in the Cx group. On unrubbed rings contracted with prostaglandin F2 alpha, the endothelium-dependent relaxations from serotonin (in the presence of 1 microM ketanserin) were reduced: The AUC was 479 +/- 24 in the Cx group versus 385 +/- 22 in the control group (p < 0.02). Larger AUC values were also found for bradykinin and substance P in the Cx group: 158 +/- 18 versus 55 +/- 17 (in the control group, p < 0.01) and 198 +/- 8 versus 145 +/- 12 (p < 0.01), respectively. Nevertheless, no alteration in calcium ionophore-induced relaxations was observed: The AUC was 217 +/- 10 in the Cx group and 224 +/- 18 in the control group (NS). Indomethacin incubation (10 microM) did not prevent the impairment in endothelium-dependent relaxations and did not attenuate the cyclosporine-induced augmentation of acetylcholine-induced contractions. Thus, chronic administration of cyclosporine to piglets impairs the coronary endothelial function and produces functional changes in smooth muscle cells. These alterations may play a role in the occurrence of cardiac graft vasculopathy.

Acetylcholine↗

PubMed1996

Effect of dietary supplementation with fish oil on cyclosporine A-induced vascular toxicity.

We wished to determine whether dietary supplementation with fish oil prevents the vascular toxicity of cyclosporine (Cx). In a first set of experiments, we assessed the endothelial function of aortas isolated from rats supplemented for 6 weeks with fish oil (FO), administered by gavage, and providing 150 mg/kg/day of eicosapentaenoic acid and 100 mg/kg/day of docosahexaenoic acid. FO treatment altered neither acetylcholine- and histamine-induced relaxations, nor serotonin-induced contractions (NS vs. control group). Thereafter, three groups of rats were treated in parallel. Group 1 received FO supplementation (by gavage) for 6 weeks, and Cx (10 mg/kg/day po) was added during the last 2 weeks, group 2 received Cx only (10 mg/kg/day po) for 2 weeks, and group 3 served as a control. Both acetylcholine-and histamine-induced relaxations were reduced in group 2 compared with the control group, as indicated by the area under the curve (AUC), which was significantly higher: 296 +/- 17 vs. 138 +/- 32, and 392 +/- 38 vs. 318 +/- 25 for acetylcholine and histamine, respectively. In group 1, AUC for acetylcholine remained significantly different from the control (241 +/- 31 vs. 138 +/- 32), whereas AUC for histamine was 367 +/- 28 (NS vs. control). The serotonin-induced contractions were also enhanced in group 2 compared with those of the control group, and this alteration was not attenuated in group 1. After mechanical removal of the endothelium, the increased responsiveness to serotonin persisted in groups 1 and 2, suggesting this functional alteration to be located in the smooth muscle cells. Thus, in the rat the attenuation of Cx-induced vascular toxicity by fish oil supplementation is only partial, that is, it involves a slight improvement in endothelial function, but with persistence of functional changes in smooth muscle.

Administration, Oral↗

PubMed1996

Ultrastructural localization of Sm28 GST protective antigen in Schistosoma mansoni adult worms.

The localization of the 28 kDa Schistosoma mansoni glutathione S-transferase (Sm28 GST) has been investigated using immunohistochemistry and electron microscopy and the results compared with previously published data. This study confirms the wide distribution of this antigen in the parasite. In male and female worms, Sm28 GST is localized in the tegument, the parenchyma, the oesophageal epithelium and in genital organs. Sm28 GST was clearly detected in germinal and sustentacular cells. The decrease of staining intensity during the differentiation of germinal cells suggests a down-regulated expression of the molecule. At the ultrastructural level, this antigen was abundant in nuclei and less present in the cytoplasm. The marked heterogeneity observed in the staining of individual worms indicates that Sm28 GST seems to be closely associated with the parasite's metabolism. The results are discussed in relation to the biological and protective functions of the protein.

Animals↗

PubMed1995

Chronic angiotensin-converting enzyme inhibition and endothelial function of rat aorta.

To determine whether chronic angiotensin-converting enzyme (ACE) inhibition produces functional changes in the aorta normotensive rats, four groups of rats were studied in parallel for 6 weeks. Group 1 orally received ramipril and beta 2-kinin antagonist HOE140 500 micrograms/kg per day s.c. by injection for the remaining 2 weeks; group 3, hydralazine 100 mg/kg per day PO for 6 weeks; group 4 (control), subcutaneous injections of saline solution during the last 2 of 6 weeks. In aorta isolated from group 1 the relaxations induced by bradykinin, acetylcholine, and histamine were significantly potentiated compared with those of group 4. In group 3, despite a decrease in systolic blood pressure similar to that induced by ramipril treatment, the responses to these three endothelium-dependent vasodilators were not different from those of group 4. In group 2, bradykinin-induced relaxations were completely abolished whereas acetylcholine-induced and histamine-induced relaxations were to those of group 4. The inhibitory effect of the endothelium on serotonin-induced contractions was significantly increased in preparations of group 1 compared with those of groups 2 through 4. Indirect measurements of nitric oxide formation such as contractions evoked by NG-monomethyl-L-arginine (L-NMMA) and aortic cGMP content were also significantly enhanced in preparations from group 1 compared with those of groups 2 through 4. Moreover, because the relaxations to nitroglycerin and nitroprusside were similar in groups 1, 2, and 4 an alteration of the guanylate cyclase activity by ramipril treatment is quite unlikely. Thus long-term treatment with ramipril potentiates the endothelium-dependent responses in the rat aorta by enhancing nitric oxide availability.

Adrenergic beta-Antagonists↗