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Biomedical subjects

P Bouchard

Publications and source records attributed to P Bouchard.

At least 91 records · Page 5Linked to original sources

[3H]1,3-di(2-tolyl)guanidine and [3H](+)pentazocine binding sites in the rat brain: autoradiographic visualization of the putative sigma1 and sigma2 receptor subtypes.

Sigma (sigma) receptors have generated a great deal of interest on the basis of their possible role in psychosis and on locomotor behaviors. The effects of sigma drugs on these various functions are apparently mediated by different sigma receptor subtypes (sigma1 and sigma2). However, little information is currently available on the discrete anatomical distribution of these putative sigma receptor subtypes in the rat brain. The aim of the present study was to investigate, by quantitative autoradiography, the respective distribution of purported sigma1 and sigma2 receptor subtypes in the rat brain using [3H]1,3-di(2-tolyl)guanidine, a universal sigma ligand, and [3H](+)pentazocine, a selective sigma1 ligand. Putative sigma2 receptor sites were visualized using [3H]1,3-di(2-tolyl)guanidine in presence of a saturating concentration of (+)pentazocine. Specific [3H]1,3-di(tolyl)guanidine and [3H](+)pentazocine binding sites were found to be widely but discretely distributed in the rat brain. The highest densities of specific labeling were seen in various cranial nerve nuclei, followed by certain hippocampal sub-fields and laminae, the red nucleus, the interpeduncular nucleus and mid-layers of primary and secondary motor cortices. Lower amounts of specific binding were present in various other structures including most thalamic and hypothalamic nuclei, and the cerebellum. Interestingly, [3H]1,3-di(2-tolyl)guanidine binding in the motor cortex was found to be particularly resistant to a saturating concentration of (+)pentazocine suggesting an enrichment in the putative sigma2 receptor subtype. This also applies for a few other structures such as the nucleus accumbens, substantia nigra pars reticulata, central gray matter, occulomotor nucleus and cerebellum. On the other hand, the sigma1 subtype is more abundant in most other regions with the highest densities seen in the dentate gyrus of the hippocampal formation, facial nucleus, and various thalamic and hypothalamic nuclei. The comparative localization of the sigma1 and sigma2 receptor binding sites probably relates to the differential effects of sigma1 and sigma2 drugs in the rat brain.

Analgesics, Opioid↗

Neuropeptide Y and the calcitonin gene-related peptide attenuate learning impairments induced by MK-801 via a sigma receptor-related mechanism.

It has been shown recently that low doses of sigma (sigma) receptor ligands like 1,3-di-(2-tolyl)guanidine (DTG), (+)N-allylnormetazocine [(+)SKF 10,047] and (+)pentazocine can antagonize learning impairments induced by dizocilpine (MK-801), a non-competitive antagonist at the NMDA receptor channel. This antagonism has been proposed to involve sigma receptor sites since it is blocked by the administration of purported sigma antagonists such as NE-100 and BMY-14802. It has also been demonstrated that peptides of the neuropeptide Y (NPY) and calcitonin gene-related peptide (CGRP) families modulate, in vivo, sigma labelling and electrophysiological effects in the hippocampal formation. Accordingly, we investigated if NPY- and CGRP-related peptides modulate cognitive processes by interacting with sigma sites in mice. In order to test this hypothesis, a step-down passive avoidance task was used. Interestingly, similarly to various sigma agonists, NPY, peptide YY (PYY) and the Y1 agonist [Leu31Pro34]NPY (but not NPY[13-36], a purported Y2 agonist), as well as hCGRPalpha and the purported CGRP2 agonist [Cys(ACM)2-7]hCGRPalpha (but not CGRP[8-37], a CGRP1 receptor antagonist), significantly attenuated learning impairments induced by MK-801. Furthermore, the effects of NPY, [Leu31Pro34]NPY, hCGRPalpha and [Cys(ACM)2-7]hCGRPalpha were blocked by the administration of the sigma antagonist, BMY-14802. The present data suggest that NPY- and CGRP-related peptides can indirectly interact in vivo with sigma receptors to modulate cognitive processes associated with NMDA receptor function.

Animals↗

Clinical evaluation of a bioabsorbable regenerative material in mandibular class II furcation therapy.

30 periodontally compromised adult subjects with mandibular buccal class II furcation defects were recruited for this study. All selected defects were treated according to the biological principles of guided tissue regeneration. The subjects were randomly assigned to 2 parallel groups. The test group (n=15) received a bioabsorbable polyglycolic-polylactic membrane (PGA/PLA group); the control group (n=15) received a non-resorbable expanded polytetrafluoroethylene membrane (ePTFE group). After initial therapy, baseline measurements were recorded including plaque index, gingival index, vertical and horizontal probing depths, clinical attachment level and depth of the recession. Recall visits were made at 1, 2, 4, 6, 8, 12, and 24 weeks. At 12 months, all baseline clinical parameters were again measured. The data analysis did not demonstrate a significant difference between the 2 groups. The vertical probing depth and attachment level changes were statistically significant in each group. The postoperative recession was 0.6 mm in the ePTFE group (p<0.05) and 0.8 mm (p<0.05) in the PGA/PLA group. Compared to the initial measurements, the mean changes in horizontal probing depth were 2.7 mm and 2.5 mm (p<0.001), corresponding to mean reductions of 41.5% and 40.9% for the ePTFE and the PGA/PLA groups respectively. The results of this study suggest that 12 months after initial surgery, similar clinical improvements can be obtained in GTR therapy of buccal class II furcation lesions, regardless of whether bioabsorbable PGA/PLA membranes or non-resorbable ePTFE membranes are used.

Adult↗

Scanning electron microscopic evaluation of the effects of an air-abrasive system on dental implants: a comparative in vitro study between machined and plasma-sprayed titanium surfaces.

An in vitro comparative study was conducted in order to evaluate the effects of an air-abrasive system on dental implant surfaces. Eight new titanium dental implants, four standard machined implants (machined group), and four standard plasma-sprayed implants (plasma-sprayed group) were selected for investigation. Both neck and body surfaces of the implants were analyzed. Each pair of implants in each group was treated as follows: the spray of the air-abrasive unit was applied to each area for 5 seconds on the first implant and 15 seconds on the second implant. A total of 24 areas were observed: 16 test implants and 8 controls. Scanning electron photomicrographs were analyzed by 3 examiners using a category rating scale (kappa = 0.594). The images were also computerized for texture analysis. The results indicate that a single air-powder abrasive treatment of the dental implants selected for this study modified their exposed surfaces. After treatment, the threaded neck surface of a machined group implant was least affected, whereas the body was the most altered. In the plasma-sprayed group, comparisons between implant surfaces showed little change. In the machined group, more change was observed in both neck and body areas. In all specimens, a 5-second exposure to the air-powder abrasive did not induce deep changes in the surfaces. A 15-second exposure modified all the specimen surfaces. Further studies are needed to evaluate the effect of these changes on the biological osseointegration process.

Air↗

Clinical evaluation of tetracycline HCl conditioning in the treatment of gingival recessions. A comparative study.

Thirty Class I and Class II recessions in 30 patients were treated with a modified subepithelial connective tissue graft procedure. Fifteen recessions in the test group received a tetracycline hydrochloride (50 mg/ml) root treatment for 5 minutes (TTC-HCl group); the remaining 15 recessions composed the control group and received a citric acid root treatment for 3 minutes (CA group). Clinical assessments were taken at baseline and at 6 months. The differences between treatments were not statistically significant. In the central area of the recession, the mean percentage of root coverage was 81.7% corresponding to a mean percentage of 79.3% and 84.0% for the TTC-HCl and the CA group, respectively. In the test group, 6 of the 15 recessions exhibited complete root coverage; the gingival augmentation was 57.8%. In the control group, 8 of the 15 recessions exhibited complete root coverage; the gingival augmentation was 43.6%. The mean surface area of root exposure was reduced from 11.53 mm2 and 13.30 mm2 to 0.34 mm2 and 0.29 mm2 for the TTC-HCl group and the CA group, respectively. This reduction corresponds to a mean percentage of 97.4% root coverage for both groups. Within the limits of this study, the results indicate that tetracycline hydrochloride and citric acid root conditioning have comparable clinical effects in root coverage surgical therapy. The data also suggest that the measurement of the surface area of the recession is a more accurate criterion in the evaluation of the mean percentage of root coverage than a single central vertical linear measurement.

Administration, Topical↗

Bioassays of gonadotropins based on cloned receptors.

Because of the microheterogeneities of gonadotropins, immunoreactive measurements of gonadotropins do not necessarily reflect their bioactivity. Follicle-stimulating hormone (FSH) bioassays have relied on measurement of aromatase activity in primary cultures of immature rat Sertoli cells or rat granulosa cells (GAB assay). Luteinizing hormone (LH) bioassays have relied on measurement of androgen production in primary cultures of rat interstitial testicular cells (RICT) or mouse Leydig cells. Those bioassays are cumbersome because they rely on primary culture and on indirect measurement of estradiol or testosterone by RIAs. The cloning of the cDNAs of FSH and LH receptors has allowed the establishment of cell lines expressing human receptors. The cotransfection of the recombinant gonadotropin receptor with a cAMP reporter gene allows a nonisotopic measurement of gonadotropin bioactivity. Furthermore, patient serum can be tested directly without prior extraction. We and other groups have developed a CHO cell line expressing the human FSH receptor and a luciferase reporter gene (CHO-FSHR). The CHO-FSHR assays is specific for FSH and free of serum interference up to a final concentration of 20%. The clinical sensitivity is 3 IU/l, the interCV 16%, the intraCV 8%. Studies were performed in normal women (n = 11) during the menstrual cycle using the CHO-FSHR cells. The ratio of bioactive to immunoactive FSH (B/I) equals 1.1 +/- 0.04 across the follicular and early luteal phase. During the mid to late luteal phase the mean B/I rises significantly to 1.65 +/- 0.07 (P < 0.001). Gonadotropin bioassays based on cloned receptors have been used to search for immunoglobulins, directed against the FSH or the LH receptors in premature ovarian failure patients. No blocking antibodies were found among the 38 women studied. A recent study of FSH bioactivity in patients with FSH secreting pituitary adenomas shows increased values of the B/I ratio. In summary, cell lines expressing the LH and the FSH human receptors are now available. Those homologous systems enable clinicians to study potential forms of mutated FSH or antibodies directed against gonadotropin receptors. Furthermore, bioassays based on cloned receptors are interesting tools to test anti-LH or anti-FSH molecules mainly in contraceptive research.

Animals↗

Immunomodulatory effects of IL-12 on allergic lung inflammation depend on timing of doses.

We investigated the effects of IL-12 on a murine model of allergic lung inflammation. Administration of IL-12 was timed to interfere with either allergic sensitization (early dosage) or the hypersensitivity inflammatory response in the lung (late dosage), or both (early and late dosages). Comparisons of IL-12- and PBS-treated animals within each treatment group revealed several noticeable effects of IL-12. Early dosage, and the combination of early and late dosages, strikingly decreased ragweed-specific serum IgE, tracheal ring reactivity to acetylcholine, and BAL eosinophilia following allergen challenge. In contrast, late dosage had no effect on IgE levels and only a minimal effect on tracheal ring reactivity, but had a modest effect on recruitment of eosinophils. Early dosage down-regulated IL-5 and IL-10, but did not alter IL-4 or IFN-gamma expression. Late dosage down-regulated IL-5, up-regulated IL-10 and IFN-gamma, but did not change IL-4 expression. The combination of early and late dosage down-regulated IL-4, IL-5, and IL-10 expression, but increased IFN-gamma expression and production in the BAL cells and fluids. Taken together, these results indicate that IL-12 has potent immunomodulatory effects on allergic lung inflammation that depend on the timing of IL-12 administration relative to allergic sensitization and allergen challenge.

Acetylcholine↗

Positive effect of overexpressed protein-tyrosine phosphatase PTP1C on mitogen-activated signaling in 293 cells.

PTP1C, an SH2 domain-containing protein-tyrosine phosphatase, is predominantly expressed in hematopoietic cells, in which it negatively regulates cellular signaling. However, this enzyme is also expressed in many non-hematopoietic cells. We demonstrate here that in non-hematopoietic 293 cells, overexpression of a catalytically inactive mutant of PTP1C strongly suppressed the stimulatory effects of the epidermal growth factor or serum on cell proliferation, early gene transcription, and DNA synthesis. Similarly, the phosphorylation of the mitogen-activated protein kinase and mitogen-activated protein kinase kinase activity was markedly inhibited by overexpression of mutant PTP1C. The inhibitory effect of mutant PTP1C was overcome by cotransfection with wild-type PTP1C, but not with the structurally related PTP2C. Furthermore, expression of the mutant phosphatase resulted in hyperphosphorylation on tyrosine of a 95-kDa protein that was co-immunoprecipitated with the mutant, but not with the wild-type protein. These results suggest that, unlike in hematopoietic cells, PTP1C in 293 cells plays a positive role in epidermal growth factor- or serum-activated mitogenesis. Thus, PTP1C participates in multiple signaling pathways, where the enzyme, depending on its target molecules, may function as either a positive or negative mediator.

Cell Division↗

Serum hormone concentrations during treatment with multiple rising doses of recombinant follicle stimulating hormone (Puregon) in men with hypogonadotropic hypogonadism.

OBJECTIVE: To study increases of serum FSH and gonadal response in gonadotropin-deficient men treated with recombinant FSH (Puregon; NV Organon, Oss, The Netherlands). DESIGN: An open, prospective, multiple rising dose study in which volunteers received single daily IM doses of recombinant FSH for 3 weeks. The dose administered was increased at weekly intervals: the first 7 days, 75 IU/d; the subsequent 7 days, 150 IU/d; and the last 7 days, 225 IU/d. PARTICIPANTS: Nine men suffering from isolated gonadotropin deficiency or panhypopituitarism. MAIN OUTCOME MEASUREMENTS: Immunoreactive FSH, LH, inhibin, T, and androstenedione. RESULTS: Serum immunoreactive FSH (median) rose in accordance with the recombinant FSH doses administered from 0.5 mIU/mL (range < 0.05 to 1.9 mIU/mL) at baseline to 4.3 mIU/mL (range 2.0 to 8.5 mIU/mL), 8.4 mIU/mL (range 4.9 to 17.8 mIU/mL), and 13.6 mIU/mL (5.6 to 28.4 mIU/mL) after 1, 2, and 3 weeks of medication, respectively. The elimination half-life of recombinant FSH was 48 +/- 5 hours (mean +/- SD), which was slightly longer than that reported after single dose administration of recombinant FSH (32 +/- 12 hours). The bioactivity of recombinant FSH was reflected by serum inhibin levels, which rose from 116 U/L (range 34 to 356 U/L) at baseline to 350 U/L (range 63 to 1,109 U/L) at day 22. However, serum FSH and inhibin levels did not correlate when compared after 1, 2, and 3 weeks of recombinant FSH administration. Serum immunoreactive LH, T, androstenedione, and E2 were 0.2 mIU/mL (range < 0.05 to 0.7 mIU/mL [conversion factor to SI unit, 1.0]), 58 ng/dL (range < 12 to 222 ng/dL [conversion factor to SI unit, 0.0347]), 14 ng/dL (range 6 to 115 ng/dL [conversion factor to SI unit, 0.0349]), and 14 pg/mL (range < 14 to 16 pg/mL [conversion factor to SI unit, 3.67]), respectively, at baseline and remained unchanged during the entire treatment period. CONCLUSION: These data indicate that recombinant FSH treatment increases serum FSH in a dose-proportional fashion, increases inhibin secretion, and lacks intrinsic LH activity.

Adult↗

Triggering of ovulation by a gonadotropin-releasing hormone (GnRH) agonist in patients pretreated with a GnRH antagonist.

OBJECTIVE: To determine if GnRH-agonist (GnRH-a) could induce a LH surge in patients where a GnRH antagonist was used to prevent premature spontaneous LH surge. DESIGN: Pilot study. PATIENTS: Five patients treated with ovarian stimulation and IUI for idiopathic infertility. MAIN OUTCOME MEASURES: Luteinizing hormone, FSH, and P plasma levels. RESULTS: A LH and FSH surge as well as a P rise were obtained in the five patients studied. CONCLUSION: A GnRH-a successfully can induce an LH surge after GnRH antagonist administration. The effect of the antagonist on the quality of the GnRH-a-induced LH surge as well as the oocyte quality remain to be evaluated.

Female↗

Autoradiographic evidence for the modulation of in vivo sigma receptor labeling by neuropeptide Y and calcitonin gene-related peptide in the mouse brain.

Peptides of the neuropeptide Y (NPY) and calcitonin gene-related peptide (CGRP) families have been reported to modulate, in vivo, sigma receptor systems in the mouse and rat hippocampal formation. In an attempt to determine if these interactions were specific to the hippocampal formation, quantitative ex vivo autoradiography was used with (+)(-)[3H]SKF 10,047 as sigma ligand after i.c.v. injections of various NPY and CGRP peptides. High levels of specific (+)(-)[3H]SKF 10,047 labeling were concentrated in various cranial nerve nuclei, whereas lower but still significant amounts of labeling were seen in the cortex, hippocampus, various hypothalamic nuclei, red nucleus, substantia nigra, central gray and cerebellum. In all brain areas enriched with specific (+)(-)[3H]SKF 10,047/sigma labeling, the Y1 receptor subtype agonist [Leu31Pro34]-NPY, as well as peptide YY and rCGRP beta, inhibited, to a rather similar extent, (+)(-)[3H]SKF 10,047 labeling. The Y2 receptor agonist NPY13-36 had no effect in any of the regions studied. These results extend findings obtained in the hippocampal formation and demonstrate the existence of in vivo modulatory effects of NPY and CGRP-related peptides on sigma sites throughout the mouse brain.

Animals↗

[Double kidney-total pancreas transplantation with bladder reimplantation. 25 cases].

Twenty five double kidney-pancreas transplantations were performed according to the total pancreas transplantation technique with drainage of exocrine secretions into the bladder via a vesicoduodenostomy. 72% of kidney-pancreas grafts were functional at one year and 59% were functional at four years. The authors observed a slightly higher rejection rate (0.56 versus 0.34) and a higher incidence of urinary tract infection (60% versus 35%) following double pancreas and renal transplantation than after isolated renal transplantation. Complications were rare: two venous thromboses and two cases of urethritis requiring of rediversion of the duodenum into the intestine. These good results, comparable to those reported in the international registry, reflect the value of the pancreatic and renal transplantation technique using a total pancreas drained into the bladder. It would probably be preferable to transplant patients earlier, when chronic renal failure secondary to insulin-dependent diabetes induces end-stage renal failure and the need for haemodialysis.

Adolescent↗

[Study of the variability of Leuciscus soufia, cyprinidae fish, by analysis of enzyme polymorphism and meristic characteres].

An analysis of 30 presumptive enzyme loci and 7 meristic characters has been used to study different populations of the cyprinid Leuciscus (Telestes) soufia. This fish is considered autochthonous in south-eastern France, with 3 described sub-species. The estimates of gene diversity were similar to results from studies on Cyprinidae from North America. The sample from the upper reaches of the river Durance showed higher levels of gene diversity; heterozygosity and percentage of polymorphic loci than all other samples. Furthermore, the samples from the Durance, as a whole, seem to embrace a population with little or no subdivision. Six of the 7 measured meristic characters yielded no significant differences between samples. The population sample of the sub-species soufia from the river Var differs from the other samples only by allele frequencies, low level of heterozygosity and the number of gill rakers. It is argued that these characters are quite insufficient and may cast doubt as to the validity of the subspecies rank of this population.

Alleles↗