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Biomedical subjects

P Bouchard

Publications and source records attributed to P Bouchard.

214 records · Page 12Linked to original sources
PubMed1966

Effect of sex and gonadal hormones on rat plasma lipids during the development of an essential fatty acid deficiency.

1. Male, female and castrated rats treated with oestradiol (30mug./week) or testosterone (2mg./week) were given an essential fatty acid-deficient diet containing 10% of hydrogenated coconut oil for 9 weeks. The concentrations and fatty acid composition of plasma phospholipids, cholesteryl esters and triglycerides were determined. 2. Between the second and third weeks of the deficiency, concentrations of plasma cholesteryl esters, phospholipids and triglycerides decreased, then remained relatively constant. There were no significant differences between males and females, but oestradiol caused a significant rise in plasma phospholipids and triglycerides as compared with testosterone-treated animals. 3. During the first 2 weeks of the deficiency, linoleic acid in the plasma lipids of all groups decreased to low concentrations and changed very little thereafter. 4. Female rats maintained higher percentages and concentrations of arachidonic acid and stearic acid in plasma phospholipids and arachidonic acid in cholesteryl esters than did males. Males had higher proportions of eicosatrienoic acid and oleic acid. There was no sex difference in the fatty acid composition of plasma triglycerides. 5. Oestradiol-treated rats had concentrations of cholesteryl and phospholipid arachidonate comparable with those of female rats and higher than the testosterone-treated group. Eicosatrienoic acid in the oestradiol-treated rats was high and resembled that of the male rats, apparently because of the higher concentration of plasma phospho lipids in this group. 6. Supplementation of the essential fatty acid-deficient rats with linoleate restored plasma cholesteryl and phospholipid linoleate and arachidonate nearly to normal concentrations in a single day. The increase in arachidonic acid in these fractions was accompanied by a similar quantitative decrease in eicosatrienoic acid. 7. These sex differences appear to be related to the smaller size of the female rat and to a more direct influence of oestradiol on the formation or maintenance of phospholipids rich in arachidonic acid.

Animals↗
PubMed1965

Influence of sex and gonadal hormones on rat-liver and carcass lipids during the development of an essential fatty acid deficiency.

1. Groups of intact male and female rats and castrated rats injected with oestradiol or testosterone were given a diet containing hydrogenated coconut oil for 9 weeks, and at intervals the amounts and fatty acid compositions of the carcass and liver lipids were determined. 2. Male rats grew faster and larger, and exhibited typical external essential fatty acid deficiency symptoms sooner than did females. Testosterone-treated castrated male rats were similar to males, and oestradiol-injected castrated male rats resembled females. 3. Intact females maintained a higher linoleic acid concentration in their carcass than did males. Total amounts of carcass linoleic acid remained similar for all groups, only 200mg. being removed in 9 weeks regardless of body size. 4. The amounts of total cholesteryl esters were independent of liver size. They were higher in males and testosterone-treated castrated male rats than in females and oestrogen-treated castrated male rats. 5. Phospholipids represented about 80% of the liver lipids. The total amounts of the phospholipid linoleic acid and arachidonic acid were similar for all groups regardless of liver size, and were not affected appreciably by the deficiency. Females and oestrogen-treated castrated male rats maintained a higher proportion of phospholipid arachidonic acid for longer periods than did their male counterparts. Both the total amounts and the proportions of eicosatrienoic acid and palmitic acid were higher in males than in females. 6. Supplementation of the essential fatty acid-deficient diet with linoleic acid caused a rapid loss of eicosatrienoic acid and palmitic acid with a concomitant increase in stearic acid and arachidonic acid. 7. There were no obvious differences in the way that the essential fatty acids were metabolized or mobilized from adipose tissue of male or female rats during essential fatty acid deficiency. 8. The results indicated that the greater growth rate of the male rats caused them to require and synthesize more phospholipids than did the females. In the absence of adequate amounts of arachidonic acid, eicosatrienoic acid was substituted into the additional phospholipid. The earlier symptoms of essential fatty acid deficiency in the male rat could therefore be ascribed to the higher tissue concentrations of this unnatural phospholipid and its inability to perform the normal metabolic functions of phospholipids.

Journal Article↗
PubMedDate not supplied

Neuroendocrine effects of progesterone.

Progesterone (P) is secreted by the corpus luteum under the control of gonadotropin releasing hormone (GnRH)/luteinizing hormone (LH). Progesterone (P) is essential for reproduction because: (1) it induces in the endometrium the transcription of specific genes involved in the implantation of the blastocyst, (2) it modulates GnRH/LH secretion by decreasing GnRH pulse frequency, which in turn enriches the gonadotroph cells in FSH and avoids a second LH surge. Using the ewe as a model, we investigated the immediate GnRH and LH responses to acute changes of circulating P levels. Our results show that P changes cause dramatic modifications in GnRH pulse frequency: P removal induces an acceleration of the pulse generator, while P administration slows the pulse frequency. LH secretion was modified in parallel to the changes in GnRH. Other experiments proved that these neuroendocrine effects of P are mediated by P itself, not by its hydroxylated metabolites, and occur at the level of P receptors. Finally, these effects require priming by estradiol. Additionally, in the final stage of the follicular phase, P plays a role in the triggering of the LH surge. This has been shown in rodents, non-human primates, and in women. Such a phenomenon is not observed in ewes, although in these species luteal P modulates the amplitude of the estradiol-induced LH surge.

Animals↗
PubMedDate not supplied

Mutations of the GnRH receptor gene: a new cause of autosomal-recessive hypogonadotropic hypogonadism.

Mutations in a few genes have been identified in hypogonadotropic hypogonadism (HH): the gene KAL-1 is involved in X-linked Kallmann syndrome associated with anosmia and mutations in transcription factors, namely, DAX-1 and Prop-1 were also evidenced when associated with other pituitary or endocrine defects. Recently, compound heterozygote mutations in the GnRH receptor gene were described both in males and females and hormonal resistance was confirmed in vitro. There is a wide spectrum of phenotype, ranging from complete HH with lack of pubertal development and cryptorchidism to partial hypogonadism with an arrest of pubertal development. In complete GnRH resistance, endogenous LH secretory patterns were abnormal, either apulsatile or characterized by a low-normal pulse frequency with small pulses or erratic pulses of low amplitude. In patients with partial resistance, basal LH plasma concentration was low, but FSH level was in the normal range. LH pulse analysis revealed normal frequency with decreased amplitude. Mutations are distributed along the coding sequence, as reported for other GPCRs. However, two hot-spots, Q106R and the R262Q, were observed, regardless of the geographic origin of the patients. In most cases, patients responded to GnRH administration, making the GnRH test inappropriate for screening GnRH resistance in IHH.

Amino Acid Sequence↗
PubMedDate not supplied

Protective effect of rhIL-11 in a murine model of acetaminophen-induced hepatotoxicity.

Acetaminophen intoxication results in hepatotoxicity associated with increased serum concentrations of hepatocellular leakage enzymes such as aspartate aminotransferase, lactate dehydrogenase, and alanine aminotransferase, centrilobular degeneration and necrosis, and activation of Kupffer cells. Recombinant human Interleukin-11 (rhIL-11) downregulates the production of proinflammatory mediators from activated macrophages and has direct effects on hepatocyte gene expression. Based on these biological activities of rhIL-11, the effect of pretreatment with rhIL-11 in a murine model of acetaminophen-induced hepatotoxicity was examined. Administration of 500 microg/kg acetaminophen to B6C3F1 mice resulted in progressive hepatotoxicity as demonstrated by elevated serum concentrations of hepatocellular leakage enzymes and TNFalpha and histopathology. Pretreatment with 250 or 500 microg/kg of subcutaneously administered rhIL-11 2 hours before acetaminophen administration reduced serum concentrations of hepatocellular leakage enzymes and TNFalpha by 40-50%. This was associated with a statistically significant decrease in mean severity score for centrilobular hemorrhage and necrosis from grade 3 to grade 2 for rhIL-11-treated animals compared to vehicle. These results indicate that treatment with rhIL-11 has a protective effect in a model of acetaminophen-induced liver damage.

Acetaminophen↗
PubMedDate not supplied

GnRH antagonist in single-dose applications.

Previous studies on ovarian stimulation have confirmed the efficacy of a single dose of the gonadotrophin-releasing hormone (GnRH) antagonist, Cetrorelix, in preventing premature LH surges. The single-dose protocol is easy to use and assures patient compliance. When compared with the long protocol using a depot administration of the GnRH agonist, triptorelin, the IVF results in patients treated with Cetrorelix showed a shorter treatment duration, reduced amount of human menopausal gonadotrophin (HMG) required and a lower occurrence of ovarian hyperstimulation syndrome (OHSS). The pregnancy rates did not differ significantly between the two treatments. The use of Cetrorelix in natural cycles associated with gonadotrophins reduced the rate of premature LH surges and, therefore, the cancellation rate. The stimulation was minimal and the preliminary pregnancy rates were satisfactory. If a larger study confirms the results of the natural cycle with HMG support, the single-dose administration of GnRH antagonist could represent an interesting first-choice IVF treatment in selected indications. The tolerance of Cetrorelix was excellent in all patients, with only mild and transitory reactions at the injection site. New GnRH antagonists are already available for clinical use in some countries, and they will certainly change ovarian stimulation protocols. If the pregnancy rates are confirmed, the main advantages of these new compounds are the reduction in side-effects and complications of the stimulation protocol; a clear benefit to the patients.

Drug Administration Schedule↗
PubMedDate not supplied

The LHRH antagonist cetrorelix: a review.

In those clinical situations in which an immediate and profound suppression of gonadotrophins is desired, LHRH agonists have the disadvantage of producing an initial stimulatory effect on hormone secretion. Therefore, the use of GnRH antagonists which cause an immediate and dose-related inhibition of LH and FSH by competitive blockade of the receptors is much more advantageous. One of the most advanced antagonist produced to date is Cetrorelix, a decapeptide which has been shown to be safe and effective in inhibiting LH and sex-steroid secretion in a variety of animal species and in clinical studies as well. Clinical trials in patients suffering from advanced carcinoma of the prostate, benign prostate hyperplasia, and ovarian cancer are currently in progress and have already shown the usefulness of this new treatment modality. In particular, the concept that a complete suppression of sex-steroids may not be necessary in indications such as uterine fibroma, endometriosis and benign prostatic hyperplasia represents a promising novel perspective for treatment of these diseases. Following completion of phase III trials in controlled ovarian stimulation for IVF regimens, Cetrorelix was given marketing approval and, thus, became the first LHRH antagonist available clinically.

Animals↗
PubMedDate not supplied

The use of GnRH antagonists in ovarian stimulation.

GnRH antagonists induce a rapid decrease in LH and FSH, preventing and interrupting LH surges. Their properties do not require a desensitization period, and this allows their use in the late follicular phase. GnRH antagonists could replace GnRH agonists in controlled ovarian stimulation without their side-effects and their long desensitization period. Two protocols for assisted reproduction technology (ART) cycles were designed: the single-dose protocol allies simplicity and efficacy, while the multiple-dose protocol is efficient and could reduce monitoring of the cycle, though compliance is mandatory. A review of the available literature on GnRH antagonists in ART cycles is presented, focusing on phase III controlled trials and ART results. Both protocols using GnRH antagonists were associated with the need for a smaller dose of gonadotrophin, a shorter stimulation period and a lower incidence of ovarian hyperstimulation syndrome (OHSS), albeit with statistically comparable pregnancy rates. A trend is observed in all studies showing a lower pregnancy rates in GnRH antagonist cycles as compared with GnRH agonist cycles. The role of the lower number of embryos, and the potential adverse effects of GnRH antagonists on endometrium or follicle must be studied. More cycles using GnRH antagonists are necessary to confirm their equivalent pregnancy rates. There is room for improvement in both protocols with regard to scheduling, antagonist dose level and the timing of its administration. Until further studies have been conducted, luteal support seems to remain mandatory. Perinatal outcome appears similar to that with other stimulation regimens. Triggering of ovulation can be obtained with GnRH agonist for patients at risk of OHSS. With regard to GnRH antagonists, questions remain regarding pregnancy rates, the indications of their use in patients with polycystic ovary syndrome or poor responders, and in ovarian stimulation outside IVF.

Controlled Clinical Trials as Topic↗
PubMedDate not supplied

Post-traumatic diabetes insipidus: MR demonstration of pituitary stalk rupture.

We report the magnetic resonance findings in a case of post-traumatic diabetes insipidus (DI). They consisted of pituitary stalk rupture shown on both coronal and sagittal planes with associated disappearance of the normal high signal intensity of the posterior lobe on T1 images. This last sign, previously described in nontraumatic DI, appears to represent a finding indicating nonfunctioning neurohypophysis.

Adult↗
PubMedDate not supplied

[Ante- and posthypophyseal insufficiency with infundibulum abnormalities].

The hypopituitarism and the diabetes insipidus are often idiopathic. A retrospective study of 6 cases of diabetes insipidus and 8 cases of partial or total idiopathic antehypophyseal insufficiency has shown the value of MRI to demonstrate anomalies of the infundibulum or hypothalamic-hypophysis "stages". MRI allows to bring together some cases of idiopathic hypopituitarism in a new entity which is the hypopituitarism due to a newborn section of the infundibulum.

Adult↗
PubMedDate not supplied

Monitoring and treatment of minimal residual cancer of the prostate.

In manifest prostatic carcinoma, partial and complete remissions are obtained in 14-44% of patients as judged by different sets of criteria, but in up to 61% as judged by a decrease in prostatic acid phosphatase. Moreover, this decrease is poorly correlated to that of prostatic size. Prostatic acid phosphatase is therefore considered to be a relatively non-specific tumor marker. A complete remission, i.e. a stage of minimal residual disease, is obtained in about 25% of the patients. Continued endocrine treatment involves the risk of a flare-up of the disease, which is probably small. Additionally, in minimal residual disease, prolonged maintenance treatment requires minimization of side effects. D-Trp-6-LH-RH appears to lead to less gynecomastia and thromboembolism than some other forms of adjuvant therapy.

Adenocarcinoma↗
PubMedDate not supplied

[Molecular basis of sperm movement (author's transl)].

Sperm flagella like somatic cilia consist of an axoneme of 9 + 2 microtubules. Several projections protrude form the A subfiber of each microtubule doublets: the 2 rows of Dynein arms, the Radial Spokes and the Nexin Links. All the axonemal components constitute the flagellar motor. The energy necessary to generate microtubule sliding, responsible of the flagellar beat, is provided by Mg2+-ATP hydrolysis by Dynein ATPase. The Dynein ATPase is a group microtubule A called Dynein arms. Mg2+-ATP binding and hydrolysis generate transient cross-bridges that cause the microtubule doublets walk one upon another. The transformation of sliding to bending is produced by the Radial Spokes which eventually go through a cycle of transient attachment to the central sheath. The flagellar movement is controlled by intra-flagellar factors mostly Ca2+, responsible for the symmetry of the beat and the arrest of flagellar motility. Further, cAMP increase is associated in certain conditions with the initiation or increase of sperm motility. Extrinsic factors seem to play a major role in the control of sperm motility, such as proteins that coat the sperm membrane or factors associated with the egg, like the peptide "speract", extracted from sea urchin egg, which stimulates sperm respiration rate and increases cAMP and cGMP concentrations.

Dyneins↗