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Biomedical subjects

P Franchimont

Publications and source records attributed to P Franchimont.

At least 127 records · Page 7Linked to original sources

In vitro assays of chondrocyte functions: the influence of drugs and hormones.

Human articular chondrocytes may be cultured in three dimensions, according to a method already validated. This model allows us to study the repair processes of the cartilage, by measuring the proliferative activity of chondrocytes and the synthesis of two major constituents of matrix: proteoglycans and type II collagen. Some substances are characterised by stimulatory effect on DNA synthesis and no effect or a defective effect on matrix components: this is the case for Epidermal Growth Factor. Others are able to stimulate (hGH) or to depress (acetyl salicylic acid) both chondrocyte proliferation and matrix components synthesis. Finally, some substances called "chondroprotective", such as the glycosaminoglycan-peptide complex, GP-C (Rumalon) stimulate either the proliferative response or the synthesis of proteoglycans and type II collagen, according to the dose.

Anti-Inflammatory Agents, Non-Steroidal↗

The ability of normal human monocytes to phagocytose IgG-coated red blood cells is related to the number of accessible galactosyl and mannosyl residues in the Fc domain of the anti-red blood cell IgG antibody molecules.

The percentage of normal human monocytes (MCs) that are able to form rosettes with, and subsequently phagocytose, IgG-coated red blood cells (RBCs) has been determined in vitro using five batches of anti-RBC IgG antibodies. These antibodies differed from each other by their capacity to bind to lectins recognizing two of the oligosaccharide structures of the Fc domain, namely, peanut agglutinin (PNA) and concanavalin A (ConA) which specifically bind to beta-galactosyl and alpha-mannosyl residues, respectively. The threshold between high (H) and low (L) binding capacities (BC) was arbitrarily fixed at 15% of mean specific binding. For each level of RBC sensitization tested (1500-6000 Ab molecules/one RBC), the percentage of MCs binding at least three IgG-RBCs was similar whatever the IgG Ab preparations used. In contrast, the percentage of MCs capable of phagocytosing at least three IgG-RBCs coated with 3000, 4500 and 6000 IgG/cell, as well as the phagocytosis index (number of IgG-RBCs ingested/100 MCs) of IgG-RBCs coated with 1500, 3000, 4500 and 6000 IgG/cell, were significantly lower (P less than 0.01 at least) using IgG Ab molecules with either [(PNA-H)(ConA-H)] BC, [(PNA-L) (ConA-H)] BC or with [(PNA-L)(ConA-L)] BC than the corresponding values measured using RBCs coated with IgG Ab molecules exhibiting [(PNA-H)(ConA-L)] BC. The binding to MCs of 125I-labelled anti-RBC IgG Ab molecules exhibiting different binding profiles to PNA and to ConA was studied by Scatchard plot analysis. A single class of binding sites was observed in each case. MCs bound a mean of 23,000 IgG molecules with a mean association constant (Ka) for IgG binding of about 1.4 X 10(8) M-1. These data indicate that terminal (and/or accessible) galactosyl and mannosyl residues of IgG Ab molecules play a role in the ingestion of IgG-RBCs by human MCs, despite the fact IgG Ab binding to IgG(Fc) receptors is not significantly affected. Thus, when studying the phagocytosis of IgG-coated RBC by human MC monolayers, the assay should be performed not only using similar RBC/MC ratios and IgG coating values, but also with IgG antibodies having comparable mean PNA and ConA binding capacities.

Adult↗

Effects of etodolac on human chondrocytes cultivated in three dimensional culture.

Human chondrocytes in three-dimensional culture were incubated for up to 20 days in the presence of etodolac, a nonsteroidal anti-inflammatory drug which penetrates readily into the synovial fluid. Even at an etodolac concentration of 80 micrograms/ml, DNA synthesis, proteoglycan synthesis, and type-II collagen synthesis were unchanged. Collagenase production was also unaffected by etodolac (60 micrograms/ml). In contrast, prostaglandin E2 production was reduced by 84% in the presence of 60 micrograms/ml of etodolac. The 80 micrograms/ml concentration is 5 times that found in the serum of subjects treated with 200 mg of etodolac twice a day for 6 days, and 33 times the concentration in synovial fluid of arthritic patients treated with etodolac 200 mg twice a day for 7 days. These in vitro results indicate that anti-inflammatory levels of etodolac may not damage articular cartilage in vivo.

Anti-Inflammatory Agents, Non-Steroidal↗

Inhibin and related peptides: mechanisms of action and regulation of secretion.

The structure of inhibin is known; it consists of a heterodimer composed of one alpha and one beta subunit. The homodimer of beta A (beta A-beta A) and the heterodimer beta A-beta B, called activin A and B, respectively, stimulate the release and synthesis of FSH by gonadotrophs. Inhibin exerts effects at the hypophyseal, hypothalamic, and gonadal levels. Produced by granulosa cells in the female and by Sertoli cells in the male, inhibin synthesis is stimulated by FSH and reduced by hypophysectomy and progesterone. At present, there is no evidence for a signal from germinal cells to modify inhibin production. Inhibin secretion evolves in parallel with follicular maturation and aromatase activity, whereas luteinization arrests its production. Nevertheless, important differences in the regulation of inhibin secretion seem to exist from one species to another. Sperm inhibin levels can be correlated with spermatozoa number. Administration of inhibin to sheep induces either anovulation or an increase in the rate of ovulation depending on the scheme of treatment.

Animals↗

[Endocrine, paracrine and autocrine mechanisms of aromatase activity].

The endocrine, paracrine and autocrine mechanisms involved in aromatase activity. Development of a single follicle during the menstrual cycle is under control of hormones stimulating follicular maturation, ovulation and luteogenesis. Several factors intervene locally to avoid other follicles developing at the same time as the dominant follicle. These other follicles remain quiescent or go on to atresia. Atresia results from the action of several endocrine, paracrine and autocrine mechanisms which synergistically inhibit aromatase activity. The subsequent lack of estrogens reduces granulosa cell multiplication.

Aromatase↗

[Treatment of ovarian polycystic syndrome in vitro. Physiopathogenetic considerations].

More than 60% of patients with polycystic ovary disease (PCO) cannot conceive after repeated ovulation inductions with Clomifene citrate although there is ovulation or more frequently follicle luteinization. Because of hyperstimulation, therapy with hMG has been superseded by low doses of purified FSH with variable results according to authors. It has been even claimed that there was no benefit to replace hMG with FSH. However, on the basis of the PCO physico-pathology, namely LH hypersecretion and androgen hyperproduction, it would be rational to associate the desensitization of the pituitary with LH-RH agonist and the ovary stimulation with variable doses of hMG or purified FSH. In the series where such therapy associating LH-RH agonists with purified FSH was applied, the results concerning suppression of LH and androgen secretion, and the occurrence of pregnancy were interesting. However, the risk of hyperstimulation still occurred. Thus, the first part concerns the critical review of these results while, in the second part, our experience in in vitro fecundation will be reported.

Androgens↗

Correlation between follicular fluid content and the results of in vitro fertilization and embryo transfer. I. Sex steroids.

The steroid content of 72 follicular fluids (FF) obtained from 42 women subjected to ovulation induction with the luteinizing hormone-releasing hormone analogue D-Trp6 and human menopausal gonadotropin was studied in terms of the evolution of in vitro fertilization (IVF) and embryo transfer (ET) results. The FF were classified into several categories based on oocyte evolution. Individual values of FF estrone and estradiol (E2), as well as androstenedione and testosterone could not be correlated with ET outcome. However, FF progesterone (P) levels for follicles leading to pregnancy were significantly lower when compared with those in the other categories. The correlation between the E2/P ratio and E2 permitted the definition of a band wherein IVF-ET outcome was successful and enabled the characterization of different functional follicular maturational states.

Androstenedione↗

Tumor necrosis factor and interleukin-1 serum levels during severe sepsis in humans.

In a study of serum levels of tumor necrosis factor (TNF alpha) and interleukin-1 beta (IL-1 beta) in patients developing sepsis in the ICU, high TNF alpha levels were found in patients with septic shock. Normal values are 75 +/- 15 pg/ml; in these patients, TNF alpha serum level ranged from 100 to 5000 pg/ml with a mean of 701 +/- 339 pg/ml and a median of 250 pg/ml. There was a correlation between TNF alpha level and sepsis severity score as well as with mortality. In contrast, IL-1 beta serum levels were only slightly increased and were not correlated with severity or mortality.

Adolescent↗

Direct activation of gonadotropin-releasing hormone secretion through different receptors to neuroexcitatory amino acids.

In order to evaluate the involvement of gonadotropin-releasing hormone (GnRH) in the effects of neuroexcitatory amino acids on luteinizing hormone (LH) secretion, N-methyl-D,L-aspartate (NMDA; 30 mg/kg s.c.) was administered to 50-day-old male rats. The in vitro release of GnRH from the hypothalamus showed a maximal increase (4.6-fold) in animals sacrificed 7.5 min after NMDA injection, while serum LH levels rose concomitantly. Incubation of rat hypothalami in vitro with kainate or NMDA concentrations greater than 0.1 mM resulted in a dose-related release of GnRH, NMDA being twofold more potent than kainate. Quisqualate (10 mM) did not affect the release of GnRH. On a molar basis, quinolinate (50 mM), a possible endogenous ligand for NMDA receptors, was the most effective in inducing GnRH secretion (34.9 +/- 4.9 pg/7.5 min, mean increment +/- SEM, n = 10). The effects of kainate and NMDA were mediated through different types of receptors, since GnRH response to kainate was unchanged in the absence of glycine or in the presence of increased concentrations of Mg2+ (2 mM) or Ca2+ (5.8 mM). In contrast, the GnRH response to NMDA was reduced by Ca2+ (5.8 mM) and abolished in the absence of glycine or in the presence of Mg2+ (2 mM). In addition, D,L-amino-5-phosphonopentanoic acid (AP5), a competitive antagonist of NMDA receptors, prevented the NMDA-induced release of GnRH. The permissive effect of glycine on GnRH response to NMDA was 2.7-fold more important using glycine concentrations of 0.01 microM than when concentrations greater than or equal to 100 microM were used.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗