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J Descotes

Publications and source records attributed to J Descotes.

At least 109 records · Page 6Linked to original sources

Enhancement of antibody response and delayed-type hypersensitivity by thalidomide in mice.

Renewed interest in thalidomide stemmed from the suggestion by several authors that it might prove useful against immune-related diseases. Despite interesting preliminary findings, little is actually known regarding its immunoenhancing properties in vivo. Male and female Swiss mice, aged 6-8 wk, were given 0.5 or 25 mg/kg/day of thalidomide orally for 4 wk. Various immunological parameters were then assessed. When compared to controls, mice exposed to the higher dose presented with a significantly increased thymus weight index, whereas spleen weight index remained unchanged. Anti-sheep erythrocyte plaque-forming cells and hemagglutinin titers were increased by 44% and 29%, respectively. Contact hypersensitivity to picryl chloride was enhanced by 62%. Finally, colloidal carbon clearance was not altered. Interestingly, the lower dose (5 mg/kg/day) exerted no effect whatsoever.

Animals↗

Influence of tetanus and typhoid vaccines on hepatic drug metabolism.

Several experiments suggested that vaccines might inhibit liver drug-metabolizing enzymes, an assumption in agreement with other findings obtained with most immuno-enhancing agents. A direct, non-specific activation of macrophages with subsequent release of interleukin 1 may account for this inhibition. The purpose of the present study was to investigate whether tetanus and typhoid vaccines exerted such an influence on pentobarbital sleeping time in mice and antipyrine elimination in rabbits, both in vivo correlates of the activity of these enzymes. It is shown that tetanus (unlike typhoid) vaccination in both species can lead to a marked but transient impairment of hepatic drug metabolism in these conditions. The reason for this discrepancy is unclear. The assumption that aluminium hydroxide might play a critical role, as this adjuvant is included in the formulation of tetanus vaccine in contrast to that of typhoid vaccine, is not supported by our findings since aluminium hydroxide alone failed to exert any influence in our experimental conditions. Further studies are therefore warranted to elucidate the mechanism of this inhibition of the activity of hepatic drug-metabolizing enzymes.

Aluminum Hydroxide↗

Method for the assessment of diagnosis in human toxicology.

A method for the assessment of diagnosis in human toxicology is presented. This method follows an approach similar to that already used in postmarketing drug surveillance for the validation of drug-induced side effects. It is based on criteria of exposure and semiological/chronological criteria. A scale for objectively assessing these criteria allows one to appreciate the information available in each case report (i.e., informativity), and when this is considered sufficient, the causal relationship (i.e., imputability) can be evaluated. This mode of systematic and objective assessment should allow one to achieve a consistent case-by-case recording of data in occupational as well as human toxicology in general, to stimulate the search for lacking information, to use a common language for all those recording and reporting such data, and, finally, to improve the reliability and usefulness of published reports.

Humans↗

Influence of heavy metals on the resistance of mice toward infection.

Previous studies have shown that heavy metals may exert marked immunomodulatory effects, at least in rodents, despite some discrepancies. However, the mechanism of their influence on the immune system is still unclear. As host resistance assays against experimental infections are generally considered as the most relevant criteria when predicting the immunotoxicity of drugs and chemicals, the effects of lead acetate, nickel chloride and sodium selenite on the resistance toward experimental Klebsiella pneumoniae infection was investigated in mice, with particular emphasis on the interference of the time of toxic exposure with the infectious challenge. Interestingly, one single intraperitoneal dose of 24 mg/kg lead or 4 mg/kg nickel enhanced the resistance of mice against Klebsiella pneumoniae when administered 24 hours before the infectious challenge, whereas host resistance proved to be impaired when the same dose was injected 5 hours after the infectious challenge. A 3-day pretreatment with 8 or 12 mg/kg lead also enhanced the resistance of mice but decreased it with 0.5 or 1 mg/kg nickel. In all cases, sodium selenite increased the resistance of mice toward infection. As lead, nickel and selenium appear to exert complex and possibly opposite effects on antibody response and phagocytosis, it remains to establish which immunotoxic consequences if any, an acute or chronic exposure to these heavy metals is likely to have in man.

Animals↗

Selective T cell defects induced by dopamine administration in mice.

Dopamine administration in BALB/c mice depressed the overall delayed-type hypersensitivity reaction to sheep red blood cells, the mixed-lymphocyte culture responses, the generation of cytotoxic T cells, and the number of spleen T cell populations. Conversely, dopamine enhanced concanavalin A stimulation of spleen cells, and had no effect on stimulation by PHA, on total spleen and thymus cell number, and on distribution of thymus Ly-t1+ or Ly-t2+ cell subsets. These results indicate that dopamine produces selective T cell defects probably mediated by a direct peripheral action of the drug on subsets of T lymphocytes.

Animals↗

Impaired T-dependent immune response in L-dopa treated BALB/c mice.

Various neurotransmitters and neuropharmacological agents can affect lymphocyte responses. The purpose of the present study was to investigate the potential immunological effects of L-dihydroxyphenylalanine (L-dopa), the direct precursor of dopamine, by examining the influence of the in vivo administration of the drug on different functional and phenotypic parameters in BALB/c mice. L-dopa at the dose of 100 mg/kg/day altered T-dependent immune responses. The antibody response to sheep red blood cells (SRBC) was abolished by the drug. The delayed-type hypersensitivity reaction to SRBC was also depressed. Lymphocyte proliferation and generation of cytotoxic T cells in response to allogeneic stimulator cells in vitro were decreased by L-dopa treatment. These suppressive effects were correlated with a decrease in spleen T cells number. However, the proliferative response of spleen cells to concanavalin A was greatly enhanced by the L-dopa treatment. Conversely, there was no evidence for alteration of T-independent immune responses by L-dopa. Hence, the antibody response to TNP-Ficoll, and the proliferation of B spleen cells induced by E. coli lipopolysaccharide were unchanged. Altogether, these results showed that L-dopa which is converted to dopamine in the organism, could selectively affect T-dependent immune responses. The integration of these findings in the immune-neuroendocrine interactions, and the possible sites and mechanisms of action are discussed.

Animals↗

[Antibiotics and chemotaxis in agarose. The role of incubation conditions and application to several fluoroquinolones].

Nelson's agarose technique for the in vitro measurement of leukocyte chemotaxis proved to be well suited in the context of pharmaco-toxicological testings, despite several discrepancies in the literature, probably due to varied incubation conditions. Thus, doxycycline (25 micrograms/ml) when added to both the leukocyte suspension and the agarose was shown to exert a significantly more pronounced depressant effect. Using these conditions of improved sensitivity, three fluoroquinolones, i.e. norfloxacin, ofloxacin and pefloxacin (2, 10 or 25 micrograms/ml) failed to depress chemotaxis markedly.

Anti-Infective Agents↗

Histological cartilage changes in a rabbit model of osteoarthritis.

The anterior cruciate ligament was severed in the right knee of 36 rabbits which were then killed 12 weeks after surgery. Changes in water content and fixed charge density were correlated with the surface area of induced cartilage fibrillation. Histological changes including cartilage hypertrophy, reduced cell density, matrix alterations, cystic lesions, and enlarged perichondrocytic lacunae were found to precede cartilage fibrillation. The observed histological changes are in agreement with an enzymatic degradation of articular cartilage in osteoarthritis.

Animals↗

[Progressive complications associated with polyester arterial prostheses. Study of 61 specimens following surgical excision].

Reports of individual surgical cases tend to be anecdotal because of the unique circumstances surrounding the patient, the surgeon, the intervention and, where applicable, the prosthetic device. To overcome this limitation the authors have taken a wider collaborative approach and report the analysis of 61 explanted polyester arterial prostheses associated with delayed complications on 53 patients reoperated upon in six different French hospitals. One advantage of such an independent and centralized retrieval programme is that the impact of centre specific factors, such as patient selection and surgical techniques, is minimized. Consequently, by following a standardized protocol for the evaluation of the morphologic, pathologic and mineralogic characteristics of the tissue surrounding the excised grafts, as well as the textile structure of the prostheses themselves, it has been possible to distinguish between iatrogenic and disease related complications and to demonstrate a number of general findings associated with the clinical performance of polyester arterial prostheses. Complications such as thromboses, infections and false aneurysms appear to occur randomly after different lengths of implantation, thicker fibrous tissue capsules are associated with velour grafts with highly textured yarns, the incidence of mineralized tissue and of endothelialized luminal surfaces is rare, weft knitted textile prostheses appear less mechanically stable and more sensitive to iatrogenic trauma than warp knitted, and the incidences of lipid and cholesterol adsorption, bacterial colonization and sterile fluid loss need further investigation. These observations lead to the recommendation that for patients with longer life expectancies surgeons should consider selecting low porosity, woven or warped knitted prostheses which contain yarns that have not been highly textured.

Adult↗