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Biomedical subjects

F Floc'h

Publications and source records attributed to F Floc'h.

At least 19 recordsLinked to original sources

Biologically active casein peptides implicated in immunomodulation.

Maternal milk should not only be considered as a nutrient, but also as a protecting agent against aggressions from the neonate's new environment. Breast-feeding facilitates transmission of a passive immunity by multifunctional factors which have a direct effect on the neonate's resistance to bacterial and viral infections. Among these factors are the main milk proteins, the caseins: during enzymic digestion of human and bovine caseins, immunomodulating peptides are released. Corresponding synthetic peptides stimulated in vitro phagocytic activity of murine and of human macrophages and exerted in vivo a protective effect against Klebsiella pneumoniae infection of mice. These data suggest that casein peptides may exert a stimulating function on the immune system of the newborn.

Animals

Immunomodulating and antitumor activities of a synthetic lauroyltripeptide (RP 56 142).

Lauroyltripeptide (RP 56 142) (N2-[N-(N-lauroyl-L-alanyl)-gamma-D-glutamyl]-L,L-2,6-diaminopimelami c acid) was shown in murine models to activate several immune mechanisms involved in host defense against tumors. RP 56 142 induced macrophage activation and enhanced cytotoxicity of natural killer cells in spleen, blood, and liver. These activities correlated with prophylactic and therapeutic effects of RP 56 142 on artificial liver metastases of M5076 histiocytosarcoma. RP 56 142 alone did not inhibit spontaneous liver metastases of M5076 sarcoma; however, in combination with surgery or suboptimal doses of cisplatin, the compound exerted synergistic antimetastatic effects in the same model. These findings suggest that RP 56 142 could be used in cancer patients as an immunotherapeutic agent in combination with surgery, radiotherapy and/or conventional chemotherapy.

Adjuvants, Immunologic

Immunopotentiating activities of a low molecular weight lipopeptide, RP 56 142--studies in infectious models.

RP 56 142, N2-[N-(N-lauroyl-L-alanyl)-gamma-D glutamyl] L,L-2,6-diaminopimelamic acid belongs to a family of immunomodulating lipopeptides. Its structure is directly derived from that of lauroyltetrapeptide RP 40 639 which is a mixture of two stereoisomers, one of which (with D,D-2,6 diaminopimelamic acid) is totally devoid of in vivo activity. RP 56 142 displayed potent protective activities against bacterial infections such as K. pneumoniae, L. monocytogenes or S. typhimurium (at doses ranging between 0.03 and 100 mg/kg s.c., i.p., i.v.). In combined treatment protocols, suboptimal doses of RP 56 142 given preventively (day-1) or curatively (day 0 + 4h) significantly protected mice receiving antibiotics at doses which were ineffective when administered by themselves. Given s.c. 1 or 2 days before infectious challenge, RP 56 142 was able to normalize and even enhance significantly the resistance of mice previously immunocompromised by lomustine, 5-fluorouracile or hydrocortisone. These results correlated with the stimulation of the clearance of a virulent Salmonella typhimurium strain and with an important production of colony-stimulating factor in RP 56 142-treated mice.

Adjuvants, Immunologic

[Beneficial effects of the combination of antibiotics and immunomodulating lipopeptides].

Although antibiotics are efficient therapeutic weapons, their actions is limited in immunocompromised patients. The efficacy of immunomodulators which restore the immune system could be improved if they were associated to infra-active doses of antibiotics which prepare the bacteria to the immune system attack. Thus it seems possible to obtain a therapeutic gain with such an association and, consequently, to avoid the emergence of antibiotic-resistant germs.

Adjuvants, Immunologic

[Immunostimulating and adjuvant activities of a low molecular weight lipopeptide].

From crude extracts of a Streptomyces strain exhibiting immunopotentiating effects, a tetrapeptide was isolated and its structure established as L Ala leads to D isoGlu leads to L, L Dap comes from Gly. This peptide was devoid of biological activity but its chemical coupling with lauric acid gave a substance endowed with adjuvant and immunostimulating properties. This substance and the corresponding synthetic lauroyltetrapeptide were as active in this respect as the muramyl-dipeptide, thus far considered as the minimal adjuvant-active structure of bacterial cell walls: the presence of a sugar moiety is therefore not a prerequisite for immunopotentiating activities.

Adjuvants, Immunologic

Adjuvant and immunostimulating activities (in the absence of freund's incomplete adjuvant) of chemically modified low molecular weight mycobacterial peptidoglycans.

Relatively low molecular weight peptidoglycan fragments extracted from two strains of Mycobacterium tuberculosis var. hominis were chemically coupled with lauric acid. The fatty acid conjugates were compared with the native substances with respect to some immunopotentiating activities. In vitro, the mitogenic effect on murine spleen lymphocytes was significantly enhanced following conjugation. One of the lauric acid conjugates stimulated, upon intravenous administration in mice, the formation of antibody-producing cells in the spleen, while the native substance was devoid of such activity. In adjuvanticity tests performed in the guinea pig in the absence of mineral oil, the fatty acid conjugates generally exerted a higher adjuvant effect on antibody production or on delayed type hypersensitivity reactions than did the native preparations.

Adjuvants, Immunologic

Adjuvant activities of chemically modified water-soluble substances from Mycobacterium tuberculosis.

Water-soluble peptidoglycan fragments extracted from the cells of two strains of Mycobacterium tuberculosis var. hominis were chemically conjugated with lauric or with palmitic acid. The coupling reaction was confirmed by physicochemical procedures. The native and the fatty acid-conjugated substances were studied for their adjuvant activity in the induction of delayed type hypersensitivity (DTH) reactions in guinea-pigs and on the production of circulating antibodies in the rabbit. Palmitic acid conjugation of one of the substances increased its adjuvanticity on DTH in the presence of mineral oil; lauric or palmitic acid conjugation rendered the substances adjuvant-active on DTH in the absence of mineral oil. Lauric acid, but not palmitic acid conjugation conferred on both substances an adjuvant activity on antibody production in the absence of mineral oil. Furthermore, lauric acid conjugation of one of the substances led to the appearance of an in vitro mitogen-like activity for murine spleen lymphocytes. In conclusion, fatty acid conjugation exerted a significant modifying effect on the immuno-potentiating activities of these peptidoglycan fragments, and such a chemical procedure may lead to the development of substances exerting a full adjuvant activity without the need of injecting them in an oily vehicle.

Adjuvants, Immunologic

In vivo antiviral activity of D-glucosamine.

Intraperitoneal treatments with D-glucosamine, an inhibitor of the glycosylation of the viral envelope, decreased the growth rate of tumors induced in quails or in chicks by Rous sarcoma virus and increased the survival of mice inoculated with human influenza virus.

Animals

Low molecular weight water-soluble peptidoglycans as adjuvants and immunostimulants.

The tetrasaccharide-heptapeptide (TH), when injected with mineral oil, exerted a strong adjuvant effect. It stimulated B and T cells, but did not increase the phagocytic activity of the reticulo-endothelial system. While BCG exerted significant preventive effect on the growth of sarcoma 180, leucosarcomatosis an EHRLICH ascitic tumor, TH, at the doses used, was devoid of such activity.

Adjuvants, Immunologic