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P Gepner

Publications and source records attributed to P Gepner.

30 records · Page 2Linked to original sources
PubMed1990

In vivo beneficial effects of cyclosporin A and 1,25-dihydroxyvitamin D3 on the induction of experimental autoimmune thyroiditis.

In a recent work, we provided evidence that the in vitro inhibitory effect of cyclosporin A (CsA) was potentiated by the addition of another immunosuppressive molecule, the 1,25-dihydroxyvitamin D3 (1,25(OH)2D3). In the present study, we investigated the in vivo influence of the association of both drugs administered at infratherapeutic doses, using an experimental model of autoimmune thyroiditis in CBA mice. Treatment regimen of the animals was initiated at priming with thyroglobulin (Tg) and consisted of daily administration of CsA (10 and 20 mg/kg/day, intragastrically) and/or 1,25(OH)2D3 (0.1 and 0.2 microgram/kg/day, ip) for 21 days. Control mice that were given a placebo preparation orally and the vehicle of vitamin D3 metabolite ip developed a severe disease as assessed by histological examination on Day 28 postimmunization and detection of circulating anti-Tg antibodies. Treatment with either drug administered alone at the doses mentioned above did not affect the incidence of thyroiditis and only reduced by up to 26% the severity of histological lesions. In contrast, the mice treated simultaneously with both drugs exhibited a lower incidence of thyroid pathology and developed a significantly milder disease (P less than 0.001) as compared to controls. However, there was no alteration in the levels of anti-Tg antibodies. This in vivo beneficial effect of low doses of CsA and 1,25(OH)2D3 was not due to an accumulation of CsA in the blood of treated mice since the levels of CsA were similar, regardless of the administration of 1,25(OH)2D3. Our data suggest that these two immunomodulatory agents used together at low doses may be an effective therapy of autoimmune disorders with fewer side effects.

Animals↗
PubMed1989

1,25-dihydroxyvitamin D3 potentiates the in vitro inhibitory effects of cyclosporin A on T cells from rheumatoid arthritis patients.

Treatment of rheumatoid arthritis (RA) with cyclosporin A (CsA) has been successful, but the adverse effects of the drug have limited its use. We investigated the capacity of another immunosuppressive agent, 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], to augment the effects of CsA on in vitro T cell functions. Exposure of CD4+ cells from RA patients or from normal subjects to either molecule alone resulted in a dose-dependent inhibition of phytohemagglutinin stimulation and interleukin-2 (IL-2) production that was more pronounced in cells from RA patients than in cells from normal subjects. Moreover, the action of CsA and 1,25(OH)2D3 on RA patient T cell functions in vitro was synergistic. Thus, in the presence of the vitamin D3 metabolite, only one-hundredth the concentration of CsA was required to produce the same effect on IL-2 production as that produced by CsA alone. IL-2 receptor expression was also reduced by the addition of both drugs. In contrast, IL-1 production by RA monocytes was not affected by CsA and 1,25(OH)2D3, either together or alone, and addition of IL-1 did not restore the ability of CD4+ cells from RA patients to secrete IL-2. Exogenous IL-2 reversed a large part of the inhibitory effect induced by both CsA and 1,25(OH)2D3, indicating that the immunosuppressive properties of these agents are mediated by the inhibition of IL-2 secretion. This synergy between 2 molecules that are biochemically very different suggests the existence of one or several sites of interaction that take place during the early stages of T cell activation.

Arthritis, Rheumatoid↗
PubMed1988

[Immunotolerance of RU 41740].

RU 41740 is an immunomodulator of organic origin to be used preventively against recurrent respiratory infections in both adults and children. The immunological safety of the drug was first studied on NZB-NZW mice which spontaneously develop a disease resembling lupus erythematosus. The survival rate of these mice and the amounts of protein excreted in the urine were not modified by the compound. Clinically, RU 41740 was well tolerated by the adult mice and their offspring. Studies on immunological safety were also conducted in human adults and children. Compared with pre-treatment values, there were no pathological changes in blood count and differential, erythrocyte sedimentation rate, immunoglobulins E, A, M and G levels, apolipoproteins, haptoglobin, haemolytic complement, antinuclear factors, rheumatic serology and anti-red cell antibodies. In addition, the drug was well tolerated by atopic subjects.

Acute Disease↗
PubMed1985

[Hypovolemic shock caused by increased capillary permeability associated with monoclonal gammopathy. New case and review of the literature].

The authors report another case of hypovolaemic shock due to increased capillary permeability and review previous reports in the medical literature. It is a rare condition with all patients presenting hypovolaemic shock of sudden onset with varying degrees of hypoproteinaemia and increased haematocrit. A monoclonal globulin peak is usually observed on serum electrophoresis during and between episodes of shock. The pathological role of this globulin in the increased capillary permeability has not been established.

Capillary Permeability↗
PubMedDate not supplied

[Hypothyroid myopathy: apropos of a case with a great increase of creatine phosphokinase, myoglobinemia and transient kidney failure].

Clinical, usually moderate myopathy, frequently develops in patients with hypothyroidism and may reveal the thyroid dysfunction. Biological signs of myolysis, essentially a, usually moderate, rise in creatine phosphokinase plasma levels, are often found. On the other hand, rhabdomyolysis seems to be exceptional in this context. We report a case where an extremely severe clinical and biological myopathy associated with transient renal failure revealed hypothyroidism due to prolonged intake of amiodarone.

Acute Kidney Injury↗