[Biological effects of SIN-1 in the vascular wall]. / Effects biologiques du SIN-1 dans la paroi vasculaire.

The biological effects of two vasodilatory drugs, SIN-1 (the active metabolite of molsidomine) and nitroglycerin were analysed in the arterial endothelium and vascular muscle. Both drugs induce the secretion of prostacyclin in endothelial cells in culture, but this secretion is short-lived and occurs for high doses of the two drugs (above 10(-5)M). These same drugs induce a dose-dependent relaxing effect on the smooth muscle contracted either by norepinephrine or 5-hydroxytryptamine with an ED50 of 5.10(-7)M. This relaxation is neither secondary to an endothelium-derived product nor to a cyclooxygenase or lipoxygenase-derived product.

Characterization of monoclonal antibodies against prostaglandin E2: fine specificity and neutralization of biological effects.

The specificity and heterogeneity of the immune response of BALB/c mice immunized with prostaglandin E2 (PGE2) coupled to thyroglobulin was studied. All the animals (n = 50) responded to PGB2, a transformation product of PGE2. However, following repeated injections most of the animals (n = 30) were also able to respond to PGE2. Cellular hybridizations were performed and five anti-PGE2 monoclonal antibodies were isolated and analysed. They are mainly directed against the ring and the omega-chain of PGE2 but their specificity toward the alpha-chain is more limited. The association constants are greater than to 1 X 10(9) M-1. The monoclonal antibody 8E.57.71 (Ka = 1.3 X 10(10) M-1) is particularly convenient for sensitive radioimmunoassays (detection limit 25pg/ml, when iodinated tracer is used). Anti-PGE2 monoclonal antibodies were found to neutralize the specific binding of [3H]PGE2 to rat brain hypothalamic receptors and to inhibit the PGE2 induction of rat fundus muscular contraction.

[Histamine production in mixed culture between allograft donor and recipient lymphocytes]. / Production d'histamine dans les cultures lymphocytaires mixtes (MLC) entre donneur et receveur d'allogreffe.

An increased production of histamine has been demonstrated during mixed cultures between allograft donor and recipient lymphocytes. This phenomenon could result from the action of a non-dialysable factor released by recipient cells in the presence of donor cells. This factor is able to increase histamine production from normal spleen cells. Little or no increase in histamine production is found during primary and mixed lymphocyte cultures (without previous allograft).

Mechanism of inhibition of tumour growth by aspirin and indomethacin.

The growth of a 3-methylcholanthrene-induced fibrosarcoma of C3H mice was inhibited by aspirin and indomethacin. While the tumour contained relatively high concentrations of PGE2-like material, that were markedly diminished by indomethacin treatment, our results did not confirm the recently proposed hypothesis that the anti-tumour effect arises from a restoration of depressed immune function. For example, mice that had completely eliminated their tumours under indomethacin administration were not immune to rechallenge. The tumour-bearing animals were not non-specifically immunodepressed, as their splenic PFC responses against SRBC were enhanced. However, while indomethacin augmented the PFC response in normal mice, this adjuvant effect was depressed in tumour-bearing animals. The spleen-cell PHA responses of tumour bearers were severely depressed, and such cells suppressed the PHA response of normal cells. Only after prolonged indomethacin treatment did animals (with comparable tumour burdens) show weak PHA responses and somewhat diminished suppressive activity. Possible alternative mechanisms, such as direct cytotoxicity, or inhibition of inflammation, phosphodiesterase activity, blood coagulation or calcium availability were not implicated (nor definitively excluded) in the anti-tumour effect.

[Effect of lymphokines produced in a grafted system on production of prostaglandins by macrophages]. / Action des lymphokines produites en système de greffe sur la production de prostaglandines par les macrophages.

Mice peritoneal macrophages cultured in vitro release a prostaglandin-like activity as evaluated by a bio-assay using Rat stomach fundus. The prostaglandin release is greatly increased when macrophages are incubated with the supernatant of mixed lymphocyte cultures between recipient and donor of a skin allograft. This phenomenon was found in all strains of Mice tested except C3H/HeJ Mice, a strain already known for its defective responsiveness to bacterial lipopolysaccharide (LPS).

[Production of prostaglandins in mixed lymphocyte cultures (MLC) between allograft donors and recipients]. / Production de prostaglandines dans les cultures lymphocytaires mixtes (MLC) entre donneur et receiveur d'allogreffe.

A prostaglandin-like activity, as evaluated by a bio-assay using the fundus of Rat stomach, has been demonstrated in supernatants of lymphocyte cultures. This activity undergoes a striking increase in supernatants of mixed cultures of allograft donor and recipient cells, when compared with control supernatants of donor or recipient cells cultured alone. This phenomenon is observed after 24 hrs. of culture. It disappears if the supernatant is dialyzed. Little or no increase in prostaglandin-like activity is found in supernatants of primary mixed lymphocyte cultures (without previous allograft), at lest in the first two days of culture.

Distribution of radioactivity of tritiated prostaglandins E2 and A2 in rat tissues including a renal autoradiographic study.

Distribution of radioactivity in different tissues has been studied by liquid scintillation counting 60 sec after administration of [3H] PGE2 and [3H] PGA2 in the rat. In addition, renal autoradiographs were prepared 15 sec and 60 sec after tritiated PG administration. In some experiments, [3H] PGE2 was accompanied by a large dose of PGE2 (isotopic dilution). 60 sec after [3H] PGE2 administration, radioactivity concentrates principally in the kidney, followed by the liver and the lung. Within the kidney, radioactivity concentrated predominantly in the cortex. Isotopic dilution diminished radioactivity due to [3H] PGE2 in all regions of the kidney. Renal autoradiographs 15 sec after [3H] PGE2 administration showed cortical radioactivity to be higher in glomeruli than in tubules. After [3H] PGA2 radioactivity also concentrates in the kidney, liver and lung but to a lesser extent than after [3H] PGE2 and no glomerular concentration of radioactivity was found.

[Early renal hemodynamic modifications following the ablation of the controlateral kidney]. / Modifications hémodynamiques rénales précoces, à l'exclusion du ren controlatéral

Instantaneous measurements of renal blood flow (RBF) and glomerular filtration rate (GFR) have been performed in anesthetized dogs to determine if removal of one kidney induces early functional adaptation in the remaining kidney. Increases in RBF (10%) and GFR (20%) were observed within the first minutes after exclusion of controlateral kidney; these are the earliest events described until now. These observations favour the concept that a functional adjustement may contribute to development of compensatory renal hypertrophy.