The therapeutic efficacy and the incidence of early antivenom reactions (EARs) were compared in a clinical trial performed in 79 patients bitten by Bothrops sp. in Urabá, Colombia. Patients were randomized into three groups according to the antivenom administered: A (n ϭ 30, Butantan polyspecific, pepsin-digested Bothrops antivenom); B (n ϭ 27, Butantan polyspecific, whole IgG Bothrops antivenom); and C (n ϭ 22, Colombian commercial, monovalent, whole IgG Bothrops antivenom). The groups were comparable in all clinical and epidemiologic aspects; 33 patients had mild, 22 moderate, and 24 severe envenoming. At the doses used (two, four, and six vials [10 ml/vial] for mild, moderate, and severe envenomings, respectively) there were no differences between the antivenoms in restoring normal hemostatic parameters within 24 hr. The evolution of local envenoming was comparable in the three groups. Serum venom/antivenom kinetics determined by ELISA showed a complete clearance of venom levels 1 hr after treatment in mild/moderate envenomings. In severe cases, venom levels remained detectable up to 24 hr and recurrence of antigenemia was observed in some cases. Antivenom concentrations remained at high levels up to 24 hr of treatment. The incidence of EARs was significantly different in the groups: A (36.7%), B (11.1.%), and C (81.8%). There were no life-threatening anaphylactic reactions. We conclude that the efficacy of the three antivenoms was similar in neutralizing human Bothrops envenomings and that the production of whole IgG antivenoms by caprylic acid fractionation is a good alternative for reducing the incidence of EARs.
Administration of poly I:C (1 mg/kg i.v.) to rabbits 24 h after an ovulating injection of hCG caused accelerated ovum transport; only 30% of the ova were still found in the oviducts 24 h later compared with 79% of ova in control animals. This action of poly I:C was prevented by concomitant administration of indomethacin. Poly I:C (0.5 mg/kg i.v.) given to anaesthetized rabbits produced significantly increased levels of prostaglandins (PGs) E and F in uterine vein blood up to 2 h later. Production of PGs by lung, oviduct and myometrium was unaffected 2 h after poly I:C administration, but production of both PGE and PGF by endometrium was significantly elevated at the same time. Metabolism of PGs by cytosols of lung, oviduct and uterus was inhibited to various degrees at 2 h after poly I:C (1 mg/kg i.v.), but by 4 h after treatment this process was reduced to 70--80% of pretreatment values. It is concluded that poly I:C accelerates ovum transport through the oviduct by a PG-mediated mechanism, and that elevated levels of PGs in oviduct are due to inhibition of metabolism of PGs.
We studied the effects of dipyridamole and RA-642 on the production of superoxide anions and on oxygen radicals-induced lipid peroxidation in lens tissue homogenates from normal rats and rats given dipyridamole or RA-642 intraperitoneally. Superoxide production was evaluated by phenazine methosulphate (PMS)-induced nitroblue tetrazolium (NBT) reduction and lipid peroxidation by ferrous sulfate and ascorbic acid (FeAs)-induced malondialdehyde (MDA) production. Dipyridamole and RA-642 showed an inhibitory effect on both assays in the experiments with lens tissue homogenates from untreated or treated rats. The extent of inhibition, however, was significantly higher in pyrimidopyrimidinic-treated rats (range of inhibition at different times of incubation was 18% versus 23-57% for dipyridamole and 14% versus 73-80% for RA-642 in the assay of MDA production, and 10% versus 33-37% for dipyridamole and 2.5% versus 11-32% for RA-642 in the assay of NBT reduction). Concentrations of dipyridamole and RA-642 in lens tissue from treated animals could not be determined (less than 0.001 micrograms/mg of tissue). Although both compounds inhibited lipid peroxidation induced by oxygen free radicals, the mechanism of action might include the role of adenosine as a mediator.
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