Efficacy and safety of two whole IgG polyvalent antivenoms, refined by caprylic acid fractionation with or without beta-propiolactone, in the treatment of Bothrops asper bites in Colombia.

The efficacy and safety of two whole IgG polyvalent antivenoms (A and B) were compared in a randomised, blinded clinical trial in 67 patients systemically envenomed by Bothrops asper in Colombia. Both antivenoms were fractionated by caprylic acid precipitation and had similar neutralising potencies, protein concentrations and aggregate contents. Antivenom B was additionally treated with beta-propiolactone to lower its anticomplementary activity. Analysing all treatment regimens together, there were no significant differences between the two antivenoms (A=34 patients; B=33 patients) in the time taken to reverse venom-induced bleeding and coagulopathy, to restore physiological fibrinogen concentrations and to clear serum venom antigenaemia. Blood coagulability was restored within 6-24 h in 97% of patients, all of whom had normal coagulation and plasma fibrinogen levels 48 h after the start of antivenom treatment. Two patients (3.0%) had recurrent coagulopathy and eight patients suffered recurrence of antigenaemia within 72 h of treatment. None of the dosage regimens of either antivenom used guaranteed resolution of venom-induced coagulopathy within 6 h, nor did they prevent recurrences. A further dose of antivenom at 6 h also did not guarantee resolution of coagulopathy within 12-24 h in all patients. The incidence of early adverse reactions (all mild) was similar for both antivenoms (15% and 24%; P>0.05).

Ontogenetic variability of Bothrops atrox and Bothrops asper snake venoms from Colombia.

The lancehead snakes Bothrops asper and Bothrops atrox inflict 70-90% of the 3000 bites reported every year in Colombia. In this work, the venoms of B. atrox from Meta (Villavicencio, 33 specimens) and B. asper from Antioquia (San Carlos, 45 specimens), all of them born in captivity, were obtained at different ages (0-6 months; 1, 2 and 3-years old) and compared in terms of their pharmacological and immunochemical characteristics. A conspicuous ontogenetic variability was observed in venom samples from both species. Venoms from newborn and juvenile specimens showed higher lethal, hemorrhagic, edema-forming and coagulant activities, whereas venoms from 3-year old specimens showed higher indirect hemolytic, i.e. phospholipase A2 activity, being more significant in the case of B. asper. SDS-polyacrylamide gel electrophoresis of whole venom for both species evidenced a predominance of high mol. mass bands in the venoms from specimens of <1 year of age, with a change towards bands having lower mol. mass as snakes aged. Gel filtration chromatography showed five peaks in the venoms of B. asper of <6 months and in those from 3-year old specimens. Venom of adult specimens showed a higher number of peaks with indirect hemolytic activity than venom of newborn specimens. Polyvalent antivenom produced in Costa Rica recognized all the bands of both venoms from specimens at all ages tested, when assayed by Western blotting.

Inmunosenectud y enfermedades reumaticas / Immunesenescence and rheumatic diseases

La inmunosenectud se refiere a los cambios en el funcionamiento del sistema inmune que ocurren con el envejecimiento. En general, se presenta una redistribución de las poblaciones leucocitarias circulantes: se aumentan los neutrófílos, las células asesinas naturales (NK), los linfocitos T CD8+, los linfocitos B-l (productores de autoanticuerpos) y se disminuyen los linfocitos T CD3+CD56+ (relacionados con el control de autoinmunidad). La función fagocítica y microbicida de los neutrófílos se vuelve deficiente, al igual que la actividad de las células NK. La respuesta de los linfocitos T y B contra antígenos extraños se disminuye pero, a pesar de ello, en algunos individuos los linfocitos T estimulados con autoantígenos o mitógenos se tornan mejores productores de IFN-y. Se produce una desviación de la respuesta T hacia un patrón Th2 y hay un aumento en la producción de citoquinas pro inflamatorias. Estos cambios en el sistema inmune pueden estar dados por una desregulación del sistema debido a alteraciones en receptores y en señales bioquímicas intracelulares. Los cambios inmunes en la vejez, asociados con factores genéticos y ambientales, pueden contribuir al desarrollo de ciertas enfermedades reumáticas propias del viejo como la arteritis de células gigantes y la polimialgia reumática, en las cuales el interferón y y las citoquinas pro inflamatorias tienen un papel patogénico fundamental. Igualmente, la aparición de Lupus Eritematoso Sistémico (LES) podría explicarse por el aumento de citoquinas tipo Th2 como la IL-6 y la IL-10 y el incremento de linfocitos B-l productores de autoanticuerpos. Conocer la base genética y los mecanismos moleculares de estas alteraciones, puede ayudar en un futuro a descubrir estrategias que permitan controlar la desregulación inmune y el desarrollo de enfermedades en la vejez.