Fil: de Roodt, Adolfo Rafael. Ministerio de Salud de la Nacion. Direccion Nacional de Institutos ... more Fil: de Roodt, Adolfo Rafael. Ministerio de Salud de la Nacion. Direccion Nacional de Institutos de Investigacion. Administracion Nacional de Laboratorios e Institutos de Salud "Doctor Carlos G. Malbran". Instituto Nacional de Produccion de Biologicos; Argentina. Universidad de Buenos Aires. Facultad de Medicina; Argentina
We developed experimental equine polyvalent and monovalent antivenoms against the venoms of Micru... more We developed experimental equine polyvalent and monovalent antivenoms against the venoms of Micrurus (M.) fulvius, M. nigrocinctus and M. surinamensis and studied their immunochemical reactivity on the venoms used as immunogens and on M. pyrrhocryptus, M altirostris and M. balyocoriphus venoms. Assessment of the neutralizing capacity of the polyvalent experimental antivenom was based on inhibition of lethality (preincubation and rescue assay experiments in mice) and indirect hemolytic and phospholipase activities. The immunochemical reactivity and neutralizing capacity were compared with those of two therapeutic antivenoms used for the treatment of coral snake envenomation in North America and in Argentina. In general, the experimental antivenom conferred a comparable level of neutralization against the venoms used as immunogens when compared to the therapeutic antivenoms and a certain level of cross-neutralization against the other venoms. The results suggest the need for additional venoms in the immunogenic mixture used, in order to obtain a broad spectrum anti-Micrurus antivenom with a good neutralizing potency. Paraspecific neutralization of South American coral snake venoms, although present at a higher level than the neutralization conferred by available nonspecific Micrurus therapeutic antivenoms, was rather low in relation to the specific neutralizing capacity.
Mass-vaccination against COVID-19 is still a distant goal for most low-to-middle income countries... more Mass-vaccination against COVID-19 is still a distant goal for most low-to-middle income countries. The experience gained through decades producing polyclonal immunotherapeutics (such as antivenoms) in many of those countries is being redirected to develop similar products able to neutralize SARS-CoV-2 infection. In this study we analyzed the biological activity (viral neutralization or NtAb) and immunochemical properties of hyperimmune horses’ sera (HHS) obtained during initial immunization (I) and posterior re-immunization (R) cycles using the RBD domain of the SARS-CoV-2 spike protein as antigen. HHS at the end of the R cycle showed higher NtAb titers when compared to those after the I cycle (35,585 vs. 7000 mean NtAb, respectively). Moreover, this increase paralleled an increase in avidity (95.2% to 65.2% mean avidity units, respectively). The results presented herein are relevant for manufacturers of these therapeutic tools against COVID-19.
Comparamos caracteres corporales y produccion de veneno de ejemplares de Bothropsalternatus de un... more Comparamos caracteres corporales y produccion de veneno de ejemplares de Bothropsalternatus de una poblacion aislada geograficamente (Olavarria, region de Tandilia, BuenosAires) con otra en su area de distribucion continua de Concordia (Entre Rios). Estudiamos ellargo corporal, peso, separacion entre dientes inoculadores, cantidad de veneno y de proteinasen el veneno por ejemplar. No se hallaron diferencias en los caracteres estudiados entreambas poblaciones (p > 0.05). Las hembras fueron mayores que los machos en ambas muestras,entre un 12-18% (p 0.5; Olavarria: 142 ± 65 mg/animal,Concordia: 160 ± 80 mg/animal), aun ajustando la cantidad de veneno producida respecto altamano, mediante el cociente veneno/largo corporal (p >0.6). Tampoco hubo diferencias enel contenido proteico, siendo para ambas muestras de 0.697 ± 0.096 mg de proteinas/mg deveneno seco. Nuestros datos sugieren que los ejemplares de la poblacion aislada de Tandiliano presentan variaciones en el tamano
Proceedings of 1st International Electronic Conference on Toxins, 2021
Crotalus atrox is one of the species of venomous snakes most commonly found in herpetological col... more Crotalus atrox is one of the species of venomous snakes most commonly found in herpetological collections around the world and it is usually commercialized in the black market. Several collections have specimens but lack of the specific antivenom. We tested the toxicity of venom of adults and young snakes (2 to 3 years old) specimens of C. atrox in captivity and the para-specific neutralization provided by the antivenoms most used in Argentina. The i.p. lethal potency of the venoms were 100(95-105) μg and 43(42-45) μg20g mouse and the indirect hemolytic activity was 7.9 (6.7-9.2) μg and 9.0(8.3-9.9) for adults and juvenile venoms. Despite the adult´s venoms lower lethal potency, these venoms were more difficult to neutralize, around 1.5 ml of antibothropic Antivenom (AB) were necessaries to neutralize 1 mg of venom in contrast to 0.54 ml required to neutralize young´s venoms. The neutralization by the Anticrotalic (AC) antivenom was despicable. The dose of AB required for the neutra...
Bothrops jararacussu is one of the most venomous snakes of medicalimportance in South America, ma... more Bothrops jararacussu is one of the most venomous snakes of medicalimportance in South America, mainly due to the toxicity of their venom and thelarge amount of that which can be injected in a single bite. The venomof this snake is required for the production, process and control of thetherapeutic antivenoms used to treat Bothropsenvenomation, so it is one of the Bothropsspecies common in Serpentarium located in Argentina and Brazil dedicated tothe production of antivenoms. We reported two cases of ophyophagy due captiveadult B. jararacussu females on Bothrops and Phylodriassnakes and the aggression ofspecimens of this species is also described.Despite well known resistance to homologous venom of Bothrops species, the bite of thisspecie on other snakes of the same species and also other Bothrops snakes, produce serious injuries. Theseobservations are important for professionals whom must maintain incaptivity these species of snakes by educational or venomproduction purposes.
Samples of Apis mellifera mellifera venom from different hives in two regions of the Buenos Aires... more Samples of Apis mellifera mellifera venom from different hives in two regions of the Buenos Aires province and its pool were analyzed for their lethal potency, myotoxic, defibrinogenating, hemolytic and inflammatory-edematizing activity and for the histological alterations they produce in the heart, lungs, kidneys, skeletal muscle and liver of mice. In vitro studies focused on the venom's hemolytic activity in different systems and species (horse, man, sheep and rabbit), the cytotoxicity in cellular lines, and on the proteolytic and coagulant activity in plasma and fibrinogen. Hemolytic activity, either observed in vitro or in vivo, showed similar toxicity levels for all samples. Erythrocytes of different species varied in their sensitivity to the venom pool, equines being the most sensitive and sheep the most resistant to direct hemolytic action. Local and systemic myotoxicity was evidenced by either the elevation of serum creatine kinase and/or histopathological lesions, observed in different muscles. All samples caused significant pathological alterations; pulmonary, cardiac, renal and skeletal muscle lesions were substantive and can be related to the pathophysiological mechanisms of envenomation. The venoms from different apiaries and regions of the Buenos Aires province showed very similar toxicological characteristics. These results suggest that severity of envenomation in case of a swarming could therefore be more related to the number of bees than to the differential toxicity of the venom from different regions of the province. This is the first study on the toxicity and toxicological characteristics of Apis mellifera venom in Argentina.
Toxicon : official journal of the International Society on Toxinology, Jan 15, 2017
The venom of Crotalus durissus terrificus produces a neurotoxic and myotoxic syndrome that can le... more The venom of Crotalus durissus terrificus produces a neurotoxic and myotoxic syndrome that can lead to the death. Specific antivenom is the only treatment to neutralize the toxicity of the venom and the precocity in applying the antivenom is crucial for the efficiency of the treatment. We studied the variation of the immunochemical reactivity and neutralizing capacity of the specific antivenom on this venom in pre-incubation and rescue experiments, at different times. ELISA titers increased with longer venom-antivenom incubation times (p < 0.05) nevertheless incubation times had no effect on the neutralizing capacity of the antivenom. The antivenom dose necessary to rescue mice injected with 1.5 MMD (minimal mortal dose) 30 min after venom inoculation was over ten folds the dose of antivenom theoretically required to neutralize the same dose of venom according values obtained from pre-incubation experiments. Results showed that the in vitro immunochemical reactivity is not direct...
Fil: de Roodt, Adolfo Rafael. Ministerio de Salud de la Nacion. Direccion Nacional de Institutos ... more Fil: de Roodt, Adolfo Rafael. Ministerio de Salud de la Nacion. Direccion Nacional de Institutos de Investigacion. Administracion Nacional de Laboratorios e Institutos de Salud "Doctor Carlos G. Malbran". Instituto Nacional de Produccion de Biologicos; Argentina. Universidad de Buenos Aires. Facultad de Medicina; Argentina
We developed experimental equine polyvalent and monovalent antivenoms against the venoms of Micru... more We developed experimental equine polyvalent and monovalent antivenoms against the venoms of Micrurus (M.) fulvius, M. nigrocinctus and M. surinamensis and studied their immunochemical reactivity on the venoms used as immunogens and on M. pyrrhocryptus, M altirostris and M. balyocoriphus venoms. Assessment of the neutralizing capacity of the polyvalent experimental antivenom was based on inhibition of lethality (preincubation and rescue assay experiments in mice) and indirect hemolytic and phospholipase activities. The immunochemical reactivity and neutralizing capacity were compared with those of two therapeutic antivenoms used for the treatment of coral snake envenomation in North America and in Argentina. In general, the experimental antivenom conferred a comparable level of neutralization against the venoms used as immunogens when compared to the therapeutic antivenoms and a certain level of cross-neutralization against the other venoms. The results suggest the need for additional venoms in the immunogenic mixture used, in order to obtain a broad spectrum anti-Micrurus antivenom with a good neutralizing potency. Paraspecific neutralization of South American coral snake venoms, although present at a higher level than the neutralization conferred by available nonspecific Micrurus therapeutic antivenoms, was rather low in relation to the specific neutralizing capacity.
Mass-vaccination against COVID-19 is still a distant goal for most low-to-middle income countries... more Mass-vaccination against COVID-19 is still a distant goal for most low-to-middle income countries. The experience gained through decades producing polyclonal immunotherapeutics (such as antivenoms) in many of those countries is being redirected to develop similar products able to neutralize SARS-CoV-2 infection. In this study we analyzed the biological activity (viral neutralization or NtAb) and immunochemical properties of hyperimmune horses’ sera (HHS) obtained during initial immunization (I) and posterior re-immunization (R) cycles using the RBD domain of the SARS-CoV-2 spike protein as antigen. HHS at the end of the R cycle showed higher NtAb titers when compared to those after the I cycle (35,585 vs. 7000 mean NtAb, respectively). Moreover, this increase paralleled an increase in avidity (95.2% to 65.2% mean avidity units, respectively). The results presented herein are relevant for manufacturers of these therapeutic tools against COVID-19.
Comparamos caracteres corporales y produccion de veneno de ejemplares de Bothropsalternatus de un... more Comparamos caracteres corporales y produccion de veneno de ejemplares de Bothropsalternatus de una poblacion aislada geograficamente (Olavarria, region de Tandilia, BuenosAires) con otra en su area de distribucion continua de Concordia (Entre Rios). Estudiamos ellargo corporal, peso, separacion entre dientes inoculadores, cantidad de veneno y de proteinasen el veneno por ejemplar. No se hallaron diferencias en los caracteres estudiados entreambas poblaciones (p > 0.05). Las hembras fueron mayores que los machos en ambas muestras,entre un 12-18% (p 0.5; Olavarria: 142 ± 65 mg/animal,Concordia: 160 ± 80 mg/animal), aun ajustando la cantidad de veneno producida respecto altamano, mediante el cociente veneno/largo corporal (p >0.6). Tampoco hubo diferencias enel contenido proteico, siendo para ambas muestras de 0.697 ± 0.096 mg de proteinas/mg deveneno seco. Nuestros datos sugieren que los ejemplares de la poblacion aislada de Tandiliano presentan variaciones en el tamano
Proceedings of 1st International Electronic Conference on Toxins, 2021
Crotalus atrox is one of the species of venomous snakes most commonly found in herpetological col... more Crotalus atrox is one of the species of venomous snakes most commonly found in herpetological collections around the world and it is usually commercialized in the black market. Several collections have specimens but lack of the specific antivenom. We tested the toxicity of venom of adults and young snakes (2 to 3 years old) specimens of C. atrox in captivity and the para-specific neutralization provided by the antivenoms most used in Argentina. The i.p. lethal potency of the venoms were 100(95-105) μg and 43(42-45) μg20g mouse and the indirect hemolytic activity was 7.9 (6.7-9.2) μg and 9.0(8.3-9.9) for adults and juvenile venoms. Despite the adult´s venoms lower lethal potency, these venoms were more difficult to neutralize, around 1.5 ml of antibothropic Antivenom (AB) were necessaries to neutralize 1 mg of venom in contrast to 0.54 ml required to neutralize young´s venoms. The neutralization by the Anticrotalic (AC) antivenom was despicable. The dose of AB required for the neutra...
Bothrops jararacussu is one of the most venomous snakes of medicalimportance in South America, ma... more Bothrops jararacussu is one of the most venomous snakes of medicalimportance in South America, mainly due to the toxicity of their venom and thelarge amount of that which can be injected in a single bite. The venomof this snake is required for the production, process and control of thetherapeutic antivenoms used to treat Bothropsenvenomation, so it is one of the Bothropsspecies common in Serpentarium located in Argentina and Brazil dedicated tothe production of antivenoms. We reported two cases of ophyophagy due captiveadult B. jararacussu females on Bothrops and Phylodriassnakes and the aggression ofspecimens of this species is also described.Despite well known resistance to homologous venom of Bothrops species, the bite of thisspecie on other snakes of the same species and also other Bothrops snakes, produce serious injuries. Theseobservations are important for professionals whom must maintain incaptivity these species of snakes by educational or venomproduction purposes.
Samples of Apis mellifera mellifera venom from different hives in two regions of the Buenos Aires... more Samples of Apis mellifera mellifera venom from different hives in two regions of the Buenos Aires province and its pool were analyzed for their lethal potency, myotoxic, defibrinogenating, hemolytic and inflammatory-edematizing activity and for the histological alterations they produce in the heart, lungs, kidneys, skeletal muscle and liver of mice. In vitro studies focused on the venom's hemolytic activity in different systems and species (horse, man, sheep and rabbit), the cytotoxicity in cellular lines, and on the proteolytic and coagulant activity in plasma and fibrinogen. Hemolytic activity, either observed in vitro or in vivo, showed similar toxicity levels for all samples. Erythrocytes of different species varied in their sensitivity to the venom pool, equines being the most sensitive and sheep the most resistant to direct hemolytic action. Local and systemic myotoxicity was evidenced by either the elevation of serum creatine kinase and/or histopathological lesions, observed in different muscles. All samples caused significant pathological alterations; pulmonary, cardiac, renal and skeletal muscle lesions were substantive and can be related to the pathophysiological mechanisms of envenomation. The venoms from different apiaries and regions of the Buenos Aires province showed very similar toxicological characteristics. These results suggest that severity of envenomation in case of a swarming could therefore be more related to the number of bees than to the differential toxicity of the venom from different regions of the province. This is the first study on the toxicity and toxicological characteristics of Apis mellifera venom in Argentina.
Toxicon : official journal of the International Society on Toxinology, Jan 15, 2017
The venom of Crotalus durissus terrificus produces a neurotoxic and myotoxic syndrome that can le... more The venom of Crotalus durissus terrificus produces a neurotoxic and myotoxic syndrome that can lead to the death. Specific antivenom is the only treatment to neutralize the toxicity of the venom and the precocity in applying the antivenom is crucial for the efficiency of the treatment. We studied the variation of the immunochemical reactivity and neutralizing capacity of the specific antivenom on this venom in pre-incubation and rescue experiments, at different times. ELISA titers increased with longer venom-antivenom incubation times (p < 0.05) nevertheless incubation times had no effect on the neutralizing capacity of the antivenom. The antivenom dose necessary to rescue mice injected with 1.5 MMD (minimal mortal dose) 30 min after venom inoculation was over ten folds the dose of antivenom theoretically required to neutralize the same dose of venom according values obtained from pre-incubation experiments. Results showed that the in vitro immunochemical reactivity is not direct...
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