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Venomics across the Bothrops neuwiedi Species Complex Revealed a P‑III Snake Venom Metalloproteases/K49-PLA2 Dichotomy and a Remarkable Paraspecific Neutralization of the Brazilian Pentabothropic Antivenom

2026-03-05T13:00:51Z

Title: Venomics across the Bothrops neuwiedi Species Complex Revealed a P‑III Snake Venom Metalloproteases/K49-PLA2 Dichotomy and a Remarkable Paraspecific Neutralization of the Brazilian Pentabothropic Antivenom Authors: Costa Galizio, Nathália; Serino Silva, Caroline; Rodrigues Stuginski, Daniel; Bittencourt Rodrigues, Caroline Fabri; Teixeira da Rocha, Marisa Maria; Oliveira Serapicos, Eliana; Barbarini, Cibele Cintia; de Oliveira, Roberto Baptista; Sant’Anna, Sávio Stefanini; Fernandes Grego, Kathleen; Sanz, Libia; Tena-Garcés, Jordi; de Roodt, Adolfo R.; Calvete, Juan J.; Mitico Tanaka-Azevedo, Anita; de Morais Zani, Karen Abstract: Snakes of the Bothrops neuwiedi complex are widely distributed and represent medically important species in Brazil. Here, we report compositional and functional profiles of the venom of seven species of Bothrops neuwiedi group: Bothrops mattogrossensis, Bothrops pauloensis, Bothrops pubescens, Bothrops diporus, Bothrops neuwiedi, Bothrops marmoratus, and Bothrops erythromelas. Toxin composition of individual and pooled venoms showed remarkable inter- and intraspecific variability of the relative abundance of toxins (evidenced by SDS-PAGE and RP-HPLC) and enzymatic activities (proteolytic, PLA2, and thrombin-like activities). In vivo analyses showed that B. erythromelas venom is the most hemorrhagic, B. diporus was the most lethal, and B. pubescens showed the highest myotoxic activity. Histopathological analysis showed that all venoms induced edema, hemorrhage, inflammatory infiltrate, and necrosis of muscle fibers. Consistent with large research evidence on the paraspecificity of various commercial antivenoms generated in Latin America, the pentabothropic antivenom produced by Instituto Butantan showed a high profile of immunoreactivity and lethality neutralization capability toward the venoms of the seven species of the B. neuwiedi clade. Interpreted through the prism of evolution, our data revealed a PIII-SVMP/K49-PLA2 compositional dichotomy and a remarkable conservation of immunological cross-reactivity across congeneric venoms throughout the 12−16 million years of Bothrops phylogeny.

Development, Implementation, Pharmacokinetic and Safety Evaluation of an Immunotherapeutic Treatment for COVID-19: Double-blind Randomized Placebo-controlled Trial

2025-10-28T15:45:42Z

Title: Development, Implementation, Pharmacokinetic and Safety Evaluation of an Immunotherapeutic Treatment for COVID-19: Double-blind Randomized Placebo-controlled Trial Authors: Keller, Guillermo; Miranda, Silvia; de Roodt, Adolfo R.; Salvi, Roxana; Colaianni, Ivana; García, Elizabeth; Bramuglia, Guillermo; Calderon, Leandro; Mazza, Diego; Lanari, Laura Cecilia; Perez, Oscar; Fingermann, Matías; Temprano, Guillermo; Di Girolamo, Guillermo; Bonel, Claudio; Dokmetjian, José Christian Abstract: Passive immunotherapy has been evaluated in many infections. The present study aims to evaluate purified F(ab’)2 fraction of equine hyperimmune IgG (anti-SARS-CoV-2) in the treatment of coronavirus lung disease. Patients with coronavirus disease of 2019 (COVID-19) with World Health Organization (WHO) score 3, 4 or 5 up to 72 hours of evolution from the onset of symptoms were included. They were randomly assigned to anti-SARS-CoV-2 or placebo. Follow-up was performed for 28 days to assess efficacy, safety, pharmacokinetics, detection of anti-horse antibodies, circulating cytokines and determination of anti-SARS neutralizing activity. The 20 initial patients (44±14 years) were included. On the third day of treatment there was an improvement (P=0.02) in arterial saturation (95±1.6 vs. 93±2.5%) with increasing differences over time between treatments (day 8: 97±0.1 vs. 94±0.3%). The length of oxygen therapy treatment was 2±0.8 vs. 3±0.9 (0.048) in patients falling within WHO 5 category (no difference to WHO 4). Mean hospitalization was 13±2.5 vs. 14±0.8 days (P=0.095) and time to clinical improvement was 2±0.5 vs. 3±0.9 days (P=0.048) in patients with initial 5 WHO category, with no differences to patients who started with WHO stage 4. The time to nasal swab negativization was 10±2.1 vs. 12±0 day (P=0.015). No adverse reactions or intercurrences were detected. All patients presented heterophile antibodies without clinical correlate. The new treatment shows improvement in arterial saturation (days 3 to 12), and a decrease on detectable viral RNA (days 8 to 11) with good pharmacokinetic and safety profile. Description: Fil: Keller, Guillermo Alberto. Administración Nacional de Laboratorios e Institutos de Salud “Dr. Carlos G. Malbrán” (ANLIS-Malbrán), Instituto Nacional de Producción de Biológicos (INPB), Buenos Aires, Argentina; Hospital General de Agudos Donación Francisco J. Santojanni, Buenos Aires, Argentina; Instituto Alberto C. Taquini de Investigaciones en Medicina Traslacional (IATIMET), Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina. Fil: Miranda, Silvia. Instituto Alberto C. Taquini de Investigaciones en Medicina Traslacional (IATIMET), Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina. Fil: De Roodt, Alberto Rafael. Administración Nacional de Laboratorios e Institutos de Salud “Dr. Carlos G. Malbrán” (ANLIS-Malbrán), Instituto Nacional de Producción de Biológicos (INPB), Buenos Aires, Argentina. Fil: Salvi, Roxana. Hospital General de Agudos Donación Francisco J. Santojanni, Buenos Aires, Argentina. Fil: Colaianni, Ivana. Hospital General de Agudos Donación Francisco J. Santojanni, Buenos Aires, Argentina. Fil: García, Elizabeth. Hospital General de Agudos Donación Francisco J. Santojanni, Buenos Aires, Argentina. Fil: Bramuglia, Guillermo. Instituto Alberto C. Taquini de Investigaciones en Medicina Traslacional (IATIMET), Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina. Fil: Calderón, Leandro. Administración Nacional de Laboratorios e Institutos de Salud “Dr. Carlos G. Malbrán” (ANLIS-Malbrán), Instituto Nacional de Producción de Biológicos (INPB), Buenos Aires, Argentina. Fil: Mazza, Diego. Administración Nacional de Laboratorios e Institutos de Salud “Dr. Carlos G. Malbrán” (ANLIS-Malbrán), Instituto Nacional de Producción de Biológicos (INPB), Buenos Aires, Argentina. Fil: Lanari, Laura. Administración Nacional de Laboratorios e Institutos de Salud “Dr. Carlos G. Malbrán” (ANLIS-Malbrán), Instituto Nacional de Producción de Biológicos (INPB), Buenos Aires, Argentina. Fil: Pérez Oscar. Administración Nacional de Laboratorios e Institutos de Salud “Dr. Carlos G. Malbrán” (ANLIS-Malbrán), Instituto Nacional de Producción de Biológicos (INPB), Buenos Aires, Argentina. Fil: Fingermann, Matias. Administración Nacional de Laboratorios e Institutos de Salud “Dr. Carlos G. Malbrán” (ANLIS-Malbrán), Instituto Nacional de Producción de Biológicos (INPB), Buenos Aires, Argentina. Fil: Temprano, Guillermo. Administración Nacional de Laboratorios e Institutos de Salud “Dr. Carlos G. Malbrán” (ANLIS-Malbrán), Instituto Nacional de Producción de Biológicos (INPB), Buenos Aires, Argentina. Fil: Di Girolamo, Guillermo. Instituto Alberto C. Taquini de Investigaciones en Medicina Traslacional (IATIMET), Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina. Fil: Bonel, Claudio. Administración Nacional de Laboratorios e Institutos de Salud “Dr. Carlos G. Malbrán” (ANLIS-Malbrán), Instituto Nacional de Producción de Biológicos (INPB), Buenos Aires, Argentina. Fil: Dokmetjian, José Christian. Administración Nacional de Laboratorios e Institutos de Salud “Dr. Carlos G. Malbrán” (ANLIS-Malbrán), Instituto Nacional de Producción de Biológicos (INPB), Buenos Aires, Argentina.

Neutralization of "Chaco eagle" (Buteogallus coronatus) serum on some activities of Bothrops spp. venoms

2022-08-17T16:49:09Z

Title: Neutralization of "Chaco eagle" (Buteogallus coronatus) serum on some activities of Bothrops spp. venoms Authors: Regner, Pablo I.; Saggese, Miguel D; de Oliveira, Vanessa C; Lanari, Laura C; Desio, Marcela A; Quaglia, Agustín I E; Wiemeyer, Guillermo; Capdevielle, Andrés; Zuñiga, Silvina N; de Roodt, Carolina J I; de Roodt, Adolfo R. Abstract: Several species of reptiles and mammals have components in their sera that can neutralize toxic components present in snake venoms. In this manuscript, we studied the neutralizing capacity of Chaco eagle's (Buteogallus coronatus) serum. This South American bird of prey eats snakes as a regular part of its diet and has anatomical features that protect from snakes' bites. The neutralizing potency of the Chaco eagle's serum was tested on lethal, hemorrhagic, procoagulant, and phospholipase activities of the venom of "yarará grande" (Bothrops alternatus) and on phospholipase activity of "yarará ñata" (Bothrops ammodytoides) venom; both snakes are known to be the prey of Chaco eagle. Sera of crested caracara (Caracara plancus-a scavenger, omnivorous pan-American bird of prey), secretary bird (Saggitarius serpentarius-an omnivorous bird of prey from Africa that can include venomous snakes in its diet), common hen (Gallus gallus), rat (Rattus norvegicus), mouse (Mus musculus), horse (Equus caballus), and dog (Canis lupus familiaris) were also tested to compare the inhibitory capacity of neutralization. To test isologous and xenologous neutralization, sera from Bothrops alternatus and white-eared opossum (Didelphis albiventris), respectively, were used due to their known inhibitory activity on Bothrops venoms. As a control for the neutralization activity, antibothropic antivenom was used. Chaco eagle's serum neutralized hemorrhagic and phospholipasic activity and slightly neutralized the coagulation and the lethal activity of Bothrops spp. venom. The neutralizing capacity was present in the non-immunoglobulin fraction of the serum, which showed components of acidic characteristics and lower molecular weight than IgY, in correspondence with the characteristics of PLA2s and SVMPs inhibitors described in sera from some snakes and mammals. These studies showed that Chaco eagle's serum neutralizes all toxic activities tested at a higher level than sera from animal species in which inhibitors of snake venoms have not been described (p < 0.05), while it is lower or similar in neutralizing capacity to white-eared opossum and B. alternatus sera.

Cytokines expression from altered motor thalamus and behavior deficits following sublethal administration of Shiga toxin 2a involve the induction of the globotriaosylceramide receptor

2026-05-08T19:43:12Z

Title: Cytokines expression from altered motor thalamus and behavior deficits following sublethal administration of Shiga toxin 2a involve the induction of the globotriaosylceramide receptor Authors: Arenas-Mosquera, David; Pinto, Alipio; Cerny, Natacha; Berdasco, Clara; Cangelosi, Adriana; Geoghegan, Patricia A.; Malchiodi, Emilio Luis; De Marzi, Mauricio C; Goldstein, Jorge Abstract: Encephalopathy associated with hemolytic uremic syndrome is produced by enterohemorrhagic E. coli (EHEC) infection, which releases the virulence factors Shiga toxin (Stx) and lipopolysaccharide (LPS). Neurological compromise is a poor prognosis and mortality factor of the disease, and the thalamus is one of the brain areas most frequently affected. We have previously demonstrated the effectiveness of anti-inflammatory drugs to ameliorate the deleterious effects of these toxins. However, the thalamic production of cytokines involved in pro-inflammatory processes has not yet been acknowledged. The aim of this work attempts to determine whether systemic sublethal Stx2a or co-administration of Stx2a with LPS are able to rise a proinflammatory profile accompanying alterations of the neurovascular unit in anterior and lateral ventral nuclei of the thalamus (VA-VL) and motor behavior in mice. After 4 days of treatment, Stx2a affected the lectin-bound microvasculature distribution while increasing the expression of GFAP in reactive astrocytes and producing aberrant NeuN distribution in degenerative neurons. In addition, increased swimming latency was observed in a motor behavioral test. All these alterations were heightened when Stx2a was co-administered with LPS. The expression of pro-inflammatory cytokines TNFα, INF-γ and IL-2 was detected in VA-VL. All these effects were concomitant with increased expression of the Stx receptor globotriaosylceramide (Gb3), which hints at receptor involvement in the neuroinflammatory process as a key finding of this study. In conclusion, Stx2a to Gb3 may be determinant in triggering a neuroinflammatory event, which may resemble clinical outcomes and should thus be considered in the development of preventive strategies.