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Estudio ultraestructural de la mionecrosis inducida en raton por el veneno de terciopelo (Bothrops asper) de Costa Rica
(1981-06-01) Arroyo Gutiérrez, Olga; Gutiérrez, José María
Skeletal muscle from white mice was examined one and three hr after i.m. injection of 50 μg of Bothrops asper venom. At the light microscopic level we observed nectoric fibers with myolitic appearance, as early as the first hr and more marked by the third hr. At the ultrastructural level three kinds of fibers were observed: (a) fibers with normal morphology, (b) fibers with slight alteration at the sarcoplasmic reticulum and (c) fibers with strong alterations in several organelles; in these fibers, the main pathological feature was the disruption of myofibril architecture. This disruption started with the disappearance of A, H, I and M bands, followed by the alteration of Z line. At the end of this process an amorphous mass of proteins was observed. Shortly following envenomation, sarcoplasmic reticulum showed moderate dilatation and proliferation, but when degenerative changes were more evident, smaller and more abundant vacuoles were seen. Also, the plasma membrane was altered and disrupted in some fibers, whereas many mitochondria showed a swollen appearance and, in some cells, they were disrupted. An amorphous extracellular material was also observed as a consequence of envenomation. It is proposed that the ultrastructural basis of the muscular necrosis induced by terciopelo venom is the disruption and severe alteration of the myofibril architecture.
Traces of Bothrops snake venoms in necrotic muscle preclude myotube formation in vitro
(2022-05) Van de Velde, Andrea C.; Fusco, Luciano Sebastián; Echeverría, Silvana; Sasovsky, Daniela Jaqueline; Leiva de Vila, Laura Cristina Ana; Gutiérrez, José María; Bustillo, Soledad
Deficient skeletal muscle regeneration, which often leads to permanent sequelae, is a common clinical finding in envenomations caused by snakes of the family Viperidae, such as those of Bothrops alternatus and B. diporus in South America. The causes of such poor muscle regenerative outcome are still incompletely understood. Using a murine experimental model of envenomation by the venoms of these two species, we assessed whether traces of venom components that remain in muscle tissue days after envenomation affect myoblasts and myotube formation in culture. The kinetics of drop in venom concentration in the tissue was assessed by ELISA and Western blot, and by the quantification of venom phospholipase A2 activity. A rapid drop of venom components was observed in muscle, although a band of 58–63 kDa remained even 168 h after venom injection, and venom phospholipase A2 activity was detected in muscle tissue days after envenomation. Muscle homogenates from envenomated animals were cytotoxic to myoblasts in culture and inhibited the formation of myotubes even in conditions where homogenates were devoid of cytotoxicity. These deleterious effects were abrogated when homogenates were incubated with antivenom. Our findings agree with previous observations with the venom of Bothrops asper and provide further evidence that one of the causes of the poor skeletal muscle regeneration after Bothrops sp venom-induced myonecrosis is the deleterious action on myogenic cells of traces of venom components remaining in the tissue.
Epidemiology of snakebites in El Salvador (2014–2019)
(2020-10-30) Gutiérrez, José María; Castillo, Luis; Díaz de Naves, Karla Marina; Masís, Jenny; Alape Girón, Alberto
This study describes the basic epidemiological features of snakebites in El Salvador for the period 2014–2019 on the basis of data provided by the national system of information on morbidity and mortality (Sistema de Morbi-Mortalidad via Web, SIMMOW) of the Ministry of Health of El Salvador. The total number of cases per year ranged from 161 (2017) to 215 (2016). Incidences ranged from 2.52 cases to 3.38 cases per 100,000 population per year, corresponding to the years 2017 and 2016, respectively. Five deaths were recorded in the six-year period, four in 2015 and one in 2016, for a case fatality rate of 0.44%. Snakebites peaked during the rainy season (May to November) and mostly affected people in the age groups of 10–30 years. The male/female ratio was 1.59. The Departments (local political units) showing the highest number of cases were Santa Ana, Libertad, Chalatenango, Sonsonate, and La Unión. Most cases were attended at departmental and regional hospitals (second level of attention). The incidence and mortality due to snakebite envenoming in El Salvador are the lowest reported for Central America. This may be related to the fact that Bothrops asper, the medically most important snake species in the region, is not distributed in El Salvador, where the rattlesnake Crotalus simus predominates.
Third-generation antivenomics analysis of the preclinical efficacy of Bothrofav® antivenom towards Bothrops lanceolatus venom
(2019-01) Pla Ferrer, Davinia; Rodríguez, Yania; Resiere, Dabor; Mehdaoui, Hossein; Gutiérrez, José María; Calvete Chornet, Juan José
Bothrops lanceolatus inflicts severe envenomings in the Lesser Caribbean island of Martinique. Bothrofav®, a monospecific antivenom against B. lanceolatus venom, has proven highly effective at the preclinical and clinical levels. Here, we report a detailed third-generation antivenomics quantitative analysis of Bothrofav®. With the exception of poorly-immunogenic peptides, Bothrofav® immunocaptured all the major protein components. These results, along with previous preclinical and clinical observations, underscore the high neutralizing efficacy of the antivenom against B. lanceolatus venom.
Antivenoms: Life-saving drugs for envenomings by animal bites and stings
(2018-08) Gutiérrez, José María
Envenomings from animal bites and stings affect millions annually, with snakebites alone causing 1.8 to 2.7 million cases and 81,000 to 138,000 deaths globally. Survivors often face permanent physical and psychological aftereffects. Historically minimal attention from health authorities is changing due to a concerted international effort led by numerous organizations, raising awareness and prompting the WHO to classify snakebite envenoming as a neglected tropical disease in 2017. This led to a resolution for member states to address the issue, with plans for a strategic road map by the WHO.Addressing snakebite envenoming requires multifaceted interventions, including scientific research, development of new antivenoms, public health system strengthening, and community engagement. Antivenoms, the only effective treatment, face quality and accessibility challenges, exacerbated by regulatory deficiencies and economic issues leading to low production profitability. New recombinant antibody technologies are emerging, yet significant gaps remain in effective antivenom production and standardization.This special issue of Toxicon discusses advancements and challenges in the antivenom field, covering historical developments, production technologies, and economic analyses. It aims to foster understanding of antivenom complexities to enhance the quality and accessibility of these critical medical interventions, ultimately reducing the human suffering associated with envenomings.