Natural resistance to snake venoms

La resistencia natural de algunos animales a los venenos de serpientes se ha logrado demostrar en el suero sanguíneo de mamíferos (Zarigüeyas, erizos, mangostas) y de serpientes. En este artículo se presenta el estado actual del conocimiento acerca de estas proteínas que no son anticuerpos, los métodos de caracterización y los mecanismos de acción de las mismas.The natural resistance of some animals to snake venoms has been demonstrated in the blood serum of mammals (possums, hedgehogs, mongooses) and snakes. This article presents the current state of knowledge about these non-antibody proteins, their characterization methods, and their mechanisms of action

Spider poisoning in the Americas

Las arañas de verdadero interés médico en el mundo pertenecen a los géneros Phoneutria, Loxosceles,Latrodectus y Atrax, el primero de los cuales se distribuye desde Costa Rica hasta Bolivia. El género Atrax se encuentra en Australia, Nueva Guinea y las islas Salomón. Loxosceles spp y Latrodectusspp son arañas cosmopolitas. El accidente aracnídico en América es un problema de salud pública en países como Chile, Estados Unidos y Brasil, siendo las mordeduras por Loxosceles spp más frecuentes en los dos primeros países y por Phoneutria spp en Brasil. En Colombia no conocemos publicaciones sobre accidentes por Loxosceles spp pero sí por Latrodectus spp en la primera mitad del siglo XX, y relatos recientes (1990s) de accidentes por Phoneutria spp en Antioquia. Se presenta una revisión de los aspectos taxonómicos, toxinológicos y clínicos del aracnidismo, de tal manera que nos permita estar atentos para diagnosticar y tratar correctamente estos accidentes.The spiders of true medical interest in the world belong to the genera Phoneutria, Loxosceles, Latrodectus and Atrax, the first of which is distributed from Costa Rica to Bolivia. The genus Atrax is found in Australia, New Guinea and the Solomon Islands. Loxosceles spp and Latrodectusspp are cosmopolitan spiders. The arachnid accident in America is a public health problem in countries such as Chile, the United States and Brazil, with bites by Loxosceles spp being more frequent in the first two countries and by Phoneutria spp in Brazil. In Colombia we do not know of publications on accidents due to Loxosceles spp but we do know about Latrodectus spp in the first half of the 20th century, and recent reports (1990s) of accidents due to Phoneutria spp in Antioquia. A review of the taxonomic, toxinological and clinical aspects of arachnidism is presented, in such a way that it allows us to be attentive to correctly diagnose and treat these accidents

Toxinological, clinical and epidemiological aspects of the envenomation produced by the scorpion Tityus fuhrmanni Kraepelin

Con el objetivo de determinar las características toxinológicas, clínicas y epidemiológicas del envenenamiento producido por el escorpión T. fuhrmanni, se realizó durante un año un estudio prospectivo en un sector de la ciudad de Medellín (cerro El Volador y los barrios aledaños San Germán y El Volador), en una muestra del9,6% de las casas (180) y del 9,4% de la población del área (719 habitantes). Se incluyó también la recolección de especímenes vivos (128) y de veneno para la parte experimental. La dispersión de escorpiones para el área de estudio fue del 100%, con alta infestación domiciliaria en las viviendas del cerro y del barrio San Germán (100% y 32,3%, respectivamente). Durante todo el estudio se detectaron 32 accidentes por T.fuhrmanni, 7 (21,9%) en niños, 15 en el cerro y 10 en el barrio San Germán, con tasas de ataque del 83% y del 3,9%, respectivamente. Dieciocho (56,3%) accidentes ocurrieron en el interior de las viviendas, principalmente en las manos (31,3%), la cabeza y el cuello (18,8%) y durante la noche o en las primeras horas de la mañana (62,5%). El 90,6% de los casos fueron leves y el 9,4% (3 niños) tuvieron envenenamiento moderado con signos sistémicos (sudoración generalizada, dolor abdominal). No hubo casos graves y los pacientes no requirieron hospitalización. Tityus fuhrmanni produjo 0,56 ± 0,27 mg de veneno por ordeño, ysu DL50 (i.p.) en ratones (18-20 g) fue 79,2 μg (3,9 mg veneno/kg). Los animales presentaron sialorrea, piloerección, somnolencia, sudoración generalizada, taquipnea, cianosis, ataxia y convulsiones antes de morir. La rápida aparición (10-15 min) de los signos de envenenamiento en los ratones y su pronta desaparición(2 horas) en los sobrevivientes, permiten concluir que el veneno es de rápida absorción, distribución y eliminación. [Gómez JP, Otero R, Núñez V, Saldarriaga M, Díaz A, Velásquez P. Aspectos toxinológicos, clínicos y epidemiológicos del envenenamiento producido por el escorpión Tityus fuhrmanni Kraepelin.MEDUNAB 2002; 5(15): 159-65]In order to determine the toxinological, clinical and epidemiological characteristics of the poisoning produced by the scorpion T. fuhrmanni, a prospective study was carried out for a year in a sector of the city of Medellín (Cerro El Volador and the neighboring neighborhoods San Germán and El Volador), in a sample of 9.6% of the houses (180) and 9.4% of the population of the area (719 inhabitants). The collection of live specimens (128) and poison for the experimental part was also included. The dispersion of scorpions for the study area was 100%, with high home infestation in the homes of the hill and the San Germán neighborhood (100% and 32.3%, respectively). Throughout the study, 32 accidents were detected by T. fuhrmanni, 7 (21.9%) in children, 15 in the hill and 10 in the San Germán neighborhood, with attack rates of 83% and 3.9%, respectively. . Eighteen (56.3%) accidents occurred inside homes, mainly in the hands (31.3%), head and neck (18.8%) and during the night or in the early hours of the morning (62.5%). 90.6% of the cases were mild and 9.4% (3 children) had moderate poisoning with systemic signs (generalized sweating, abdominal pain). There were no serious cases and the patients did not require hospitalization. Tityus fuhrmanni produced 0.56 ± 0.27 mg of venom per milking, and its LD50 (i.p.) in mice (18-20 g) was 79.2 μg (3.9 mg venom / kg). The animals presented with salivation, piloerection, drowsiness, generalized sweating, tachypnea, cyanosis, ataxia and seizures before dying. The rapid appearance (10-15 min) of the poisoning signs in the mice and their prompt disappearance (2 hours) in the survivors, allow us to conclude that the venom is of rapid absorption, distribution and elimination. [Gómez JP, Otero R, Núñez V, Saldarriaga M, Díaz A, Velásquez P. Toxinological, clinical and epidemiological aspects of the poisoning produced by the scorpion Tityus fuhrmanni Kraepelin.MEDUNAB 2002; 5 (15): 159-65

Neutralizing capacity of a new monovalent anti-Bothrops atrox antivenom: Comparison with two commercial antivenoms

Three horse-derived antivenoms were tested for their ability to neutralize lethal, hemorrhagic, edema-forming, defibrinating and myotoxic activities induced by the venom of Bothrops atr-ox from Antioquia and Choco (Colombia). The following antivenoms were used: a) polyvalent (crotaline) antivenom produced by Institute Clodomiro Picado (Costa Rica), b) monovalent antibothropic antivenom produced by Institute Nacional de Salud-INS (Bogota), and c) a new monovalent anti-B. atrox antivenom produced with the venom of B. atrox from Antioquia and Choco. The three antivenoms neutralized all toxic activities tested albeit with different potencies. The new monovalent anti-B. atrox antivenom showed the highest neutralizing ability against edema-forming and defibrinating effects of B. atrox venom (41 +/- 2 and 100 +/- 32 mu l antivenom/mg venom, respectively), suggesting that it should be useful in the treatment of B. atrox envenomation in Antioquia and Choco.Universidad de Costa Rica//UCR/Costa RicaUCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias de la Salud::Instituto Clodomiro Picado (ICP

Mortality and Advanced Support Requirement for Patients With Cancer With COVID-19 : A Mathematical Dynamic Model for Latin America

PURPOSE: In the midst of a global pandemic, evidence suggests that similar to other severe respiratory viral infections, patients with cancer are at higher risk of becoming infected by COVID-19 and have a poorer prognosis. METHODS: We have modeled the mortality and the intensive care unit (ICU) requirement for the care of patients with cancer infected with COVID-19 in Latin America. A dynamic multistate Markov model was constructed. Transition probabilities were estimated on the basis of published reports for cumulative probability of complications. Basic reproductive number (R0) values were modeled with R using the EpiEstim package. Estimations of days of ICU requirement and absolute mortality were calculated by imputing number of cumulative cases in the Markov model. RESULTS: Estimated median time of ICU requirement was 12.7 days, median time to mortality was 16.3 days after infection, and median time to severe event was 8.1 days. Peak ICU occupancy for patients with cancer was calculated at 16 days after infection. Deterministic sensitivity analysis revealed an interval for mortality between 18.5% and 30.4%. With the actual incidence tendency, Latin America would be expected to lose approximately 111,725 patients with cancer to SARS-CoV-2 (range, 87,116-143,154 patients) by the 60th day since the start of the outbreak. Losses calculated vary between < 1% to 17.6% of all patients with cancer in the region. CONCLUSION: Cancer-related cases and deaths attributable to SARS-CoV-2 will put a great strain on health care systems in Latin America. Early implementation of interventions on the basis of data given by disease modeling could mitigate both infections and deaths among patients with cancer

Multigene mutation profiling and clinical characteristics of small-cell lung cancer in never-smokers vs. seavy smokers (Geno1.3-CLICaP)

Objectives: Lung cancer is a heterogeneous disease. Presentation and prognosis are known to vary according to several factors, such as genetic and demographic characteristics. Small-cell lung cancer incidence is increasing in never-smokers. However, the disease phenotype in this population is different compared with patients who have a smoking history. Material and Methods: To further investigate the clinical and genetic characteristics of this patient subgroup, a cohort of small cell lung cancer patients was divided into smokers (n = 10) and never/ever-smokers (n = 10). A somatic mutation profile was obtained using a comprehensive NGS assay. Clinical outcomes were compared using the Kaplan-Meier method and Cox proportional models. Results: Median age was 63 years (46–81), 40% were men, and 90% had extended disease. Smoker patients had significantly more cerebral metastases (p = 0.04) and were older (p = 0.03) compared to their non-smoker counterparts. For never/ever smokers, the main genetic mutations were TP53 (80%), RB1 (40%), CYLD (30%), and EGFR (30%). Smoker patients had more RB1 (80%, p = 0.04), CDKN2A (30%, p = 0.05), and CEBPA (30%, p = 0.05) mutations. Response rates to first-line therapy with etoposide plus cisplatin/carboplatin were 50% in smokers and 90% in never/ever smokers (p = 0.141). Median overall survival was significantly longer in never smokers compared with smokers (29.1 months [23.5–34.6] vs. 17.3 months [4.8–29.7]; p = 0.0054). Never/ever smoking history (HR 0.543, 95% CI 0.41–0.80), limited-stage disease (HR 0.56, 95% CI 0.40–0.91) and response to first-line platinum-based chemotherapy (HR 0.63, 95% CI 0.60–0.92) were independently associated with good prognosis. Conclusion: Our data supports that never/ever smoker patients with small-cell lung cancer have better prognosis compared to their smoker counterparts. Further, patients with never/ever smoking history who present with small-cell lung cancer have a different mutation profile compared with smokers, including a high frequency of EGFR, MET, and SMAD4 mutations. Further studies are required to assess whether the differential mutation profile is a consequence of a diverse pathological mechanism for disease onset

Multigene Mutation Profiling and Clinical Characteristics of Small-Cell Lung Cancer in Never-Smokers vs. Heavy Smokers (Geno1.3-CLICaP)

Objectives: Lung cancer is a heterogeneous disease. Presentation and prognosis are known to vary according to several factors, such as genetic and demographic characteristics. Small-cell lung cancer incidence is increasing in never-smokers. However, the disease phenotype in this population is different compared with patients who have a smoking history.Material and Methods: To further investigate the clinical and genetic characteristics of this patient subgroup, a cohort of small cell lung cancer patients was divided into smokers (n = 10) and never/ever-smokers (n = 10). A somatic mutation profile was obtained using a comprehensive NGS assay. Clinical outcomes were compared using the Kaplan-Meier method and Cox proportional models.Results: Median age was 63 years (46–81), 40% were men, and 90% had extended disease. Smoker patients had significantly more cerebral metastases (p = 0.04) and were older (p = 0.03) compared to their non-smoker counterparts. For never/ever smokers, the main genetic mutations were TP53 (80%), RB1 (40%), CYLD (30%), and EGFR (30%). Smoker patients had more RB1 (80%, p = 0.04), CDKN2A (30%, p = 0.05), and CEBPA (30%, p = 0.05) mutations. Response rates to first-line therapy with etoposide plus cisplatin/carboplatin were 50% in smokers and 90% in never/ever smokers (p = 0.141). Median overall survival was significantly longer in never smokers compared with smokers (29.1 months [23.5–34.6] vs. 17.3 months [4.8–29.7]; p = 0.0054). Never/ever smoking history (HR 0.543, 95% CI 0.41–0.80), limited-stage disease (HR 0.56, 95% CI 0.40–0.91) and response to first-line platinum-based chemotherapy (HR 0.63, 95% CI 0.60–0.92) were independently associated with good prognosis.Conclusion: Our data supports that never/ever smoker patients with small-cell lung cancer have better prognosis compared to their smoker counterparts. Further, patients with never/ever smoking history who present with small-cell lung cancer have a different mutation profile compared with smokers, including a high frequency of EGFR, MET, and SMAD4 mutations. Further studies are required to assess whether the differential mutation profile is a consequence of a diverse pathological mechanism for disease onset

Differential clinical characteristics and prognosis of intraventricular conduction defects in patients with chronic heart failure

Intraventricular conduction defects (IVCDs) can impair prognosis of heart failure (HF), but their specific impact is not well established. This study aimed to analyse the clinical profile and outcomes of HF patients with LBBB, right bundle branch block (RBBB), left anterior fascicular block (LAFB), and no IVCDs. Clinical variables and outcomes after a median follow-up of 21 months were analysed in 1762 patients with chronic HF and LBBB (n = 532), RBBB (n = 134), LAFB (n = 154), and no IVCDs (n = 942). LBBB was associated with more marked LV dilation, depressed LVEF, and mitral valve regurgitation. Patients with RBBB presented overt signs of congestive HF and depressed right ventricular motion. The LAFB group presented intermediate clinical characteristics, and patients with no IVCDs were more often women with less enlarged left ventricles and less depressed LVEF. Death occurred in 332 patients (interannual mortality = 10.8%): cardiovascular in 257, extravascular in 61, and of unknown origin in 14 patients. Cardiac death occurred in 230 (pump failure in 171 and sudden death in 59). An adjusted Cox model showed higher risk of cardiac death and pump failure death in the LBBB and RBBB than in the LAFB and the no IVCD groups. LBBB and RBBB are associated with different clinical profiles and both are independent predictors of increased risk of cardiac death in patients with HF. A more favourable prognosis was observed in patients with LAFB and in those free of IVCDs. Further research in HF patients with RBBB is warranted

Resistencia natural a los venenos de serpientes

ResumenLa resistencia natural de algunos animales a los venenos de serpientes se ha logrado demostrar en el suero sangu&iacute;neo de mamiferos (Zarigueyas, erizos, mangostas) y de serpientes. En este art&iacute;culo se presenta el estado actual del conocimiento acerca de estas prote&iacute;nas que no son anticuerpos, los m&eacute;todos de caracterizaci&oacute;n y los mecanismos de acci&oacute;n de las mismas.Palabras clave: Venenos de serpientes, Hemorragias, Neurotoxinas, Miotoxinas, Resistencia natural

Los escorpiones: aspectos ecológicos, biológicos y toxinológicos

ResumenLos escorpiones son artr&oacute;podos quelicerados distribuidos en las regiones tropicales y subtropicales del mundo. Su veneno es una mezcla bioqu&iacute;mica compleja, formada principalmente por proteinas neurot&oacute;xicas de bajo peso molecular que ejercen su acci&oacute;n sobre los canales i&oacute;nicos, ocasionando efectos nocivos en sus victimas.Palabras clave: Escorpiones, tox&iacute;nas, canales i&oacute;nicos