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Platelets support a protective immune response to LCMV by preventing splenic necrosis
(2013) David Loria, Gilbert; Romagnoli, Pablo Alberto; Moseley, Nelson B.; Rucavado Romero,; Altman, John D.
Severe arenaviral infections in humans are characterized by clinical findings common to other viral hemorrhagic fevers (VHFs), including thrombocytopenia, leukopenia, skin and internal organ hemorrhages, high viral replication, splenic necrosis, and death. Host responses, rather than direct damage by the arenaviral replication, account for most of the observed pathology, but it is not known what protective roles platelets may have in each of the manifestations. To address this issue in an animal model, we compared nondepleted (100%), partially depleted (15%), and profoundly (< 2.5%) platelet-depletedmice infected with the mouse arenavirus lymphocytic choriomeningitis virus (LCMV). Here, we describe that systemic bleedings and death were seen only in those animals receiving the stronger depletion treatment. Furthermore, we showed that the nonhemorrhagic but partially platelet-depleted mice were unable to control the viral replication because of generalized splenic necrosis, affecting innate and adaptive immune cells. These data suggest that, by their supportive roles in hemostasis, platelets may be preventing the severe pathology observed in human arenaviral infections.
Neutralización de los efectos locales del veneno de Bothrops asper por un antiveneno polivalente
(1981-12) Gutiérrez Gutierrez, José Maria; Chaves Mora, Fernando A.; Bolaños Herrera, Róger; Cerdas Fallas, Luis; Rojas Umaña, Ermila Maria; Arroyo Gutierrez, Olga; Portilla Brizuela, Elsa
Neutralization of lethality, myonecrosis, hemorrhage and edema induced by Bothrops asper venom in mice was studied using the polyvalent antivenom produced in the Instituto Clodomiro Picado. The neutralizing effect (ed50) on each of these toxic activities varied; the neutralization of lethal and hemorrhagic effects being more effective than the neutralization of myonecrosis and edema. With independent inoculation of venom and antivenom, antivenom was not effective in neutralizing edema-forming activity. The myonecrotic effect was only partially neutralized when serum was given i.v. immediately after envenomation; however, antivenin effectively neutralized the hemorrhagic activity. The ineffectiveness of antivenom in neutralizing edema and myonecrosis could be partially explained by the rapid development of these effects. Hence, the time interval between envenomation and antivenom administration and the route of serum administration both play an important role in the neutralization of local effects.
Intrageneric cross-reactivity of monospecific rabbit antisera against venoms of the medically most important Bitis spp. and Echis spp. African snakes
(2022-08-12) Gómez Arguello, Aarón; Sánchez Brenes, Andrés; Durán Blanco, Gina; Cordero, Daniel; Segura Ruiz, Álvaro; Vargas Arroyo, Mariángela; Solano Centeno, Daniela; Herrera Vega, María; Chaves-Araya, Stephanie; Villalta Arrieta, Mauren; Sánchez Cháves, Melvin; Arguedas Gómez, Mauricio; Díaz Oreiro, Cecilia; Gutiérrez Gutiérrez, José María; León Montero, Guillermo
Snakebite envenomation exerts a heavy toll in sub-Saharan Africa. Antivenom is the only valid therapy for these envenomations. However, owing to the wide variety of snake species and the large variation in venom composition, the selection of the best combination of venoms to generate effective polyclonal antivenoms of wider neutralizing coverage is challenging. In this study, an experimental protocol was developed based on the generation of monospecific antisera in rabbits immunized with venoms of Bitis spp. or Echis spp. from Africa. Cross-reactivity of monospecific antisera was assessed by immunochemical analyses and by neutralization of toxic effects. Results revealed a large extent of intrageneric cross-reactivity by all antisera, with few exceptions. The venoms that generated antisera with the highest cross-reactivity and neutralizing ability among Bitis spp. were those of Bitis gabonica and B. rhinoceros, and of Echis leucogaster in Echis spp. These results provide evidence for the selection of the best combination of venoms for preparing antivenoms of high neutralizing scope within these two medically relevant genera of African viperid species. These results in rabbits must be translated to large animals used in antivenom production to assess whether these predictions are confirmed.
Supporting UX Evaluation with Open Text Word Clustering
(2024-09-25) Díaz Oreiro, Ignacio; López Herrera, Gustavo
This research work proposes using word clustering to identify concepts associated with the user experience (UX) evaluation of a version of the standardized User Experience Questionnaire (UEQ), where the usual written of responses is replaced by input through a voice interface. The clusters were made from a Word2vec model of word embeddings that was built based on sentences contributed by participants who evaluated the implementation of the voice interface, using traditional quantitative questionnaires and which they complemented with open text comments. The results show clusters around keywords such as ’assistant’, ’understand’, ’response’ and ’survey’, which allow the identification of words associated with both the voice implementation and the UEQ questionnaire itself, and provide information about attitudes researchers could investigate in more detail about the assistant implemented, for example in a subsequent evaluation to be carried out through a focus group or semi-structured interviews.
Individual and mixture effect of selected high-hazard pharmaceuticals on aquatic primary producers
(2025-04-27) Montiel Mora, José Rolando; Lizano Fallas, Verónica; Méndez Rivera, Michael; Marín González, Alexandra; Cambronero Heinrichs, Juan Carlos; Rodríguez Rodríguez, Carlos E.
The extensive use of pharmaceuticals has led to their occurrence in surface waters due to insufficient treatment processes for their removal. Their environmental impact remains largely unexplored for certain trophic levels, particularly plants and algae. Pharmaceuticals often occur in mixtures with other pollutants, highlighting the need for comprehensive toxicological ssessments that evaluate their combined interactions. This study evaluated the acute toxicity of four high-hazard pharmaceuticals —diphenhydramine, fluoxetine, ketoprofen, and trimethoprim— and their binary mixtures, on the green microalgae Raphidocelis subcapitata and the aquatic macrophyte Lemna gibba. For individual compounds, R. subcapitata growth rate was inhibited in all cases, with fluoxetine, ketoprofen and diphenhydramine exhibiting moderate toxicity (EC 50 = 0.34, 0.14, and 4.88 mg/L, respectively), while trimethoprim showed low toxicity (EC 50 = 332.35 mg/L). Similar trends were observed in L. gibba, except for diphenhydramine, which also showed low toxicity (EC 50 = 26.57 mg/L). Binary mixtures demonstrated a synergistic interaction towards the microalgae in the presence of ketoprofen, except ketoprofen-trimethoprim combination (antagonism, p < 0.0001). In contrast, most interactions in L. gibba exhibited antagonism, except ketoprofen-fluoxetine (synergism, p = 0.0042). Differences were observed between the two model organisms for individual compounds and mixtures. No correlation was found between L. gibba experimental data and QSAR predictions derived from R. subcapitata. Our results highlight the need for: i. further studies including mixtures of relevant pharmaceuticals; ii. caution in the use of predictive models or extrapolation between taxa; and iii. the inclusion of fluoxetine and ketoprofen as priority compounds in future risk assessments.