José María Gutiérrez

University of Costa Rica | UCR · Instituto Clodomiro Picado (ICP)

The monocled cobra (Naja kaouthia) is among the most feared snakes in Southeast Asia due to its toxicity, which is predominantly derived from long-chain α-neurotoxins. The only specific treatment for snakebite envenoming is antivenom based on animal-derived polyclonal antibodies. Despite the lifesaving importance of these medicines, major limitatio...

Venom-induced haemorrhage constitutes a severe pathology in snakebite envenomings, especially those inflicted by viperid species. To both explore venom activity accurately and evaluate the efficacy of viperid antivenoms for the neutralisation of haemorrhagic activity it is essential to have available a precise, quantitative tool for empirically det...

Scientific diasporas have been identified as valuable resources to strengthen science, technology, and innovation in their countries of origin. In this context, our paper seeks to contribute by addressing the following research questions: What are the main features of the Costa Rican scientific diaspora, and what policy lessons can be extracted fro...

There are few scientific studies that explore the use of medicinal plants for snakebite envenoming in Central America, although plant-based therapies have been traditionally used in the region. This work reviews the studies conducted in Central America to assess the ability of extracts obtained from plants of local ethnomedical use to inhibit toxic...

Snake venoms are a complex biological mixture of proteins with or without enzymatic activity, peptides, and nucleotides, among other components. It is produced in specialized secretory glands located in the maxillary region, being the result of millions of years of evolution and whose biological functions are defense, immobilization, and digestion...

Platelets play key roles in hemostasis, inflammation, immune response, and tissue repair. Although it is known that viperid snake venoms induce thrombocytopenia and platelet hypoaggregation, the roles of these effects in the overall outcome of envenoming are poorly known. This study aimed to assess the effect of platelet depletion on several toxic...

Availability and accessibility of safe and effective antivenoms are key elements for the successful treatment of snakebite envenoming (SBE). This study provides a preliminary analysis on the way antivenoms are managed by the public health system in Costa Rica and on the role played by pharmacists in the overall management of antivenoms. This was an...

Adjuvant emulsions are widely used to enhance the antibody response in animals used as immunoglobulin source to produce snake antivenoms. We tested the performance of four commercial emulsion adjuvants (Montanide, Freund, Carbigen, and Emulsigen-D) and an experimental adjuvant (QH-769) in the antibody response of horses towards venoms of the Africa...

Snakebite envenoming was reintroduced as a Category A Neglected Tropical Disease by the World Health Organization in 2017. Since then, increased attention has been directed towards this affliction and towards the development of a deeper understanding of how snake venoms exert their toxic effects and how antivenoms can counter them. However, most of...

Resumen: Se analizan los retos que tienen las universidades públicas latinoamericanas. Estas instituciones deben mantener incólume su ethos, centrado en su carácter público y democrático, su autonomía y búsqueda permanente de la excelencia académica y el bien común. Al mismo tiempo, deben analizar críticamente sus acciones, y efectuar las transform...

Longitudinal metabolomics and lipidomics analyses were carried out on the blood plasma of mice injected intramuscularly with venoms of the viperid species Bothrops asper or Daboia russelii. Blood samples were collected 1, 3, 6, and 24 h after venom injection, and a control group of non-envenomed mice was included. Significant perturbations in metab...

Background Snakebite envenomation exerts a heavy toll in sub-Saharan Africa. The design and production of effective polyspecific antivenoms for this region demand a better understanding of the immunological characteristics of the different venoms from the most medically important snakes, to select the most appropriate venom combinations for generat...

Venom-induced haemorrhage constitutes a severe pathology in snakebite envenomings, especially those inflicted by viperid species. In order to both explore venom compositions accurately, and evaluate the efficacy of viperid antivenoms for the neutralisation of haemorrhagic activity it is essential to have available a precise, quantitative tool for e...

Snake envenoming is a major but neglected human disease in tropical and subtropical regions. Among venomous snakes in the Americas, coral snakes of the genus Micrurus are particularly dangerous because they cause a peripheral neuroparalysis that can persist for many days or, in severe cases, progress to death. Ventilatory support and the use of sna...

Snakebite envenoming continues to claim many lives across the globe, necessitating the development of improved therapies. To this end, human monoclonal antibodies may possess advantages over current plasma-derived antivenoms by offering superior safety and improved neutralization capacity. However, as new antivenom products may need to be polyvalen...

Morbidity from snakebite envenoming affects approximately 400,000 people annually. Tissue damage at the bite-site often leaves victims with catastrophic life-long injuries and is largely untreatable by currently available antivenoms. Repurposing small molecule drugs that inhibit specific snake venom toxins offers a potential new treatment strategy...

The venom of the South American rattlesnake Crotalus durissus terrificus causes an irreversible neuromuscular blockade in isolated preparations due to action of the presynaptically-acting heterodimeric phospholipase A2 (PLA2) crotoxin. Some populations of this subspecies contain, in addition to crotoxin, the toxin crotamine, which acts directly on...

Viperid snakebite envenoming is often characterized by a venom-induced consumption coagulopathy due to the procoagulant effect of venom components, resulting in the alteration of clotting laboratory tests. There is a growing trend to use rotational thromboelastometry in the assessment of clotting disturbances in a variety of pathologies, although i...

Many snake venom toxins cause local tissue damage in prey and victims, which constitutes an important pathology that is challenging to treat with existing antivenoms. One of the notorious toxins that causes such effects is myotoxin II present in the venom of the Central and Northern South American viper, Bothrops asper. This Lys49 PLA2 homologue is...

The foreseen global changes of the next decades will modify human and livestock interactions with venomous animals throughout the planet. Advancing the knowledge about the distribution of venomous animal species and their possible impact in humans and livestock will be essential not only to prevent and treat envenomings but also to conserve the pla...

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 experimen...

Coralsnakes belong to the family Elapidae and possess venoms which are lethal to humans and can be grouped based on the predominance of either three finger toxins (3FTxs) or phospholipases A2 (PLA2s). A proteomic and toxicological analysis of the venom of the coralsnake Micrurus yatesi was performed. This species, distributed in southeastern Costa...

Snakes are reptiles of great biomedical significance. The accurate identification of snakes is particularly important for healthcare workers to diagnose and treat victims of snakebite envenoming. Further, snake identification is vital for the general population, especially to those who live in areas of high snakebite incidence. Owing to the great d...

The lethality neutralization assay in mice is the gold standard for the evaluation of the preclinical efficacy and specification fulfillment of snake antivenoms. However, owing to the animal suffering involved, this assay is a candidate to be replaced by in vitro alternatives or, at least, improved by the reduction of the number of animals used per...

Ethnopharmacological relevance Snakebite envenoming is a public health problem of high impact in Central America. Bothrops asper, known as barba amarilla, terciopelo, and equis, is the snake species responsible for most snakebites in Central America. In this region, there is a long-standing tradition on the use of plants in the management of snakeb...

Viperid snake venoms contain a unique family of cytotoxic proteins, the Lys49 PLA2 homologs, which are devoid of enzymatic activity but disrupt the integrity of cell membranes. They are known to induce skeletal muscle damage and are therefore named ‘myotoxins’. Single intact and skinned (devoid of membranes and cytoplasm but with intact sarcomeric...

The monocled cobra ( Naja kaouthia ) is one of the most feared snakes in Southeast Asia. It is a highly dangerous species with a potent venom deriving its toxicity predominantly from abundant long-chain α-neurotoxins. The only specific treatment for snakebite envenoming is antivenom, which is based on animal-derived polyclonal antibodies. Despite t...

SARS-CoV-2 variants of concern show reduced neutralization by vaccine-induced and therapeutic monoclonal antibodies; therefore, treatment alternatives are needed. We tested therapeutic equine polyclonal antibodies (pAbs) that are being assessed in clinical trials in Costa Rica against five globally circulating variants of concern: alpha, beta, epsi...

Instituto Butantan (São Paulo, Brazil) and Instituto Clodomiro Picado (San José, Costa Rica) are public institutions devoted to scientific and technological research, production of antivenoms and other immunobiologicals, and a variety of public health interventions aimed at confronting the problem of snakebite envenoming in their countries and else...

SARS-CoV-2 variants of concern show reduced neutralization by vaccine-induced and therapeutic monoclonal antibodies; therefore, treatment alternatives are needed. We tested therapeutic equine polyclonal antibodies (pAbs) that are being assessed in clinical trials in Costa Rica against five globally circulating variants of concern: alpha, beta, epsi...

Snakebite envenoming is one of the world’s most neglected tropical diseases, each year resulting in tens of thousands of deaths. The only effective treatment for envenoming is antivenom derived from the plasma of animals immunized with snake venom. However, due to its heterologous nature, these antivenoms are associated with adverse reactions. The...

The proteomic, enzymatic, toxicological, and immunogenic profiles of the venom of C. d. pifanorum were studied. It was found that venom of C. d. pifanorum is composed of 63% phospholipases A2 (PLA2s), 13% serine proteinases (SVSPs), 8% bradykinin-potentiating peptides (BPPs), 4% L-amino acid oxidases (LAAOs), 3% metalloproteinases (SVMPs), and othe...

Neurolaena lobata es utilizada tradicionalmente en Centroamérica para tratar la mordedura de serpiente, pero su efectividad para contrarrestar el envenenamiento producido por Bothrops asper ha sido poco estudiada. Se evaluó la capacidad del extracto etanólico de sus hojas para inhibir las actividades proteolítica, fosfolipasa A2 (PLA2; evaluada com...

A global strategy, under the coordination of the World Health Organization, is being unfolded to reduce the impact of snakebite envenoming. One of the pillars of this strategy is to ensure safe and effective treatments. The mainstay in the therapy of snakebite envenoming is the administration of animal-derived antivenoms. In addition, new therapeut...

SARS-CoV-2 variants of concern show reduced neutralization by vaccine-induced and therapeutic monoclonal antibodies; therefore, treatment alternatives are needed. We tested therapeutic equine polyclonal antibodies (pAbs) that are being assessed in clinical trials in Costa Rica against five globally circulating variants of concern: alpha, beta, epsi...

Snakebite envenomation is a public health problem of high impact, particularly for the developing world. Antivenom, that contains whole or protease‐digested immunoglobulin G, purified from the plasma of hyper‐immunized animals (mainly horses), is the mainstay for the treatment of snakebite envenomation. The success of antivenom therapy depends upon...

In the current global emergency due to SARS-CoV-2 outbreak, passive immunotherapy emerges as a promising treatment for COVID-19. Among animal-derived products, equine formulations are still the cornerstone therapy for treating envenomations due to animal bites and stings. Therefore, drawing upon decades of experience in manufacturing snake antiveno...

Snakebite envenoming is a neglected tropical disease that predominantly affects impoverished rural communities in sub-Saharan Africa, Asia, and Latin America. The global efforts to reduce the impact of this disease must consider the local national contexts and, therefore, comparative studies on envenomings in different countries are necessary to id...

Snakebite envenoming is a neglected tropical disease affecting millions of people every year, especially in vulnerable rural populations in the developing world. Viperid snakes cause envenomings characterized by a complex pathophysiology which includes local and systemic hemorrhage due to the action of snake venom metalloproteinases (SVMPs). The pa...

Cobras are the most medically important elapid snakes in Africa. The African genera Naja and Hemachatus include snakes with neurotoxic and cytotoxic venoms, with shared biochemical, toxinological and antigenic characteristics. We have studied the antigenic cross-reactivity of four sub-Saharan Africa cobra venoms against an experimental monospecific...

The toxin composition of snake venoms and, thus, their functional activity, can vary between and within species. Intraspecific venom variation across a species’ geographic range is a major concern for antivenom treatment of envenomations, particularly for countries like French Guiana that lack a locally produced antivenom. Bothrops asper and Bothro...

Convergent evolution provides insights into the selective drivers underlying evolutionary change. Snake venoms, with a direct genetic basis and clearly defined functional phenotype, provide a model system for exploring the repeated evolution of adaptations. While snakes use venom primarily for predation, and venom composition often reflects diet sp...

Skeletal muscle regeneration is impaired after myonecrosis induced by viperid snake venoms, but the mechanisms behind such poor regenerative outcome are not fully understood. This study compared the changes in basement membrane (BM) components in mouse skeletal muscle in two different scenarios of muscle injury: (a) injection of Bothrops asper veno...

There is an urgent need to strengthen the implementation of the 3Rs principle (Replacement, Reduction and Refinement) in the use of experimental animals in toxinological research and in the assessment of the neutralizing efficacy of snake antivenoms. This is a challenging task owing to the inherent complexity of snake venoms. The state of the art o...

Introduction: It is estimated that 2 000 snakebites occur in Panama every year, 70 % of which are inflicted by Bothrops asper. Objective: To determine the biochemical and toxicologic effects and to assess the immunochemical characteristics of a reference pool of B. asper venom representative of Panama. Methods: The reference venom was prepared as...

Snakebite in children can often be severe or potentially fatal, owing to the lower volume of distribution relative to the amount of venom injected, and there is potential for long-term sequelae. In the second of a two paper series, we describe the pathophysiology of snakebite envenoming including the local and systemic effects. We also describe the...

In the current global emergency due to SARS-CoV-2 outbreak, passive immunotherapy emerges as a promising treatment for COVID-19. Among animal-derived products, equine formulations are still the cornerstone therapy for treating envenomations due to animal bites and stings. Therefore, drawing upon decades of experience in manufacturing snake antiveno...

Background: Detection and quantification of snake venom in envenomed patients' blood is important for identifying the species responsible for the bite, determining administration of antivenom, confirming whether sufficient antivenom has been given, detecting recurrence of envenoming, and in forensic investigation. Currently, snake venom detection...

Esta obra didáctica nace con el objetivo de presentar a sus lectores una visión introductoria sobre el fenómeno científico actual, sus orígenes, su contexto costarricense, y posteriormente presentar las principales destrezas generales que involucra la investigación científica y tecnológica. El texto va dirigido especialmente, aunque no exclusivamen...

Snakebite disproportionally affects children living in impoverished rural communities. The WHO has recently reinstated snakebites on its list of Neglected Tropical Diseases and launched a comprehensive Strategy for the Prevention and Control of Snakebite Envenoming. In the first of a two paper series, we describe the epidemiology, socioeconomic imp...

Polymorphonuclear neutrophils are the most abundant leukocytes in the blood and constitute key components of the innate immunity. Upon infection or tissue damage, neutrophils are recruited to tissues, where they exert a variety of effects, such as microbicidal activity, phagocytosis, degranulation, formation of reactive oxygen species (ROS), releas...

Objectives Although devastating acute effects associated with snake envenoming are well described, the long-term sequelae resulting from these envenomings have not been adequately addressed, especially in the paediatric population. The aim of our study is to describe the clinical characteristics among paediatric patients in Costa Rica who developed...

Objetivo: Efectuar un análisis de los logros en Costa Rica en cuanto al problema de los envenenamientos por mordeduras de serpientes, y señalar tareas pendientes para reducir aún más el impacto de esta patología. Metodología: Se efectuó una revisión de bibliografía relacionada con el estudio del envenenamiento ofídico en Costa Rica y con los avanc...

[This corrects the article DOI: 10.1371/journal.pntd.0005969.].