Negativización de carga viral en pacientes positivos persistentes SARS-CoV-2 y uso de plasma de convalecientes / Negative viral load in persistent positive SARS-CoV-2 patients and use of convalescent plasma

No existe medicación específica contra el SARS-CoV-2 y el tratamiento consiste fundamentalmente en medidas de soporte. La transfusión de plasma de convalecientes consiste en administrar pasivamente anticuerpos policlonales, que generan una respuesta inmune inmediata y disminuyen la carga viral. El objetivo del estudio fue describir la estadía hospitalaria y negativización de reacción en cadena de la polimerasa en tiempo real en pacientes positivos persistentes con el uso de plasma de convalecientes. Se realizó un estudio descriptivo transversal, prospectivo, en 8 pacientes positivos persistentes que recibieron dicho plasma, en el Hospital Universitario Clínico Quirúrgico «Cmdte. Manuel Fajardo» de septiembre a noviembre de 2020. El mayor por ciento de casos necesitó una dosis de plasma de convalecientes para negativizar el PCR-TR. La estadía hospitalaria más frecuente fue de 14 a 19 días, el 62,50 % de los pacientes, 24 horas después de administrada la última dosis de este plasma, negativizó el RCP-TR evolutivo.

There is no specific medication against SARS-CoV-2 and the treatment consists mainly of supportive measures. Convalescent plasma transfusion consists of passively administered polyclonal antibodies, which generate an immediate immune response and decrease viral load. The objective of the study was to describe hospital stay and real-time polymerase chain reaction negativization in persistently positive patients with the use of convalescent plasma. A prospective, cross-sectional and descriptive study was carried out in 8 persistently positive patients who received such plasma at "Cmdte. Manuel Fajardo" Clinical and Surgical University Hospital from September to November 2020. The highest percentage of cases required a dose of convalescent plasma to make the RT-PCR negative. The most frequent hospital stay was from 14 to 19 days; 62.50% of the patients had a negative evolutionary RT-PCR, 24 hours after administering the last dose of this plasma.

Neutralización del virus SARS-CoV-2 (linaje B.1.1) por suero hiperinmune de llama (Lama glama) en cultivo de células Vero / Neutralization of SARS-CoV-2 (lineage B.1.1) by hyperimmune llama (Lama glama) serum in Vero cell culture

Objetivo. Evaluar la respuesta serológica de anticuerpos de una llama (Lama glama) a la inmunización del virus SARS-CoV-2 (linaje B.1.1) y la capacidad neutralizante del suero de llama hiperinmune frente al virus SARS-CoV-2 (linaje B.1.1) en células Vero. Materiales y métodos. Se inmunizó una llama con el virus SARS-CoV-2 inactivado (Linaje B.1.1) y se analizaron muestras de suero para evaluar el nivel de anticuerpos mediante ELISA, así como la reactividad a antígenos de SARS-CoV-2 mediante Western Blot. Además, se evaluó la neutralización viral en cultivos celulares por la Prueba de Neutralización por Reducción de Placas (PRNT, por sus siglas en inglés). Resultados. Se observó un aumento en la serorreactividad en la llama inmunizada desde la semana 4 en adelante. Los títulos de anticuerpos fueron más elevados en el séptimo refuerzo de inmunización. Los resultados de Western Blot confirmaron los hallazgos positivos del ELISA, y los anticuerpos del suero inmune reconocieron varias proteínas virales. El ensayo de neutralización (PRNT) mostró una neutralización viral visible, concordante con los resultados de ELISA y Western Blot. Conclusiones. Los hallazgos sugieren que el suero hiperinmune de llama podría constituir una fuente de anticuerpos terapéuticos contra las infecciones por el virus SARS-CoV-2 (linaje B.1.1) y que deberá ser evaluado en estudios posteriores.

Objective. To evaluate the serological antibody response of a llama (Lama glama) to SARS-CoV-2 (B.1.1 lineage) immunization and the neutralizing capacity of hyperimmune llama serum against SARS-CoV-2 virus (B.1.1 lineage) in Vero cells. Materials and methods. A llama was immunized with inactivated SARS-CoV-2 (B.1.1 lineage). Serum samples were analyzed to evaluate the level of antibodies by ELISA, as well as reactivity to SARS-CoV-2 antigens by Western Blot. In addition, viral neutralization in cell cultures was assessed by the Plate Reduction Neutralization Test (PRNT). Results . Seroreactivity increased in the immunized llama from week 4 onwards. Antibody titers were the highest after the seventh immunization booster. Western blot results confirmed the positive ELISA findings, and immune serum antibodies recognized several viral proteins. The neutralization assay (PRNT) showed visible viral neutralization, which was in accordance with the ELISA and Western Blot results. Conclusions. The findings suggest that hyperimmune llama serum could constitute a source of therapeutic antibodies against SARS-CoV-2 infections (lineage B.1.1), and should be studied in further research.

Convalescent Plasma Infusion doesnot Appear to Change the Prognosis in Italian Patients Hospitalized with Sars-Cov-2 Pneumonia

Aims:This case-control prospective study aimed to describe the effects of COVID convalescent plasma (CCP) on late mortality in hospitalized patients with coronavirus disease 2019 (COVID-19) pneumonia. StudyDesign:In this study were enrolled 214 consecutive patients with moderate to severe COVID-19 pneumonia hospitalized during the fourth trimester of 2020 in Venice Prefecture (North-East Italy). admitted to COVID-19 Hospitals of our district were enrolled.Methodology: Confirmation of SARS-CoV-2 infection was made through reverse transcription-polymerase chain reaction test in nasopharyngeal swabs. The severity of each patient’s clinical condition was determined considering the Berlin scoreradiological findings and ventilatory data. Clinical data, risk factors and comorbidity, laboratory test reports and imaging diagnosis of all patients were recorded at hospitalization. In Italy, during the fourth trimester 2020 standard therapy for COVID-19 Pneumoniawas: NSAIDs, ventilator support, LMWH, steroids, antibiotics and antiviral drugs; 108 patients received standard therapy alone and 106 received standard therapy in combination with CCP. The endpoint was mortality at 30 days.Results:Patients series were comparable for gender, age, comorbidity and risk factors, Berlin score, PaO2/FiO2. Data concerning radiological findings and data concerning ventilatory support suggested a higher severity of patients treated with standard therapy plus CCP.Mortality rateat 30 days was 30.6% among subjects treated with standard therapy versus 30.2% among subjects treated with standard therapy plus CCP. The mortality observed in the two groups did not differ significantly. In the present study, however, we observed a higher mortality than reported in the literature. This result may be attributable to the greater severity of the patients considered.Conclusions:This case-control prospective study showed that in a cohort of hospitalized patients suffering from severe 19 pneumonia, the addition of CCP to the standard therapy did not impact the mortality rate at 30 days. However, we believe that further studies are needed to evaluate the effectiveness of convalescent plasma therapy.

Retrospective analysis on efficacy of convalescent plasma in acute respiratory distress syndrome due to COVID-19

ABSTRACT BACKGROUND: Coronavirus disease 2019 (COVID-19) is an ongoing global health threat. However, currently, no standard therapy has been approved for the disease. OBJECTIVES: To evaluate the clinical effectiveness of convalescent plasma (CP) in patients with acute respiratory distress syndrome (ARDS) due to COVID-19. DESIGN AND SETTING: Retrospective study conducted at Kayseri City Education and Research Hospital, Kayseri, Turkey. METHODS: The case group consisted of adult patients (> 18 years) with ARDS due to COVID-19 who received CP in combination with antiviral and supportive treatment. These patients were compared with others who only received antiviral and supportive treatment. RESULTS: During the study period, a total of 30 patients with ARDS due to COVID-19 were included. Eleven patients (36%) received CP in combination with antiviral and supportive treatment, whereas nineteen patients (64%) in the control group only received antiviral and supportive treatment. On admission, the median age, demographic and clinical data and initial laboratory test results were similar between the groups (P > 0.05). On the 14th day of treatment, the laboratory values remained similar between the groups (P > 0.05). The mortality rates were not significantly different between the groups. CONCLUSION: CP treatment did not affect mortality or lead to clinical improvement for COVID-19 patients with ARDS.

Efectos del tratamiento con plasma de convaleciente con COVID-19 Revisión sistemática y metaanálisis / Effects of convalescent plasma treatment in patients with COVID-19: systematic review and meta-analysis

INTRODUCCIÓN: Se ha sugerido que el tratamiento con plasma de convaleciente en la enfermedad por coronavirus (COVID-19) mejora la evolución clínica en los casos moderados a graves. Este estudio fue diseñado para evaluar los efectos de este tratamiento en comparación con el tratamiento estándar o placebo en la mortalidad, el ingreso a asistencia ventilatoria mecánica y otros desenlaces críticos en personas hospitalizados con COVID-19 moderada a grave. MÉTODOS: Se siguieron los lineamientos PRISMA para la realización de una revisión sistemática. Se realizó una búsqueda sistemática en la plataforma L·OVE (Living OVerview of Evidence) de COVID-19 hasta el 15 de enero de 2021. Se incluyeron ensayos clínicos en los cuales se estudiaron personas con COVID-19 moderada, grave o crítica. La certeza de la evidencia se analizó mediante el enfoque de evaluación, desarrollo y evaluación de recomendaciones (GRADE, por su sigla en inglés). RESULTADOS: Se identificaron 10 ensayos controlados aleatorizados que incluyeron 11 854 pacientes, en los que se comparó el tratamiento con plasma de convaleciente y las medidas estándares de cuidado o placebo en pacientes con COVID-19. Estos no mostraron diferencias significativas sobre la mortalidad (riesgo relativo: 1,02; intervalo de confianza del 95%: 0,94-1,12). Podría producir un aumento marginal en el ingreso a ventilación mecánica y de los eventos adversos graves. DISCUSION: La evidencia actual muestra que el uso de plasma de convaleciente no tiene efecto en desenlaces críticos en pacientes con COVID-19 moderada o grave.

INTRODUCTION: It has been suggested that treatment with convalescent plasma in coronavirus disease (COVID-19) improves the clinical course in moderate to severe cases. This study was designed to evaluate the effects of this treatment compared to standard treatment or placebo on mortality, admission to mechanical ventilation, and other critical outcomes in people hospitalized with moderate to severe COVID-19. METHODS: The PRISMA guidelines were followed to carry out a systematic review. A systematic search was carried out on the L·OVE (Living OVerview of Evidence) platform for COVID-19 until January 15, 2021. Clinical trials were included in which people with moderate, severe or critical COVID-19 were studied. The certainty of the evidence was analyzed using the recommendation evaluation, development and evaluation (GRADE) approach. RESULTS: We identified 10 randomized controlled trials involving 11 854 patients in which convalescent plasma treatment and standard measures of care or placebo were compared in patients with COVID-19. These did not show significant differences on mortality (relative risk: 1.02; 95% confidence interval: 0.94-1.12). It could produce a marginal increase in admission to mechanical ventilation and serious adverse events. DISCUSSION: Current evidence shows that the use of convalescent plasma has no effect on critical outcomes in patients with moderate or severe COVID-19

Sueros antiofídicos en colombia: análisis de la producción, abastecimiento y recomendaciones para el mejoramiento de la red de producción / Anti-ophidic sera in colombia: analysis of production, supply, and recommendations for the improvement of the production network

RESUMEN La ofidiotoxicosis o accidente ofídico es un evento frecuente en Colombia. En el país hay dos familias de serpientes de importancia clínica y epidemiológica, las víboras y las corales. Para el tratamiento de la ofidiotoxicosis es obligatoria la utilización de la terapia antivenenosa; los sueros son fabricados a partir de inmunoglobulinas de caballo, estos productos a pesar de que fueron descubiertos hace más de 100 años todavía hoy están en constante cambio. Hoy su industria requiere ser altamente tecnificada, con procesos de eficacia, seguridad y con altos estándares de calidad en Colombia. Los sueros antiofídicos no son productos químico-farmacéuticos, son biológicos, por lo tanto no se caracterizan por su composición química sino por sus propiedades terapéuticas, estos se clasifican en monovalentes y polivalentes, que según su composición física permite neutralizar diferentes tipos de venenos. En el país existen dos productores nacionales (Instituto Nacional de Salud y Laboratorios Probiol) y uno importado de México (Bioclon); la capacidad neutralizante y calidad varía según su composición y proceso de fabricación asociado a la cantidad de proteínas y agregados que influenciarán en el tipo y cantidad de reacciones adversas al medicamento. Se pretende contextualizar al lector en el proceso de fabricación, en la problemática de la escasez y calidad de los sueros antiofídicos en Colombia, dando valoración de conceptos y presentando fundamentos teóricos que aporten a esta temática, además de opinar sobre sobre la actual coyuntura por la escasez de este producto en Colombia.

ABSTRACT Ophidiotoxicosis or snake accident is a recurring event in Colombia. There are two snake families of epidemiological and clinical importance in the country, vipers and coral snakes. For the snake poisoning treatment, the use of anti-poisonous therapy is mandatory. The sera are manufactured with horse immunoglobulins. Even though these products were discovered more than 100 years ago, still today are constantly changing. Today its industry in Colombia requires a high technification, with processes of efficiency, safety, and high-quality standards. The anti snake sera are not chemical-pharmaceutical products; they are biological products. Therefore, they are not characterized by their chemical composition, but by their therapeutic properties. They are classified as monovalent and polyvalent that, depending on their physical composition, allow neutralizing different kinds of poisons. There are two domestic producers in Colombia (Instituto Nacional De Salud and Probiol Laboratories), and imports are done with a producer from Mexico (Bioclon). The neutralizing capacity and quality vary depending on their composition and manufacturing process associated with some proteins and aggregates, which will influence the type and number of adverse reactions to the medicine. This article intends to contextualize the reader in the manufacturing process, in the problem of scarcity and quality of anti-snake sera in Colombia, providing a valuation to concepts and presenting theoretical foundations that contribute to this issue, and besides, commenting on the current situation of the country because of the shortage of this product.

Paths to the discovery of antivenom serotherapy in France

The current study presents a descriptive chronological survey of the articles published by Césaire Auguste Phisalix and Albert Calmette on snake poison, with the aim of shedding a light on the areas of research and reasoning followed by these scientists, leading up to their simultaneous discovery of antivenom serotherapy in 1894. The path taken by Phisalix is revealed in 15 articles that demonstrate the motivation of a naturalist and the way he confronted the puzzle of immunity against snake venom. In the case of Calmette, two articles preceded the discovery; microbiology was his theoretical base and the Pasteurian spirit of solving health problems his driving force. These two researchers followed distinct paths, mobilized by different motivations, but produced one single result. It is incontestable that the discovery of antivenom serotherapy was the work of two groups of researchers who deserve equal recognition, but who, in fact, did not receive it. Following the discovery both Calmette and Phisalix returned to their previous motivations. Calmette put the discovery into practice and began to produce antivenom serum in Lille. He came to be generally considered as the sole discoverer of antivenom serotherapy and was the recipient of a number of prestigious prizes. Phisalix, on the other hand, received little recognition and returned to his original interests, devoting himself to research on natural immunity. In Brazil, the discovery of antivenom serum therapy had a profound impact on the work of Vital Brazil Mineiro da Campanha, a researcher known worldwide for his scientific discoveries and for the evidence of the specificity of antivenom serums.

Paths to the discovery of antivenom serotherapy in France

The current study presents a descriptive chronological survey of the articles published by Césaire Auguste Phisalix and Albert Calmette on snake poison, with the aim of shedding a light on the areas of research and reasoning followed by these scientists, leading up to their simultaneous discovery of antivenom serotherapy in 1894. The path taken by Phisalix is revealed in 15 articles that demonstrate the motivation of a naturalist and the way he confronted the puzzle of immunity against snake venom. In the case of Calmette, two articles preceded the discovery; microbiology was his theoretical base and the Pasteurian spirit of solving health problems his driving force. These two researchers followed distinct paths, mobilized by different motivations, but produced one single result. It is incontestable that the discovery of antivenom serotherapy was the work of two groups of researchers who deserve equal recognition, but who, in fact, did not receive it. Following the discovery both Calmette and Phisalix returned to their previous motivations. Calmette put the discovery into practice and began to produce antivenom serum in Lille. He came to be generally considered as the sole discoverer of antivenom serotherapy and was the recipient of a number of prestigious prizes. Phisalix, on the other hand, received little recognition and returned to his original interests, devoting himself to research on natural immunity. In Brazil, the discovery of antivenom serum therapy had a profound impact on the work of Vital Brazil Mineiro da Campanha, a researcher known worldwide for his scientific discoveries and for the evidence of the specificity of antivenom serums.(AU)

Accidents caused by Bothrops and Bothropoides in the State of Paraiba: epidemiological and clinical aspects / Acidentes causados por serpentes dos gêneros Bothrops e Bothropoides no Estado da Paraíba: aspectos clínicos e epidemiológicos

INTRODUCTION: Bothrops and Bothropoides snakes cause 70 percent of the ophidic accidents in Brazil. The species that cause ophidic accidents in State of Paraíba are Bothropoides erythromelas, Bothrops leucurus and Bothropoides neuwiedi. METHODS: This is a prospective and transverse study, following a quantitative approach of accidents involving Bothrops and Bothropoides admitted to the Toxicological Assistance and Information Centers of Campina Grande and João Pessoa (Ceatox-CG and Ceatox-JP), aimed at identifying the epidemiological and clinical profile of such accidents. All of the patients admitted had medical diagnoses and were monitored at Ceatox-CG or Ceatox-JP. RESULTS: The genera Bothrops and Bothropoides caused 91.7 percent of the ophidic accidents reported. Snake bites were frequent in men (75.1 percent), rural workers (65.1 percent), literate individuals (69 percent) between 11 and 20 years-old (21.7 percent), and toes the most common area attacked (52.7 percent). Most (86.6 percent) patients were admitted within 6 hours after the accident/bite, with a predominance of mild cases (64.6 percent). The annual occurrence in Paraíba was 5.5 accidents/100,000 inhabitants and lethality was 0.2 percent. CONCLUSIONS: Positive changes in the profiles of these accidents were verified, such as the non-application of inadequate solutions, including the use of tourniquet, coffee grounds, garlic, suction and/or cutting the bitten area. Moreover, the Itinerant Laboratory project, linked to Paraíba State University in partnership with Ceatox-CG, has contributed positively, providing several cities of the state with information regarding the prevention of accidents involving venomous animals. The local press has also contributed, reporting the educational work developed by the centers.

INTRODUÇÃO: As serpentes Bothrops e Bothropoides são responsáveis por 70 por cento dos acidentes ofídicos ocorridos no Brasil. As espécies causadoras de acidentes na Paraíba são Bothropoides erythromelas, Bothrops leucurus e Bothropoides neuwiedi. MÉTODOS: Tratou-se de um estudo prospectivo e transversal, com abordagem quantitativa dos acidentes botrópicos e botropóidicos atendidos e registrados pelos Centros de Assistência e Informação Toxicológica de Campina Grande e João Pessoa (Ceatox-CG e Ceatox-JP), com o objetivo de conhecer o perfil epidemiológico e clínico deste agravo. Todos os pacientes atendidos tiveram diagnóstico médico e acompanhamento pelos Ceatox CG e JP. RESULTADOS: Os gêneros Bothrops e Bothropoides foram responsáveis por 91,7 por cento dos acidentes ofídicos notificados. Atingindo frequentemente o sexo masculino (75,1 por cento), trabalhadores rurais (65,1 por cento), alfabetizados (69 por cento) e na faixa etária entre 11 a 20 anos (21,7 por cento), os dedos dos pés foram as regiões anatômicas mais acometidas (52,7 por cento). A maioria (86,6 por cento) dos pacientes foi atendida em até 6 horas após o acidente/picada com predominância de casos leves (64,6 por cento). A incidência anual no estado foi 5,5 acidentes/100.000 habitantes e a letalidade 0,2 por cento. CONCLUSÕES: Verificaram-se mudanças positivas no perfil desses acidentes, como a não utilização de medidas consideradas inadequadas (uso de torniquetes, borra de café, alho, incisão com sucção e outras). Além disso, o projeto Laboratório Itinerante, ligado a Universidade Estadual da Paraíba em parceria com o Ceatox-CG, tem contribuído positivamente, levando a várias cidades do estado informações sobre prevenção e tratamento dos acidentes causados por animais peçonhentos. A imprensa local também tem contribuído, divulgando esse trabalho educativo.

Retrospective analysis of post-exposure to human anti-rabies treatment in Botucatu, São Paulo State, Brazil

This analysis aimed to identify characteristics of accidents that would, probably, provoke rabies infection. A total of 14,409 survey questionnaires for surveillance of human rabies from the Brazilian Information System for Disease Notification (SINAN), from 2000 to 2005, were analyzed. Regarding demographics, it was observed that 7,377 (51.5 percent) of the victims were white, 4,458 (30.93 percent) were children and 8,008 (55.58 percent) were males. Urban cases were prevalent (88.10 percent) while dogs were the animals most frequently involved in accidents, in 11,700 cases (81.19 percent). Bites (84.35 percent) and scratches (19.15 percent) were the most prevalent exposure types, and occurred predominantly on victims' extremities (38.79 percent). The prophylactic measure taken in 6,179 cases comprised anti-rabies vaccine; of these victims, 421 (2.92 percent) showed systemic reactions while 693 (4.80 percent) reported no response. The importance of developing awareness in professionals that should correctly report post-exposure immunoprophylaxis cases is emphasized given the high number of individuals who receive this type of treatment annually.

Antivenom reversal of biochemical alterations induced by black scorpion Heterometrus fastigiousus Couzijn venom in mice

In the present study, Heterometrus fastigiousus venom (HFV) was employed as antigen to produce species-specific scorpion antivenom (SAV) in albino mice (NIH) strain. To determine SAV efficacy, it was pre-incubated with 10 LD50 of HFV and then injected subcutaneously into mice. Subsequently, mortality was observed after 24 hours. Minimum effective dose (MED) was 12.5 LD50 of HFV/mL of SAV. SAV effectiveness to reverse HFV-induced biochemical alterations in mice was analyzed by challenge method. Simultaneously, mice received subcutaneously 40% of 24-hour-LD50 of HFV and intravenously SAV. After four hours, changes in serum glucose, free amino acids, uric acids, pyruvic acid, cholesterol, total protein, alkaline phosphatase, acid phosphatase, lactic dehydrogenase and glutamate-pyruvate transaminase enzyme level were determined. Treatment with species-specific SAV resulted in the reversal of HFV-induced biochemical alterations.

Antivenom reversal of biochemical alterations induced by black scorpion Heterometrus fastigiousus Couzijn venom in mice

In the present study, Heterometrus fastigiousus venom (HFV) was employed as antigen to produce species-specific scorpion antivenom (SAV) in albino mice (NIH) strain. To determine SAV efficacy, it was pre-incubated with 10 LD50 of HFV and then injected subcutaneously into mice. Subsequently, mortality was observed after 24 hours. Minimum effective dose (MED) was 12.5 LD50 of HFV/mL of SAV. SAV effectiveness to reverse HFV-induced biochemical alterations in mice was analyzed by challenge method. Simultaneously, mice received subcutaneously 40 percent of 24-hour-LD50 of HFV and intravenously SAV. After four hours, changes in serum glucose, free amino acids, uric acids, pyruvic acid, cholesterol, total protein, alkaline phosphatase, acid phosphatase, lactic dehydrogenase and glutamate-pyruvate transaminase enzyme level were determined. Treatment with species-specific SAV resulted in the reversal of HFV-induced biochemical alterations.(AU)

Investigations on the role of insulin and scorpion antivenom in scorpion envenoming syndrome

Acute myocardiopathy in alloxan treated experimental dogs and rabbits was induced by subcutaneous (SQ) injection of scorpion venom from Mesobuthus tamulus concanesis, Pocock. Envenoming resulted in an initial transient hypertension (180-320 mm Hg.) followed by hypotension. Simultaneous administration of venom and species-specific scorpion antivenom (SAV) prevented hypertension and hypotension. Hypotension did not occur when SAV was given 60 min after envenoming. Blood glucose, triglycerides, cholesterol, amylase, insulin, glucagon, cortisol, hematocrit, mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), platelet count, red blood cell (RBC) count, hemoglobin (Hb), 2,3-diphosphoglycerate (2,3-DPG), and glutathione levels were increased 60 and 90 min after envenoming. Total white blood cell (WBC) count was reduced 60 min and increased 90 min after envenoming. Simultaneous administration of venom and SAV did not alter Hb, MCHC, and packed cell volume (PCV) levels, or ECG, and cardiovascular, biochemical, metabolic, and hormonal changes. Hematological parameters were reversed when SAV was given 30 and 60 min after envenoming. PCV, Hb, and MCHC values returned to normal 120 min after SAV. Alloxan-treated dogs showed increased blood glucose, cholesterol, glucagon, cortisol levels; reduced glycogen content of liver, cardiac and skeletal muscles; and reduced insulin levels and insulin/ glucagon ratio (I/G ratio). Envenoming in the alloxan pre-treated dogs further increased these levels and reduced tissue glycogen content, insulin levels, and I/G ratio. Administration of 4 U of insulin to alloxan pre-treated envenomed rabbits caused a biochemical and clinical improvement and increased glycogen content of all tissues in comparison with the values from those administered with SAV to alloxan pre-treated envenomed animals. SAV administration to envenomed alloxan pre-treated rabbits did not cause clinical or biochemical improvement. Severe scorpion envenoming causes an autonomic storm with a massive release of catecholamines and other counter-regulatory hormones; changes in insulin secretion resulting in fuel energy deficits producing multi-system-organ-failure (MSOF); and death. Administration of either insulin or SAV (through the release of insulin) appears to be the physiological basis for the control of the metabolic support to control the adverse effects triggered by counter-regulatory hormones.