Oxidative stress and changes in hematological and biochemical biomarkers in Crotalus durissus terrificus (South American rattlesnake) venom-induced acute kidney injury in rats / Estrés oxidativo y alteraciones en biomarcadores hematológicos y bioquímicos en lesión renal aguda inducida por el veneno de Crotalus durissus terrificus (cascabel de America del Sur) en ratones

Abstract Acute kidney injury (AKI) is the major cause of mortality following bites by the South American rattlesnake Crotalus durissus terrificus. We investigated the early onset of Crotalus durissus terrificus venom-induced AKI in rats within 2 h of venom injection and its attenuation by antivenom. Several biomarkers were used to monitor AKI in the absence or presence of antivenom. Male Wistar rats were divided into five groups (n=5 each): G1, rats injected with saline (control); G2, rats injected with venom (6 mg kg-1, intraperitoneally) and euthanized after 2 h to evaluate AKI; G3 and G4, rats injected with 0.9% sterile saline or antivenom 2 h after venom, respectively, and monitored until death or up to 24 h post-venom, and G5, rats injected with antivenom alone and monitored for 24 h. Blood, urine and renal tissue samples were collected immediately after death to assess oxidative stress, hematological and biochemical alterations, and renal histological damage. Venom caused AKI within 2 h (G2) that persisted for up to 8.2 ± 1.6 h (G3), as confirmed by increases in blood urea, creatinine, and renal proteinuria; these increases were attenuated by antivenom. There were no changes in blood protein concentrations in G2 and G3, whereas there were increases in blood reduced glutathione, glutathione peroxidase, and plasma TBARS (but not in catalase) that were attenuated to varying extents by antivenom. There were no marked changes in platelets or leukocytes, but an increase in erythrocytes after 8.2 h with venom alone was attenuated by antivenom. Renal glomerular and tubular damage was greatest after 2 h post-venom groups alone was attenuated by antivenom. Renal glomerular and tubular damage was greatest after 2 h post-venom and declined thereafter. Venom caused early-onset AKI, with variable effects on lipid peroxidation and oxidative stress. Antivenom attenuated the AKI, as shown by the decrease in blood urea and the normalization of proteinuria, without protecting against lipid peroxidation.

Resumen La injuria o lesión renal aguda (LRA) es la mayor causa de mortalidad debido a las mordeduras por cascabeles Crotalus durissus terrificus. Se estudió la instalación precoz de LRA, en ratas, inducida por el veneno de Crotalus durissus terrificus después de 2 h de su inoculación y la atenuación por el antiveneno. Se utilizaron diversos biomarcadores para monitorear LRA en ausencia o presencia del antiveneno. Ratas Wistar machos fueron divididos en 5 grupos (n=5 por grupo): G1, ratas inoculadas con solución salina (control); G2, ratas inoculadas con veneno (6 mg kg-1 dosis, vía intraperitoneal), y sacrificadas después de 2 h para evaluar LRA; G3 y G4, ratas inoculadas con 0.9% de solución salina esterilizada o antiveneno luego de 2 h después de inoculado el veneno, respectivamente, y monitoreadas hasta su muerte o hasta 24 h después de inoculado el veneno; y G5, ratas inoculadas con antiveneno solo y monitoreadas durante 24 h. Las muestras de sangre, orina, y tejido renal fueron colectadas inmediatamente después de la muerte de los animales para evaluar estrés oxidativo, alteraciones hematológicas y bioquímicas, y daño histológico renal. El veneno causó LRA dentro de las 2 h (G2) persistiendo durante más de 8,2 ± 1,6 h (G3), estando esto confirmado por el incremento de urea sanguínea, creatinina, y proteinuria renal; estos aumentos disminuyeron con la aplicación del antiveneno. No se observaron alteraciones en las concentraciones de proteínas sanguíneas en G2 y G3, mientras que se encontraron incrementos en glutatión reducido sanguíneo, glutatión peroxidasa y TBARS plasmática (pero no en catalasa), que disminuyeron con la aplicación del antiveneno aunque en diferente grado. No ocurrieron alteraciones marcadas de plaquetas o leucocitos, mientras que el aumento de glóbulos rojos observado luego de 8,2 h de la inoculación con veneno, disminuyó con el antiveneno. El daño renal glomerular y tubular fue más importante luego de 2 h de la inoculación con veneno y posteriormente disminuyó. El veneno causó LRA precoz a las 2 h, con efectos variables sobre la peroxidación lipídica y el estrés oxidativo. El antiveneno redujo el daño renal, conforme lo demostrado por la disminución en la urea sanguínea y por la normalización de la proteinuria, aunque no se observó protección contra la peroxidación lipídica.

Temporal evolution of dermonecrosis in loxoscelism assessed by photodocumentation

ABSTRACT Background: Although loxoscelism (bites by brown spiders of the genus Loxosceles) frequently results in dermonecrosis, no previous clinical reports have provided detailed temporal photodocumentation of the evolution of dermonecrotic lesions in a case series. Methods This was a retrospective cohort study involving a case series of loxoscelism. Only cases of dermonecrosis with photodocumentation of lesion evolution (from admission until complete or almost complete healing) were included. Results: Eight patients (six men, two women; median age, 38 years) fulfilled the inclusion criteria. The bite sites included the thigh (n = 4), forearm (n = 2), abdomen (n = 1), and trunk (n = 1). Time interval between the bite and first contact with our service ranged from 15 to 216 h (median = 29 h). The main clinical manifestations included local erythematous and ischemic violaceous lesions overlying a base of indurated edema (livedoid plaque, 8), local pain (8), exanthema (6), serohemorrhagic vesicles/blisters (5), fever (5), and jaundice (1). Based on a previously established classification, the cases were classified as probable cutaneous-necrotic loxoscelism (CNL, n = 4), presumptive CNL (n = 3), and presumptive cutaneous-hemolytic loxoscelism (n = 1). Seven patients were treated with anti-arachnidic antivenom (AV; median time post-bite = 46 h). Complete lesion healing ranged from 34 to 98 days post-bite (median, 68 days; six patients). None of the patients required reconstructive plastic surgery. Conclusions The sequential photographic documentation showed considerable variation in the process of wound healing, with complete epithelialization requiring up to 3 months after the bite.

Biochemical characterization and cytotoxic effect of the skin secretion from the red-spotted Argentina frog Argenteohyla siemersi (Anura: Hylidae)

Argenteohyla siemersi (red-spotted Argentina frog) is a casque-headed tree frog species belonging to the Hylidae family. This species has a complex combination of anti-predator defense mechanisms that include a highly lethal skin secretion. However, biochemical composition and biological effects of this secretion have not yet been studied. Methods: The A. siemersi skin secretion samples were analyzed by mass spectrometry and chromatographic analysis (MALDI-TOF/MS, RP-HPLC and GC-MS). Proteins were also studied by SDS-PAGE. Among the biological activities evaluated, several enzymatic activities (hemolytic, phospholipase A2, clotting, proteolytic and amidolytic) were assessed. Furthermore, the cytotoxic activity (cytolysis and fluorescence staining) was evaluated on myoblasts of the C2C12 cell line. Results: The MALDI-TOF/MS analysis identified polypeptides and proteins in the aqueous solution of A. siemersi skin secretion. SDS-PAGE revealed the presence of proteins with molecular masses from 15 to 55 kDa. Steroids, but no alkaloids or peptides (less than 5 KDa), were detected using mass spectrometry. Skin secretion revealed the presence of lipids in methanolic extract, as analyzed by CG-MS. This secretion showed hemolytic and phospholipase A2 activities, but was devoid of amidolytic, proteolytic or clotting activities. Moreover, dose-dependent cytotoxicity in cultured C2C12 myoblasts of the skin secretion was demonstrated. Morphological analysis, quantification of lactate dehydrogenase release and fluorescence staining indicated that the cell death triggered by this secretion involved necrosis. Conclusions: Results presented herein evidence the biochemical composition and biological effects of A. siemersi skin secretion and contribute to the knowledge on the defense mechanisms of casque-headed frogs.(AU)

Antidote availability in the municipality of Campinas, São Paulo, Brazil / Disponibilidade de antídotos no município de Campinas, São Paulo

ABSTRACT CONTEXT AND OBJECTIVE: The lack of availability of antidotes in emergency services is a worldwide concern. The aim of the present study was to evaluate the availability of antidotes used for treating poisoning in Campinas (SP). DESIGN AND SETTING: This was a cross-sectional study of emergency services in Campinas, conducted in 2010-2012. METHODS: The availability, amount in stock, place of storage and access time for 26 antidotal treatments was investigated. In the hospitals, the availability of at least one complete treatment for a 70 kg adult over the first 24 hours of admission was evaluated based on stock and access recommendations contained in two international guidelines. RESULTS: 14 out of 17 functioning emergency services participated in the study, comprising pre-hospital services such as the public emergency ambulance service (SAMU; n = 1) and public emergency rooms for admissions lasting ≤ 24 hours (UPAs; n = 3), and 10 hospitals with emergency services. Six antidotes (atropine, sodium bicarbonate, diazepam, Phytomenadione, flumazenil and calcium gluconate) were stocked in all the services, followed by 13 units that also stocked activated charcoal, naloxone and diphenhydramine or biperiden. No service stocked all of the recommended antidotes; only the regional Poison Control Center had stocks close to recommended (22/26 antidotal treatments). The 10 hospitals had almost half of the antidotes for starting treatments, but only one quarter of the antidotes was present with stocks sufficient for providing treatment for 24 hours. CONCLUSION: The stock of antidotes for attending poisoning emergencies in the municipality of Campinas is incomplete and needs to be improved.

RESUMO CONTEXTO E OBJETIVO: A carência de disponibilidade de antídotos nas salas de emergência é uma preocupação mundial. O objetivo foi avaliar a disponibilidade de antídotos usados no tratamento de pacientes intoxicados no município de Campinas (SP). TIPO DE ESTUDO E LOCAL: Trata-se de estudo transversal de serviços de emergência de Campinas, realizado de 2010-2012. MÉTODOS: A disponibilidade, quantidade estocada, local de armazenamento e tempo de acesso a 26 tratamentos antidotais foi investigada. Nos hospitais, foi avaliada também a disponibilidade de pelo menos um tratamento complete para um adulto de 70 kg nas primeiras 24 horas da admissão, com base em recomendações de estoques e acesso contidas em duas diretrizes internacionais. RESULTADOS: 14 dentre 17 serviços de emergência em funcionamento participaram do estudo, que incluiu serviços pré-hospitalares, como o Serviço de Atendimento Móvel de Urgência (SAMU, n = 1) e três Unidades de Pronto Atendimento (UPAs, internação limitada até 24 horas), além de 10 hospitais com emergência. Seis antídotos (atropina, bicarbonate de sódio, diazepam, fitomenadiona, flumazenil e gluconate de cálcio) estavam estocados em todos os serviços, seguidos de 13 que também estocavam carvão ativado, naloxona, difenidramina ou biperideno. Nenhum serviço tinha estoque de todos os antídotos recomendados; somente o Centro de Controle de Intoxicações regional tinha estoque próximo ao perfil recomendado (22/26 opções terapêuticas). Os 10 hospitais tinham quase metade dos antídotos necessários para iniciar tratamento, mas somente um quarto dos antídotos estava em estoques suficientes para oferecer tratamento por 24 horas. CONCLUSÃO: O estoque de antídotos para atendimento de emergências toxicológicas no município de Campinas é incompleto e deve ser melhorado.

Low-intensity laser therapy improves tetanic contractions in mouse anterior tibialis muscle injected with Bothrops jararaca snake venom

Abstract Introduction Envenomation by Bothrops snakes can produce local pain, edema, hemorrhage and myonecrosis. However, standard antivenom therapy is generally ineffective in neutralizing these effects so that alternative methods of treatment have been investigated. In experimental animals, low-level laser therapy (LLLT) attenuates the local effects of Bothrops venoms, but the benefits of LLLT on muscle function after envenomation are unclear. In this study, we examined the influence of LLLT on the contractile activity of mouse skeletal muscle injected with venom from Bothrops jararaca, the principal cause of snakebite in southeastern Brazil. Methods Twenty-seven male mice were used. Mice were injected with venom (40 μg in 50 μl) in the right anterior tibialis muscle, after which the muscle tendon was exposed, connected to an isometric transducer and subjected to a resting tension of 1 g. A bipolar electrode was attached to the tibial nerve for electrical stimulation. The mice were randomly allocated to five groups: A – Control (n = 3), B – Venom 3 h (n = 6), C – Venom 9 h (n = 6), D – Venom + Laser 3 h (n = 6), E – Venom + Laser 9 h (n = 6). Results The two groups that received LLLT post-venom showed improved muscle contraction and contracture in relation to muscle treated with venom alone. Conclusion These results indicate that LLLT can improve muscle function after damage induced by B. jararaca venom.

Effect of low-level laser therapy (GaAlAs - λ660 nm) on muscle function

Introduction:Low-level laser therapy (LLLT) is effective in preventing fatigue and in stimulating the microcirculation and cellular activity. In this study, we examined the effect of LLLT on injured tibial muscle in vivo by assessing muscle function during fatigue.MethodsTwenty-four male mice were used. Each mouse received an injection of sterile 0.9% saline solution (50 µL) in the right tibialis anterior muscle, after which the tendon of the muscle was exposed, connected to an isometric transducer and subjected to a resting tension of 1 g. A bipolar electrode was attached to the tibial nerve for electrical stimulation. The mice were randomly allocated to one of two groups: G1 (control: 3 h – n=8 and 9 h – n=5) and G2 (treated with GaAlAs laser, λ660 nm, 35 mW, 0.6 J, 17 s: 3 h – n=6 and 9 h – n=5).ResultsIn G1 mice, the amplitude of the tetanic contracture in response to induced fatigue remained unchanged during six consecutive tetani. The amplitude of the tetanic contractions in response to electrical stimulation (4-8 mV) was also unchanged. These results indicated muscle intactness in response to the load imposed by tetanus. In G2 mice, there was an increase in the amplitude of contraction after 3 h and 9 h when compared to G1 at 83% tetanus.ConclusionThese results indicate that exposure of muscle to LLLT enhanced the contractile force and increased the resistance to muscle fatigue without causing morphological damage to cellular structures.

Acute liver failure in a term neonate after repeated paracetamol administration / Falencia hepatica aguda en neonato a termino despues de la ingestion de dosis repetidas de paracetamol / Falencia hepatica aguda em neonato de termo apos ingestao de doses repetidas de paracetamol

Objective: Severe hepatotoxicity caused by paracetamol is rare in neonates. We report a case of paracetamol-induced acute liver failure in a term neonate. Case description: A 26-day-old boy was admitted with intestinal bleeding, shock signs, slight liver enlargement, coagulopathy, metabolic acidosis (pH=7.21; bicarbonate: 7.1mEq/L), hypoglycemia (18mg/dL), increased serum aminotransferase activity (AST=4,039IU/L; ALT=1,087IU/L) and hyperbilirubinemia (total: 9.57mg/dL; direct: 6.18mg/dL) after receiving oral paracetamol (10mg/kg/dose every 4 hours) for three consecutive days (total dose around 180mg/kg; serum concentration 36-48 hours after the last dose of 77µg/ mL). Apart from supportive measures, the patient was successfully treated with intravenous N-acetylcysteine infusion during 11 consecutive days, and was discharged on day 34. The follow-up revealed full recovery of clinical and of laboratory findings of hepatic function. Comments: The paracetamol pharmacokinetics and pharmacodynamics in neonates and infants differ substantially from those in older children and adults. Despite the reduced rates of metabolism by the P-450 CYP2E1 enzyme system and the increased ability to synthesize glutathione - which provides greater resistance after overdoses -, it is possible to produce hepatotoxic metabolites (N-acetyl-p-benzoquinone) that cause hepatocellular damage, if glutathione sources are depleted. Paracetamol clearance is reduced and the half-life of elimination is prolonged. Therefore, a particular dosing regimen should be followed due to the toxicity risk of cumulative doses. This report highlights the risk for severe hepatotoxicity in neonates after paracetamol multiple doses for more than two to three days. .

Objetivo: La hepatotoxicidad grave inducida por el paracetamol es muy rara en neonatos. Se relata el caso de un neonato a término que desarrolló falencia hepática aguda después del uso de paracetamol. Descripción del caso: Niño, 26 días, admitido con sangrado intestinal, señales de choque, discreta hepatomegalia, coagulopatía, acidosis metabólica (pH=7,21; bicarbonato: 7,1mEq/L), hipoglucemia (18mg/dL), aumento de las aminotransferasas séricas (AST=4.039UI/L; ALT=1.087UI/L) e hiperbilirrubinemia (total: 9,75mg/dL; directa: 6,18mg/dL), después del uso de paracetamol por vía oral (10mg/kg/dosis a cada cuatro horas) durante tres días consecutivos (dosis alrededor de 180mg/kg; nivel sérico de 36-48 horas después de la última dosis de 77µg/mL). Además de las medidas de soporte, el paciente fue tratado con N-acetilcisteína (infusión intravenosa continua por 11 días consecutivos), recibiendo alta después de 34 días de internación. El seguimiento mostró recuperación clínica y de los parámetros laboratoriales de la función hepática. Comentarios : La farmacocinética y la farmacodinámica del paracetamol en neonatos y lactantes jóvenes (menores de un año) difieren substancialmente de niños más grandes y adultos. A pesar de que las tasas de metabolismo del sistema enzimático P-450 CYP2E1 están reducidas y la capacidad de generar glutatión, aumentada - confiriendo más protección después de superdosis -, existe la posibilidad de producción de metabólitos hepatotóxicos (N-acetil-pbenzoquinoneimina) que determinan lisis celular, caso se agoten las reservas de glutatión. La depuración es reducida y la media vida de la eliminación, alargada, recomendándose posología distinta por el riesgo de toxicidad ...

Objetivo: A hepatoxicidade grave induzida pelo paracetamol é muito rara em neonatos. Relata-se o caso de um neonato de termo que desenvolveu falência hepática aguda após o uso de paracetamol. Descrição do caso: Menino, 26 dias, admitido com sangramento intestinal, sinais de choque, discreta hepatomegalia, coagulopatia, acidose metabólica (pH=7,21; bicarbonato: 7,1mEq/L), hipoglicemia (18mg/dL), aumento das aminotransferases séricas (AST=4.039UI/L; ALT=1.087UI/L) e hiperbilirrubinemia (total: 9,57mg/dL; direta: 6,18mg/dL), após uso de paracetamol via oral (10mg/kg/dose a cada quatro horas) por três dias consecutivos (dose total ao redor de 180mg/kg; nível sérico de 36-48 horas após a última dose de 77µg/mL). Além das medidas de suporte, o paciente foi tratado com N-acetilcisteína (infusão intravenosa contínua por 11 dias consecutivos), recebendo alta após 34 dias de internação. O seguimento mostrou recuperação clínica e dos parâmetros laboratoriais da função hepática. Comentários: A farmacocinética e a farmacodinâmica do paracetamol em neonatos e lactentes jovens (menores de um ano) diferem substancialmente de crianças maiores e adultos. Apesar de as taxas de metabolismo do sistema enzimático P-450 CYP2E1 estarem diminuídas e a capacidade de gerar glutationa, aumentadas - conferindo maior proteção após superdosagens -, existe a possibilidade de produção de metabólitos hepatotóxicos (N-acetil-p-benzoquinoneimina) que determinam lise celular, caso se esgotem as reservas de glutationa. A depuração é diminuída e a meia-vida de eliminação é prolongada, recomendando-se posologia distinta pelo risco de toxicidade de doses cumulativas. O presente relato destaca o risco de hepatotoxicidade grave ...

Purification and characterization of a hyaluronidase from venom of the spider Vitalius dubius (Araneae, Theraphosidae)

Background: Venom hyaluronidase (Hyase) contributes to the diffusion of venom from the inoculation site. In this work, we purified and characterized Hyase from the venom of Vitalius dubius (Araneae, Theraphosidae), a large theraphosid found in southeastern Brazil. Venom obtained by electrical stimulation of adult male and female V. dubius was initially fractionated by gel filtration on a Superdex® 75 column. Active fractions were pooled and applied to a heparin-sepharose affinity column. The proteins were eluted with a linear NaCl gradient. Results: Active fractions were pooled and assessed for purity by SDS-PAGE and RP-HPLC. The physicochemical tests included optimum pH, heat stability, presence of isoforms, neutralization by flavonoids and assessment of commercial antivenoms. Hyase was purified and presented a specific activity of 148 turbidity-reducing units (TRU)/mg (venom: 36 TRU/mg; purification factor of ~4). Hyase displayed a molecular mass of 43 kDa by SDS-PAGE. Zymography in hyaluronic-acid-containing gels indicated an absence of enzyme isoforms. The optimum pH was 4-5, with highest activity at 37°C. Hyase was stable up to 60°C; but its activity was lost at higher temperatures and maintained after several freeze-thaw cycles. The NaCl concentration (up to 1 M) did not influence activity. Hyase had greater action towards hyaluronic acid compared to chondroitin sulfate, and was completely neutralized by polyvalent antiarachnid sera, but not by caterpillar, scorpion or snakes antivenoms. Conclusion: The neutralization by arachnid but not scorpion antivenom indicates that this enzyme shares antigenic epitopes with similar enzymes in other spider venoms. The biochemical properties of this Hyase are comparable to others described.

Presynaptic neuromuscular action of a methanolic extract from the venom of Rhinella schneideri toad

Rhinella schneideri, previously known as Bufo paracnemis, is a common toad in many regions of Brazil. Its venom exerts important cardiovascular effects on humans and other animals. Although this toad venom has been the subject of intense investigations, little is known about its neuromuscular activity. The neurotoxicity of a methanolic extract of R. schneideri venom was tested on mouse phrenic nerve-diaphragm (PND) preparations mounted for conventional twitch tension recording – in response to indirect stimulation – and for electrophysiological measurements.

Presynaptic neuromuscular action of a methanolic extract from the venom of Rhinella schneideri toad

Rhinella schneideri, previously known as Bufo paracnemis, is a common toad in many regions of Brazil. Its venom exerts important cardiovascular effects on humans and other animals. Although this toad venom has been the subject of intense investigations, little is known about its neuromuscular activity. The neurotoxicity of a methanolic extract of R. schneideri venom was tested on mouse phrenic nerve-diaphragm (PND) preparations mounted for conventional twitch tension recording – in response to indirect stimulation – and for electrophysiological measurements.

Coma blisters after poisoning caused by central nervous system depressants: case report including histopathological findings / Bolhas do coma pós-intoxicação por depressores do sistema nervoso central: relato de caso incluindo achados histopatológicos

Blister formation and eccrine sweat gland necrosis is a cutaneous manifestation associated with states of impaired consciousness, most frequently reported after overdoses of central nervous system depressants, particularly phenobarbital. The case of a 45-year-old woman who developed "coma blisters" at six distinct anatomic sites after confirmed (laboratory) phenobarbital poisoning, associated with other central nervous system depressants (clonazepam, promethazine, oxcarbazepine and quetiapine), is presented. A biopsy from the left thumb blister taken on day 4 revealed focal necrosis of the epidermis and necrosis of sweat gland epithelial cells; direct immunofluorescence was strongly positive for IgG in superficial blood vessel walls but negative for IgM, IgA, C3 and C1q. The patient was discharged on day 21 with no sequelae.

Formação de bolhas e necrose de glândula sudoríparas écrinas é uma manifestação cutânea associada com estados de diminuição da consciência, mais frequentemente relatada após superdosagens de depressores do sistema nervoso central, particularmente fenobabital. Relatamos o caso de uma paciente de 45 anos que desenvolveu "bolhas do coma" após tentativa de suicídio por fenobarbital (confirmada laboratorialmente), associada a outros depressores do sistema nervoso central (clonazepam, prometazina, oxcarbazepina e quetiapina). Biópsia da bolha do 1o quirodáctilo esquerdo no 4o dia de internação revelou necrose focal da epiderme e necrose de células epiteliais de glândula sudorípara; a imunofluorescência direta foi fortemente positiva para IgG na parede superficial dos vasos sanguíneos, mas negativa para IgM, IgA, C3 e C1q. A paciente teve alta no 21o dia, sem seqüelas.

Bites by coral snakes (Micrurus spp) in Campinas, State of São Paulo, Southeastern Brazil

As serpentes corais (Micrurus spp.) são as principais representantes dos elapídeos na América do Sul. Todavia, acidentes com essas serpentes são raros. Foram revisados retrospectivamente os prontuários de 11 pacientes mordidos por corais num período de 20 anos. Destes 11 casos, quatro foram casos confirmados por identificação da serpente e sete como casos altamente suspeitos de envenenamento elapídico por apresentarem manifestações neuromusculares indicativas de miastenia aguda. Os casos foram classificados como não envenenados [n = 1, causado por M. lemniscatus, não recebeu antiveneno (AV)], leves (manifestações locais sem miastenia, n = 2, causados por M. frontalis e M. spp.), moderados (miastenia leve, n = 5) e graves (miastenia intensa, n = 3, um causado por M. frontalis). Os principais achados clínicos à admissão foram: parestesia (local, n = 9; generalizada, n = 2), dor local (n = 8), ptose palpebral (n = 8), fraqueza (n = 4), incapacidade de se manter na posição ereta (n = 3). Nenhum paciente desenvolveu insuficiência respiratória. O AV elapídico foi empregado em 10 casos, ocorrendo reações precoces leves em três. Em três pacientes foram administrados anticolinesterásicos, com resposta favorável em dois. Não ocorreram óbitos. A despeito da alta toxicidade dos venenos de Micrurus spp., o prognóstico do envenenamento é bom. Nos casos graves determinados por M. frontalis e M. lemniscatus, cujos venenos atuam pós-sinapticamente, o uso de anticolinesterásicos pode ser considerado caso o AV não seja disponível; caso ocorra um atraso para a sua obtenção; ou nos pacientes que receberam as mais altas doses de AV recomendadas sem melhora da paralisia ou demora na reversão desses sintomas.

Snakebites by Crotalus durissus ssp in children in Campinas, Säo Paulo, Brazil

From January, 1984 to March, 1999, 31 children under 15 y old (ages 1-14 y, median 8 y) were admitted after being bitten by rattlesnakes (Crotalus durissus ssp). One patient was classified as "dry-bite", 3 as mild envenoming, 9 as moderate envenoming and 18 as severe envenoming. Most patients had neuromuscular manifestations, such as palpebral ptosis (27/31), myalgia (23/31) and weakness (20/31). Laboratory tests suggesting rhabdomyolysis included an increase in total blood creatine kinase (CK, 28/29) and lactate dehydrogenase (LDH, 25/25) levels and myoglobinuria (14/15). The main local signs and symptoms were slight edema (20/31) and erythema (19/31). Before antivenom (AV) administration, blood coagulation disorders were observed in 20/25 children that received AV only at our hospital (incoagulable blood in 17/25). AV early reactions were observed in 20 of these 25 cases (9/9 patients not pretreated and 11/16 patients pretreated with hydrocortisone and histamine H1 and H2 antagonists). There were no significant differences in the frequency of patients with AV early reactions between the groups that were and were not pretreated (Fisher's exact test, p = 0.12). Patients admitted less than and more than 6 h after the bite showed the same risk of developing severe envenoming (Fisher's exact test, p = 1). No children of the first group (< 6 h) showed severe complications whereas 3/6 children admitted more than 6 h post-bite developed acute renal failure. Patients bitten in the legs had a higher risk of developing severe envenoming (Fisher's exact test, p = 0.04). There was a significant association between both total CK and LDH blood enzyme levels and severity (p < 0.001 for CK and p < 0.001 for LDH; Mann-Whitney U test). No deaths were recorded

Snakebites by Bothrops spp in children in Campinas, Säo Paulo, Brazil

From January, 1984 to March, 1999, 73 children under 15 y old (ages 1-14 y, median 9 y) were admitted after being bitten by snakes of the genus Bothrops. Twenty-six percent of the children were classified as mild envenoming, 50.7 percent as moderate envenoming and 20.6 percent as severe envenoming. Two patients (2.7 percent) showed no signs of envenoming. Most of the patients presented local manifestations, mainly edema (94.5 percent), pain (94.5 percent) ecchymosis (73.9 percent) and blisters (11 percent). Local and/or systemic bleeding was observed in 28.8 percent of the patients. Before antivenom (AV) administration, blood coagulation disorders were observed in 60.7 percent (incoagulable blood in 39.3 percent) of the 56 children that received AV only in our hospital. AV early reactions, most of which were considered mild, were observed in 44.6 percent of these cases (in 15/30 patients not pretreated and in 10/26 patients pretreated with hydrocortisone and histamine H1 and H2 antagonists). The main clinical complications observed were local infection (15.1 percent), compartment syndrome (4.1 percent), gangrene (1.4 percent) and acute renal failure (1.4 percent). No deaths were recorded. There were no significant differences with regard to severity of envenoming versus the frequency of blood coagulation disorders among the three categories of envenoming (p = 0.75) or in the frequency of patients with AV early reactions between the groups that were and were not pretreated (p = 0.55). The frequency of local infection was significantly greater in severe cases (p < 0.001). Patients admitted more than 6 h after the bite had a higher risk of developing severe envenoming (p = 0.04)

A clinico-epidemiological study of bites by spiders of the genus Phoneutria

From January, 1984 to December, 1996, 422 patients (ages 9 m-99 y, median 29 y) were admitted after being bitten by spiders which were brought and identified as Phoneutria spp. Most of the bites occurred at March and April months (29.2 percent), in the houses (54.5 percent), during the day (76.5 percent), and in the limbs (feet 40.9 percent, hands 34.3 percent). Upon hospital admission, most patients presented only local complaints, mainly pain (92.1 percent) and edema (33.1 percent) and were classified as presenting mild (89.8 percent), moderate (8.5 percent) and severe (0.5 percent) envenomation. Few patients (1.2 percent) did not present signs of envenomation. Severe accidents were only confirmed in two children (9 m, 3 y). Both developed acute pulmonary edema, and the older died 9 h after the accident. Patients more than 70 year-old had a significantly greater (0.05) frequency of moderate envenomations compared to the 10-70-year-old individuals. Proceedings to relief local pain were frequently performed (local anesthesia alone 32.0 percent, local anesthesia plus analgesics 20.6 percent and oral analgesics alone 25.1 percent). Only 2.3 percent of the patients (two cases classified as severe and eight as moderate, eight of them in children) were treated with i.v. antiarachnid antivenom. No antivenom early reaction was observed. In conclusion, accidents involving the genus Phoneutria are common in the region of Campinas, with the highest risk groups being children under 10 years of age and adults over 70 years of age. Cases of serious envenomation are rare (0.5 percent)