Alteraciones hemostáticas provocadas por el veneno de la culebra mapanare (Porthidium lansbergii hutmanni) en pacientes venezolanos / Haemostatic alterations caused by the venom of Lansberg's hognosed pitviper (Porthidium lansbergii hutmanni) in Venezuelan patients

Objective: to describe the haemostatic characteristics of the venom as well as the potency appraisal of the polyvalent antiophidic serum against haemotoxicity from Porthidium lansbergii hutmani experimental envenomation. Methods: Evaluation was performed of the venom's lethality, haemorrhagic activity, effects on coagulation and platelet aggregation, proteolytic activity, and neutralization by the commercial antivenom available in the country. Results: Several components with haemostatic activities were found in Porthidium l. hutmanni venom when a study of fibrinogenolytic, haemorrhagic and proteolytic activities was conducted of a pool of P.l.h venom. Porthidium l. hutmanni venom lacked the coagulant and defibrinating activities that are characteristic of bothropic venoms. Porthidium l. hutmanni venom showed very high haemorrhagic and anticoagulant activities. These findings could be related to the presence of multiple metalloproteases, which was evidenced in this study, and also the possible presence of phospholipases or other anticoagulant activity proteins that were not defined here. They inhibited platelet aggregation, suggesting that the venom had some proteins with marked effects on haemostasis. The commercial antivenom proved to be of little effectiveness in neutralizing the crude venom haemorrhagic activity. Conclusions: These toxins cause many physiopathological alterations in bitten patients, creating a clinical picture characterized by oedema, local and systemic haemorrhages, and even necrosis, comparable to that seen in bothropic envenomation. Porthidium l. hutmanni venom has no in vitro procoagulant activity, typical of bothropic venoms, suggesting there are variances in its protein conformation. Porthidium l. hutmanni venom is used for horse immunization. However, in order to preserve the patient's life, it is necessary to improve the immunization process to produce antivenom containing high avidity and specificity antibodies against the major toxins present in this venom. Porthidium l. hutmanni venom has demonstrated being a venom with high lethal, haemorrhagic, proteolytic and procoagulant activities, whose description will have enormous utility among clinicians who deal with these accidents in its geographical distribution areas(AU)

Objetivo: Describir las características hemostáticas del veneno y evaluar la potencia del suero polivalente antiofídico contra la hemotoxicidad provocada por el envenenamiento experimental por Porthidium lansbergii hutmanni. Métodos: Se realizó una evaluación de la letalidad, actividad hemorrágica, efectos en la coagulación y agregación plaquetaria, actividad proteolítica y neutralización por el antiveneno disponible comercialmente en el país. Resultados: Se encontraron varios componentes con actividad hemostática en el veneno de Porthidium l. hutmanni al realizarse un estudio de la actividad fibrinogenolítica, hemorrágica y proteolítica de una muestra de veneno de Porthidium l. hutmanni. El veneno de Porthidium l. hutmanni no mostró la actividad coagulante o defibrinante característica de los venenos botrópicos. El veneno de Porthidium l. hutmanni mostró una elevada actividad hemorrágica y anticoagulante. Estos resultados podrían estar relacionados con la presencia de múltiples metaloproteasas, la que quedó demostrado en el estudio, y también a la posible presencia de fosfolipasas u otras proteínas de actividad anticoagulante que no se definen en el mismo. La inhibición de la agregación plaquetaria sugiere que el veneno contiene algunas proteínas con un marcado efecto sobre la hemostasis. El antiveneno comercial mostró poca efectividad en la neutralización de la actividad hemorrágica del veneno crudo. Conclusiones: Estas toxinas provocan muchas alteraciones fisiopatológicas en las víctimas de mordeduras, creando un cuadro clínico caracterizado por edema, hemorragias locales y sistémicas e incluso necrosis comparable con la que ocurre en el envenenamiento botrópico. El veneno de Porthidium l. hutmanni no tiene la actividad procoagulante in vitro típica de los venenos botrópicos, lo que apunta a variaciones en su conformación proteica. El veneno de Porthidium l. hutmanni de utiliza en la inmunización de los caballos. Sin embargo, para preservar la vida del paciente, es necesario mejorar el proceso de inmunización con vistas a producir un antiveneno que contenga anticuerpos de elevada avidez y especificidad contra las principales toxinas presentes en el veneno. El veneno de Porthidium l. hutmanni ha mostrado ser un veneno de elevada actividad letal, hemorrágica, proteolítica y procoagulante, cuya descripción tendrá una enorme utilidad para los médicos que atienden esos accidentes en sus áreas de distribución geográfica(AU)

Histopathological evaluation in experimental envenomation of dogs with Crotalus durissus terrificus venom

The present work evaluated histopathological aspects in experimental envenomation of dogs with Crotalus durissus terrificus venom. Twenty-eight mixed breed adult dogs were divided into three groups of seven animals each: Group I - only venom; Group II - venom + 50ml antiophidic serum + fluid therapy; Group III - venom + 50ml antiophidic serum + fluid therapy + urine alkalization. Lyophilized venom of Crotalus durissus terrificus was reconstituted in saline solution and inoculated subcutaneously at the dose of 1mg/kg body weight. Three animals of each group were subjected to euthanasia, and their muscular tissue, brain, spleen, kidneys, heart, lungs, stomach, small and large intestines, and popliteal lymph node fragments were collected for histopathological evaluation. There was myonecrosis in the inoculated limb, renal tubular degeneration, lymphoid hyperplasia of spleen, and unspecific reactive hepatitis. These results show the antigenicity and action of the venom on the immune system.

Kinetics of venom and antivenom serum levels, clinical evaluation and therapeutic effectiveness in dogs inoculated with Crotalus durissus terrificus venom

This work evaluated the clinical and therapeutic aspects as well as serum levels of venom and antivenom IgG by enzyme-linked immunosorbent assay (ELISA) in experimental envenomation of dogs with Crotalus durissus terrificus venom. Twenty-eight mixed breed adult dogs were divided into four groups of seven animals each, Group I: only venom; Group II, venom + 50 ml of anti-bothropic-crotalic serum (50mg) + fluid therapy; Group III, venom + 50 ml of anti-bothropic-crotalic serum + fluid therapy + urine alkalination; Group IV, 50 ml of anti-bothropic-crotalic serum. The lyophilized venom of Crotalus durissus terrificus was reconstituted in saline solution and subcutaneously inoculated at the dose of 1mg/kg body weight. The dogs presented clinical signs of local pain, weakness, mandibular ptosis, mydriasis, emesis and salivation. The venom levels detected by ELISA ranged from 0 to 90ng/ml, according to the severity of the clinical signs. Serum antivenom ranged from 0 to 3ug/ml and was detected for up to 138h after treatment. ELISA results showed the effectiveness of the serum therapy for the venom neutralization.

Clinical and hematological alterations in dogs during experimental envenomation with Crotalus durissus terrificus venom and treated with antiophidic serum

The present work aimed to evaluate the clinical and hematological aspects during experimental envenomation by Crotalus durissus terrificus in dogs treated with different antiophidic serum doses. Sixteen dogs were divided into two groups of eight animals each. Group I received 1mg/kg venom subcutaneously and 30mg antiophidic serum intravenously; Group II received 1mg/kg venom subcutaneously and 60mg antiophidic serum intravenously. In the clinical evaluation, we observed ataxia, moderate sedation, dilated pupils, sialorrhea, flaccid paralysis of mandibular muscles, and discreet edema at the site of venom inoculation. Evaluating red and white blood cells, we observed a decrease of hemoglobins, globular volume and erythrocytes, and an increase of plasmatic proteins, leukocytes, neutrophils, monocytes and lymphocytes. Clotting time increased and there was blood incoagulability with return to normal clotting time six hours after antiophidic serum administration. Animals treated with six antiophidic serum flasks had a faster recovery than the animals that received three serum flasks

Alteraçöes renais no envenenamento crotálico experimental (crotalus durissus terrificus): estudo funcional e anatomopatológico / Renal changes in experimental crotalic poisoning. Functional and anatomopathological study

Foram estudadas as alterações funcionais e histopatológicas renais na inoculação da peçonha de Crotalus durissus terrificus em ratos Wistar. A creatinina e a creatino-fosfoquinase mostraram elevações e a histopatologia mostrou necrose tubular aguda (NTA) e positividade à mioglobina. Todos os animais experimentais apresentaram positividade à mioglobina,variando do grau 1(positividade restrita à borda em escova dos túbulos proximais) ao grau 5 (positividade forte na borda em escova e no citoplasma da célula tubular com grande quantidade de cilindros), sendo a positividade mais intensa também no grupo experimental que se utilizou da dose de 0,50 mg/100 gramas de rato. A mioglobina filtrada nos túbulos renais pode lesar o rim, demorando um tempo para se expressar a NTA. Talvez seja o mecanismo pelo qual se explica a correlação negativa enter a NTA e apositividade à mioglobina observada. O escore para mioglobina e os valores encontrados de creatina sanguínea não foi considerado significativo, assim como quando o escore mioglobina é correlacionado com os valoers de CPK. A patogênese da insuficiencia renal aguda (IRA) no empeçonhamento crotálico experimental em ratos Wistar tem implicação multifatorial, sendo a rabdomiólise um dos fatores patogenéticos responsáveis pela insuficiencia renal aguda induzida pela peçonha.

Intraspecific variation in neurotoxic and myotoxic activities of Bothrops neuwiedii venoms

Snake venoms frequently vary in composition. In this work, we compared the neurotoxic and myotoxic activities of 16 lots of Bothrops neuwiedii venoms from different regions of Brazil, using chick biventer cervicis preparations. The neuromuscular blockade varied from 2 per cent to 100 per cent after 120 min incubation with venoms (50µg/ml). In all cases, this blockade was irreversible and concentration-dependent; at low concentrations (10-20 µg/ml), 15 of the 16 venom lots failed to abolish responses to acetylcholine (110µM), but blocked responses to KCI (13.4mM), and induced contracture. At 5-20µg/ml, the most active venom totally blocked twitch-tension without affecting responses to acetylcholine and KCI. Polyacrylamine gel electrophoresis for basic proteins showed that the most active samples contained a band that was absent in the less active venoms. These results indicate that there may be considerable intraspecific variation in the neurotoxic activity of B. ineuwiedii venoms, whereas myotoxic activity is less variable.

Tissue damage caused by Bothrops sp envenoming evaluated by magnetic resonance imaging (MRI)

The objective of this clinical study was to evaluate local tissue damage caused by Bothrops sp envenoming in relation to lesion type and damaged tissues using magnetic resonance imaging (MRI). Fifteen patients bitten by Bothrops snakes were treated at the Emergency Unit of the Tropical Diseases Unit at the University Hospital, Botucatu School of Medicine, UNESP, Säo Paulo State, Brazil. After receiving specific serotherapy, the patients were submitted to MR of the bite site. T1 spin-echo MRI were obtained revealing the following lesions: edema (n=9), edema associated with hemorrhage (n=5), and hemorrhage (n=1). Perimuscular areas (n=6) and subcutaneous tissues (n=5) were the most affected, followed by muscular tissues (n=4). It is important to mention that MRI did not show myonecrosis of the bite site, a widely reported finding in anatomical and histopathological experimental studies.

Tissue necrosis after canine bothropic envenoming: a case report

The authors report a case of bothropic envenoming in a male Cocker Spaniel. The animal was bitten in the ventral thoracic region, receiving treatment 4 hours later. Clinical examination revealed an extensive, painful and area of firm edema, absence of local or systemic hemorrhage, without evident neurological alterations. Clinical diagnosis was mild bothropic envenoming. Treatment consisted of 5 vials of polyvalent snake antivenom, two vials administered intravenously and three subcutaneously.Blood clotting time was always within normal values. Two days after envenoming, the animal showed hyperthermia and received enrofloxacin (5mg/kg/24h) for 10 days and ketoprofen (1mg/kg/24h) for 5 days. Seventy-two hours after envenoming, extensive subcutaneous, muscle fiber, and skin necrosis of approximately 10 cm in diameter was observed. After débridement of necrotic tissues, the area was cleaned with antiseptic solutions. Complete healing was observed 55 days after envenoming. The authors discuss whether heterologous serotherapy is effective in preventing tissue necrosis after bothropic envenoming.

Análisis clínico y epidemiológico de los accidentes por mordeduras de serpientes del gÚnero Bothrops en Venezuela [A clinical and epidemiological analysis of accidental bites by snakes of the genus Bothrops in Venezuela]

Clinical register of 60 patients bitten by Bothrops snake who assisted at Leopoldo Manrique Hospital and the Institute of Tropical Medicine (HLM-IMT) in Caracas during 1996-1997 were analysed. The accident was more frequent in males (45/75). In 32 cases (53.3) the snake was classified and 26 were Bothrops lanceolatus, 4 Bothrops venezuelensis and 2 Bothrops atrox. Anatomic regions more frequent bitten were superior members (40/66.6): hands (36/60), forearm (2/3.3), elbow (1/1.6) and arm (1/1.6). On inferior members (20/33.3): legs (6/10), feet (10/16.7), ankle (2/3.3), and the hip (2:3.3). The most frequent clinical manifestations in moderate and severe cases (33 patient) were pain (100), oedema (98), ecchymosis (76), blisters (20), necrosis (12), abscess (6) bleeding (19), heart failure (1/1.6), renal failure (1/1.6). The blood clotting was evaluated in 60 (100) cases and it was altered in 33 (55) patients. No deaths were recorded.

Efeitos do soro antibotrópico nas alterações hemodinâmicas induzidas em cães pelo veneno de Bothrops moojeni / Effects of bothropic antivenom in the haemodynamics changes induced in dogs by the Bothrops moojeni poison

Para determinar o efeito do soro antibotrópico nas alterações hemodinâmicas utilizou-se 16 cães machos mestiços, sedados e mantidos intubados sob respiração espontânea. O soro antibotrópico foi eficaz para neutralizar a ação hipotensora, bem como evitou a queda do débito cardíaco e elevação da resistência vascular pulmonar, sem elevação da resistência vascular sistêmica, da frequência cardíaca e da pressão em capilar pulmonar nas condições experimentais acima assinaladas.

Actividades hemorrágicas y coagulante del veneno de Bothrops alternatus de Argentina / Haemorrhagic and clotting activities of Argentina B. alternatus venon

Se trabajó con veneno crudo de Bothrops alternatus para determinar sus actividades hemorrágica y coagulante. Para hallar la actividad hemorrágica se inocularon ratones, en forma intradérmica, con diluciones seriadas de veneno, en un volumen de 0,1 ml de solución salina amortiguada con fosfato, pH 7,2. Luego de 2 horas, se sacrificaron con éter y se midió el área hemorrágica. La Dosis Hemorrágica Mínima (DHM) es la cantidad de veneno que produce un área hemorrágica mínima de 10 mm de diámetro, para el veneno de B. alternatus fue de 3,6 µg. El estudio de la Dosis Coagulante Mínima (DCM) se realizó confrontando diluciones seriadas de veneno con plasma humano. La DMC, capaz de coagular el plasma humano en 60 seg, fue de 14,5 µg/ml. Al igual que otras especies del género Bothrops de Latinoamérica, el veneno de B. alternatus de Argentina posee marcada actividad hemorrágica y coagulante

Detection and neutralization of B. jararaca venom in mice

1. Bothrops jararaca venom was detected by ELISA at different times in the skin, muscle, blood, liver, lung, heart, kidney and spleen of mice injected with venom im or id. 2. The results showed that even 10 min after im injection the venom is detected mostly in skin rather than in the muscle of the venom injection site. A small amount of venom was detected in the kidney up to 12 h after im venom injection, and none was detected in tissues of lung, heart, liver or spleen. 3. However, in mice injected id, the venom could be detected in the skin up to 24 h after injection. Local necrosis and haemorrhage could be neutralized by antivenom injected by the id or iv routes only if the antivenom was given a short time after venom injection, even when antivenom is adminsitered in high concentration. 4. In contrast, experiments performed in mice receiving venom id and treated by id or iv routes with antivenom injected at different times after envenoming showed that the effect of venom on blood coagulation could be counteracted by antivenom administered by either route up to 2 h after venom injection 5. We suggest that a feasible amount of antivenom administered id could be given as a first aid measure after a snake bite accident. However, further experimental studies using the id route for antivenom administration are essential to confirm this possibility

Sleep evaluation in human envenomation by south american rattlesnake Crotalus: polysomnography and multiple sleep latency test / Alteraçöes do sono no acidente ofídico (Crotalus): polissonografia e teste das latências múltiplas do sono

ten patients were hospitalized 3-6 h after having been envenomed by South American rattlesnake Crotalus. They were treated with specific serum therapy and developed the usual neurological signs of unir or bilateral ptosis, miastenic facies of Rosenfeld, pupilary diameter changes, extraoculr palsy, difficulty in accomodation, blurred vision, douboe vision, equilibrium impairment, cerebellar gait and decreased deep tendon reflexes. The daytime sleepiness was quantified by means of the Multiple Sleep Latency Test, showing an increase in sleepiness for two weeks after the envenomation. All-night polysomnography showed increase in REM sleep as well as REM density and decrease in REM latency, up to a period of two weeks after envenomation

Estudo clínico-epidemiológico de doentes picados por serpentes venenosas, na regiäo de Botucatu (SP) / Clinical-epidemiological study of the patient pricked by poisonous snakes, in Botucatu region (SP)

De novembro de 1987 a dezembro de 1992 foram avaliados 120 pacientes picados por serpentes venenosas e atendidos na Enfermaria de Doenças Tropicais da Faculdade de Medicina de Botucatú - Unesp. Dos doentes, 96 (80 por cento) foram picados por serpentes do gênero Bothrops e 24 (20 por cento) por Crotalus. A maioria dos acidentes ocorreu nos pacientes do sexo masculino (76,6 por cento), lavradores (60 por cento), com idades entre 16 e 35 anos (47,5 por cento) e os membros inferiores foram os mais acometidos (75,8 por cento). Os meses de maior ocorrência dos acidentes foram fevereiro e novembro/dezembro, respectivamente para os acidentes botrópicos e crotálicos. Houve duas seqüelas nos doentes do grupo Bothrops e as reaçoes alérgicas ocorreram em 12 (12,5 por cento) pacientes do grupo Bothrops e em dois (8,33 por cento) do grupo Crotallus. Os autores salientam a maior prevalência dos acidentes crotálicos na regiao de Botucatu, comparada com outras regioes do país.

Comprometimento respiratorio a acidente ofidico crotalico (Crotalus durissus) / Respiratory compromising secondary to crotalid ophidian accident (Crotalus durissus)

Sao analisados tres pacientes que apresentaram comprometimento da funcao respiratoria apos acidente por Crotalus durissus. As manifestacoes respiratorias surgiram nas primeiras 48 horas apos a picada do ofidio e consistiram de dispneia, taquipneia, uso da musculatura acessoria da respiracao (casos 1 e 2) e batimento das aletas nasais (caso 2). Dois pacientes (casos 1 e 2) apresentaram insuficiencia respiratoria aguda. O diagnostico desta complicacao no caso 1 foi clinico pois o paciente apresentou apneia. O paciente do caso 2, 24 horas apos o acidente ofidico apresentou dificuldade respiratoria intensa e periodos de apneia sendo intubado, permanecendo em respiracao espontanea. Houve agravamento dos sinais clinicos de insuficiencia respiratoria e a determinacao de pH e gases do sangue arterial mostrou em relacao ao exame inicial elevacao da pressao parcial de gas carbonico (40 mmHg para 50,3 mmHg) caracterizando insuficiencia ventilatoria aguda. Ambos foram tratados com emprego de ventilacao artificial mecanica, tendo o paciente do caso 1 permanecido no ventilador durante 33 dias e o do caso 2 durante 15 dias. Ambos desenvolveram insuficiencia renal aguda, necessitaram de dialise peritoneal e recuperaram a funcao renal. A paciente do caso 3, apesar dos sintomas e sinais de comprometimento respiratorio...

The species of green pit viper in Bangkok.

The aims of this study were to delineate the species of Green pit viper and clinical patterns in Bangkok areas. This study was a blind independent comparison. Among 188 Green pit vipers collected only two species, i.e. Trimeresurus alborabris and T. macrops were found. There were no differences in snake sizes and in clinical patterns of snake bite. The majority of the clinical cases (90.1%) was classified as of mild degree of severity and severe envenomation was observed only in T. alborabris victims. The ratio between T. alborabris and T. macrops victims in Bangkok residents was 1.7:1 but the ratio was reversed in Thonburi residents.

Insuficiência renal aguda secundária a acidentes ofídicos botrópico e crotálico: análise de 63 casos / Acute renal insuficiency secondary to ophidian bothropic and crotalic accidents

Sessenta e três pacientes com insuficiência renal aguda secundária a acidente ofídico foram tratados no CTI do Hospital das Clínicas da UFMG. Em 32 pacientes (51%) o acidente foi produzido por serpentes do gênero Bothrops (grupo botrópico) e em 32 pacientes (49%) pela cascavel sul-americana (grupo crotálico). As principais complicaçöes apresentadas pelos pacientes foram a uremia (100%) dos casos), hiperpotassemia (89% dos casos), anemia (78% dos casos), infecçäo urinária (37% dos casos), hiper-hidrataçäo (17% dos casos), parada cardíaca (14% dos casos) e edema agudo dos pulmöes (11% dos casos). Cinco pacientes do grupo crotálico (16%) tiveram insuficiência respiratória aguda atribuída à açäo neurotóxica do veneno,quatro dos quais se recuperaram completamente. Sete pacientes do grupo botrópico (22%) tiveram necrose cortical renal diagnosticada em cinco através da biópsia renal e em dois na necrópsia. Quarenta e cinco pacientes (71%) foram tratados com diálise peritoneal e a hemodiálise foi necessária em dois pacientes, um dos quais havia sido submetido a diálise peritoneal. Em 17 pacientes (27%) o tratamento foi conservador. Cinqüenta e cinco pacientes receberam alta hospitalar, quatro dos quais com insuficiência renal crônica secundária a necrose cortical renal e oito (13%) faleceram. Os óbitos foram atribuídos a edema pulmonar agudo em quatro pacientes, a estado de choque em dois pacientes e a coma e infecçäo respiratória após parada cardíaca em dois pacientes

Rabdomiólise secundária a acidente ofídico crotálica (Crotalus durissus terrificus) / Rhabdomyolysis following Crotalus durissus terrificus snake bite

Relatam-se dois casos de rabdomiólise secundária a envenenamento produzido por Crotalus durissus terrificus. O diagnóstico da rabdomiólise baseou-se na mialgia intensa e generalizada apresentada pelos pacientes e na constataçäo de níveis séricos elevados de CPK, TGO e DHL. A confirmaçäo do diagnóstico foi obtida no caso n§ 2 pela detecçäo de mioglobina no soro através de imunoeletroforese contra soro antimioglobina humana e por biópsia muscular. Esse paciente desenvolveu também, como complicaçäo do envenenamento ofídico, quadro clínico e laboratorial de insuficiência renal aguda. Essa complicaçäo foi atribuida à açäo nefrotóxica e hemolítica do veneno crotálico e à hipotensäo arterial apresentada pelo paciente, näo se afastando a possibilidade de que a rabdomiólise tenha sido um fator contribuinte para a sua instalaçäo. Foram constatadas hipocalcemia, hiperuricemia e hiperfosfatemia grave na fase oligúria da insuficiência renal aguda, alteraçöes peculiares quando essa condiçäo está associada à rabdomiólise