Quantificação de citocinas no soro e homogenato da pata na intoxicação experimental com veneno de Bothropoides jararaca em ratos Wistar tratados com soroterapia e Mikania glomerata / Quantification of cytokines in serum and paw homogenate of experimental intoxication for venom of the Bothropoides jararaca in Wistar rats treated with antivenom and Mikania glomerata

O presente estudo teve como objetivo quantificar os níveis de citocinas pró-inflamatórias, entre as quais TNF-α, interleucina-1β (IL-1β), IL-6, e anti-inflamatórias, como IL-10, interferon-γ (INF-γ), bem como comparar o efeito do tratamento convencional com o efeito do tratamento complementado pelo extrato da planta Mikania glomerata, na intoxicação experimental por Bothropoides jararaca. Foram usados ratos Wistar,divididos em três grupos: C - controle, VB - veneno botrópico + soro antiofídico e VBM - veneno botrópico + soro antiofídico + Mikania glomerata. As citocinas foram quantificadas, no soro e no homogenato desses animais, pelo teste ELISA, em três momentos (M1 - 30 minutos, M2 - seis horas e M3 - 24 horas após a inoculação do veneno). Os resultados obtidos evidenciaram que a intoxicação por veneno botrópico estimula principalmente a produção de IL-6 no soro e TNF-α, IL-1β, IL-6 no homogenato da pata de animais experimentalmente intoxicados. O tratamento complementar, com o extrato da planta Mikania glomerata, teve influência principalmente na produção de IL-6, IL-10 e IFN-γ no soro e IL-6, IL-1β e IFN-γ no homogenato. Porém, são necessários novos estudos com o extrato de Mikania glomerata para que se possa entender a ação dessa planta sobre a intoxicação botrópica, bem como verificar qual a melhor via para administrá-lo...

This experiment aimed to quantify the pro-inflammatory cytokine levels, including TNF-α, interleukin-1β (IL-1β) and IL-6 as well as the anti-inflammatory ones such as IL-10 and INF-γ. It was also proposed to compare the effect of the conventional treatment to a treatment in which was added the Mikania glomerata plant in the experimental intoxication using Bothropoides jararaca venom. It was used Wistar rats that were randomly divided into 3 groups: C - control; VB - Bothrops venom + antivenom serum; and VBM - Bothrops venom + antivenom serum + Mikania glomerata. Cytokines were quantified in the serum and paw homogenate using ELISA test in three different moments (M1- 30 minutes, M2- 6 hours and M3- 24 hours after venom injection). The intoxication by Bothropoides jararaca venoms mainly stimulated the production of IL-6 in the serum and TNF-α, IL-1β, IL-6 in paw homogenate of animals experimentally intoxicated. Adjunctive treatment with the extract of the Mikania glomerata plant mainly influenced the production of IL-6, IL-10 and IFN-γ in the serum and IL-6, IL1β and IFN-γ in paw homogenate. Further research is necessary with the extract of Mikania glomerata in order to understand the action of this plant on the Bothropoides poisoning and also to verify the best way to manage it...

Clinical and electrocardiographic evaluation during experimental toad poisoning in dogs

Accidents involving toad poisoning are frequent and dogs are the most common victims; they become poisoned by biting or ingesting a toad. When released in the organism, the venom is absorbed by both the oral mucosa and the digestive tract, initiating its toxic action. The aim of this work was to evaluate the clinical and electrocardiographic aspects of dogs subjected to experimental toad poisoning, as well as their response to treatment with propranolol. Twenty dogs were divided into two groups, a control group (n = 5) and a poisoned group (n = 15). After general anesthesia, the control group received a placebo, while the poisoned group received a venom aliquot through an orogastric tube. Results were tested through multivariate analysis (p < 0.05). The animals in the poisoned group had gastrointestinal symptoms including emesis, intense salivation, hyperemic or congested oral mucosa and pasty diarrhea. Non-responsive mydriasis, nystagmus, depression, stupor, tachypnea, opisthotonus and ataxia were also manifested by 100 percent of the poisoned animals. Affected dogs had an increase in blood pressure, statistically significant throughout study. Five poisoned animals developed ventricular tachycardia and were treated with propranolol (0.5 mg/kg IV). All propranolol-treated animals returned to normal sinus rhythm, which evidences the efficacy of this drug to treat ventricular arrhythmias caused by toad venom.

Necrotic skin lesion in a dog attributed to Loxosceles (brown spider) bite: a case report

Envenomations caused by Loxosceles (brown spider) have been reported throughout the world. Clinical signs associated to bites of these spiders involve dermonecrotic lesions and intense local inflammatory response, besides systemic manifestations such as intravascular hemolysis, thrombocytopenia, disseminated intravascular coagulation and acute renal failure. The present study aimed to report and to describe dermonecrotic lesions probably caused by a Loxosceles envenomation in a four year-old poodle female dog, treated at the Dermatology Service of the Veterinary Hospital of the Veterinary Medicine and Animal Husbandry School, São Paulo State University, Botucatu, Brazil. Initially, the animal presented two skin lesions with blackish aspect that evolved into ulcerative crusts. The owner reported the presence of a brown spider near the place where the animal spent most of the time. Histological examination of lesions revealed necrosis of the epidermis extending to adnexa and panniculi, which is compatible with Loxosceles bite reaction. The animal was treated with systemic antibiotic and local curatives. Lesions healed by second intention in two months.(AU)

Toad poisoning in three dogs: case reports

Toad poisoning is frequent in dogs, but has been infrequently addressed in published case reports and review articles. Dogs can be poisoned when they bite a toad or otherwise ingest the venom. The venom effects manifest soon after the accident, since the toxin is rapidly absorbed by the mucous membrane of the digestive system. Hospital records of three dogs, diagnosed with toad poisoning, were retrospectively reviewed from January 2005 to July 2007. Poisoned dogs may present only local irritation or systemic signs in the gastrointestinal, cardiac and neurological systems. All three cases presented herein had clinical signs of gastrointestinal alterations including vomiting, sialorrhea and diarrhea. Two dogs developed abnormal cardiac rhythm and two exhibited neurological signs. A poisoned animal requires emergency care and symptomatic therapy with intense monitoring of its clinical parameters. Although there have been reports on the low mortality of dogs poisoned by toads, one animal died even after appropriate therapy. The severity of clinical signs and the risk of death must be considered by the veterinarian.

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.

Effects of experimental amitraz intoxication in cats

This work studied the effects of experimental amitraz intoxication in cats. Sixteen cats were randomly divided equally into two groups: amitraz group - animals received 1.5 percent amitraz at 1mg/kg IV; and the control group - animals without amitraz. Physiological parameters from blood, cardiorespiratory system, and sedation indicators were quantified over time up to 360 minutes. Blood profile, urea, creatinine, alananine aminotransferase and aspartate aminotransferase were not affected by amitraz. Sedation, loss of reflexes, hypothermia, bradycardia, bradyarrhythmia, hypotension, bradypnea, mydriasis, besides transitory hyperglycemia, hypoinsulinemia and decrease of cortisol levels were observed in cats experimentally exposed to amitraz. The alpha2-adrenergic effects induced by amitraz intoxication in cats are very similar to the same effects reported in others species, contributing with more information about this type of intoxication to veterinary toxicology

Este trabalho estudou os efeitos da intoxicação experimental por amitraz em 16 gatos, distribuídos, aleatoriamente, em dois grupos: grupo amitraz - animais receberam amitraz a 1,5 por cento na dose de 1,0 mg/kg IV; e grupo controle - animais sem amitraz. Parâmetros fisiológicos sangüíneos, do sistema cardiorespiratório e de sedação foram aferidos até 360min. Perfil sangüíneo, uréia, creatinina, alanina aminotransferase e aspartato aminotransferase não foram afetados pelo amitraz. Sedação, perda de reflexos, hipotermia, bradicardia, bradiarritmias, hipotensão, bradipnéia, midríase, além de transitória hiperglicemia, hipoinsulinemia e diminuição dos níveis de cortisol, foram observados nos gatos experimentalmente expostos ao amitraz. Os efeitos alfa 2-adrenérgicos induzidos pela intoxicação por amitraz em gatos são muito similares aos mesmos efeitos relatados em outras espécies, contribuindo com mais informações dessa intoxicação para a toxicologia veterinária

Biochemical and hematological study of goats envenomed with natural and 60Co-irradiated bothropic venom

Venoms from snakes of the Bothrops genus are proteolytic, coagulant, hemorrhagic and nephrotoxic, causing edema, necrosis, hemorrhage and intense pain at the bite site, besides systemic alterations. Many adjuvants have been added to the venom used in the sensitization of antiserum-producer animals to increase antigenic induction and reduce the envenomation pathological effects. Gamma radiation from 60Co has been used as an attenuating agent of the venoms toxic properties. The main objective was to study, comparatively, clinical and laboratory aspects of goats inoculated with bothropic (Bothrops jararaca) venom, natural and irradiated from a 60Co source. Twelve goats were divided into two groups of six animals: GINV, inoculated with 0.5mg/kg of natural venom; and GIIV, inoculated with 0.5mg/kg of irradiated venom. Blood samples were collected immediately before and one, two, seven, and thirty days after venom injection. Local lesions were daily evaluated. The following exams were carried out: blood tests; biochemical tests of urea, creatinine, creatine kinase (CK), aspartate amino-transferase (AST) and alanine amino-transferase (ALT); clotting time; platelets count; and total serum immunoglobulin measurement. In the conditions of the present experiment, irradiated venom was less aggressive and more immunogenic than natural venom.(AU)

Experimental envenomation with Crotalus durissus terrificus venom in dogs treated with antiophidic serum - part I: clinical evaluation, hematology and myelogram

The present study aimed at evaluating clinical and laboratory aspects during experimental envenomation by Crotalus durissus terrificus in dogs treated with antiophidic serum. Twenty-one dogs were divided into three groups of seven animals each. Group I received 1mg/kg venom (sc); Group II received 1mg/kg venom (sc), 50mg antiophidic serum (iv), and fluid therapy including 0.9 percent NaCl solution (iv); and Group III received 1mg/kg venom (sc), 50mg antiophidic serum (iv), and fluid therapy including 0.9 percent NaCl solution containing sodium bicarbonate diluted to the dose of 4mEq/kg. The clinical signs of ataxia, sedation, flaccid paralysis, mydriasis, eyeball paralysis, mandible ptosis, sialorrhea, vomiting and diarrhea observed in the dogs were very similar to those observed in humans. The decrease in hemoglobin, hematocrit, erythrocyte, platelet and fibrinogen levels, prolongation of clotting time, prothrombin time (PT) and activated partial thromboplastin time (APTT), as well as hypocellularity in the bone marrow characterized anemia, thrombocytopenia and blood incoagulability, as well as hypofibrinogenemia and decreased bone-marrow activity. Important bleeding was not observed. Increased numbers of leukocytes and neutrophils and decreased numbers of lymphocytes and eosinophils characterized an acute inflammatory response and stress caused by generalized pain. The employed antiophidic serum was effective and all animals survived.

Experimental envenomation with Crotalus durissus terrificus venom in dogs treated with antiophidic serum - part II: laboratory aspects, electrocardiogram and histopathology

The present work shows laboratory aspects, electrocardiogram and histopathology results during experimental envenomation by Crotalus durissus terrificus in dogs treated with antiophidic serum. Twenty-one dogs were divided into three groups of seven animals each. Group I received 1mg/kg venom (sc); Group II received 1mg/kg venom (sc), 50mg antiophidic serum (iv) and fluid therapy including 0.9 percent NaCl solution (iv); and Group III received 1mg/kg venom (sc), 50mg antiophidic serum (iv) and fluid therapy including 0.9 percent NaCl solution containing sodium bicarbonate diluted to the dose of 4mEq/kg. Urinalysis showed brown urine, proteinuria, occult blood and myoglobinuria. Respiratory acidosis and hypotension were also observed. At the venom inoculation site, there was discreet edema, popliteal lymph node response, musculature presenting whitish areas and necrotic myositis with myoregenerative activity. There was not evidence of electrocardiographical and biochemical alterations.

Clinical and cardiovascular alterations produced by scorpion envenomation in dogs

Scorpionism is a common problem that occurs in tropical and subtropical countries and assumes great medical-sanitary importance due to its fatal effect on sensitive individuals, being able to lead children and aged people to death. The envenomation lethal potential is responsible for the serious cardiopulmonary alterations the scorpion toxin produces in its victims. The present research evaluated the effects of Tityus serrulatus venom on dogs, using two distinct doses: a dose that simulates natural envenomation (0.4 mg/total dose), and an experimental dose (0.25 mg/kg). General clinical signs were observed at different moments after envenomation, and specific data related to the cardiopulmonary system were evaluated by systemic arterial pressure measurement, CK-MB enzymatic activity dosage, and radiographic, electrocardiographic and echocardiographic examinations. Results demonstrated that the scorpion venom, in experimental doses, was able to cause acute and reversible cardiac injury in few days, and, in the dose that simulated natural accident, it produced clinical signs of light envenomation, such as local pain, hyperesthesia, sialorrhea, vomiting, diarrhea, sneeze and prostration.

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

Envenomation by scorpion in dog - case report

A case admitted at the Small Animals Clinics Service, Veterinary Hospital, FMVZ - UNESP, in May, 1999 is described. A Brazilian Terrier dog, 3 years and 3 months old, weighing 1.7 kg was brought after 2 hours and a half from contact with a scorpion (Tityus bahiensis). The dog showed vocalization inserted with drowsiness. Physical examination showed slightly hyperemic mucous, pain, agressiveness, tachypnea, tachycardia, and discrete erythema on the rigth forelimb palmar face. An anesthetic block was performed around the stung area using 2 per cent lidocaine hydrochloride without vasoconstrictor (10mL). The animal was asymptomatic, after 24 h treatment.

Alterações clínicas e cardiopulmonares produzidas pelo envenenamento escorpiônico em cães

O artigo não apresenta resumo.

Spider envenoming of dog - case report

This report refers to a female Pinscher treated at the Veterinary Hospital of the Botucatu School of Veterinary Medicine and Animal Husbandry (FMVZ)-Säo Paulo State University (UNESP), Botucatu, 14 hours after a suspected spider envenoming. The animal showed spastic limbs, dyspnea, salivation, hypothermia, muscular fasciculation, non-responsive mydriasis, and claudication of the right hindlimb. The spider was later identified by the Center for the Study of Venoms and Venomous Animals-CEVAP/UNESP, Botucatu as Phoneutria nigriventer. The treatment with potent analgesic was efficient.

Use of lidocaine, propranolol, amiodarone, and verapamil in toad envenoming (Genus Bufo) in dogs

Toad envenoming in dogs can cause death by cardiac fibrilation (CVF). Traditional therapy consists mainly of atropine and propranolol, the last one used to prevent the CVF, that is preceded by negative ventricular deflections (NVDs) in the QRS complex of the electrocardiogram. This study intended to verify, comparatively, the lidocaine, propranolol, amiodarone, and verapamil abilities to prevent CVF in experimentally envenomed dogs. Thirty-six dogs were divided into 6 groups (GL, GP, GA, GV, GST and GSV) with n=6; the dogs were submitted to volatile anaesthesia. The animals of the groups GL, GP, GA, and GV received 0.38g of toad venom through oro-gastric catheter and were treated with the following drugs respectively: lidocaine (4mg/Kg), propranolol (0.1mg/Kg), amiodarone (8mg/Kg), and verapamil (2mg/Kg). These drugs were repeated if NVDs reappeared with cardiac frequency > 150, GST was not treated and GSV was just anaesthetized. The following results were obtained: GL, NVDs present in 4 animals, 100 per cent recuperation with 3.66 doses/animal; GP, NVDs present in 2 animals, 100 per cent recuperation with 3.66 doses/animal; GP, NVDs present in 2 animals, 100 per cent recuperation with 1.66 dose/animal, with bradycardia at the anaesthetic return; GA, NVDs present in 3 animals, 33.33 per cent recuperation with 1.5 dose/animal; GV, NVDs present in 4 animals, 100 per cent recuperation with 2.16 doses/animal; GST, NVD present in 6 animals, 100 per cent death and GSV, NVDs absent, 100 per cent recuperation. As a conclusion, the anaesthetic proceedings used, did not cause NVDs, the envenoming that was not treated was lethal, and among the antiarrhythmics drugs used, verapamil was the most efficient, as it did not cause any serious bradycardia at the anaesthetic return and did not require repeated administrations. For lidocaine, it was efficient but required various administrations; amiodarone could not prevent the death of 4 animals; propranolol was efficient in relation to NVDs control, but caused serious bradycardia at the anaesthetic return.

Developmental and behavioral effects of postnatal amitraz exposure in rats

The effects of postnatal amitraz exposure on physical and behavioral parameters were studied in Wistar rats, whose lactating dams received the pesticide (10 mg/kg) orally on days 1,4,7,10,13,16 and 19 of lactation; control dams received distilled water (1 ml/kg) on the same days. A total of 18 different litters (9 of them control and 9 experimental) born after a 21-day gestation were used. The results showed that the median effective time (ET50) for fur development, eye opening, testis descent an onset of the startle response were increased in rats postnatally exposed to amitraz (2.7, 15.1, 21.6 and 15.3 days, respectively) compared to those of the control pups (1.8, 14.0, 19.9 and 12.9 days, respectively). The ages of incisor eruption, total unfolding of the external ears, vaginal and ear opening and the time taken to perform the grasping hindlimb reflex were not affected by amitraz exposure. Pups from damps treated with amitraz during lactation took more time (in seconds) to perform the surface righting reflex on postnatal days (PND) 3 (25.0 + 2.0), 4 (12.3 + 1.2) and 5 (8.7 + 0.9) in relation to controls (10.6 + 1.2;4.5 + 0.6 and 3.4 + 0.4, respectively); the climbing response was not changed by amitraz. Postnatal amitraz exposure increased spontaneous motor activity of male and female pups in the open-field on PND 16 (140 + 11) and 17 (124 + 12), and 16 (104 + 9), 17 (137 + 9) and 18 (106 + 8), respectively. Data on spontaneous motor activity of the control male and female pups were 59 + 11 and 69 + 10 for days 16 and 17 and 49 + 9, 48 + 7 and 56 + 7 for days 16,17 and 18, respectively. Some qualitative difference were also observed in spontaneous motor behavior; thus, raising the head, shoulder and pelvis matured one or two days later in the amitraz-treated offspring. Postnatal amitraz exposure did not change locomotion and rearing frequencies or immobility time in the open-field on PND 30,60 and 90. The present findings indicate that postnatal exposure to amitraz caused transient development and behavioral changes in the exposed offspring and suggest that further investigation of the potential health risk of amitraz exposure to developing human and animal offsprings may be warranted.

Effects of amitraz on the arterial blood pressure and body rectal temperature of conscious rats

O presente trabalho estuda os efeitos da administraçäo única de amitraz (100 mg/kg) sobre a pressäo sanguínea arterial e a temperatura corporal de ratos Wistar. A administraçäo de amitraz diminuiu a pressäo sanguínea arterial e também produziu hipotermia. A administraçäo de tiramina (100,0 mg/kg) induziu um aumento significativo (p<0,05) na pressäo sanguínea arterial de ratos que receberam previamente amitraz, näo alterando a dos ratos controle. Metade dos ratos que receberam amitraz e tiramina morreram entre 3 e 10 horas após a administraçäo, fato este näo ocorrido com os animais que receberam soluçäo fisiológica e posteriormente tiramina. Os sinais de intoxicaçäo dos animais experimentais incluíram sedaçäo, falta de coordenaçäo motora e coma. A posterior administraçäo de ioimbina (10,0 mg/kg) näo alterou a hipotermia produzida pela administraçäo de amitraz (p<0,05). Apesar de näo poder ser excluída uma possível açäo do amitraz sobre alfa2-noradrenoceptores cerebrais, os resultados indicam uma provável açäo deste praguicida inibindo a enzima monoaminoxidase

Effects of amitraz on isolation-induced aggression in mice

Estudaram-se os efeitos do amitraz, um derivado farmacomidínico, no comportamento agressivo induzido pelo isolamento social em camundongos. Os resultados mostraram que o Amitraz aumentou a latência para o primeiro ataque e diminuiu näo somente a duraçäo de briga como as frequências de ataques entre esses animais. Estes resultados sugeriram que os efeitos do praguicida sobre o comportamento agressivo dos camundongos foram consequência de um efeito inibitório do mesmo sobre a atividade da enzima monoamina oxidase no Sistema Nervoso Central, e, consequentemente, de um aumento dos níveis cerebrais de serotonina

Some behavioral effects of the pesticide amitraz

Acute oral administration of the pesticide amitraz at the doses of 60 and 100 mg/kg (N = 10 per group) significantly decreased the rearing frequency of rats observed in a open field to 8 + or - 8 and 5 + or- 5, respectively, when compared to 28 + or - 5 for control rats treated with vehicle only. The same doses of amitraz (N = 10 per group) increased duration of immobility to 80 + or - 50 and 113 + or - 64 s, respectively, when compared to 113 + or - 64 s for the controls. Acute oral administration of amitraz (20, 60 or 100 mg/kg, N = 10 per group) significantly increased the convulsive threshold dose of rats for strychnine, picrotoxin and pentylenetetrazole. A mitraz administered ip to mice at the doses of 20, 60 and 100 mg/kg (N = 10 per group) significantly increased sleeping time in a dose-dependent manner to 96 + or - 26, 120 + or - 29 and 198 + or - 58 min, respectively, when compared to 45 + or - 15 min for control mice treated with vehicle only. These results indicate that amitraz produces a depressant effect on the central nervous system