Poliartrite em cão por Leishmaniose - tratamento com miltefosina / Polyarthritis in a dog due to leishmaniasis - treatment with miltefosine

Background: Canine visceral leishmaniasis causes several clinical signs, such as lymphadenomegaly, exfoliative dermatitis, ulcerative skin lesions, and lameness. The most commonly reported locomotor changes are claudication, edema, arthralgia, joint stiffness, and muscle atrophy. Radiographic exam revealed cortical and medullary destruction, increase, or decrease in medullary opacity, proliferative periosteal reaction, osteolysis, collapse of joint spaces and soft tissue edema are observed. The aim of this report is to describe the clinical and radiographic evolution of a case of erosive polyarthritis associated with leishmaniasis in a dog before, during and after treatment with miltefosine. Case: A 7-month-old mixed-breed dog was attended due pain and limited mobility. In the orthopedic evaluation, joint swelling, stiffness, and increased pain sensitivity of the four limbs, as well as neck stiffness, were noted. Radiographic examination showed joint changes compatible with edema, with increased volume and radiopacity of the soft tissues adjacent to the joints. The segments of the patient's spine showed more severe bone alterations, the cervical spine being one of the most affected regions, with multiple bone proliferations throughout the vertebral body, especially in the ventral portion (spondylosis), compatible with polyarthritis due to leishmaniasis. Due to the suspicion, lymph node and spleen cytology was performed, confirming the diagnosis. Hematological examination revealed anemia, leukopenia due to lymphopenia and thrombocytopenia in addition to increased AST (79,4 U/L; reference: 6,2 - 13 U/L), creatine kinase (517,6 U/L; reference: 1,5 - 28,4 U/L), lactate dehydrogenase (688,4 IU/L; reference: 45 - 233 IU/L) and hyperproteinemia (7,34 g/dL; reference: 5,4 - 7,1 g/dL). Treatment with miltefosine, allopurinol, domperidone, prednisone, gabapentin and dipyrone was started. Reassessments were performed monthly for 3 consecutive months. Hematological examinations showed improvement, with resolution of anemia and thrombocytopenia, and a marked decrease in creatine kinase values. Thus, it is evident that the dog did not develop liver or kidney changes during treatment. During the treatment and monitoring in this period, the dog had a clinical improvement, which started to walk without pain. In addition, joint swellings were no longer present, however, there was no improvement in the radiographic evaluation of the joints. Discussion: Clinical signs of the locomotor system are compatible with those described in animals that had osteoarticular manifestations associated with leishmaniasis, such as arthralgia, edema, and joint stiffness. In the present report, treatment with miltefosine associated with allopurinol resulted in an improvement in the clinical picture, and this therapy is therefore promising in dogs with polyarthritis due to leishmaniasis. A case published in human medicine demonstrated the intra-articular absorption capacity of this drug. There is only one study to date that describes the radiographic evolution of a dog with arthritis due to leishmaniasis after treatment with miltefosine and allopurinol. In this case described, the dog reported remained with the osteoarticular lesions after treatment, although clinical improvement was observed, as in our report. The use of miltefosine and allopurinol are in accordance with stage II staging for leishmaniasis. In this study, although there was no improvement in the radiographic examinations, the treatment was effective in the remission of the animal's clinical condition.

Clinical and parasitological impact of short-term treatment using miltefosine and allopurinol monotherapy or combination therapy in canine visceral leishmaniasis / Impacto clínico e parasitológico do tratamento de curta duração com miltefosina e alopurinol em monoterapia ou terapia combinada na leishmaniose visceral canina

Canine visceral leishmaniasis is an endemic zoonosis in Brazil. Dogs are the main hosts in urban environments. The treatment has gained popularity since the Brazilian government authorized miltefosine for canine treatment. The aim of this study was to investigate the clinical and parasitological impact of short-term treatment with miltefosine and allopurinol, alone and in combination. We evaluated the ability of pharmacotherapy to reduce clinical signs of disease, antibody levels using the indirect fluorescence antibody test (IFAT) and skin parasite load via qPCR after 28 days of treatment. The therapeutic protocols promoted a significant decline in clinical signs and in the skin parasite load in dogs (p < 0.01). We observed a moderate correlation between the skin parasite load and the clinical score in all three treatment groups (r > 0.5) Antibody levels did not decrease in this short period. It was concluded that the treatment with allopurinol reduced the number of parasites in the skin of dogs with visceral leishmaniasis in the short term. However, its efficiency is potentiated when associated with miltefosine.(AU)

A leishmaniose visceral canina é uma zoonose endêmica no Brasil. Os cães são os principais hospedeiros em ambientes urbanos. O tratamento ganhou popularidade desde que o governo brasileiro autorizou a miltefosina para tratamento canino. O objetivo deste estudo foi investigar o impacto clínico e parasitológico do tratamento a curto prazo com miltefosina e alopurinol, isoladamente e/ou em combinação. Foi avaliada a capacidade da farmacoterapia em reduzir os sinais clínicos da doença e também os níveis de anticorpos, usando-se o teste de anticorpos de fluorescência indireta (RIFI) e a carga parasitária na pele, via qPCR, após 28 dias de tratamento. Os protocolos terapêuticos promoveram declínio significativo dos sinais clínicos e da carga parasitária na pele dos cães (p < 0,01). Foi observada uma correlação moderada entre a carga parasitária da pele e o escore clínico em todos os três grupos de tratamento (r > 0,5). Já os níveis de anticorpos não diminuíram nesse curto período. Concluiu-se que o tratamento com alopurinol, em curto prazo, reduziu a quantidade de parasitos na pele dos cães com leishmaniose visceral. No entanto, sua eficiência é potencializada quando associada a miltefosina.(AU)

Defesa antioxidante no fígado de ratos Wistar pós inibição por Alopurinol / Antioxidant defense in Wistar rats liver after Alopurinol inhibition

As espécies reativas de oxigênio (EROs) são radicais livres derivadas do oxigênio. O fármaco Alopurinol (ALO) possui um efeito inibidor da enzima Xantina Oxidase, uma das vias da produção de EROs. Para combater esse ataque oxidativo no nosso organismo, existe uma defesa antioxidante enzimática, composta pelas enzimas Superóxido dismutase (SOD), Catalase (CAT) e Glutationa Peroxidase (GPX). O objetivo do presente estudo foi analisar os efeitos do alopurinol na defesa antioxidante no fígado de ratos Wistar. Foram utilizados 20 ratos machos divididos em dois grupos: Controle (C) e Alopurinol (ALO). A droga foi administrada para os animais do grupo ALO, enquanto que no grupo C houve uma administração de veículo (salina), ambos durante 3 dias. Os resultados apontaram uma redução significativa na atividade das enzimas antioxidantes no grupo ALO em comparação ao grupo C. A partir desses resultados sugeriu-se que o alopurinol foi eficiente na inibição de EROs.

Reactive oxygen species (ROS) are free radicals derived from oxygen. The drug Allopurinol (ALO) has an inhibitory effect of the enzyme Xanthine Oxidase, one of the routes of ROS production. To combat this oxidative attack in our body, there is an enzymatic antioxidant defense, composed by the enzymes Superoxide dismutase (SOD), Catalase (CAT) and Glutathione Peroxidase (GPX). The aim of the present study was to analyze the effects of allopurinol on the antioxidant defense in the liver of Wistar rats. Twenty male rats were divided into two groups: Control (C) and Allopurinol (ALO). The drug was administered to the animals of the ALO group, while in group C there was a vehicle (saline) administration, both for 3 days. The results indicated a significant reduction in the activity of the antioxidant enzymes in the ALO group compared to the group C. From these results it was suggested that allopurinol was efficient in inhibiting ROS.

Defesa antioxidante no fígado de ratos Wistar pós inibição por Alopurinol / Antioxidant defense in Wistar rats liver after Alopurinol inhibition

As espécies reativas de oxigênio (EROs) são radicais livres derivadas do oxigênio. O fármaco Alopurinol (ALO) possui um efeito inibidor da enzima Xantina Oxidase, uma das vias da produção de EROs. Para combater esse ataque oxidativo no nosso organismo, existe uma defesa antioxidante enzimática, composta pelas enzimas Superóxido dismutase (SOD), Catalase (CAT) e Glutationa Peroxidase (GPX). O objetivo do presente estudo foi analisar os efeitos do alopurinol na defesa antioxidante no fígado de ratos Wistar. Foram utilizados 20 ratos machos divididos em dois grupos: Controle (C) e Alopurinol (ALO). A droga foi administrada para os animais do grupo ALO, enquanto que no grupo C houve uma administração de veículo (salina), ambos durante 3 dias. Os resultados apontaram uma redução significativa na atividade das enzimas antioxidantes no grupo ALO em comparação ao grupo C. A partir desses resultados sugeriu-se que o alopurinol foi eficiente na inibição de EROs.(AU)

Reactive oxygen species (ROS) are free radicals derived from oxygen. The drug Allopurinol (ALO) has an inhibitory effect of the enzyme Xanthine Oxidase, one of the routes of ROS production. To combat this oxidative attack in our body, there is an enzymatic antioxidant defense, composed by the enzymes Superoxide dismutase (SOD), Catalase (CAT) and Glutathione Peroxidase (GPX). The aim of the present study was to analyze the effects of allopurinol on the antioxidant defense in the liver of Wistar rats. Twenty male rats were divided into two groups: Control (C) and Allopurinol (ALO). The drug was administered to the animals of the ALO group, while in group C there was a vehicle (saline) administration, both for 3 days. The results indicated a significant reduction in the activity of the antioxidant enzymes in the ALO group compared to the group C. From these results it was suggested that allopurinol was efficient in inhibiting ROS.(AU)

Uso da ozonioterapia e cogumelo do sol (Agaricus blazei Murill) em tratamento de cães portadores de leishmaniose - relato de 2 casos

A Leishmaniose é uma doença infecciosa, não contagiosa, causada por parasitas do gênero Leishmania, disseminada por mosquitos flebotomíneos, possui alta mobilidade e consequente mortalidade por todo o mundo, principalmente sobre países subtropicais como o Brasil. O tratamento normalmente é de longo prazo, com alto custo e com prejuizo à saude do hospedeiro pela toxidade das medidações quimioterápicas normalmente utilizadas. Sendo assim, este relato de caso de 2 animais, diagnosticados clinicamente e sorologicamente como positivos para Leishmaniose, demonstrou a eficácia de utilização de substancias naturais baseados em uma medicina veterinária integrativa no tratamento complementar da Leishmaniose. Para tanto os animais foram tratados como o gás ozônio (Ozonioterapia) e com o cogumelo do sol (Agaricus blazei Murill) sendo que após 5 meses de tratamento, foi constatado o desaparecimento dos sinais clínicos com diminuição da titulação sorológica para Leishmaniose em um dos animais e remissão em outro.

Uso da ozonioterapia e cogumelo do sol (Agaricus blazei Murill) em tratamento de cães portadores de leishmaniose - relato de 2 casos

A Leishmaniose é uma doença infecciosa, não contagiosa, causada por parasitas do gênero Leishmania, disseminada por mosquitos flebotomíneos, possui alta mobilidade e consequente mortalidade por todo o mundo, principalmente sobre países subtropicais como o Brasil. O tratamento normalmente é de longo prazo, com alto custo e com prejuizo à saude do hospedeiro pela toxidade das medidações quimioterápicas normalmente utilizadas. Sendo assim, este relato de caso de 2 animais, diagnosticados clinicamente e sorologicamente como positivos para Leishmaniose, demonstrou a eficácia de utilização de substancias naturais baseados em uma medicina veterinária integrativa no tratamento complementar da Leishmaniose. Para tanto os animais foram tratados como o gás ozônio (Ozonioterapia) e com o cogumelo do sol (Agaricus blazei Murill) sendo que após 5 meses de tratamento, foi constatado o desaparecimento dos sinais clínicos com diminuição da titulação sorológica para Leishmaniose em um dos animais e remissão em outro.(AU)

FARMACOCINÉTICA DO ALOPURINOL EM CÃES SOB TRATAMENTO PARA LEISHMANIOSE VISCERAL NATURALMENTE ADQUIRIDA

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Túnica vaginal autógena para herniorrafia perineal em cães

Trata-se de um estudo clínico prospectivo sobre a farmacocinética do alopurinol em cães naturalmente infectados por Leishmania infantum e domiciliados com seus responsáveis em área endêmica para leishmaniose visceral (LV). O objetivo do estudo foi determinar os parâmetros farmacocinéticos do alopurinol e seu metabólito oxipurinol em cães em tratamento para LV canina. Para tanto, foram avaliados 11 cães, que passaram por avaliação clínica e laboratorial. Para o estudo da farmacocinética, foram coletadas amostras de sangue de cada cão antes e 12h após a administração do alopurinol, por via oral, na dose de 10mg/kg, nos tempos 0 15, 30,1; 1,5; 2; 2,5; 3; 4; 5; 7; 10; 12 h. Amostras de urina foram coletadas nos tempos 0-3 h; 3-6 h; 6-9 h; 10-12 horas após administração do fármaco. Na avaliação clínica dos cães, os sinais mais frequentes foram linfadenomegalia, mucosas hipocaradas e alterações dermatológicas. Na análise dos exames laboratoriais, observou-se anemia em 18,2% (2/11) dos cães, hiperproteinemia em 45,4% (5/11), hiperglobulinemia em 81,8% (9/11), hipoalbuminemia em 81,8% (9/11), e níveis elevados de ALT em 18,2% (2/11) e FA em 18,2% (2/11) dos cães. A razão proteína-creatinina urinária (UPC) estava alterada em 36,4% (4/11) dos cães, porém dois tinham valores limítrofes e cinco dentro da normalidade. Na urinálise, observou-se proteinúria em 63,6% (7/11), hematúria em 9,1% (1/11), leucocitúria em 27,3% (3/11), bacteriúria em 63,6% (7/11), cristais de urato de amônio em 9,1% (1/11), cristais de urato amorfos 9,1% (1/11) e cristais de xantina em 9,1% (1/11) dos cães. Os resultados da análise de patologia clínica foram utilizados para avaliar o grau de comprometimento funcional dos órgãos acometidos pela doença nos cães. A determinação das concentrações de alopurinol e oxipurinol foram realizados por meio da técnica de HPLC de alta eficiência com leitura por UV, validada no presente estudo. Os parâmetros farmacocinéticos encontrados para o alopurinol foram Cmax de 6,00±1,78 pg/mL, Tmax de 1,50±0,67 h, Kel de 0,31±0,17 por h, e Vd/F/Kg de 1,37±0,83 L/Kg. O intervalo de clearance (Cl) encontrado foi de 0,35±0,11 L/h/Kg, e a área sob a curva (AUC) de 27,20±7,80 h*pg/mL. Para o oxipurinol, foram obtidos Cmax de 3,08±0,68 pg/mL, Tmax médio de 5,90±3,60 h e AUC de 33,87±13,10 h*pg/mL. Dessa forma, as médias dos dados farmacocinéticos obtidos para cães portadores da leishmaniose, que na sua maioria se encontravam entre estágio I e II da doença, foram próximos aos descritos na literatura para cães sadios. Conclui-se que para cães em estágios leve ou controlado da doença, a farmacocinética do alopurinol comporta-se como no cão sadio.

This is a prospective clinical study of the pharmacokinetics of allopurinol in dogs naturally infected by Leishmania sp. and domiciled with their guardians in an endemic area for visceral leishmaniasis (VL). The aim of the study was to determine the pharmacokinetic parameters of allopurinol and its metabolite oxypurinol in dogs undergoing treatment for canine visceral leishmaniasis. We evaluated 11 dogs that underwent clinical and laboratory evaluation. For the pharmacokinetic study, blood samples from each dog were collected before and 12 hours after the administration of allopurinol, orally, at a dose of 10mg / kg, at times 0 '15', 30 ', 1; 1.5; 2; 2.5; 3; 4; 5; 7; 10; 12 h. Urine samples were collected at 0-3 h; 3-6 h; 6-9 h; 10-12 hours after the drug administration. The most frequent signs observed in the clinical evaluation of the dogs were lymphadenomegaly, pale mucosa and dermatological alterations. Laboratory tests evidenced anemia in 18.2% (2/11) of the dogs, hyperproteinemia in 45.4% (5/11), hyperglobulinemia in 81.8% (9/11), hypoalbuminemia in 81.8% (9/11), elevated ALT levels in 18.2% (2/11), and high FA values in 18.2% (2/11) of the dogs. The urinary protein-creatinine ratio (UPC) was altered in 36.4% (4/11) of the dogs, two had borderline values and five results within the normal value. The urinalysis resulted in proteinuria in 63.6% (7/11), hematuria in 9.1% (1/11), leukocyturia in 27.3% (3/11), bacteriuria in 63.6% (7/11), ammonium urate crystals in 9.1% (1/11), amorphous urate crystals 9.1% (1/11), and xanthine crystals in 9.1% (1/11) of the dogs. The results of the clinical pathology analysis were used to evaluate the degree of functional impairment of the organs affected by the disease in dogs. The concentrations of allopurinol and oxypurinol were determined by HPLC with UV reading technique. The pharmacokinetic parameters found for allopurinol were Cmax of 6.00 ± 1.78 pg/mL, Tmax of 1.50 ± 0.67 h, Kel of 0.31 ± 0.17 per h, and Vd/F/kg of 1.37 ± 0.83 L/Kg. The clearance interval (Cl) was 0.35 ± 0.11 L/h/kg, and the area under the curve (AUC) was 27.20 ± 7.80 h*pg/mL. The values for oxypurinol were Cmax of 3.08 ± 0.68 pg / mL, mean Tmax 5.90 ± 3.60 h, and the area under the curve of 33.87 ± 13.10 h*pg/mL. Thus, the average values of the pharmacokinetic data obtained for dogs with leishmaniasis, which were mostly between stages I and II of the disease, were close to those described in the literature for healthy dogs. We can conclude that for dogs in mild or controlled stages of disease, the pharmacokinetics of allopurinol behave as in healthy dogs.

Effects of allopurinol and preconditioning on apoptosis due to ischemia-reperfusion on a double jejunum-segment canine model / Efeitos do alopurinol e precondicionamento na apoptose devido a isquemia-reperfusão em duplo segmento de jejuno em cães

PURPOSE: To investigate the duration of apoptosis caused by ischemia-reperfusion in the intestine in a new double jejunum-segment model, and to analyze the protective effects of allopurinol or ischemic preconditioning (IPC). METHODS: In Experiment I for harvesting the double jejunum-segment model after laparotomy a 30-cm-long jejunum part was selected on mongrel dogs (n=24). End-to-end anastomoses were performed at both ends and in the middle of the jejunum part, creating two equal segments. In one segment ischemia was induced by occluding the supplying vessels, the other segment served as control. Tissue samples for detecting apoptosis were taken at 30th minutes, 1st, 2nd, 4th, 6th, 8th, 12th and 24th hours of reperfusion. In Experiment II using the same model the 4-hour reperfusion time period, allopurinol (50 mg/kg) pre-treated and IPC (3 cycles of 5x1) groups (n=5 per each) were also investigated. RESULTS: In Experiment I the greatest apoptotic activity was detected at the 4th and 6th hour of reperfusion (14.2 ± 1.31 and 16.3 ± 1.05 per visual field at 40x magnification). In Experiment II Using the 4-hour reperfusion time period allopurinol pre-treatment increased the apoptotic activity (10.72 ± 0.47 per 50 intestinal villi) approximately two-fold than the IPC (6.72 ± 0.46 per 50 intestinal villi) did (p<0.05). CONCLUSIONS: Apoptotic activity has a characteristic time curve, reaching the highest values between the 4th and 6th hours after 30-minute intestinal ischemia. Ischemic preconditioning seemed to be protective against the morphological changes caused by intestinal ischemia-reperfusion.(AU)

OBJETIVO: Investigar a duração da apoptose causada pela isquemia-reperfusão no intestino em um novo modelo de duplo segmento de jejuno e analisar os efeitos protetores do alopurinol ou precondicionamento isquêmico (IPC). MÉTODOS: No experimento I para obter o modelo do duplo segmento de jejuno, após a laparotomia, uma parte de 30cm de comprimento de jejuno foi selecionada em cães mestiços (n=24). Anatomoses T-T foram realizadas em ambas as extremidades no meio do segmento de jejuno, criando dois segmentos iguais. Em um segmento foi induzida isquemia por oclusão dos vasos que o irrigavam e o outro segmento foi usado como controle. Amostras de tecido para detecção da apoptose foram obtidos aos 30 minutos, 1h, 2h, 4h, 6h, 8h, 12h e 24 horas de reperfusão. No experimento II usando o mesmo modelo, no tempo de reperfusão de 4 horas, foram investigados dois outros grupos (n=5 cada) usando precondicionamento com alopurinol (50 mg/kg) e IPC (3 ciclos de 5x1). RESULTADOS: No experimento I a maior atividade de apoptose detectada foi às 4h e 6h de reperfusão (14,2 ± 1,31 e 16,3 ± 1,05 no campo visual de 40x). No experimento II usando o período de 4horas de reperfusão o pré-tratamento com alopurinol aumentou a atividade apoptótica (10,72 ± 0,47) aproximadamente 2 vezes mais do que o IPC (6,72 ± 0,46) (p<0,05). CONCLUSÕES: A atividade de apoptose tem uma curva caractetística, atingindo maiores valores entre a 4ª e a 6ª horas após 30 minutos de isquemia intestinal. O precondicionamento isquêmico parece proteger contra alterações morfológicas causadas pela isquemia-reperfusão intestinal.(AU)

AVALIAÇÃO DA CARGA PARASITÁRIA EM CÃES COM INFECÇÃO NATURAL Leishmania (Leishmania) infantum chagasi, SUBMETIDOS A TRATAMENTO EXPERIMENTAL

A Leishmaniose Visceral Canina é uma doença que tem como agente etiológico no Brasil a espécie do protozoário Leishmania (Leishmania) infantum chagasi, endêmica em várias regiões, transmitida pelo inseto-vetor Lutzomyia longipalpis. O cão doméstico é considerado o mais importante reservatório do parasita. O objetivo deste trabalho foi avaliar a carga parasitária em cães naturalmente infectados com Leishmania (L.) infantum chagasi submetidos a tratamento experimental. Para tanto utilizou-se 18 cães sintomáticos, naturalmente infectados por Leishmania (L.) infantum chagasi de ambos os sexos, idades variadas submetidos a protocolo de tratamento com alopurinol 10 mg/kg a cada 12h horas, domperidona 1 mg/kg a cada 24 horas, durante doze meses, associado com a vacina inativada, três doses com intervalo de 21 dias, por via subcutânea, na diluição de duas partes do liofilizado para uma do diluente. Os animais foram submetidos à avaliação clínica, testes hematológicos, bioquímicos, imuno-histoquímica de pele e monitoramento através da Reação em Cadeia da Polimerase, nos momentos zero (M0), seis meses (M6) e doze meses (12M). Houve remissão significativa dos sinais clínicos em 100% (18/18) dos cães nos momentos pós-tratamento, bem como normalização e melhora dos parâmetros hematológicos e bioquímicos. Na imuno-histoquímica da pele, houve redução significativa e eliminação dos parasitos na pele entre os momentos. Na PCR foi detectado DNA do parasita nas amostras de pele e medula óssea após doze meses de tratamento, embora com redução significativas entre os momentos pré e pós-tratamento. Os resultados deste trabalho concluem que o tratamento com alopurinol e domperidona associado com a vacina inativada, promove a remissão dos sinais clinicos e redução da carga parasitária em animais com leishmaniose visceral.

The Canine Visceral Leishmaniasis is a disease whose etiological agent in Brazil is the species of Leishmania (Leishmania) infantum chagasi, endemic in several regions, transmitted by insect-vector Lutzomyia longipalpis. The domestic dog is considered the most important parasite reservoir. This study aimed to evaluate the parasite load in dogs naturally infected with Leishmania (L.) infantum chagasi submitted to experimental treatment. For this purpose we used 18 asymptomatic dogs naturally infected with Leishmania (L.) infantum chagasi of both sexes, various ages submitted to treatment protocol with allopurinol 10 mg / kg 12h hours, domperidone 1 mg / kg every 24 hours during twelve months, associated with inactivated vaccine, three doses at 21 days interval by the subcutaneous route at a dilution of lyophilized to two parts of a diluent. The animals were submitted to clinical evaluation, blood tests, biochemical, immunohistochemistry of skin and monitoring through the Polymerase Chain Reaction in moments zero (M0), six months (M6) and twelve months (12M). Were observed significant remission of clinical signs in 100% (18/18) of the dogs in the post-treatment times, as well as standardization and improvement of haematological and biochemical parameters. In immunohistochemistry the skin, there was a significant reduction and elimination of parasites in the skin between times. PCR detected DNA of the parasite in skin samples and bone marrow after twelve months of treatment, with significant reduction between the pre- and post-treatment. The results of this study conclude that the treatment with allopurinol and domperidone associated with inactivated vaccine, to promote remission of clinical signs and reduction of parasite burden in animals with visceral leishmaniasis.

Clinical and parasitological evaluation of dogs naturally infected by Leishmania (Leishmania) chagasi submitted to treatment with meglumine antimoniate and allopurinol / Avaliação clínica e parasitológica de cães naturalmente infectados por Leishmania (Leishmania) chagasi submetidos a tratamento com antimoniato de meglumina e alopurinol

Aiming to assess the efficacy of the treatment, to verify the occurrence of possible disease relapses and to search for the presence of parasites after the treatment, seven dogs naturally infected by Leishmania sp., were submitted to a treatment with meglumine antimoniate and allopurinol. For this, lymph node and bone marrow aspiration biopsies were carried out at seven moments. After the end of the six-month observation period all dogs were submitted to euthanasia. Then, spleen and liver “imprints” and in vitro cultures were carried out to search for amastigote forms of the parasite. All animals presented remission of the symptoms and during all the observation period no dog presented relapse of the disease, although amastigote forms of the parasite were observed in two of the animals at the end of the experiment. Thus, it was possible to conclude that the treatment promotes clinical healing but it does not eliminate the parasites completely.(AU)

Com objetivo de avaliar a eficácia do tratamento, verificar a ocorrência de possíveis recidivas da doença e pesquisar a presença de parasitas após a realização do tratamento, foram utilizados sete cães naturalmente infectados por Leishmania sp., submetidos a tratamento com antimoniato de meglumina e alopurinol. Para tanto, foram realizadas punções biópsias aspirativas de linfonodos e de medula óssea em sete momentos. Após o término dos seis meses de observação, todos os cães foram submetidos à eutanásia e realizados “imprints” e cultivo in vitro do baço e fígado para a pesquisa de formas amastigotas. Todos os animais apresentaram remissão dos sintomas e durante todo o período de observação nenhum cão apresentou recidiva da doença apesar de ter sido observada a presença de formas amastigotas do parasita em dois animais, ao término do experimento. Desta forma, foi possível concluir que o tratamento promove a cura clínica, entretanto não elimina completamente os parasitas.(AU)

Taxa de mortalidade em ratos submetidos à isquemia e reperfusão hepática, tratados ou não com alopurinol

The transitory hepatic ischemia has been frequently used. However, this procedure, benefic some times, is contrabalanced by the adverse effects from the hepatic ischemia and esplenic congestion, as well as of the reperfusion consequences. The objective of the authors is to determine the effects of the selective ischemia in pretreated and not pretreated rats with allopurinol, inhibitor of the xantine oxidase enzyme, in the mortality of the rats. Thirthy Wistar rats were used and divided into three groups: Group I (n=10): pretreated with allopurinol and submitted to laparotomy and exposition of the hepatic vessels for 45 min. Group II (n=10): pretreated with allopurinol and submitted to selective hepatic ischemia for 45 minutes. Group III (n=10): Submitted only to selective hepatic ischemia for 45 min. The postoperative mortality was evaluated each 24 hours, by one period of 10 days. Among the animals of the group 1, it wasn't observed deaths, however, in those of the groups II and III, the global rates of mortality were, respectively, 20 and 46.67%. Statistically significative difference , was bettwen the observed mortality in groups I and III (p 0.05). The postoperative mortality in the group of animals submitted to ischemia without pretreatment with allopurinol was 46.67%, while in those animals pretreated with allopurinol, there was an important decrease to 20%. Even without an statistically significative distinction, it reflects a tendency of a protector effect of the allopurinol in the hepatic ischemia and reperfusion.

A isquemia transitória hepática tem sido cada vez mais amplamente utilizada. Contudo, essa atitude, embora muitas vezes benéfica, é contrabalançada pelos efeitos adversos advindos da isquemia hepática e da congestão esplênica, assim como, das conseqüências da reperfusão. O objetivo dos autores é determinar os efeitos da isquemia seletiva em animais pré-tratados ou não com alopurinol, inibidor da xantina oxidase sobre a mortalidade dos animais. Foram utilizados 30 ratos assim divididos: Grupo I (n=10): pré-tratados com alopurinol e submetidos à laparotomia e exposição do pedículo hepático por 45 minutos. Grupo II (n=10): tratados com alopurinol e submetidos à isquemia hepática seletiva por 45 minutos. Grupo III (n=10): submetidos apenas à isquemia por 45 minutos. A mortalidade pós-operatória foi avaliada a cada 24 horas, por um período de 10 dias. Entre os animais do grupo I, não foram observados óbitos, entretanto, naqueles dos grupos II e III, as mortalidades globais foram respectivamente 20 e 46,7%. Diferença estatisticamente significativa, apenas, entre a mortalidade observada no grupo III em relação ao controle (p 0,05). A mortalidade pós-operatória no grupo de animais submetidos à isquemia sem pré-tratamento com alopurinol ascende as cifras de 46,67% dos animais, enquanto naqueles pré-tratados com alopurinol houve um importante decréscimo para 20%. Embora sem uma distinção estatisticamente significativa, reflete uma tendência de um efeito protetor do alopurinol na isquemia e reperfusão hepática.