Evaluation of different supportive treatments during packed cell volume replacement in calves naturally infected with tick fever agents.

This study evaluated the effect of different supportive treatments on PCV replacement of dairy calves naturally infected with tick fever (TF) agents, and treated with diminazene and enrofloxacin. Five products were tested as supportive treatments in four experiments. In these experiments, we used Girolando female calves (Gyr × Holstein, genetic ratio of 15/16 and 31/32 Holstein) four to six months old, raised in pasture, naturally infected with TF agents, and infested with R. microplus. Supportive treatment was administered once on day 0 of the study concurrently with specific treatment targeting TF agents. The animals were observed on days 0, 3, and 7. Oral or intravenous administration of a vitamin complex and mineral salts enhanced the increase in PCV and biochemical analytes present in the serum of calves naturally infected with TF agents. No positive effect on PCV values was observed with the administration of (1) invigorating tonic: calcium, casein-peptides and vitamin B12, (2) iron-based stimulant tonic and (3) metabolic tonic: vitamin A, vitamin D, and a fraction of polyunsaturated fatty acids. Supplementation by injection with Type III iron resulted in increased hemoglobin and PCV in treated animals. However, these results did not occur with iron citrate. Therefore, more studies with Type III iron need to be performed. Supportive treatment conferred no advantage in animals with no history of reduced PCV.

New antiglaucomatous agent for the treatment of open angle glaucoma: Polymeric inserts for drug release and in vitro and in vivo study.

A benzamidine derivative from diminazene was tested for a novel activity: treatment of primary open-angle glaucoma. This drug was incorporated into mucoadhesive polymeric inserts prepared using chitosan (Chs) and chondroitin sulfate (CS). Of current interest is the mucoadhesion, which increases the contact time with the ocular surface, resulting in improved bioavailability; also, the inserts are made to act as a prolonged release system. In the present work the inserts were prepared by the solvent casting method using different polymeric proportions (30:70, 50:50, 75:25% w/w Chs:CS and 100% Chs). Thermal analysis and infrared spectroscopy both demonstrated physical dispersion of the active drug. The most promising was the 50:50% Chs:CS which demonstrated that it was not fragile and has an in vitro release profile of up to 180 minutes. In addition, it presented greater adhesion strength in relation to the other formulations. These physicochemical results corroborate the in vivo tests performed. In this sense, we also demonstrated that the treatment with the 50:50% insert can control the intraocular pressure (IOP) for at least 3 weeks and prevents damage to the retinal ganglion cells (RGCs) compared to the placebo insert. Thus, this indicates thus that the new drug is quite viable and promising in glaucoma treatment.

ACE2 activator diminazene aceturate exerts renoprotective effects in gentamicin-induced acute renal injury in rats.

Acute Kidney Injury (AKI) comprises a rapidly developed renal failure and is associated with high mortality rates. The Renin-Angiotensin System (RAS) plays a pivotal role in AKI, as the over-active RAS axis exerts major deleterious effects in disease progression. In this sense, the conversion of Angiotensin II (Ang II) into Angiotensin-(1-7) (Ang-(1-7)) by the Angiotensin-converting enzyme 2 (ACE2) is of utmost importance to prevent worse clinical outcomes. Previous studies reported the beneficial effects of oral diminazene aceturate (DIZE) administration, an ACE2 activator, in renal diseases models. In the present study, we aimed to evaluate the therapeutic effects of DIZE administration in experimental AKI induced by gentamicin (GM) in rats. Our findings showed that treatment with DIZE improved renal function and tissue damage by increasing Ang-(1-7) and ACE2 activity, and reducing TNF-α. These results corroborate with a raising potential of ACE2 activation as a strategy for treating AKI.

Diminazene aceturate (DIZE) has cellular and in vivo antiarrhythmic effects.

Diminazene aceturate (DIZE) is an anti-protozoan compound that has been previously reported to increase the activity of the angiotensin-converting enzyme 2 (ACE2) and thus increase Angiotensin-(1-7) production, leading to cardioprotection against post-myocardial infarction dysfunction and structural remodelling. Moreover, DIZE is able to ameliorate morpho-functional changes after myocardial infarction by enhancing ACE2 activity, thus increasing Angiotensin-(1-7) production (a benefic peptide of the renin-angiotensin system). However, despite the improvement in cardiac function/structure, little is known about DIZE effects on arrhythmia suppression, contraction/excitable aspects of the heart and importantly its mechanisms of action. Thus, our aim was to test the acute effect of DIZE cardioprotection at the specific level of potential antiarrhythmic effects and modulation in excitation-contraction coupling. For this, we performed in vitro and in vivo techniques for arrhythmia induction followed by an acute administration of DIZE. For the first time, we described that DIZE can reduce arrhythmias which is explained by modulation of cardiomyocyte contraction and excitability. Such effects were independent of Mas receptor and nitric oxide release. Development of a new DIZE-based approach to ameliorate myocardial contractile and electrophysiological dysfunction requires further investigation; however, DIZE may provide the basis for a future beneficial therapy to post-myocardial infarction patients.

Clinical and therapeutic aspects of an outbreak of canine trypanosomiasis.

Trypanosomiasis caused by Trypanosoma evansi can seriously affect both domestic and wild animals. This article reports on an outbreak of canine trypanosomiasis on a farm in the Pantanal region of Brazil. The farm had 38 dogs, 20 of which died before receiving veterinary care. The remaining 18 dogs were underwent anamnesisn, clinical examination, hematological and biochemical evaluations. Blood smears and PCR analysis were performed for the diagnosis. The treatment protocols used according to the clinical recovery or parasitological cure of the dogs, using diminazene diaceturate, isometamidium chloride or quinapyramine sulfate. Post-treatment parasitological evaluation was performed by the microhematocrit technique. 7/18 dogs were PCR positive for T. evansi (confirmed by sequencing). There was clinical findings, which were consistent with both the acute and chronic stages of the disease in dogs. The infected dogs all exhibited at least one clinical sign of the disease. The hematological findings were compatible with trypanosomiasis, highlighting the hypochromic microcytic anemia as the main outcome. No treatment protocol was fully effective and the prolonged use of diminazene diaceturate caused the death of an animal. The trypanosomiasis can cause high rates of morbidity and mortality in dogs and difficulty in establishment an effective and safe therapeutic protocol.

Beneficial Effects of the Angiotensin-Converting Enzyme 2 Activator Dize in Renovascular Hypertension.

BACKGROUND: Angiotensin Converting Enzyme (ACE) 2 is an important modulator of the Renin Angiotensin System (RAS) and the RAS plays a central role in renovascular hypertension. Very few studies investigated the role of components of the counterregulatory RAS axis (ACE2, Ang-(1-7) and Mas receptor) in renovascular hypertension and the results are controversial. OBJECTIVE: The aim of this study was to investigate the effects of Diminazene Aceturate (DIZE) administration on renal function and renal inflammation parameters in 2K1C hypertensive rats. METHODS: Male Wistar rats were divided into three experimental groups: sham-operated animals, 2K1C+saline and 2K1C+DIZE orally (1 mg/kg/day). At the end of the 30 days of treatment, renal function was analyzed and kidneys from all the groups were collected and processed separately for measurement of N-acetyl-beta-D-glucosaminidase (NAG) and Myeloperoxidase (MPO) activities, cytokines, chemokines and nitric oxide levels. RESULTS: Oral DIZE administration for 4 weeks in hypertensive rats attenuated renal dysfunction and reduced the levels of MPO and NAG, cytokines and chemokines (IL1ß, IL-6, TNF-α and MCP-1) and increased urinary nitrate/nitrite levels in 2K1C hypertensive rats. CONCLUSION: Our findings showed that ACE2 activation may effectively improve renal alterations and inflammation induced by renovascular hypertension.

Clinical and therapeutic aspects of an outbreak of canine trypanosomiasis / Aspectos clínicos e terapêuticos de um surto de tripanossomíase canina

Abstract Trypanosomiasis caused by Trypanosoma evansi can seriously affect both domestic and wild animals. This article reports on an outbreak of canine trypanosomiasis on a farm in the Pantanal region of Brazil. The farm had 38 dogs, 20 of which died before receiving veterinary care. The remaining 18 dogs were underwent anamnesisn, clinical examination, hematological and biochemical evaluations. Blood smears and PCR analysis were performed for the diagnosis. The treatment protocols used according to the clinical recovery or parasitological cure of the dogs, using diminazene diaceturate, isometamidium chloride or quinapyramine sulfate. Post-treatment parasitological evaluation was performed by the microhematocrit technique. 7/18 dogs were PCR positive for T. evansi (confirmed by sequencing). There was clinical findings, which were consistent with both the acute and chronic stages of the disease in dogs. The infected dogs all exhibited at least one clinical sign of the disease. The hematological findings were compatible with trypanosomiasis, highlighting the hypochromic microcytic anemia as the main outcome. No treatment protocol was fully effective and the prolonged use of diminazene diaceturate caused the death of an animal. The trypanosomiasis can cause high rates of morbidity and mortality in dogs and difficulty in establishment an effective and safe therapeutic protocol.

Resumo A tripanossomíase causada por Trypanosoma evansi pode acometer gravemente os animais domésticos e selvagens. Este artigo relata um surto de tripanossomíase canina em uma fazenda na região do Pantanal, Brasil. Na fazenda havia 38 cães, 20 dos quais morreram antes de receber cuidados veterinários. Os 18 cães restantes foram submetidos a anamnese, exame clínico, avaliação hematológica e bioquímica. Esfregaços de sangue e análise da PCR foram realizados para o diagnóstico. Os protocolos de tratamento foram utilizados de acordo com a recuperação clínica ou cura parasitológica dos cães, utilizando diaceturato de diminazeno, cloreto de isometamídio ou sulfato de quinapiramina. A avaliação parasitológica pós-tratamento foi realizada pela técnica de microhematócrito. 7/18 cães foram PCR positivos para T. evansi (confirmado por sequenciamento). Os achados clínicos encontrados, foram consistentes com os estágios agudo e crônico da doença em cães. Todos os cães infectados exibiram pelo menos um sinal clínico da doença. Os achados hematológicos foram compatíveis com a tripanossomíase, destacando a anemia microcítica hipocrômica como principal consequência. Nenhum protocolo de tratamento foi totalmente eficaz e o uso prolongado de diaceturato de diminazeno causou a morte de um animal. A tripanossomíase pode causar altas taxas de morbidade e mortalidade em cães e dificultar o estabelecimento de um protocolo terapêutico eficaz e seguro.

The ACE 2 activator diminazene aceturate (DIZE) improves left ventricular diastolic dysfunction following myocardial infarction in rats.

Diminazene aceturate (DIZE) has been reported to enhance the catalytic efficiency of ACE-2 and presumably increases angiotensin 1-7 generation, interfering with cardiac remodeling after myocardial infarction (MI). Our aim was to investigate the chronic effects of DIZE on cardiac dysfunction post-MI. Male Wistar rats underwent myocardial infarction (MI) or SHAM surgery (SO) and were divided into groups treated with DIZE 15 mg/kg/day, s.c. or vehicle (Control). After 4 weeks, the hemodynamic variables were recorded by cardiac catheterism. Hearts were then arrested to obtain the left ventricular (LV) pressure-volume curves in situ. Cardiomyocyte hypertrophy and collagen content were determined by histology. DIZE prevented LV end-diastolic pressure increases in MI rats (MI: 26 ± 3.3 vs. MI-DIZE: 15 ± 1.6 mmHg, P < 0.001) without a significant effect on LV systolic pressure (LVSP). Moreover, DIZE improved LV contractility (+dP/dt, MI: 3014 ± 161 vs. MI-DIZE: 3884 ± 104 mmHg/s, P < 0.001) and relaxation (-dP/dt, MI: -2333 ± 91 vs. MI-DIZE: -2798 ± 120 mmHg/s, P < 0.05). Right ventricular SP was increased in the MI compared to that in the SO group (40 ± 0.6 vs. 30 ± 1.2 mmHg; P < 0.01), and DIZE partially prevented this augmentation. LV stiffness was reduced in MI-DIZE compared with that in MI (0.64 ± 0.01 vs. 0.78 ± 0.02 mmHg/mL; P < 0.01). DIZE treatment reduced the interstitial collagen content by 18% in the surviving LV myocardium. Cardiomyocyte hypertrophy remained unaffected by DIZE treatment. Our findings show that chronic DIZE treatment post-MI attenuates the morphofunctional changes induced by MI in rats. The effects on LV -dP/dt, chamber stiffness and collagen content suggest this drug can be used as a therapeutic agent to reduce interstitial fibrosis and diastolic dysfunction after MI.

Molecular diagnosis and phylogeographic analysis of Trypanosoma evansi in dogs (Canis lupus familiaris) suggest an epidemiological importance of this species in Colombia.

Surra disease is a zoonosis caused by Trypanosoma (Trypanozoon) evansi, a salivary trypanosome, originally from Africa, which affects a wide range of mammalian worldwide. Dogs are highly susceptible to T. evansi infection and they often exhibit strong clinical signs than can lead to death, even within weeks in untreated acute cases. The present survey is the first report through clinical, parasitological and molecular approaches, of two fatal cases of T. evansi in Colombian dogs. After analysing two presumptive cases of infection with Trypanosoma spp., in dogs by parasitological methods, we confirmed by molecular techniques the presence of T. evansi, finding clinical signs such as anaemia, thrombocytopenia and hepatosplenomegaly, with fatal outcomes within a week even after the treatment. A phylogenetic and phylogeographic analysis of both isolates from T. evansi, suggest a complex evolutionary relationship with species of Trypanozoon subgenus. Moreover, the haplotype H2 was observed for the first time in Colombia, in common areas where human cases of T. evansi infection has been reported. These findings imply a relevant problem for animal health in the country, and highlight the importance of this infection in domestic animals and the possibility of human cases.

Diminazene aceturate, an angiotensin-converting enzyme II activator, prevents gastric mucosal damage in mice: Role of the angiotensin-(1-7)/Mas receptor axis.

The angiotensin (Ang) II converting enzyme (ACE II) pathway has recently been shown to be associated with several beneficial effects in various organisms, including gastroprotection. ACE II is responsible for converting Ang II into an active peptide, Ang-(1-7), which in turn binds the Mas receptor. Recent studies have shown that diminazene aceturate (Dize) a trypanocidal used in animals, activates ACE II. Thus, in this study, we aimed to evaluate the gastroprotective effects of Dize via the ACE II/Ang-(1-7)/Mas receptor pathway against gastric lesions induced by ethanol and acetic acid in mice. The results showed that Dize could promote gastric protection via several mechanisms, including increased levels of antioxidants and anti-inflammatory factors (e.g., decreasing tumor necrosis factor and interleukin-6 expression and reducing myeloperoxidase activity), maturation of collagen fibers, and promotion of re-epithelialization and regeneration of gastric tissue in different injury models. Thus, Dize represents a novel potential gastroprotective agent.

Effect of the treatment with Achyrocline satureioides (free and nanocapsules essential oil) and diminazene aceturate on hematological and biochemical parameters in rats infected by Trypanosoma evansi.

This study aimed to verify the effect of the treatment with A. satureioides essential oil (free and nanoencapsulated forms) and diminazene aceturate on hematological and biochemical variables in rats infected by Trypanosoma evansi. The 56 rats were divided into seven groups with eight rats each. Groups A, C and D were composed by uninfected animals, and groups B, E, F and G were formed by infected rats with T. evansi. Rats from groups A and B were used as negative and positive control, respectively. Rats from the groups C and E were treated with A. satureioides essential oil, and groups D and F were treated with A. satureioides nanoencapsulated essential oil. Groups C, D, E and F received one dose of oil (1.5 mL kg(-1)) during five consecutive days orally. Group G was treated with diminazene aceturate (D.A.) in therapeutic dose (3.5 mg kg(-1)) in an only dose. The blood samples were collected on day 5 PI for analyses of hematological (erythrocytes and leukocytes count, hemoglobin concentration, hematocrit, mean corpuscular and mean corpuscular hemoglobin concentration) and biochemical (glucose, triglycerides, cholesterol, alanine aminotransferase (ALT), aspartate aminotransferase (AST), albumin, urea and creatinine) variables. A. satureioides administered was able to maintain low parasitemia, mainly the nanoencapsulated form, on 5 days post infection. On the infected animals with T. evansi treated with A. satureioides essential oil (free and nanocapsules) the number of total leucocytes, lymphocytes and monocytes present was similar to uninfected rats, and different from infected and not-treated animals (leukocytosis). Treatment with A. satureioides in free form elevated levels of ALT and AST, demonstrating liver damage; however, treatment with nanoencapsulated form did not cause elevation of these enzymes. Finally, treatments inhibited the increase in creatinine levels caused by infection for T. evansi. In summary, the nanoencapsulated form showed better activity on the trypanosome; it did not cause liver toxicity and prevented renal damage.

Hematologic and bone marrow changes in dogs experimentally infected with Rangelia vitalii.

BACKGROUND: Rangelia vitalii is a tick-transmitted piroplasm that causes both hemolytic and hemorrhagic disease in dogs in Brazil. OBJECTIVE: The aim of this study was to evaluate the response of the bone marrow in dogs experimentally infected with R vitalii during the acute stage of the disease. METHODS: For this study, 2 groups of a total of 12 young dogs were used. Group A was composed of healthy dogs (n = 5), and group B consisted of animals infected with R vitalii (n = 7). Blood samples were collected on days 0, 10, 20, and 30 post-inoculation and stored in EDTA tubes for a full hematology profile, including a reticulocyte count. On days 10 and 20, bone marrow samples were collected, stained, and examined. RESULTS: In infected dogs anemia was identified on days 10 and 20 post-inoculation (P < .01), and on day 20 reticulocytosis was present. Infected dogs had leukopenia due to neutropenia and eosinopenia, along with lymphocytosis and monocytosis, when compared with control animals. In bone marrow, the myeloid:erythroid ratio was significantly decreased (P < .05) in infected dogs due to increased erythroid precursors. CONCLUSIONS: Dogs experimentally infected with R vitalii develop regenerative extravascular hemolytic anemia accompanied by erythroid hyperplasia in the bone marrow. During the acute phase of the disease, leukopenia due to neutropenia and eosinopenia suggests intense tissue recruitment of these cells in response to the endothelial damage caused by this parasite.

In vitro and in vivo antileishmanial efficacy of a combination therapy of diminazene and artesunate against Leishmania donovani in BALB/c mice.

The in vitro and in vivo activity of diminazene (Dim), artesunate (Art) and combination of Dim and Art (Dim-Art) against Leishmania donovani was compared to reference drug; amphotericin B. IC50 of Dim-Art was found to be 2.28 ± 0.24 µg/mL while those of Dim and Art were 9.16 ± 0.3 µg/mL and 4.64 ± 0.48 µg/mL respectively. The IC50 for Amphot B was 0.16 ± 0.32 µg/mL against stationary-phase promastigotes. In vivo evaluation in the L. donovani BALB/c mice model indicated that treatments with the combined drug therapy at doses of 12.5 mg/kg for 28 consecutive days significantly (p < 0.001) reduced parasite burden in the spleen as compared to the single drug treatments given at the same dosages. Although parasite burden was slightly lower (p < 0.05) in the Amphot B group than in the Dim-Art treatment group, the present study demonstrates the positive advantage and the potential use of the combined therapy of Dim-Art over the constituent drugs, Dim or Art when used alone. Further evaluation is recommended to determine the most efficacious combination ratio of the two compounds.

In vitro and in vivo antileishmanial efficacy of a combination therapy of diminazene and artesunate against Leishmania donovani in BALB/c mice / Estudo in vitro e in vivo da eficácia anti leishmaniótica de terapêutica combinada de Diminazene e Artesunate contra Leishmania donovani em camundongos Balb/c

The in vitro and in vivo activity of diminazene (Dim), artesunate (Art) and combination of Dim and Art (Dim-Art) against Leishmania donovani was compared to reference drug; amphotericin B. IC50 of Dim-Art was found to be 2.28 ± 0.24 µg/mL while those of Dim and Art were 9.16 ± 0.3 µg/mL and 4.64 ± 0.48 µg/mL respectively. The IC50 for Amphot B was 0.16 ± 0.32 µg/mL against stationary-phase promastigotes. In vivo evaluation in the L. donovani BALB/c mice model indicated that treatments with the combined drug therapy at doses of 12.5 mg/kg for 28 consecutive days significantly (p < 0.001) reduced parasite burden in the spleen as compared to the single drug treatments given at the same dosages. Although parasite burden was slightly lower (p < 0.05) in the Amphot B group than in the Dim-Art treatment group, the present study demonstrates the positive advantage and the potential use of the combined therapy of Dim-Art over the constituent drugs, Dim or Art when used alone. Further evaluation is recommended to determine the most efficacious combination ratio of the two compounds.

A atividade in vitro e in vivo de Diminazene (Dim), Artezunate (Art) e a combinação Dim e Art (Dim-Art) contra Leishmania donovani foi comparada com a droga de referência Anfotericina B. IC50 da Dim-Art foi 2,28 ± 0,24 µg/mL enquanto aquelas de Dim e Art foram 9,16 ± 0,3 µg/mL e 4,64 ± 0,48 µg/mL respectivamente. O IC50 da Anfotericina B foi 0,16 ± 0,32 µg/mL contra a fase estacionária de promastigotas. A avaliação in vivo do modelo de L. donovani em camundongos Balb/c indicou que os tratamentos com a terapêutica de drogas combinadas em doses de 12,5 mg/kg por 28 dias consecutivos significantemente (p < 0,001) reduziu a carga parasitária no baço quando comparada a tratamentos com uma única droga dada nas mesmas dosagens. Embora a carga parasitária tenha sido levemente mais baixa (p < 0.05) no grupo Anfotericina B quando comparada com o grupo tratado Dim-Art, o estudo presente demonstra a vantagem positiva do uso potencial da terapêutica combinada Dim-Art sobre drogas como Dim ou Art quando usadas isoladamente. Posterior avaliação é recomendada para determinar a média de combinação mais eficaz dos dois compostos.

Experimental infection with Rangelia vitalii in dogs: acute phase, parasitemia, biological cycle, clinical-pathological aspects and treatment.

Recently we conducted the molecular characterization of Rangelia vitalii, a protozoan with high pathogenicity for young dogs in southern Brazil. To date, the descriptions of the disease have been restricted to natural infection cases. Therefore, this study aimed to evaluate the parasitemia, biological cycles and clinical-pathological findings in dogs experimentally infected with R. vitalii in the acute phase of disease, and also aimed to test a therapeutic protocol based on the diminazene aceturate. For this study, we used 12 young dogs (females), separated into two groups. Group A was composed of healthy dogs, not-infected (n=5), and Group B consisted of animals infected with R. vitalii (n=7). After infection, the animals were monitored by blood smear examinations, which showed intra-erythrocytic forms of the parasite 5 days post-infection (PI). Parasitemia increased progressively in these animals and had the highest peak of circulating parasites between 9 and 11 days PI. Subsequently, the parasitemia reduced and the protozoan was seen inside the leukocytes in days 17, 19 and 21 PI. The most prominent clinical signs observed at the 20 day PI of experiment were lethargy, fever and anorexia. We observed a decrease of hematocrit of infected animals compared with not-infected dogs, featuring a moderate anemia. Pathological evaluation of one dog in Group B at day 21 PI revealed splenomegaly, hepatomegaly, lymphadenopathy, and hemorrhages at necropsy. Histological examination showed only follicular hyperplasia in the spleen and lymph nodes, and the etiologic agent in the vascular endothelium. At 21 days PI, it was performed the treatment of dogs in Group B (n=6) with a single dose of diminazene aceturate, which showed a curative efficacy of 100% in cleaning R. vitalii from blood of infected dogs.

Diminazene aceturate associated with sodium selenite and vitamin E in the treatment of Trypanosoma evansi infection in rats.

The aim of this study was to evaluate the utilization of a standard treatment with diminazene aceturate against the infection caused by Trypanosoma evansi, associated to sodium selenite and vitamin E. In vitro tests showed trypanocidal effect related to the treatment with diminazene aceturate and sodium selenite, but vitamin E had no harmful effect on the trypanosomes. In vivo experiments utilized a total of 72 adult outbreed females rats, separated into 9 groups (A, B, C, D, E, F, G, H and I), 8 animals each. Group A was the uninfected group; groups B to I were infected with 0.2mL of blood containing 10(6) trypanosomes. Parasitemia was estimated daily by microscopic examination of blood smears. Group B served as positive control; group C was treated with diminazene aceturate; group D with sodium selenite; group E with vitamin E; group F received an association of diminazene aceturate and sodium selenite; group G received an association of diminazene aceturate and vitamin E; group H received an association of diminazene aceturate, sodium selenite and vitamin E, and group I received an association of sodium selenite and vitamin E. Diminazene aceturate was administrated in a single dose on the 3rd day post infection (PI). Sodium selenite and vitamin E were administered at the 3rd and 23rd day PI. In vivo tests showed increase of longevity in groups treated with diminazene aceturate associated with sodium selenite (groups F and H). No difference was found between groups C and E, thus the vitamin E did not increase the efficacy of treatment against T. evansi when associated to diminazene aceturate. The curative efficacy of treatments was 37.5, 87.7, 37.7 and 75% to the groups C, F, G and H, respectively. Other treatments showed no efficacy. The sodium selenite when combined with chemotherapy may represent an alternative in the treatment of trypanosomosis.

A new therherapeutic prrotocol f for dogs infectted with Trrypanosoma evansi

Background: Trypanosomosis is a disease caused by a flagellate protozoan known as Trypanosoma evansi, transmitted by hematophagous insects. It parasites showed a large diversity of mammalian hosts. Dogs may show clinical changes such as weight loss, progressive weakness, anorexia, anemia, intermittent fever, conjunctivitis, swelling of limbs and increased of superficial lymph nodes. Treatment of trypanosomosis relies on the use of diminazene aceturate which is effective for the treatment of disease in infected animals. However, a single dose of drug are not effective for horses, mules and dogs, since drug neither cross the blood-brain barrier or has insufficient doses to control the T. evansi infection. Therefore, the present study aimed to report the curative efficacy of a new therapeutic protocol, based on diminazene aceturate, for dogs infected with T. evansi. Case: The treatment against trypanosomosis was performed in a dog, male, two years old, from the municipality of Uruguaiana, RS, Brazil.. The animal showing clinical signs such as apathy, vomit, increase of left submandibular lymph node, edema of the left face and change of gait in the hind limbs when it was evaluated by veterinarians. The hematological and biochemical parameters revealed normocytic-hypochromic anemia, thrombocytopenia, hyperglobulinemia and hypoalbuminemia. Trypomastigotes of T. evansi were identified in blood smears stained by panoptic method. The parasitism by T. evansi was confirmed by blood inoculation in two rats (xenodiagnosis) and by PCR T. evansi-specific. The canine was treated with diminazene aceturate (intramuscular injection) using a dose of 3.5 mg kg-1 for 5 days at 24h of intervals. After treatment the dog showed clinical signs of health improvement, and clinical signs disappeared after the seventh day of treatment. The parasite was not found in blood smears after the third day of treatment and PCR was negative on days 30 and 50 post-treatment. During the treatment signs of drug intoxication were not observed, as well as hepatic and renal functions were not affected. The animal showed normal biochemical and hematological parameters after 30 days of treatment. Discussion: In this study, the treatment tested was effective, leading to the cure of the disease. Previously, the same protocol was used for cats experimentally infected with T. evansi, obtaining 85.7% (6/7) of curative efficacy. In a comparative study of doses of diminazene aceturate in rats infected with T. evansi, inefficiency and death of rats treated with a single dose of 3.5 and 7.0 mg kg-1 were observed. In contrast, the cure in rats occurred when animals received a dose of 3.5 and 7.0 mg kg-1 during five consecutive days. The return of the parasitemia after treatment may be related to the impossibility of the medicament pass through the blood-brain barrier or the doses is insufficient. Our data reveal that five-dose protocol obtained higher efficiency because it provided greater passage of drug molecules through blood-brain barrier, which could eliminate the parasite from brain. After treatment, all clinical signs disappeared, biochemical and hematological parameters returned to normal levels, allowing us to conclude that this new protocol tested was effective to cure of this disease in dogs.(AU)

A new therherapeutic prrotocol f for dogs infectted with Trrypanosoma evansi

Background: Trypanosomosis is a disease caused by a flagellate protozoan known as Trypanosoma evansi, transmitted by hematophagous insects. It parasites showed a large diversity of mammalian hosts. Dogs may show clinical changes such as weight loss, progressive weakness, anorexia, anemia, intermittent fever, conjunctivitis, swelling of limbs and increased of superficial lymph nodes. Treatment of trypanosomosis relies on the use of diminazene aceturate which is effective for the treatment of disease in infected animals. However, a single dose of drug are not effective for horses, mules and dogs, since drug neither cross the blood-brain barrier or has insufficient doses to control the T. evansi infection. Therefore, the present study aimed to report the curative efficacy of a new therapeutic protocol, based on diminazene aceturate, for dogs infected with T. evansi. Case: The treatment against trypanosomosis was performed in a dog, male, two years old, from the municipality of Uruguaiana, RS, Brazil.. The animal showing clinical signs such as apathy, vomit, increase of left submandibular lymph node, edema of the left face and change of gait in the hind limbs when it was evaluated by veterinarians. The hematological and biochemical parameters revealed normocytic-hypochromic anemia, thrombocytopenia, hyperglobulinemia and hypoalbuminemia. Trypomastigotes of T. evansi were identified in blood smears stained by panoptic method. The parasitism by T. evansi was confirmed by blood inoculation in two rats (xenodiagnosis) and by PCR T. evansi-specific. The canine was treated with diminazene aceturate (intramuscular injection) using a dose of 3.5 mg kg-1 for 5 days at 24h of intervals. After treatment the dog showed clinical signs of health improvement, and clinical signs disappeared after the seventh day of treatment. The parasite was not found in blood smears after the third day of treatment and PCR was negative on days 30 and 50 post-treatment. During the treatment signs of drug intoxication were not observed, as well as hepatic and renal functions were not affected. The animal showed normal biochemical and hematological parameters after 30 days of treatment. Discussion: In this study, the treatment tested was effective, leading to the cure of the disease. Previously, the same protocol was used for cats experimentally infected with T. evansi, obtaining 85.7% (6/7) of curative efficacy. In a comparative study of doses of diminazene aceturate in rats infected with T. evansi, inefficiency and death of rats treated with a single dose of 3.5 and 7.0 mg kg-1 were observed. In contrast, the cure in rats occurred when animals received a dose of 3.5 and 7.0 mg kg-1 during five consecutive days. The return of the parasitemia after treatment may be related to the impossibility of the medicament pass through the blood-brain barrier or the doses is insufficient. Our data reveal that five-dose protocol obtained higher efficiency because it provided greater passage of drug molecules through blood-brain barrier, which could eliminate the parasite from brain. After treatment, all clinical signs disappeared, biochemical and hematological parameters returned to normal levels, allowing us to conclude that this new protocol tested was effective to cure of this disease in dogs.

Diminazene aceturate in the control of Trypanosoma evansi infection in cats.

The aim of this study was to investigate the efficacy of diminazene aceturate in the control of the infection by Trypanosoma evansi in cats. Fourteen animals were infected with 10(8) trypomastigote forms each and six were used as negative control (group A). Seven of the infected cats were used as positive control (group B) and seven were treated with diminazene aceturate (3.5 mg kg(-1)) for 5 consecutive days (group C). Biochemical and hematological parameters were evaluated during the experiment. Blood with anticoagulant was collected at day 49 post-inoculation and preserved in ethanol for DNA extraction. Samples were analyzed using PCR T. evansi-specific to assess the effectiveness of treatment. The treatment with diminazene aceturate had an efficacy of 85.7%. Alanine aminotransferase, gamma-glutamyltransferase, urea, and creatinine values remained within the normal physiological range in the treated cats. Hemogram was normalized in all the cured animals. Therefore, the therapy used is effective in controlling T. evansi in cats.

Efecto de la infusión de quishuar (Buddleja incana) y diminaceno en el tratamiento de la papilomatosis oral canina / Effect infusion quishuar (Buddleja incana) and diminaceno in treating the papillomatosis oral canina

Se realizó un estudio con la finalidad de evaluar el efecto de la infusión de quishuar (Buddleja incana) y el diminaceno, sólos y combinados, en el tratamiento de la papilomatosis oral canina (POC). Para tal efecto se utilizaron 12 perros diagnosticados con la enfermedad, por métodos clínicos e histopatológicos. Se formaron cuatro grupos con igual número de animales. Se realizaron exámenes hematológicos a todos los animales antes y después del tratamiento. Mientras en el grupo T no hubo regresión de los papilomas, en el grupo T regresionaron totalmente los papilomas a los 60 días promedio, también en el grupo T se produjo la involución total de los papilomas, pero en un tiempo promedio de 21 días, y en el grupo T, dos de tres perros curaron completamente en 21 días promedio. Se concluye que el tratamiento con diminaceno en inyección intramuscular, una vez por semana es efectivo para producir involución total de los papilomas en un tiempo corto de 21 días. Asimismo, cuando se combina con administración oral de infusión de quishuar, el resultado es similar; por lo que se convierten en una real alternativa de terapia para curar la papilomatosis oral canina.

A study to evaluate the effect of the infusion of quishuar (Buddleja incana) and diminaceno, alone and in combination in the treatment of canine oral papillomatosis (POC). To this end 12 dogs were diagnosed with the disease, clinical and histopathological methods. They were divided into four groups with equal numbers of animals. Blood tests were performed on all animals before and after treatment. T0 in the group while there was no regression of papillomas in group T1 regresionaron totally papillomas to average 60 days, also in the group T2 was involution of the papillomas, but in an average time of 21 days, and T3 in group two of three dogs healed completely in 21 days on average. We conclude that treatment with diminaceno intramuscular injection once a week, is effective in producing complete regression of papillomas in a short time of 21 days. Also, when combined with oral administration of infusion quishuar, the result is similar, so it becomes a real alternative therapy to cure canine oral papillomatosis.