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Background: Loxoscelism refers to a set of clinical manifestations caused by the bite of spiders from the Loxosceles genus. The classic clinical symptoms are characterized by an intense inflammatory reaction at the bite site followed by local necrosis and can be classified as cutaneous loxoscelism. This cutaneous form presents difficult healing, and the proposed treatments are not specific or effective. This study aimed to evaluate the protective effect of mesenchymal stromal cells-derived secretome on dermonecrosis induced by Loxosceles intermedia spider venom in rabbits. Methods: Sixteen rabbits were distributed into four groups (n = 4). Except for group 1 (G1), which received only PBS, the other three groups (G2, G3, and G4) were initially challenged with 10 µg of L. intermedia venom, diluted in 100 µL of NaCl 0.9%, by intradermic injection in the interscapular region. Thirty minutes after the challenge all groups were treated with secretome, except for group 2. Group 1 (G1-control group) received intradermal injection (ID) of 60 µg of secretome in 0.15 M PBS; Group 2 (G2) received 0.9% NaCl via ID; Group 3 (G3) received 60 µg of secretome, via ID and Group 4 (G4), received 60 µg of secretome by intravenous route. Rabbits were evaluated daily and after 15 days were euthanized, necropsied and skin samples around the necrotic lesions were collected for histological analysis. Results: Rabbits of G1 did not present edema, erythema, hemorrhagic halo, or necrosis. In animals from G2, G3, and G4, edema appeared after 6h. However, minor edema was observed in the animals of G2 and G3. Hemorrhagic halo was observed in animals, six hours and three days after, on G2, G3, and G4. Macroscopically, in G4, only one animal out of four had a lesion that evolved into a dermonecrotic wound. No changes were observed in the skin of the animals of G1, by microscopic evaluation. All animals challenged with L. intermedia venom showed similar alterations, such as necrosis and heterophilic infiltration. However, animals from G4 showed fibroblast activation, early development of connective tissue, neovascularization, and tissue re-epithelialization, indicating a more prominent healing process. Conclusion: These results suggest that secretome from mesenchymal stromal cells cultured in a xeno-free and human component-free culture media can be promising to treat dermonecrosis caused after Loxosceles spiders bite envenoming.
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Anthropogenic activities are the main sources of soil, air, and water pollution by metals, including cadmium (Cd), lead (Pb), chromium (Cr), the metalloid arsenic (As), magnesium (Mg), zinc (Zn), and copper (Cu). The goal of this study was to assess the presence and concentration of toxic (As, Cd, Pb, and Cr) and essential metals (Mg, Zn, and Cu) in the liver and kidneys from 96 free-ranging rattlesnakes (Crotalus durissus) from Minas Gerais (Brazil). Bioaccumulation of Cd and Pb were significantly higher in males and heavier rattlesnakes (those with body weight above the average of the study population). Average ± standard deviations of Cd, Pb, Cr, Cu, Mg, Zn, and As in the general population (n = 96) were 3.19 ± 2.52; 5.98 ± 8.49; 0.66 ± 1.97; 3.27 ± 2.85; 776.14 ± 2982.92; 27.44 ± 29.55; and 0.32 ± 1.46; respectively. Bioaccumulation of some metals correlated positively with changes in hematologic and serum biochemical parameters. Results of this study were contrasted with previous studies assessing metal bioaccumulation in other species of terrestrial or aquatic snakes. Considering their position in the food chain and the broad range of bioaccumulation of both toxic and essential metals observed in this study, rattlesnakes may function as highly relevant biological sentinels for environmental pollution.
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Crotalus , Monitoreo del Ambiente , Metales Pesados , Animales , Metales Pesados/metabolismo , Brasil , Crotalus/metabolismo , Masculino , Bioacumulación , Femenino , Serpientes VenenosasRESUMEN
Dogs with visceral leishmaniasis play a key role in the transmission cycle of Leishmania infantum to humans in the urban environment. There is a consensus regarding the importance of developing a vaccine to control this disease. Despite many efforts to develop a protective vaccine against CVL, the ones currently available, Leish-tec® and LetiFend®, have limited effectiveness. This is due, in part, to the complexity of the immune response of the naturally infected dogs against the parasite and the complexity of the parasite transmission cycle. Thus, strategies, such as the development of a transmission-blocking vaccines (TBVs) already being applied to other vector-borne diseases like malaria and dengue, would be an attractive alternative to control leishmaniasis. TBVs induce the production of antibodies in the vertebrate host, which can inhibit parasite development in the vector and/or interfere with aspects of vector biology, leading to an interruption of parasite transmission. To date, there are few TBV studies for CVL and other leishmaniasis forms. However, the few studies that exist show promising results, thus justifying the further development of this approach.
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Paracetamol (PAR) is a drug widely used in human and veterinary medicine as an analgesic and antipyretic, often involved in cases of intoxication. The most common clinical signs result from damage to red blood cells and hepatocytes, and this intoxication is considered a model for the induction of acute liver failure. In the present study, the hepatoprotective effects of coenzyme Q10 (CoQ10) and N-acetylcysteine (NAC) against experimental paracetamol (PAR) poisoning were analysed. Thirty-five adult Wistar rats (Rattus novergicus albinus) were randomly assigned to five groups, and thirty-one of these survived the treatments. Negative control group (CON-) received 1mL of 0.9% NaCl orally (PO). Other groups received 1.2g/kg of PAR (PO). Positive control group (CON+) received only PAR. NAC group received 800 mg/kg intraperitoneally (IP) of NAC 1h after the administration of PAR and at 12 h received 1mL of 0.9% NaCl, IP. The fourth group (CoQ10) received 1h and 12 h after intoxication, CoQ10 (10mg/kg IP). And the fifth group (NAC+CoQ10) received NAC (800mg/kg, IP) and CoQ10 (10mg/kg, IP). After 12 hours, the rats were euthanized and necropsied to collect liver and kidney tissues for histopathological evaluation and electronic microscopy. A single dose of PAR caused severe acute hepatitis. NAC couldn't reverse the liver and kidney damages. The group that received CoQ10 and NAC had moderate liver damage, while the group that received only CoQ10 had lower values of liver enzymes and mild liver and kidney damage. Animals that received treatment with CoQ10 or NAC+CoQ10 presented normal hepatocyte mitochondria and nuclei. Although CoQ10 couldn't reverse PAR organ damage, results indicate promising hepatoprotection in Wistar rats.
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Acetaminofén , Acetilcisteína , Adulto , Humanos , Ratas , Animales , Acetilcisteína/farmacología , Acetilcisteína/uso terapéutico , Ratas Wistar , Solución SalinaRESUMEN
Solanum glaucophyllum Desf. is a calcinogenic plant responsible for enzootic calcinosis that affects ruminants and causes alterations in bone and cartilaginous tissues, among others. It is believed that changes in cartilage tissue, with reduced bone growth, are due to hypercalcitoninism, caused by excess vitamin D. However, we hypothesized that S. glaucophyllum Desf. can act directly on chondrocytes and therefore, chondrocyte cultures from the epiphysis of the long bones of newborn rats were used as a model to elucidate the direct effects of S. glaucophyllum Desf. on bone growth. Plant samples were collected from Cañuelas, Argentina. An aliquot of the plant extract was used to quantify vitamin D (1,25(OH)2D3). The effects of the three concentrations of the plant extract were tested in cultures of chondrocytes extracted from the epiphyses of the long bones of 32 three-day-old Wistar rats. A control group (without extract), and three groups treated with different concentrations of plant extract were formed: group 1 (100 µL/L); group 2 (1 mL/L), and group 3 (5 mL/L), containing respectively 1 × 10-9 M, 1 × 10-8 M, and 5 × 10-8 M of 1,25(OH)2D3. After 7, 14, and 21 days of culture, MTT assay for cell viability, alkaline phosphatase activity, and quantification of the percentage of areas with glycosaminoglycans (GAG) stained with periodic acid-Schiff (PAS) were performed. On day 7, all chondrocytes in group 3, that is, those with the highest concentration of plant extract, died. On days 14 and 21, groups 1 and 2 showed a significant reduction in chondrocyte viability compared to the control. At 7, 14, and 21 days, groups 1 and 2 showed significantly lower alkaline phosphatase activity than the control. On day 21, group 2 showed a significant reduction in areas with PAS + GAGs. There were no significant differences between the groups in the expression of gene transcripts for Sox9, Col2, ColX, and aggrecan. The S. glaucophyllum Desf. extract directly affected growing rat chondrocytes by reducing viability, alkaline phosphatase activity, and GAG synthesis without altering the expression of gene transcripts for Sox9, Col2, ColX, and aggrecan, which may be one of the mechanisms by which there is a reduction in bone growth in animals intoxicated by the plant.
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Condrocitos , Solanum glaucophyllum , Ratas , Animales , Condrocitos/metabolismo , Animales Recién Nacidos , Calcitriol/metabolismo , Ratas Wistar , Agrecanos/metabolismo , Fosfatasa Alcalina , Cartílago , Plantas , Vitamina D/metabolismo , Extractos Vegetales , Células CultivadasRESUMEN
Visceral leishmaniasis (VL) is a fatal disease caused by the protozoa Leishmania infantum for which dogs are the main reservoirs. A vaccine against canine visceral leishmaniasis (CVL) could be an important tool in the control of human and CVL by reducing the infection pressure of L. infantum. Despite the CVL vaccine available on the market, the Brazilian Ministry of Health did not implement the use of it in their control programs. In this sense, there is an urgent need to develop more efficient vaccines. In this study, the association between two polymeric nanoformulations, (poly (D, L-lactic) acid (PLA) polymer) loading Leishmania amazonensis antigens, was evaluated as a potential immunobiological agent against VL using golden hamsters as an experimental model. The results indicated that no significant adverse reactions were observed in animals vaccinated with LAPSmP. LAPSmP presented similar levels of total anti-Leishmania IgG as compared to LAPSmG. The LAPSmP and LAPSmG groups showed an intense reduction in liver and spleen parasitic load by qPCR. The LAPSmP and LAPSmG vaccines showed exceptional results, indicating that they may be promising candidates as a VL vaccine.
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Intravenous lipid emulsions (ILE) have been increasingly used to reverse a wide range of lipophilic drug intoxications. However, it is still unknown if these emulsions interfere with other lipophilic drugs routinely used while treating intoxicated patients, such as diazepam, one of the main antiepileptic drugs. Therefore, the objective of the present study was to evaluate whether the administration of a 20% ILE interferes with diazepam's clinical effect. We randomly allocated thirty rabbits to five groups. Three of those groups received diazepam (1.0 mg/kg, IV), one of which did not receive any additional treatment, while the two remaining groups were treated with ILE or lactated ringer solution (1.5 mL/kg followed by 0.25 mL/kg/min for 30 min). The fourth group only received lipid emulsion, and the fifth only lactated ringer. Successive neurological exams at 20 min intervals for a total of 100 min were performed to assess the rabbits' neurological state. We concluded that the ILE did not interfere with diazepam's clinical effect but, although unlikely, the possibility of recurrence of a sedative effect should be considered.
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Diazepam , Emulsiones Grasas Intravenosas , Conejos , Animales , Diazepam/farmacología , Emulsiones Grasas Intravenosas/uso terapéutico , Hipnóticos y SedantesRESUMEN
Background: Canine T-zone lymphoma (TZL) is recognized as an indolent CD45-T cell lymphoma, with low aggressiveness and high overall survival. The diagnosis is obtained by histopathology and immunohistochemistry, but also by cytological examination of the lymph node associated with immunophenotyping. Lymphocytosis is commonly identified as around 10,000 cells/µl and may reach 30,760 cells/µl. Case Description: The present report describes a case of a female Golden Retriever, nine years old, with generalized lymphadenopathy. In the cytological examination of the superficial cervical lymph node, a monomorphic population of small, "clear cells" and "hand mirror" lymphocyte shape was suggestive of TZL. The leukogram showed intense leukocytosis (160,050 cells/µl) due to small clear cell lymphocytosis (152,048 cells/µl). The myelogram showed a myeloid:erythroid ratio of 2:3; with a pyramidal distribution of cell types and the presence of 22.8% of lymphocytes in the differential count. Bone marrow, peripheral blood, and lymph node immunophenotyping resulted in lymphocyte gates with 97.3% to 99.5% CD5+, predominantly CD4-, CD8-, and CD45- confirming the diagnosis of TZL with associated leukemia. Treatment with chlorambucil and prednisolone was started. During the first month, the lymphocytosis remained above 200,000 cells/uL. After four months of treatment, there was a decrease in lymphocytes, which progressively reached a count of 10,800 cells/ul in the eleventh month. Conclusion: In the literature, lymphocytosis above 30,760 cells/µl has not been observed in TZLs. Thus, it is believed that this is the first report of extreme lymphocytosis with a slow response to chemotherapy.
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Enfermedades de los Perros , Linfocitosis , Linfoma de Células T , Perros , Animales , Femenino , Linfocitosis/diagnóstico , Linfocitosis/veterinaria , Linfocitosis/patología , Linfoma de Células T/veterinaria , Médula Ósea , Inmunohistoquímica , Enfermedades de los Perros/diagnóstico , Enfermedades de los Perros/patologíaRESUMEN
Abstract Doxorubicin (Dox) is a medication used in the treatment of cancerous tumors and hematologic malignancies with potentially serious side effects, including the risk of cardiotoxicity. Flavonoids are plant metabolites with antioxidant properties and can be extracted from Camellia sinensis (CS). The aim of this study is to evaluate the possible cardioprotective effect of CS against injuries induced by Dox in rats. A total of 32 animals were distributed into four groups: (1) control - intraperitoneal injection (I.P.) of 0.5 mL saline weekly and 1.0 mL water by gavage daily; (2) CS - 0.5 mL saline I.P. weekly and 200 mg/kg CS by gavage daily; (3) Dox - 5.0 mg/kg Dox I.P. weekly and 1.0 mL water by gavage daily; and (4) Dox+CS -5.0 mg/kg Dox I.P. weekly and 200 mg/kg CS by gavage daily. Clinical examinations, blood profiles, electrocardiograms, echocardiograms, and histological analyses of hearts were performed over 25 days. The animals in the Dox group showed changes in body weight and in erythrogram, leukogram, electrocardiography, and echocardiography readings. However, animals from the dox+CS group had significantly less change in body weight, improved cardiac function, and showed more preserved cardiac tissue. This study demonstrated that CS prevents dox-induced cardiotoxicity, despite enhancing the cytotoxic effect on blood cells
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Animales , Masculino , Ratas , Doxorrubicina/administración & dosificación , Camellia sinensis/efectos adversos , Cardiotoxicidad , Ecocardiografía/instrumentación , Neoplasias Hematológicas/patología , Electrocardiografía/instrumentación , Antioxidantes/farmacologíaRESUMEN
Cururu toad (Rhinella marina group) is widely distributed in Brazil. Lesser grison (Galitic cuja) is a South American mustelid. This is the first report of natural poisoning in a free-ranging lesser grison by Rhinella toad parotoid gland secretion (PGS). Five minutes after biting a toad, the lesser grison developed convulsion, dying within 1.5 h. Mass spectrometry analysis of a milky-whitish secretion found in the lesser grison oral cavity allowed identification of a bufotoxin and a new bufonid peptide.
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Péptidos , Animales , Brasil , Bufo marinusRESUMEN
BACKGROUND: Canine atopic dermatitis (cAD) is a chronic disease characterised by hypersensitivity to environmental allergens. Oclacitinib maleate selectively inhibits pro-inflammatory mediators associated with cAD. However, the impact of chronic oclacitinib use on immunocompetence requires further investigation. OBJECTIVES: Herein, we examined the potential immunomodulatory effects of prolonged oclacitinib treatment in dogs. ANIMALS: Thirteen privately owned dogs with cAD, treated with 0.4-0.6 mg/kg oclacitinib for 12 months. METHODS AND MATERIALS: Pruritus level was evaluated using a pruritus Visual Analog Scale (pVAS) and the canine atopic dermatitis extent and severity index, 4th iteration (CADESI IV). Peripheral blood samples were collected for routine laboratory assays and lymphocyte subtypes were analysed using flow cytometry. Antigen-specific intracellular cytokine production from CD4+ and CD8+ T lymphocytes was analysed following in vitro stimulation by Dermatophagoides farinae antigens. RESULTS: Oclacitinib treatment significantly reduced pVAS and CADESI-04 scores, by 51% and 86.7%, respectively. Flow cytometric analysis revealed increased CD4+ and CD14+ lymphocyte populations. The cytokine profile at 360 days after treatment initiation was similar to that before treatment and was not associated with clinical relapse. CONCLUSION: Oclacitinib, when administered at the currently labelled dose for one year, is associated with a significant increase in circulating CD4+ T cells, but does not alter cytokine production from antigen-stimulated T cells. The results reported do not support evidence for immunosuppression mediated by the mechanisms evaluated in this study.
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Dermatitis Atópica , Fármacos Dermatológicos , Enfermedades de los Perros , Animales , Dermatitis Atópica/complicaciones , Dermatitis Atópica/tratamiento farmacológico , Dermatitis Atópica/veterinaria , Fármacos Dermatológicos/uso terapéutico , Enfermedades de los Perros/tratamiento farmacológico , Perros , Maleatos/uso terapéutico , Pirimidinas , SulfonamidasRESUMEN
Rhipicephalus microplus, popularly known as the cattle tick, is the most important tick of livestock as it is responsible for significant economic losses. The use of chemical acaricides is still the most widely used control method despite its known disadvantages. Vaccination would be a safe alternative for the control of R. microplus and holds advantages over the use of chemical acaricides as it is environmental-friendly and leaves no residues in meat or milk. Two vaccines based on the Bm86 protein were commercialized, TickGARD® and Gavac®, with varying reported efficacies in different countries. The use of other vaccines, such as Tick Vac®, Go-Tick®, and Bovimune Ixovac® have been restricted to some countries. Several other proteins have been analyzed as possible antigens for more effective vaccines against R. microplus, including peptidases, serine proteinase inhibitors, glutathione S-transferases, metalloproteases, and ribosomal proteins, with efficacies ranging from 14% to 96%. Nonetheless, more research is needed to develop safe and efficient tick vaccines, such as the evaluation of the efficacy of antigens against other tick species to verify cross-reactivity and inclusion of additional antigens to promote the blocking of the infection and spreading of tick-borne diseases. This review summarizes the discoveries of candidate antigens for R. microplus tick vaccines as well as the methods used to test their efficacy.
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Enfermedades de los Bovinos , Rhipicephalus , Infestaciones por Garrapatas , Vacunas , Animales , Antígenos , Bovinos , Enfermedades de los Bovinos/prevención & control , Infestaciones por Garrapatas/prevención & control , Infestaciones por Garrapatas/veterinaria , VacunaciónRESUMEN
In the present study, we investigated the cardioactive glycosides oleandrin and ouabain, and compared them to digoxin in a model of cardiotoxicity induced by doxorubicin. Adult rats were distributed into four experimental groups. Each group was challenged with a single intraperitoneal application of doxorubicin at a dose of 12 mg/kg. Then, they were treated with saline solution and the glycosides oleandrin, ouabain, and digoxin at a dose of 50 µg/kg, for 7 days. They underwent echocardiography, electrocardiography, hematologic, biochemical tests, and microscopic evaluation of the heart. All animals presented congestive heart failure, which was verified by a reduction in the ejection fraction. Oleandrin and digoxin were able to significantly reduce (p < 0.05) the eccentric remodeling caused by doxorubicin. Oleandrin and digoxin were significantly lower (p < 0.05) than the control group in maintaining systolic volume and left ventricular volume in diastole. Other parameters evaluated did not show significant statistical differences. All animals showed an increase in erythrocyte count, and an increase in the duration of the QRS complex on the ECG and myocardial necrosis at the histopathological analysis. It is concluded that the glycosides oleandrin, ouabain, and digoxin in the used dosage do not present therapeutic potential for the treatment of congestive heart failure caused by doxorubicin.
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Cardenólidos/farmacología , Glicósidos Cardíacos/farmacología , Cardiotónicos/farmacología , Digoxina/farmacología , Insuficiencia Cardíaca/tratamiento farmacológico , Ouabaína/farmacología , Volumen Sistólico/efectos de los fármacos , Función Ventricular Izquierda/efectos de los fármacos , Remodelación Ventricular/efectos de los fármacos , Animales , Cardenólidos/toxicidad , Glicósidos Cardíacos/toxicidad , Cardiotónicos/toxicidad , Cardiotoxicidad , Digoxina/toxicidad , Modelos Animales de Enfermedad , Doxorrubicina , Insuficiencia Cardíaca/inducido químicamente , Insuficiencia Cardíaca/diagnóstico por imagen , Insuficiencia Cardíaca/fisiopatología , Ouabaína/toxicidad , Ratas Wistar , Recuperación de la FunciónRESUMEN
The Horse Agribusiness Complex is an important activity in the Brazilian agricultural sector. Mangalarga Marchador (MM) is the most numerous breed of horses in Brazil and its temperament and gait characteristics (4-beat stepping gait) allow for the constant growth of the breed and the performance of vs. equestrian activities. The training management currently adopted with MM horses is based on empiricism, and scientific support is necessary to improve the well-being of horses in competitions and maintain the physical integrity of these athletes. Therefore, this study aimed to verify the effects of stretching, warming up, and/or cooling down on their performance in marcha tests. 6 MM geldings (aged between 3 and 7 years and average weight of 400 kg) were used. The pre-experimental stage for the physical conditioning of the horses lasted 46 days. The experimental phase lasted 42 days and consisted of 6 marcha tests performed every 7 days. The experimental design was in a Latin square (6 × 6), in which each horse was submitted to the following exercise protocols: A) 50-min marcha test following the official regulations of the Brazilian Association of Horse Breeders Mangalarga Marchador (ABCCMM); B) 10 min of warm-up before marcha test; C) 10 min of cooling after marcha test; D) 10 min of warm-up before marcha and 10 min of cool-down after marcha test; E) 10 min of stretching before the marcha test; F) 10 min of stretching, 10 min of warm-up before and 10 min of cool-down after the test. Horses were evaluated before and after marcha tests for heart rate (HR), respiratory rate, rectal temperature, glucose, lactate, creatine kinase, aspartate aminotransferase and cortisol. Data were submitted to 2-way analysis of variance (exercise protocols and evaluation moments) and means were compared by Tukey's test (P≤0.05). The HR and blood lactate results indicated a beneficial effect of warm-up or stretching practices on the performance of Mangalarga Marchador horses submitted to simulated marcha tests in accordance with the official ABCCMM regulation and lasting 50 minutes.
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Condicionamiento Físico Animal , Ejercicio de Calentamiento , Animales , Marcha , Caballos , Ácido Láctico , Masculino , Rendimiento Físico FuncionalRESUMEN
Combination therapy between paclitaxel (PTX) and doxorubicin (DXR) is applied as the first-line treatment of breast cancer. Co-administration of drugs at synergistic ratio for treatment is facilitated with the use of nanocarriers, such as liposomes. However, despite the high response rate of solid tumors to this combination, a synergism of cardiotoxicity may limit the use. Thus, the objective of this work was to investigate the toxicity of long-circulating and fusogenic liposomes co-encapsulating PTX and DXR at the synergistic molar ratio (1:10) (LCFL-PTX/DXR). For this, clinical chemistry, histopathological analysis and electrocardiographic exams were performed on female Balb/c mice that received a single intravenous dose of LCFL-PTX/DXR. The results of the study indicated that the LD50 dose range (lethal dose for 50% of animals) of the LCFL-PTX/DXR treatment (28.9-34.7 mg/kg) is much higher than that found for free PTX/DXR treatment (20.8-23.1 mg/kg). In addition, liposomes promoted cardiac protection by not raising CK-MB levels in animals, keeping cardiomyocytes without injury or electrocardiographic changes. After 14 days of treatment, free PTX/DXR caused prolongation of the QRS interval when compared to LCFL-PTX/DXR treatment at the same dose (37.0 ± 5.01 ms and 30.83 ± 2.62 ms, respectively, with p = 0.017). The survival rate of animals treated with LCFL-PTX/DXR was three times higher than that of those treated with free drugs. Thus, it was established that the toxicity of LCFL-PTX/DXR is reduced compared to the combination of free PTX/DXR and this platform has advantages for the clinical treatment of breast cancer.
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Protocolos de Quimioterapia Combinada Antineoplásica/toxicidad , Doxorrubicina/toxicidad , Cardiopatías/inducido químicamente , Lípidos/química , Miocitos Cardíacos/efectos de los fármacos , Paclitaxel/toxicidad , Potenciales de Acción/efectos de los fármacos , Administración Intravenosa , Animales , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/química , Cardiotoxicidad , Doxorrubicina/administración & dosificación , Doxorrubicina/química , Composición de Medicamentos , Sinergismo Farmacológico , Electrocardiografía , Femenino , Cardiopatías/metabolismo , Cardiopatías/patología , Dosificación Letal Mediana , Liposomas , Ratones Endogámicos BALB C , Miocitos Cardíacos/metabolismo , Miocitos Cardíacos/patología , Paclitaxel/administración & dosificación , Paclitaxel/químicaRESUMEN
Cardiac disease is of importance in captive chimpanzee (Pan troglodytes) health. Here we report an eosinophilic and necrotizing myocarditis in a 17-y-old chimpanzee with no previous history of cardiac disease that progressed to death within 48 h. Toxic and infectious causes were ruled out. The chimpanzee had eosinophilia at different occasions in previous years. The animal had a severe, diffuse, and acute monophasic necrotizing myocarditis, with a moderate lymphoplasmacytic infiltrate that was rich in eosinophils. Ante- and postmortem investigations are compatible with an unusual eosinophilic myocarditis with clinical evolution and morphology comparable with human eosinophilic myocarditis secondary to hypereosinophilic syndrome.
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Enfermedades del Simio Antropoideo/patología , Eosinofilia/veterinaria , Miocarditis/veterinaria , Miocardio/patología , Pan troglodytes , Animales , Eosinofilia/patología , Resultado Fatal , Masculino , Miocarditis/patología , Necrosis/patología , Necrosis/veterinariaRESUMEN
Myocardial infarction (MI) is the irreversible injury of the myocardium caused by prolonged myocardial ischemia and is a major cause of heart failure and eventual death among ischemic patients. The present study assessed the protective potentials of andrographolide against isoproterenol-induced myocardial infarction in rats. Animals were randomly divided into four groups: Control (Ctr) group received 0.9% saline solution once daily for 21 days, Isoproterenol (Iso) group received 0.9% saline solution once daily for 19 days followed by 80 mg/kg/day of isoproterenol hydrochloride solution on day 20 and 21, Andrographolide (Andro) group received 20 mg/kg/day of andrographolide for 21 days, and Andrographolide plus Isoproterenol (Andro + Iso) group received 20 mg/kg/day of andrographolide for 21 days with co-administration of 80 mg/kg/day of isoproterenol hydrochloride solution on day 20 and 21. After all treatments, cardiac-specific parameters that define cardiac health and early subacute MI were measured in all groups using both biophysical and pharmacological assay methods. Isoproterenol administration significantly (P < 0.05) increased cardiac mass indexes, systemic cardiac biomarkers, infarct size and caused cardiac histological alterations; significantly (P < 0.05) increased heart rate, QRS & QTc intervals and caused ST-segment elevation; significantly (P < 0.05) increased myocytes shortening, action potential duration (APD), L-type Ca2+ current (ICa,L) density and significantly (P < 0.05) decreased transient outward K+ current (Ito) density typical of the early subacute MI. Interestingly, pretreatment with andrographolide prevented and or minimized these anomalies, notably, by reducing ICa,L density and increasing Ito density significantly. Therefore, andrographolide could be seen as a promising therapeutic agent capable of making the heart resistant to early subacute infarction and it could be used as template for the development of semisynthetic drug(s) for cardiac protection against MI.
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Bloqueadores de los Canales de Calcio/farmacología , Cardiotónicos/farmacología , Diterpenos/farmacología , Infarto del Miocardio/prevención & control , Canales de Potasio/agonistas , Potenciales de Acción/efectos de los fármacos , Animales , Bloqueadores de los Canales de Calcio/uso terapéutico , Canales de Calcio Tipo L/metabolismo , Cardiotónicos/uso terapéutico , Modelos Animales de Enfermedad , Diterpenos/uso terapéutico , Electrocardiografía/efectos de los fármacos , Humanos , Isoproterenol/administración & dosificación , Isoproterenol/toxicidad , Masculino , Infarto del Miocardio/inducido químicamente , Infarto del Miocardio/diagnóstico , Canales de Potasio/metabolismo , RatasRESUMEN
OBJECTIVE: To determine the effect and safety of IV lipid emulsion in rabbits with acute ivermectin toxicosis. DESIGN: Randomized controlled trial. SETTING: University research facility. ANIMALS: Twenty-four healthy male adult New Zealand rabbits. INTERVENTIONS: Three groups of rabbits (IV, IV_RL, and IV_LE) received 80 mg/kg of ivermectin (8 mL/kg) through a nasogastric tube, and 1 group (LE) received an equivalent volume (8 mL/kg) of 0.9% sodium chloride. Group IV_RL was treated with Ringer's lactate (2 mL/kg bolus, followed by 0.25 mL/kg/min for 60 minutes), whereas groups IV_LE and LE received 20% lipid emulsion. The rabbits were submitted to clinical and neurological evaluation, and blood samples were collected for biochemical analysis. All animals were euthanized, and tissue samples were collected and processed for histopathological evaluation and ivermectin quantification. MEASUREMENTS AND MAIN RESULTS: All animals exposed to ivermectin manifested clinical changes consistent with toxicosis, but the ones that received IV lipid emulsion infusion showed no significant clinical improvement. Intense increase in serum glucose and triglyceride concentrations was seen after ivermectin exposure, along with increased urea and creatinine concentrations, but the last 2 remained within the reference range. Lipid emulsion caused an intense increase in triglycerides and cholesterol concentrations. No pathological abnormalities were seen in the organs sampled. Toxicological analysis showed greater ivermectin concentration in adipose tissue and liver, followed by kidney and, finally, brain. The treatments did not change ivermectin tissue concentration. CONCLUSIONS: When given to rabbits intoxicated with ivermectin, IV lipid emulsion was biochemically and histologically safe but was not effective in treating, delaying, or reversing clinical signs and progression, nor did it alter ivermectin tissue concentration.
Asunto(s)
Antiparasitarios/toxicidad , Emulsiones Grasas Intravenosas/uso terapéutico , Ivermectina/toxicidad , Conejos , Animales , Antiparasitarios/administración & dosificación , Ivermectina/administración & dosificación , Masculino , Lactato de Ringer/administración & dosificaciónRESUMEN
Micrurus surinamensis is a coral snake from the Elapidae family of wide distribution in Amazonia Forest. Its venom contains neurotoxins that induce muscular and respiratory paralysis; however, its cardiovascular action is not yet characterized. The aim of this study was to investigate the cardiotoxic effects caused by M. surinamensis poisoning in rodents. Twelve guinea pigs (Cavia porcellus) were distributed in two groups (n = 6) named as control and envenomed. The control group received 0.2 ml of PBS/BSA via intramuscular injection (IM), while envenomed animals received 0.75 µg of venom per g of body weight, also via IM. Electrocardiographic examination (ECG) and biochemical serum tests were conducted before and 2 h after inoculation. ECG of the envenomed animals revealed severe progressive arrhythmias including atrioventricular block, supraventricular, and ventricular extrasystoles. Serum biochemistry showed significant increase in CK, CK-MB, and LDH enzymes corroborating the skeletal and cardiac muscle damage. Myonecrosis and degeneration were observed in both skeletal and heart muscle; nevertheless, transmission electron microscopy revealed cardiac muscle fibers fragmentation. In conclusion, M. surinamensis venom has a potent cardiotoxic activity eliciting arrhythmogenic effects and heart damage after only 2 h of envenomation.
Asunto(s)
Arritmias Cardíacas/inducido químicamente , Serpientes de Coral , Venenos Elapídicos/toxicidad , Animales , Arritmias Cardíacas/fisiopatología , Complejos Atriales Prematuros/inducido químicamente , Complejos Atriales Prematuros/fisiopatología , Bloqueo Atrioventricular/inducido químicamente , Bloqueo Atrioventricular/fisiopatología , Cardiotoxicidad , Cobayas , Frecuencia Cardíaca/efectos de los fármacos , Masculino , Músculo Esquelético/efectos de los fármacos , Músculo Esquelético/patología , Miocitos Cardíacos/efectos de los fármacos , Miocitos Cardíacos/metabolismo , Miocitos Cardíacos/ultraestructura , Necrosis , Factores de Tiempo , Complejos Prematuros Ventriculares/inducido químicamente , Complejos Prematuros Ventriculares/fisiopatologíaRESUMEN
Ticks are considered the most important vectors in veterinary medicine with a profound impact on animal health worldwide, as well as being key vectors of diseases affecting household pets. The leading strategy applied to dog tick control is the continued use of acaricides. However, this approach is not sustainable due to surging tick resistance, growing public concern over pesticide residues in food and in the environment, and the rising costs associated with their development. In contrast, tick vaccines are a cost-effective and environmentally friendly alternative against tick-borne diseases by controlling vector infestations and reducing pathogen transmission. These premises have encouraged researchers to develop an effective vaccine against ticks, with several proteins having been characterized and used in native, synthetic, and recombinant forms as antigens in immunizations. The growing interaction between domestic pets and people underscores the importance of developing new tick control measures that require effective screening platforms applied to vaccine development. However, as reviewed in this paper, very little progress has been made in controlling ectoparasite infestations in pets using the vaccine approach. The control of tick infestations and pathogen transmission could be obtained through immunization programs aimed at reducing the tick population and interfering in the pathogenic transmission that affects human and animal health on a global scale.