RESUMO
BACKGROUND: Toxocara canis (T. canis) is a helminth parasite of zoonotic and veterinary health significance that causes the disease known as Toxocariasis. This disease has been associated with conditions of poverty, especially in tropical climate zones throughout the world. Although it rarely causes important clinical manifestations, T. canis can lead to blindness, meningoencephalitis, or other nervous manifestations in humans. Moreover, some studies show its importance in the development of tumor growth, which have been associated with the parasite's ability to modulate the host's immune response. While different studies have evaluated the immune response during this disease, currently, there are no studies where the infection is analyzed from the perspective of sexual dimorphism. METHODS: To evaluate sex differences in susceptibility, we analyzed lesions and parasite loads in lung and liver at 7 days post-infection. In addition, immune cell subpopulations were analyzed in spleen, mesenteric and peripheral lymph nodes. Finally, the production of cytokines and specific antibodies were determined in the serum. Statical analyses were performed using a Two-way ANOVA and a post-hoc Bonferroni multiple comparison test. RESULTS: Female rats had a higher number of larvae in the liver, while male rats had them in the lungs. The percentages of immune cells were evaluated, and in most cases, no significant differences were observed. Regarding the cytokines production, infection can generate a decrease in Th1 such as IL-1ß in both sexes and IL-6 only in females. In the case of Th2, IL-4 increases only in infected males and IL-5 increases in males while decreasing in females due to the effect of infection. IL-10 also decreases in both sexes as a consequence of the infection, and TGF-ß only in females. Finally, the infection generates the production of antibodies against the parasite, however, their quantity is lower in females. CONCLUSIONS: This study demonstrates that T. canis infection is dimorphic and affects females more than males. This is due to a polarization of the inadequate immune response, which is reflected as a higher parasite load in this sex.
Assuntos
Toxocara canis , Toxocaríase , Humanos , Feminino , Ratos , Masculino , Animais , Toxocaríase/parasitologia , Toxocaríase/patologia , Toxocara canis/fisiologia , Caracteres Sexuais , Citocinas , ImunidadeRESUMO
Ruminant coccidiosis is a gastrointestinal disease caused by parasites of the genus Eimeria. Environmental and climatic factors are relevant for the development, survival, and transmission of coccidiosis because Eimeria oocysts are able to survive in the environment for several weeks or months in favorable conditions of moderate heat and moisture. The aim of the present study was to georeference, for the first time, the locations of Eimeria occurrences in Mexico from 1961 to 2018. A dataset was created for 3414 reports of Eimeria occurrences in cattle, sheep, and goats in Mexico. Twelve species of Eimeria that infect cattle were recorded, 11 Eimeria species of sheep are present in Mexico, and eight species of goats are geographically distributed in the country. In the current findings, it has been observed that Eimeria colonizes mainly the temperate semihumid, temperate humid, warm humid, and warm semihumid areas during spring and summer in animals younger than 1 year of age. Macroenvironmental variables like temperature and rainfall influence the prevalence of Eimeria in cattle, sheep, and goats, and for some species, the rearing system, facility type, farm size, and altitude affect the occurrence of this parasite. Results may support future studies aimed at reducing the disease prevalence of the parasite in endemic regions of Mexico. The use of recorded cases and climate variables yields a more comprehensive perspective of the epidemiology of eimeriosis, which would be difficult to infer from laboratory studies alone.
Assuntos
Doenças dos Bovinos/parasitologia , Coccidiose/veterinária , Eimeria/isolamento & purificação , Doenças dos Ovinos/parasitologia , Animais , Bovinos , Doenças dos Bovinos/epidemiologia , Clima , Coccidiose/epidemiologia , Coccidiose/parasitologia , Eimeria/classificação , Cabras , México/epidemiologia , Estações do Ano , Ovinos , Doenças dos Ovinos/epidemiologiaRESUMO
The tick genus Ripicephalus (Boophilus), particularly R. microplus, is one of the most important ectoparasites that affects livestock health and considered an epidemiological risk because it causes significant economic losses due, mainly, to restrictions in the export of infested animals to several countries. Its spatial distribution has been tied to environmental factors, mainly warm temperatures and high relative humidity. In this work, we integrated a dataset consisting of 5843 records of Rhipicephalus spp., in Mexico covering close to 50 years to know which environmental variables mostly influence this ticks' distribution. Occurrences were georeferenced using the software DIVA-GIS and the potential current distribution was modelled using the maximum entropy method (Maxent). The algorithm generated a map of high predictive capability (Area under the curve = 0.942), providing the various contribution and permutation importance of the tested variables. Precipitation seasonality, particularly in March, and isothermality were found to be the most significant climate variables in determining the probability of spatial distribution of Rhipicephalus spp. in Mexico (15.7%, 36.0% and 11.1%, respectively). Our findings demonstrate that Rhipicephalus has colonized Mexico widely, including areas characterized by different types of climate. We conclude that the Maxent distribution model using Rhipicephalus records and a set of environmental variables can predict the extent of the tick range in this country, information that should support the development of integrated control strategies.
Assuntos
Rhipicephalus , Análise Espacial , Infestações por Carrapato/epidemiologia , Animais , Bovinos , Doenças dos Bovinos/parasitologia , Conjuntos de Dados como Assunto , México/epidemiologiaRESUMO
Besnoitia besnoiti is the causative agent of bovine besnoitiosis. B. besnoiti infections lead to reduced fertility and productivity in cattle causing high economic losses, not only in Europe, but also in Asia and Africa. Mild to severe clinical signs, such as anasarca, oedema, orchitis, hyperkeratosis, and characteristic skin and mucosal cysts, are due to B. besnoiti tachyzoite and bradyzoite replication in intermediate host tissues. So far, there are no commercially available effective drugs against this parasite. Curcumin, a polyphenolic compound from Curcuma longa rhizome is well-known for its antioxidant, anti-inflammatory, immunomodulatory and also anti-protozoan effects. Hence, the objective of this study was to evaluate the effects of curcumin on viability, motility, invasive capacity, and proliferation of B. besnoiti tachyzoites replicating in primary bovine umbilical vein endothelial cells (BUVEC) in vitro. Functional inhibition assays revealed that curcumin treatments reduce tachyzoite viability and induce lethal effects in up to 57% of tachyzoites (IC50 in 5.93 µM). Referring to general motility, significant dose-dependent effects of curcumin treatments were observed. Interestingly, curcumin treatments only dampened helical gliding and twirling activities whilst longitudinal gliding motility was not significantly affected. In addition, curcumin pretreatments of tachyzoites resulted in a dose-dependent reduction of host cell invasion as detected by infections rates at 1 day p. i. These findings demonstrate feeding cattle with Curcuma longa rhizomes may represent a new strategy for besnoitiosis treatment.
RESUMO
BACKGROUND: Giardia parasites cause gastrointestinal disease in humans, dogs, and many other animals worldwide. The treatment of dogs for giardiasis requires further investigation to ascertain levels of drug efficacy and the possibility of adverse side effects. Nitazoxanide (NTZ) has shown good clinical anti-Giardia activity in humans, yet it has not been evaluated for the treatment of giardiasis in dogs. METHODS: Thirty-five dogs, naturally infected with Giardia were divided into five groups (n = 7): dogs in group NTZ1, NTZ2, and NTZ3 were treated with a single oral dose of 37.5 mg/kg, 75 mg/kg, and 150 mg/kg, respectively, of NTZ on days 0 and 14. The fourth group was treated with a commercially available regimen that includes a combination of pyrantel, praziquantel, and febantel (FEB) administered orally for three consecutive days. Additionally, an untreated control group was established. Giardia cysts from the stool of each dog were quantified on days -3, 0, 5, 7, 9, 11, 14, 18, 25, and 28. Biochemical parameters were evaluated in all dogs, before the first treatment and after concluding the experiment. RESULTS: Shedding of Giardia cysts was reduced in all treated groups when compared to untreated controls (P < 0.01). However, NTZ2, NTZ3, and FEB had a lower risk during the study. Furthermore, NTZ was also effective against another protozoan, Cryptosporidium spp. at doses of 75 mg/kg and 150 mg/kg, in contrast to the combination of febantel + pyrantel + praziquantel. Biochemical parameters of treated animals, namely, aspartate transaminase and alanine transaminase enzymes, remained within physiological ranges. CONCLUSIONS: Based on these results, the implementation of NTZ as a treatment for giardiasis in dogs is proposed. The administration of a single dose is an important advantage of NTZ because it reduces workload, particularly in animals placed in shelters and kennels, where handling of large numbers of animals is required, and personnel is frequently scarce.
Assuntos
Antiprotozoários/uso terapêutico , Doenças do Cão/tratamento farmacológico , Giardíase/veterinária , Tiazóis/efeitos adversos , Tiazóis/uso terapêutico , Administração Oral , Alanina Transaminase/sangue , Animais , Antiprotozoários/administração & dosagem , Antiprotozoários/efeitos adversos , Aspartato Aminotransferases/sangue , Criptosporidiose/tratamento farmacológico , Cryptosporidium/efeitos dos fármacos , Doenças do Cão/parasitologia , Cães , Fezes/parasitologia , Giardia/efeitos dos fármacos , Giardia/isolamento & purificação , Giardia/fisiologia , Giardíase/tratamento farmacológico , Giardíase/parasitologia , Guanidinas/administração & dosagem , Guanidinas/efeitos adversos , Guanidinas/uso terapêutico , Humanos , Nitrocompostos , Praziquantel/administração & dosagem , Praziquantel/efeitos adversos , Praziquantel/uso terapêutico , Pamoato de Pirantel/administração & dosagem , Pamoato de Pirantel/efeitos adversos , Pamoato de Pirantel/uso terapêutico , Tiazóis/administração & dosagemRESUMO
The current study aimed to determine the anti-Eimeria efficacy of an extract of grapefruit peels (GF) and commercial naringenin (NAR) in naturally-infected lambs, as well as the influence of these flavonoids on the oxidative status during ovine coccidiosis. Pharmacokinetic profiles were also determined. Extracts were administered per os to Eimeria naturally infected growing lambs during 90 consecutive days. The commercial anticoccidial drug toltrazuril (TTZ) was included in this trial as a standard. Twenty-four lambs were divided into four groups: NAR, lambs given a daily dose of 5mg of a commercial naringenin extract of 98% higher purity per kg body weight; GF, lambs that recived a daily dose of 5mg of ethanolic extract of grapefruit peels per kg body weight; TTZ, lambs treated with 20mg of toltrazuril/kg body weight on days 0 and 15 of the experiment; and CTRL, untreated lambs that received daily dose of 30ml of water. Daily doses of GF and NAR were dissolved in 30ml of water and orally given to animals; whereas toltrazuril was administered as a single dose of an undiluted suspension to lambs of the TTZ group. The CTRL group received 30ml of water; as well as the TTZ group for the period after the single dose administration. Fecal and serum samples were collected from all lambs. Anticoccidial efficacy was estimated by coprological techniques. Generation of nitric oxide levels and the antioxidant capacity of the experimental compounds were determined by the Griess and ABTS assays, respectively. The pharmacokinetic parameters of NAR and the GF extract were obtained. On day 30 post-ingestion, anticoccidial efficacy was 91.76% (NAR) and 89.65% (GF); whereas 99.63% of efficacy was achieved with TTZ 15days after treatment. NAR, GF and TTZ significantly reduced oxidative stress in infected animals. The mean daily weight gain for each group was 122g (NAR), 122g (GF), 143g (TTZ) and 98g (CTRL). Following the oral administration of NAR and GF, values in plasma approached maximum concentrations within 2.1 to 2.5h. In conclusion, the administration of NAR and the GF extract reduced Eimeria oocyst output, oxidative stress and promoted higher mean daily weight gains in infected lambs.
Assuntos
Citrus paradisi/química , Coccidiose/veterinária , Flavanonas/uso terapêutico , Extratos Vegetais/uso terapêutico , Doenças dos Ovinos/tratamento farmacológico , Animais , Coccidiose/tratamento farmacológico , Coccidiostáticos/farmacologia , Coccidiostáticos/uso terapêutico , Eimeria , Feminino , Flavanonas/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/farmacologia , Ovinos , Resultado do Tratamento , Triazinas/farmacologia , Triazinas/uso terapêutico , Aumento de Peso/efeitos dos fármacosRESUMO
A family of 15 N-substituted phenothiazines was designed, synthesized and their acaricidal activity against Rhipicephalus microplus was determined in vitro. The synthetic methodology is simple and can be employed in multigram scale. The rationale for the structure-based design of these compounds is the potential for azines and phenothiazine to engage in π-π interactions; these fragments, joined together by a short, flexible alkoxide linker, structurally resemble phenothiazine-based cholinesterase inhibitors, while their weak basicity implies a neutral active form, rather than a cationic one, thus facilitating penetration of the cuticle of ticks. One compound displayed excellent acaricidal activity (LD50=0.58 µg/mL). Preliminary SAR analysis suggests that the activity is influenced by the presence of a weakly basic nitrogen atom, as well as the substitution pattern within the heterocycles.
Assuntos
Desenho de Fármacos , Fenotiazinas/farmacologia , Rhipicephalus/efeitos dos fármacos , Controle de Ácaros e Carrapatos , Animais , Relação Dose-Resposta a Droga , Estrutura Molecular , Fenotiazinas/síntese química , Fenotiazinas/química , Relação Estrutura-AtividadeRESUMO
Fasciola hepatica secretes proteolytic enzymes during liver invasion. The present study examined the effects of the cysteine protease inhibitor Ep-475 on sheep considering the following variables: serum levels of aspartate aminotransferase, L-lactate dehydrogenase, and gamma-glutamyltransferase, liver fluke fecundity, egg viability, parasite burden, and size. Twenty-four male sheep were randomly allocated in four groups of six animals each as follows: group A was infected with F. hepatica metacercariae and treated with 50 mg/kg of Ep-475, group B was infected and untreated, group C was uninfected and treated, and group D was uninfected and untreated. All animals were euthanized 10 weeks after the experimental infection. Serum activities of enzymes in infected animals were significantly lower in Ep-475-treated sheep than in untreated controls, although liver damage was produced. No significant reduction in total worm burden was observed between treated and untreated sheep. However, there was a significant difference on the average size, structure development, ova counts, and egg viability of liver flukes from these two groups. Results showed that Ep-475 reduces liver damage due to fasciolosis and induces an impairment of liver fluke growth and fecundity. These effects pinpoint liver fluke proteases as potential targets for pharmacological intervention.
Assuntos
Inibidores de Cisteína Proteinase/farmacologia , Fasciola hepatica/efeitos dos fármacos , Fasciolíase/veterinária , Fertilidade/efeitos dos fármacos , Leucina/análogos & derivados , Óvulo/efeitos dos fármacos , Doenças dos Ovinos/parasitologia , Animais , Inibidores de Cisteína Proteinase/uso terapêutico , Fasciola hepatica/enzimologia , Fasciola hepatica/fisiologia , Fasciolíase/tratamento farmacológico , Fasciolíase/parasitologia , Leucina/farmacologia , Leucina/uso terapêutico , Ovinos , Doenças dos Ovinos/tratamento farmacológicoRESUMO
Using the film in situ zymography (FIZ) technique, it has been demonstrated that N-[N-(L: -3-trans-carboxyoxirane-2-carbonyl)-L: -leucyl]-agmatine (E-64) inhibits Fasciola hepatica proteolytic activity in vivo. The aim of this study was to establish the dose-response relationship of the inhibition of proteolysis as assessed by FIZ with E-64 at different dosages in a murine model of fasciolosis. Maximum effective inhibition of proteolysis was achieved at 50 mg/kg/day (87%). Mice treated with this dose survived for a mean of 10.92 days more than untreated controls, and their ova counts and egg viability were significantly (P<0.05) lower than this latter group. These results indicate that intraperitoneal administration of E-64 not only inhibited liver proteolytic activity in a dose-dependent manner but also produced anti-fecundity and anti-embryonation effects, delaying the progression of fasciolosis. Yet, residual proteolysis may suggest that other E-64-non-sensitive enzymes are involved, or that E-64-enzyme chemical interactions are only capable of a partial agonistic-like effect.