RESUMEN
Type 2 diabetes mellitus is a metabolic disorder that causes chronic high blood sugar levels, and diabetic patients are more susceptible to infections. American cutaneous leishmaniasis is an infectious disease caused by a parasite that affects the skin and mucous membranes, leading to one or multiple ulcerative lesions. Chronic inflammation and functional changes in various organs and systems, including the immune system, are the primary causes of both diseases. Melatonin, an essential immunomodulatory, antioxidant, and neuroprotective agent, can benefit many immunological processes and infectious diseases, including leishmaniasis. Although, limited reports are available on diabetic patients with leishmaniasis. The literature suggests that melatonin may play a promising role in inflammatory disorders. This study was designed to assess melatonin levels and inflammatory mediators in diabetic patients affected by leishmaniasis. Blood samples from 25 individuals were analyzed and divided into four groups: a control group (without any diseases), a Leishmania-positive group, patients with type 2 diabetes mellitus, and patients with a combination of both diseases. This study measured the serum levels of melatonin through ELISA, while IL-4 and TNF-α were measured using flow cytometry, and C-reactive protein was measured through turbidimetry. This study found that patients with leishmaniasis significantly increased TNF-α and decreased melatonin levels. However, the group of diabetic patients with leishmaniasis showed higher melatonin levels than the control group. These observations suggest that TNF-α may influence melatonin production in patients with American cutaneous leishmaniasis, potentially contributing to the inflammatory characteristics of both diseases.
Asunto(s)
Diabetes Mellitus Tipo 2 , Hiperglucemia , Inflamación , Melatonina , Factor de Necrosis Tumoral alfa , Melatonina/sangre , Melatonina/metabolismo , Humanos , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/inmunología , Masculino , Femenino , Persona de Mediana Edad , Hiperglucemia/metabolismo , Hiperglucemia/sangre , Factor de Necrosis Tumoral alfa/sangre , Factor de Necrosis Tumoral alfa/metabolismo , Inflamación/metabolismo , Inflamación/sangre , Adulto , Interleucina-4/sangre , Leishmaniasis Cutánea/sangre , Leishmaniasis Cutánea/inmunología , Leishmaniasis Cutánea/parasitología , Leishmaniasis Cutánea/metabolismo , Proteína C-Reactiva/metabolismo , Leishmaniasis/sangre , Leishmaniasis/inmunología , Leishmaniasis/metabolismo , Leishmaniasis/parasitología , AncianoRESUMEN
Leishmania infantum causes canine leishmaniasis. Using parasitological and molecular analyses, we identified L. infantum in the reproductive organs of male and female dogs. Using histochemistry, immunohistochemistry, and PCR, we examined tissue samples from the reproductive organs of 8 male dogs and 16 female dogs diagnosed with leishmaniasis. Despite the absence of macroscopic or microscopic lesions in these organs, we observed L. infantum amastigotes in tissue samples from the testis and the uterus. PCR and sequencing of these tissues revealed sequences that matched 100% with L. infantum DNA available at GenBank. The presence of L. infantum amastigotes and DNA in testicular and uterine tissue samples suggested that these organs can harbor the parasite without associated macroscopic or microscopic lesions, and this can be especially important in the vertical and venereal transmission of leishmaniasis in dogs.(AU)
Leishmania infantum é agente etiológico da leishmaniose canina. Por meio de análises parasitológicas e moleculares, a presença do parasita foi investigada em órgãos reprodutivos de cães machos e fêmeas. Amostras de tecidos dos órgãos reprodutivos de 8 cães machos e 16 fêmeas diagnosticados com leishmaniose foram avaliadas por histoquímica, imunohistoquímica e PCR. Apesar de não terem sido observadas lesões macroscópicas ou microscópicas nos órgãos reprodutivos desses cães, formas amastigotas de L. infantum foram observadas em amostras teciduais do testículo e útero. A PCR e o sequenciamento do DNA extraído desses tecidos revelaram sequências 100% idênticas a L. infantum depositadas no GenBank. Nossos resultados sugerem que os testículos e o útero podem abrigar o parasita, sem associação com lesões macroscópicas ou microscópicas, o que pode ter uma grande importância na transmissão venérea e vertical da leishmaniose entre cães.(AU)
Asunto(s)
Animales , Perros , Enfermedades de los Perros/parasitología , Leishmaniasis/sangre , Leishmaniasis/diagnóstico , Leishmaniasis/genética , Leishmaniasis/veterinariaRESUMEN
Leishmania infantum causes canine leishmaniasis. Using parasitological and molecular analyses, we identified L. infantum in the reproductive organs of male and female dogs. Using histochemistry, immunohistochemistry, and PCR, we examined tissue samples from the reproductive organs of 8 male dogs and 16 female dogs diagnosed with leishmaniasis. Despite the absence of macroscopic or microscopic lesions in these organs, we observed L. infantum amastigotes in tissue samples from the testis and the uterus. PCR and sequencing of these tissues revealed sequences that matched 100% with L. infantum DNA available at GenBank. The presence of L. infantum amastigotes and DNA in testicular and uterine tissue samples suggested that these organs can harbor the parasite without associated macroscopic or microscopic lesions, and this can be especially important in the vertical and venereal transmission of leishmaniasis in dogs.
Leishmania infantum é agente etiológico da leishmaniose canina. Por meio de análises parasitológicas e moleculares, a presença do parasita foi investigada em órgãos reprodutivos de cães machos e fêmeas. Amostras de tecidos dos órgãos reprodutivos de 8 cães machos e 16 fêmeas diagnosticados com leishmaniose foram avaliadas por histoquímica, imunohistoquímica e PCR. Apesar de não terem sido observadas lesões macroscópicas ou microscópicas nos órgãos reprodutivos desses cães, formas amastigotas de L. infantum foram observadas em amostras teciduais do testículo e útero. A PCR e o sequenciamento do DNA extraído desses tecidos revelaram sequências 100% idênticas a L. infantum depositadas no GenBank. Nossos resultados sugerem que os testículos e o útero podem abrigar o parasita, sem associação com lesões macroscópicas ou microscópicas, o que pode ter uma grande importância na transmissão venérea e vertical da leishmaniose entre cães.
Asunto(s)
Animales , Perros , Enfermedades de los Perros/parasitología , Leishmaniasis/diagnóstico , Leishmaniasis/genética , Leishmaniasis/sangre , Leishmaniasis/veterinariaRESUMEN
Serum levels of interleukin 2 (IL-2), interleukin 4 (IL-4), interleukin 6 (IL-6), interleukin 10 (IL-10), interleukin 17 (IL-17), interferon gamma (IFN-γ), tumor necrosis factor α (TNF-α), and interleukin 1ß (IL-1ß), cytokines involved in the immune response, were investigated in 75 Leishmania-positive blood donors living in endemic areas. Based on their status in 2011 and 2015, the subjects were clustered into three groups: positive for at least one diagnostic method in both years, but lacking clinical progression to disease (G1); positive on at least one method in 2011 but negative in 2015 (G2); negative on all methods in both years (G3). Donors were interviewed for sociodemographic data collection and underwent clinical evaluation and laboratory tests. Serum cytokines were quantified using a CBA Flex set (BD Biosciences). Significant differences were found for all the cytokines evaluated, with lower concentrations in consistently Leishmania-negative individuals. The exception was IFN-γ, with similar levels among all donors. No changes consistent with active disease were observed in the laboratory results for Leishmania-positive donors who underwent clinical evaluation, none of whom progressed to disease. This suggests that infection control is associated with serum IL-17 levels. Resolution of Leishmania infection in positive donors may be related to high levels of IL-17 and low levels of IL-10, highlighting the role played by IL-17 in asymptomatic Leishmania-infected individuals.
Asunto(s)
Donantes de Sangre/estadística & datos numéricos , Citocinas/sangre , Leishmania/inmunología , Leishmaniasis/inmunología , Adulto , Enfermedades Asintomáticas , Femenino , Humanos , Interleucina-10/sangre , Interleucina-17/sangre , Leishmaniasis/sangre , Masculino , Persona de Mediana Edad , Regulación hacia Arriba , Adulto JovenRESUMEN
ABSTRACT Cysteine proteinases are well-known virulence factors of Leishmania spp. with demonstrated actions in both experimental mouse infection and human infection. However, studies on these enzymes in canine leishmaniasis are scarce. Here, we show, for the first time, the reactivity of sera from dogs living in an endemic area to a recombinant protein from the COOH-terminal region of cysteine B protease. In this work, enzyme-linked immunosorbent assays were performed using a 14 kDa rcyspep protein obtained through a pET28-a expression system in Escherichia coli. First, 96-well plates were coated with rcyspep (500 ng/well) and incubated with sera from dogs (1:100). Subsequently, IgG antibody detection was performed using rabbit anti-dog IgG antibodies conjugated with peroxidase. Sera from dogs (n = 114), including suspect (n = 30) and positive (n = 50) dogs from a leishmaniasis-endemic area and dogs from a nonendemic area, (n = 34), negative for leishmaniasis, were assessed. The results showed that sera from the suspect (42%) and positive (68%) groups responded differently to the antigen titers tested above the cut-off (Optical Density = 0.166). This finding suggests that the immune response detected against cyspep may be related to clinical disorders present in these animals. Collectively, the data gathered here suggest that cyspep can sensitize the immune systems of dogs from a leishmaniasis-endemic area to elicit a humoral response, an immunological parameter indicating the contribution of this protein in host-parasite interaction.
Asunto(s)
Animales , Perros , Humanos , Ratones , Conejos , Leishmaniasis/sangre , Enfermedades de los Perros/sangre , Proteasas de Cisteína/sangre , Leishmania , Ensayo de Inmunoadsorción Enzimática , Anticuerpos Antiprotozoarios , Leishmaniasis/veterinaria , Leishmania infantum , Cisteína , Leishmaniasis VisceralRESUMEN
Cysteine proteinases are well-known virulence factors of Leishmania spp. with demonstrated actions in both experimental mouse infection and human infection. However, studies on these enzymes in canine leishmaniasis are scarce. Here, we show, for the first time, the reactivity of sera from dogs living in an endemic area to a recombinant protein from the COOH-terminal region of cysteine B protease. In this work, enzyme-linked immunosorbent assays were performed using a 14kDa rcyspep protein obtained through a pET28-a expression system in Escherichia coli. First, 96-well plates were coated with rcyspep (500ng/well) and incubated with sera from dogs (1:100). Subsequently, IgG antibody detection was performed using rabbit anti-dog IgG antibodies conjugated with peroxidase. Sera from dogs (n=114), including suspect (n=30) and positive (n=50) dogs from a leishmaniasis-endemic area and dogs from a nonendemic area, (n=34), negative for leishmaniasis, were assessed. The results showed that sera from the suspect (42%) and positive (68%) groups responded differently to the antigen titers tested above the cut-off (Optical Density=0.166). This finding suggests that the immune response detected against cyspep may be related to clinical disorders present in these animals. Collectively, the data gathered here suggest that cyspep can sensitize the immune systems of dogs from a leishmaniasis-endemic area to elicit a humoral response, an immunological parameter indicating the contribution of this protein in host-parasite interaction.
Asunto(s)
Proteasas de Cisteína/sangre , Enfermedades de los Perros/sangre , Leishmania , Leishmaniasis/sangre , Animales , Anticuerpos Antiprotozoarios , Cisteína , Perros , Ensayo de Inmunoadsorción Enzimática , Humanos , Leishmania infantum , Leishmaniasis/veterinaria , Leishmaniasis Visceral , Ratones , ConejosRESUMEN
In this study, we evaluated the performance of a new enzyme-linked immunosorbent assay (ELISA) variant known as indirect "plasmonic ELISA" (pELISA) for the detection of Leishmania spp. infection. Serum samples from 170 dogs from an area where canine leishmaniosis (CanL) is endemic and from 26 healthy dogs from a nonendemic area were tested by indirect pELISA, and the results were compared to those of an indirect ELISA (both with recombinant antigen rK28) and those of an immunochromatographic test (dual-path platform, TR-DPP®) using real-time PCR on blood samples or conjunctival swabs as the gold standard. The pELISA, indirect rK28 ELISA and the TR-DPP® immunochromatographic test presented sensitivities of 94.7%, 89.5% and 79.0% and specificities of 100%, 92.7% and 91.5%, respectively. The analysis of the results revealed that the specificity of the indirect pELISA was greater than that of the method recommended by the Ministry of Health in Brazil and may increase the feasibility of diagnosis in resource-constrained countries because it does not require sophisticated instruments to read. Thus, this method can be used as an additional tool for the detection of Leishmania spp. infection in these areas.
Asunto(s)
Enfermedades de los Perros/diagnóstico , Ensayo de Inmunoadsorción Enzimática/métodos , Leishmaniasis/veterinaria , Animales , Anticuerpos Antiprotozoarios/sangre , Antígenos de Protozoos/análisis , Brasil , Enfermedades de los Perros/sangre , Perros , Leishmaniasis/sangre , Leishmaniasis/diagnóstico , Reacción en Cadena en Tiempo Real de la Polimerasa/veterinaria , Sensibilidad y Especificidad , Pruebas Serológicas/métodosRESUMEN
Antibodies to pathogens of public health importance were investigated in 33 free-ranging six-banded armadillos (Euphractus sexcinctus) from Brazil. The frequency of seropositive animals for Toxoplasma gondii, Leishmania spp., and Leptospira spp. were two, three, and two, respectively.
Asunto(s)
Armadillos/sangre , Leishmania/aislamiento & purificación , Leptospira/inmunología , Toxoplasma/inmunología , Animales , Brasil/epidemiología , Leishmaniasis/sangre , Leishmaniasis/epidemiología , Leishmaniasis/veterinaria , Leptospirosis/sangre , Leptospirosis/epidemiología , Leptospirosis/veterinaria , Toxoplasmosis Animal/sangre , Toxoplasmosis Animal/epidemiologíaRESUMEN
The role of cats in the epidemiological cycle of leishmaniasis remains unclear. To better understand the occurrence of leishmaniasis in cats, we studied the frequency of Leishmania in serum samples of 100 cats living in an endemic region for canine and human leishmaniasis by serological, parasitological, and molecular methods. Of the 100 cats, 54 were seropositive for Leishmania antibodies by immunofluorescence antibody test. None of the bone marrow aspirates collected from these cats tested positive for the parasite in culture or upon polymerase chain reaction (PCR) analysis. Biopsy samples of the ears also tested negative for Leishmania upon PCR analysis. These findings may indicate that the region is endemic for canine leishmaniasis and cats are infected by Leishmania; or that cross-reaction with antibodies against other parasites increases the frequency of seropositivity; or that cats respond to Leishmania infection by producing antibodies when few or no parasites are present in bone marrow and tissue samples. Overall, our results suggest that cats can be infected by Leishmania ; however, we failed to demonstrate feline parasitosis. These findings highlight the need to study leishmaniasis in cats, since sandflies feed on cats, these animals may act as a reservoir for the parasite.(AU)
O papel dos gatos no ciclo epidemiológico da leishmaniose ainda não está claro. Para entender melhor a ocorrência de leishmaniose em gatos, estudou-se a frequência de Leishmania em amostras de soro de 100 gatos, os quais vivem em uma região endêmica para leishmaniose canina e humana, por métodos sorológicos, parasitológicos e moleculares. Dos 100 gatos, 54 foram soropositivos para anticorpos de Leishmania por teste de anticorpos de imunofluorescência. Nenhum dos aspirados de medula óssea coletados desses gatos mostrou-se positivo para o parasita em cultura, ou após a realização da reação em cadeia da polimerase (PCR). Amostras de biópsia das orelhas também foram negativas para Leishmania submetidas a PCR. Esses achados indicam que na região estudada endêmica para leishmaniose canina, os gatos podem se infectar por Leishmania; ou que a reação cruzada com anticorpos contra outros parasitas aumenta a frequência de soropositividade; ou que os gatos respondem à infecção por Leishmania produzindo anticorpos quando poucos ou nenhum parasita estão presentes na medula óssea e em amostras de tecido. Em geral, os resultados sugerem que os gatos podem ser estar infectados por Leishmania spp. No entanto, não foi possível demonstrar parasitismo felino. Essas descobertas evidenciam a necessidade de estudar a leishmaniose em gatos, uma vez que, como os flebotomíneos se alimentam em gatos, e esses animais podem atuar como um reservatório para o parasita.(AU)
Asunto(s)
Animales , Gatos , Leishmania/aislamiento & purificación , Leishmaniasis/sangre , Leishmaniasis/diagnóstico , Leishmaniasis/veterinaria , Vectores de Enfermedades , Reacción en Cadena de la Polimerasa/veterinaria , BrasilRESUMEN
Transfusion-transmitted leishmaniasis has been a concern in regions endemic for the disease. Whether immediate or delayed, the risks posed by this mode of transmission call for careful assessment. The purpose of this study was to detect Leishmania infection in blood donors living in an endemic area and to investigate progression to the disease in these individuals. Immunofluorescent antibody test, enzyme-linked immunosorbent assay, leishmaniasis rapid test, and the polymerase chain reaction were applied to 430 donors in an initial evaluation. Of those donors with at least one positive test, 50 were reevaluated four years later by the same methods, as were 25 controls who had been negative on the same tests. In the first evaluation, Leishmania infection was detected in 41.4% (95% CI: 36.7-46.1) of donors (n = 430). None of the 75 reevaluated individuals had developed the disease, but retesting revealed positivity in at least one test in 36.0% (95% CI: 25.1-46.9) of donors. Of the 50 initially testing positive, 50% remained so on retesting. Of the 25 initially negative controls, two tested positive in the subsequent evaluation. The severity of the parasitosis and the risk of transfusion transmission warrant investigation of the potential inclusion of methods for Leishmania detection into blood banks for effective screening of infected donors.
Asunto(s)
Donantes de Sangre , Seguridad de la Sangre/métodos , Selección de Donante/métodos , Leishmania , Leishmaniasis/sangre , Adolescente , Adulto , Anciano , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Leishmaniasis/transmisión , Masculino , Persona de Mediana EdadRESUMEN
Abstract The aim of this study were to detect antibodies anti-Leishmania spp. and anti-Trypanosoma cruzi in two different populations of domestic cats (Felis catus domesticus) from North Paraná referred for surgical castration and to determine which characteristics of the animals studied may be associated with seropositivity. Serum samples from 679 cats were analyzed using enzyme-linked immunosorbent assay (ELISA) and indirect immunofluorescence antibody test (IFAT) in series. Associations between age, sex, race, year of care and animal group were verified using the simple logistic regression. Percentage of 8.5% (58/679) of cats were positive for Leishmania spp. and 7.6% (51/673) for T. cruzi by the tests ELISA and IFAT. Animals collected by non-governmental animal protection organizations presented more seropositivity for Leishmania spp. (p<0.0001). Results shown that Leishmania spp. and T. cruzi are present in domestic cats in the northern part of the state of Paraná, as well as, owners of non-governmental animal protection organizations may be more exposed to leishmaniasis when compared to other animal owners evaluated in the present study.
Resumo O objetivo desse estudo foi detectar a presença de anticorpos IgG anti-Leishmania spp. e anti-Trypanosoma cruzi em duas populações de gatos domésticos (Felis catus domesticus) do Norte do Paraná encaminhados para castração cirúrgica e determinar quais as características dos animais estudados que podem estar associadas à soropositividade. Amostras de soro de 679 gatos foram analisadas utilizando-se os testes imunoenzimático (ELISA) e a reação de imunofluorescência indireta (RIFI), em série. Associações entre idade, sexo, raça, ano de atendimento e grupo animal foram verificadas usando regressão logística simples. Um percentual de 8,5% (58/679) dos gatos apresentou positividade para Leishmania spp. e 7,6% (51/673) para T. cruzi pelos testes ELISA e RIFI. Gatos mantidos em organizações não governamentais de proteção animal apresentaram maior sororeatividade para Leishmania spp. (p<0.0001). As sorologias reativas para Leishmania spp. e Trypanosoma cruzi mostram que esses agentes estão presentes em gatos domésticos na parte norte do estado do Paraná, bem como, os proprietários de organizações não governamentais de proteção animal podem estar mais expostos à leishmaniose quando comparados com outros proprietários de animais avaliados no presente estudo.
Asunto(s)
Animales , Masculino , Femenino , Trypanosoma cruzi/inmunología , Anticuerpos Antiprotozoarios/sangre , Enfermedades de los Gatos/parasitología , Enfermedades de los Gatos/sangre , Leishmaniasis/veterinaria , Gatos/parasitología , Enfermedad de Chagas/veterinaria , Leishmania/inmunología , Brasil/epidemiología , Enfermedades de los Gatos/epidemiología , Leishmaniasis/sangre , Leishmaniasis/epidemiología , Estudios Seroepidemiológicos , Enfermedad de Chagas/sangre , Enfermedad de Chagas/epidemiología , Medición de RiesgoRESUMEN
The aim of this study were to detect antibodies anti-Leishmania spp. and anti-Trypanosoma cruzi in two different populations of domestic cats (Felis catus domesticus) from North Paraná referred for surgical castration and to determine which characteristics of the animals studied may be associated with seropositivity. Serum samples from 679 cats were analyzed using enzyme-linked immunosorbent assay (ELISA) and indirect immunofluorescence antibody test (IFAT) in series. Associations between age, sex, race, year of care and animal group were verified using the simple logistic regression. Percentage of 8.5% (58/679) of cats were positive for Leishmania spp. and 7.6% (51/673) for T. cruzi by the tests ELISA and IFAT. Animals collected by non-governmental animal protection organizations presented more seropositivity for Leishmania spp. (p<0.0001). Results shown that Leishmania spp. and T. cruzi are present in domestic cats in the northern part of the state of Paraná, as well as, owners of non-governmental animal protection organizations may be more exposed to leishmaniasis when compared to other animal owners evaluated in the present study.
Asunto(s)
Anticuerpos Antiprotozoarios/sangre , Enfermedades de los Gatos/sangre , Enfermedades de los Gatos/parasitología , Gatos/parasitología , Enfermedad de Chagas/veterinaria , Leishmania/inmunología , Leishmaniasis/veterinaria , Trypanosoma cruzi/inmunología , Animales , Brasil/epidemiología , Enfermedades de los Gatos/epidemiología , Enfermedad de Chagas/sangre , Enfermedad de Chagas/epidemiología , Femenino , Leishmaniasis/sangre , Leishmaniasis/epidemiología , Masculino , Medición de Riesgo , Estudios SeroepidemiológicosRESUMEN
HIV aspartyl protease inhibitors are able to modulate multiple defense mechanisms. However, their influence on the immune response against Leishmania has rarely been investigated. The aim of our study was to investigate whether in vivo treatment with HIV aspartyl protease inhibitors is able to modulate the immune response during Leishmania infection. Using Leishmania (L.) amazonensis-infected mice, we analyzed the disease evolution and parasite load, immunophenotypic profiles of splenic T and B lymphocytes, numbers of lymphoid aggregates in the spleen, percentages of circulating atypical lymphocytes and reactive monocytes, and serum levels of cytokines and nitric oxide (NO) after 30â¯days of oral treatment with lopinavir/ritonavir (LPV/RTV) or atazanavir (ATV). We observed that LPV/RTV and ATV did not modify the disease evolution or parasite load. However, the antiretroviral treatment induced an increase in activated lymphocytes in the spleen and blood, as well as a decrease in CD69 expression in T and B lymphocytes in the spleen. The treatment also resulted in an increase in activated monocytes in the blood. In addition, antiretrovirals decreased levels of IL-17A and increased levels of NO in sera from Leishmania-infected mice. Thus, our results demonstrate for the first time that in vivo treatment with HIV aspartyl protease inhibitors modifies innate and adaptative immune responses during Leishmania infection and suggest that these drugs could change the clinical course of leishmaniasis in HIV infected-individuals.
Asunto(s)
Inhibidores de la Proteasa del VIH/farmacología , Inhibidores de la Proteasa del VIH/uso terapéutico , Leishmaniasis/tratamiento farmacológico , Animales , Sulfato de Atazanavir/farmacología , Sulfato de Atazanavir/uso terapéutico , Citocinas/sangre , Femenino , Leishmaniasis/sangre , Leishmaniasis/parasitología , Recuento de Leucocitos , Leucocitos/efectos de los fármacos , Lopinavir/farmacología , Lopinavir/uso terapéutico , Ratones Endogámicos BALB C , Óxido Nítrico/sangre , Ritonavir/farmacología , Ritonavir/uso terapéutico , Piel/efectos de los fármacos , Piel/parasitología , Bazo/efectos de los fármacos , Bazo/inmunología , Bazo/parasitologíaRESUMEN
1. LASSBio-1736 ((E)-1-4(trifluoromethyl) benzylidene)-5-(2-4-dichlorozoyl) carbonylhydrazine) is proposed to be an oral cysteine protease leishmanicidal inhibitor. 2. This work aimed to investigate plasma pharmacokinetics, protein binding and tissue distribution of LASSBio-1736 in male Wistar rats. 3. LASSBio-1736 was administered to male Wistar rats at doses of 3.2 mg/kg intravenously and 12.6 mg/kg oral and intraperitoneal. The individual plasma-concentration profiles were determined by HPLC-UV and evaluated by non-compartmental and population pharmacokinetic analysis (Monolix 2016R1, Lixoft). Tissue distribution was evaluated after iv injection of 3.2 mg/kg drug by non-compartmental approach. 4. After intravenous administration, Vdss (1.79 L/kg), t ½ (23.1 h) and CLtot (56.1 mL/h/kg) were determined, and they were statistically similar (α =0.05) to oral and intraperitoneal pharmacokinetic parameters. The plasma profiles obtained after intravenous, oral and intraperitoneal administration of the compound were best fitted to a three-compartment and one-compartment open model with first-order absorption. 5. The intraperitoneal and oral bioavailability were around 40 and 15%, respectively. 6. Liver, spleen and skin tissues showed penetration of 340, 130 and 40%, respectively, with t ½ like plasma values. 7. LASSBio-1736 protein binding was 95 ± 2%. 8. The t ½, CLtot and tissue distribution of the compound agreed with the desired drug characteristics for leishmanicidal activity.
Asunto(s)
Antiprotozoarios/farmacología , Antiprotozoarios/farmacocinética , Inhibidores de Cisteína Proteinasa/farmacología , Inhibidores de Cisteína Proteinasa/farmacocinética , Animales , Leishmaniasis/sangre , Leishmaniasis/tratamiento farmacológico , Masculino , Ratas , Ratas WistarRESUMEN
Previous studies have indicated that the balance between different eicosanoids reflect the intensity of the inflammatory profile in patients with tegumentary leishmaniasis. More recently, pro-resolution lipid mediators have been shown to play critical roles in dampening pathological inflammatory processes to reestablish homeostasis in a diverse range of experimental settings. Among these lipid mediator, resolvins from D series have been described as potent anti-inflammatory and immunomodulatory mediators, and its activities include inhibition of leukocyte chemotaxis and blockage production of proinflammatory cytokines, while increasing the expression of regulatory mediators. Whether resolvins play significant roles in establishment and persistence of Leishmania infection is currently unknown. We addressed this question in the current study by assessing circulating levels of D-series resolvins in tegumentary leishmaniasis patients presenting with localized or diffuse disease. We found heightened expression of resolvin D1 in diffuse cutaneous leishmaniasis which was correlated with expression profile of biomarkers associated with disease pathogenesis. Additional in vitro experiments using primary human macrophages indicated that resolvin D1 may promote intracellular Leishmania amazonensis replication through a mechanism associated with induction of heme oxygenase-1. These results suggest that targeting resolvin D1 could serve as potential strategy for host directed therapy in diffuse cutaneous leishmaniasis.
Asunto(s)
Ácidos Docosahexaenoicos/sangre , Leishmaniasis/sangre , Macrófagos/parasitología , Adolescente , Adulto , Biomarcadores/metabolismo , Niño , Femenino , Humanos , Leishmania , Macrófagos/metabolismo , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
Leishmania species are dimorphic protozoan parasites that live and replicate in the gut of sand flies as promastigotes or in mammalian hosts as amastigotes. Different immune cells, including DCs, and receptors differ in their involvement in phagocytosis of promastigotes and amastigotes and in recognition of different Leishmania species. In the case of L. mexicana, differences in phagocytosis of promastigotes and amastigotes by DCs and participation of C-type lectin receptors (CLRs) have not been established. In the present study, flow cytometry and confocal microscopy were used to investigate the phagocytosis by monocyte-derived dendritic cells (moDCs) of L. mexicana promastigotes and amastigotes in the presence or absence of immune serum during various periods of time. Blocking antibodies against mannose receptors and DC-SIGN were used to explore the participation of these receptors in the phagocytosis of L. mexicana by moDC. The major differences in interactions of L. mexicana promastigotes and amastigotes with moDC were found to occur within the first 3 hr, during which phagocytosis of promastigotes predominated as compared with opsonization of promastigotes and amastigotes. However, after 6 hr of incubation, opsonized promastigotes were preferentially phagocytosed as compared with unopsonized promastigotes and amastigotes and after 24 hr of incubation there were no differences in the phagocytosis of promastigotes and amastigotes. Finally, after 3 hr incubation, DC-SIGN was involved in the phagocytosis of promastigotes, but not of amastigotes.
Asunto(s)
Células Dendríticas/inmunología , Células Dendríticas/parasitología , Leishmania mexicana/inmunología , Monocitos/inmunología , Monocitos/parasitología , Fagocitosis/fisiología , Animales , Moléculas de Adhesión Celular/inmunología , Células Cultivadas , Células Dendríticas/citología , Citometría de Flujo/métodos , Interacciones Huésped-Parásitos , Humanos , Lectinas Tipo C/inmunología , Leishmaniasis/sangre , Leishmaniasis/inmunología , Leishmaniasis/parasitología , Macrófagos/inmunología , Macrófagos/parasitología , Receptor de Manosa , Lectinas de Unión a Manosa/inmunología , Ratones Endogámicos BALB C , Microscopía Confocal/métodos , Monocitos/citología , Receptores de Superficie Celular/inmunologíaRESUMEN
Background: Hemoparasitoses have major importance in clinical diseases of small animals for infections are highly prevalent, easily transmitted and difficult to control. Clinical signs are nonspecific, but laboratory abnormalities are frequent, especially changes in serum biochemistry. In veterinary medicine, laboratorial findings may favor the diagnosis of hemoparasitoses and improve the quality of treatment given to these patients. The present study aimed at evaluating changes in serum biochemistry in dogs with molecular diagnosis of hemoparasites (Ehrlichia canis, Anaplasma platys and Leishmania sp.).Materials, Methods & Results: Molecular diagnosis for Ehrlichia canis, Anaplasma platys and Leishmania sp. were obtained in 26 dogs. A complete serum biochemical profile was determined in biochemical analyzer COBAS Mira. Biochemical analyzes, using commercial kits from Synermed, included total and partial protein by colorimetric method, creatinine by the kinetic method, urea, alanine aminotransferase (ALT), aspartate aminotrasnferase (AST), gamma glutamyl transferase (GGT) and alkaline phosphatase by enzymatic method. Considering reference values for canine species, it was observed an increase in the average value for serum urea concentration in dogs with leishmaniasis. These dogs also presented higher globulin concentration, while presenting reduction in serum albumin...(AU)
Asunto(s)
Animales , Perros , Ehrlichia canis , Anaplasma , Leishmania , Leishmaniasis/sangre , Anaplasmosis/sangre , Ehrlichiosis/sangre , Albúmina Sérica , Enfermedades Parasitarias en Animales/sangreRESUMEN
O objetivo deste trabalho foi detectar as alterações bioquímicas e hematológicas em cães naturalmente infectados por Leishmania (infantum) chagasi. Dividiram-se os cães em três grupos: controle (n = 32) com diagnóstico sorológico e parasitológico negativos e sem sinais clínicos; oligossintomático (n = 48) com diagnóstico sorológico e parasitológico positivos, e de um a três sinais clínicos; polissintomático (n = 50) com diagnóstico sorológico e parasitológico positivos, e com mais de três sinais clínicos. Observou-se nos grupos dos animais com LV oligossintomático e polissintomático: redução da albumina sérica e do número de eritrócitos, linfócitos, eosinófilos em relação ao grupo controle. O grupo polissintomático também apresentou aumento na dosagem sérica de globulina. Conclui-se que quanto maior a quantidade de sinais clínicos apresentados por cães com leishmaniose, maior o número de alterações nos parâmetros bioquímicos e hematológicos.
The aim of this study was to detect the biochemical and hematological disorders found in dogs naturally infected with Leishmania (infantum) chagasi. Dogs were divided into three groups: control (n = 32), with negative serological and parasitological diagnosis and without clinical signs; oligosymptomatic (n = 48), with positive serological and parasitological diagnosis and one to three clinical signs; and polysymptomatic (n = 50) with positive serological and parasitological diagnosis and over three clinical signs. Animais in the oligosymptomatic and polysymptomatic groups were found to have a reduction in serum albumin and in the number of erythrocytes, Iymphocytes and eosinophils when compared to the control group. The polysymptomatic group also presented an increase in serum globulin. We conclude that the greater the number of clinical signs in dogs with leishmaniasis, the larger the changes in hematological and biochemical parameters.
El objetivo del presente trabajo fue evaluar las alteraciones bioquímicas y hematológicas en perros infectados en forma natural con Leishmania (infantum) chagasi. Los perros fueron divididos en tres grupos: control (n = 32), con diagnósticos serológico y parasitológico negativos y sin signos clínicos; oligosintomáticos (n = 48), con diagnósticos serológico y parasitológico positivos y con uno a tres signos clínicos; y polisintomáticos (n = 50), con diagnósticos serológico y parasitológico positivos y con más de tres signos clínicos. Se pudo observar que en los grupos oligo y polisintomático habia una reducción de la albúmina sérica y del número de eritrocitos, linfocitos y eosinófilos en relación al grupo control. El grupo polisintomático también presentó un aumento sérico de globulinas. Se concluye que cuanto mayor número de signos clínicos presentes en perros con leishmaniosis, mayor será el número de alteraciones en los parámetros bioquímicos y hematológicos.
Asunto(s)
Animales , Perros , Albúminas , Anemia/veterinaria , Fenómenos Bioquímicos , Leishmania infantum , Leishmaniasis/sangre , Leishmaniasis/veterinaria , Pruebas Hematológicas/veterinariaRESUMEN
O objetivo deste trabalho foi detectar as alterações bioquímicas e hematológicas em cães naturalmente infectados por Leishmania (infantum) chagasi. Dividiram-se os cães em três grupos: controle (n = 32) com diagnóstico sorológico e parasitológico negativos e sem sinais clínicos; oligossintomático (n = 48) com diagnóstico sorológico e parasitológico positivos, e de um a três sinais clínicos; polissintomático (n = 50) com diagnóstico sorológico e parasitológico positivos, e com mais de três sinais clínicos. Observou-se nos grupos dos animais com LV oligossintomático e polissintomático: redução da albumina sérica e do número de eritrócitos, linfócitos, eosinófilos em relação ao grupo controle. O grupo polissintomático também apresentou aumento na dosagem sérica de globulina. Conclui-se que quanto maior a quantidade de sinais clínicos apresentados por cães com leishmaniose, maior o número de alterações nos parâmetros bioquímicos e hematológicos.(AU)
The aim of this study was to detect the biochemical and hematological disorders found in dogs naturally infected with Leishmania (infantum) chagasi. Dogs were divided into three groups: control (n = 32), with negative serological and parasitological diagnosis and without clinical signs; oligosymptomatic (n = 48), with positive serological and parasitological diagnosis and one to three clinical signs; and polysymptomatic (n = 50) with positive serological and parasitological diagnosis and over three clinical signs. Animais in the oligosymptomatic and polysymptomatic groups were found to have a reduction in serum albumin and in the number of erythrocytes, Iymphocytes and eosinophils when compared to the control group. The polysymptomatic group also presented an increase in serum globulin. We conclude that the greater the number of clinical signs in dogs with leishmaniasis, the larger the changes in hematological and biochemical parameters.(AU)
El objetivo del presente trabajo fue evaluar las alteraciones bioquímicas y hematológicas en perros infectados en forma natural con Leishmania (infantum) chagasi. Los perros fueron divididos en tres grupos: control (n = 32), con diagnósticos serológico y parasitológico negativos y sin signos clínicos; oligosintomáticos (n = 48), con diagnósticos serológico y parasitológico positivos y con uno a tres signos clínicos; y polisintomáticos (n = 50), con diagnósticos serológico y parasitológico positivos y con más de tres signos clínicos. Se pudo observar que en los grupos oligo y polisintomático habia una reducción de la albúmina sérica y del número de eritrocitos, linfocitos y eosinófilos en relación al grupo control. El grupo polisintomático también presentó un aumento sérico de globulinas. Se concluye que cuanto mayor número de signos clínicos presentes en perros con leishmaniosis, mayor será el número de alteraciones en los parámetros bioquímicos y hematológicos.(AU)
Asunto(s)
Animales , Perros , Leishmania infantum , Fenómenos Bioquímicos , Anemia/veterinaria , Albúminas , Leishmaniasis/sangre , Leishmaniasis/veterinaria , Pruebas Hematológicas/veterinariaRESUMEN
Background: Hemoparasitoses have major importance in clinical diseases of small animals for infections are highly prevalent, easily transmitted and difficult to control. Clinical signs are nonspecific, but laboratory abnormalities are frequent, especially changes in serum biochemistry. In veterinary medicine, laboratorial findings may favor the diagnosis of hemoparasitoses and improve the quality of treatment given to these patients. The present study aimed at evaluating changes in serum biochemistry in dogs with molecular diagnosis of hemoparasites (Ehrlichia canis, Anaplasma platys and Leishmania sp.).Materials, Methods & Results: Molecular diagnosis for Ehrlichia canis, Anaplasma platys and Leishmania sp. were obtained in 26 dogs. A complete serum biochemical profile was determined in biochemical analyzer COBAS Mira. Biochemical analyzes, using commercial kits from Synermed, included total and partial protein by colorimetric method, creatinine by the kinetic method, urea, alanine aminotransferase (ALT), aspartate aminotrasnferase (AST), gamma glutamyl transferase (GGT) and alkaline phosphatase by enzymatic method. Considering reference values for canine species, it was observed an increase in the average value for serum urea concentration in dogs with leishmaniasis. These dogs also presented higher globulin concentration, while presenting reduction in serum albumin...