Characterization of macrophage polarization in lesions of dogs inoculated with Leishmania (Leishmania) infantum (BH401) strain

The aim of this work was to describe the anatomical pathology of dogs experimentally infected with Leishmania (Leishmania) infantum strain MCAN / BR / 2002 / BH401, a Brazilian form of L. infantum isolated from a symptomatic dog from an endemic area. For this, five beagles (three months old and both sexes) composed the experimental group. Markers of macrophage subpopulations M1 and M2 (related to resistance and susceptibility to visceral leishmaniasis) and the tissue cytokine transforming growth factor beta 1 (TGF-ß1) (one of the main cytokines related to the fibrosis process and anti-inflammatory action) were evaluated in livers, lungs and kidneys. The BH 401 L. infantum strain induced classical lesions of the visceral disease where all evaluated organs showed a chronic inflammatory reaction and tissue parasitism associated with a higher expression of CD163 and TGF-ß1 markers, might be related to the progression of the disease. In this work it was possible to conclude that the BH 401 strain reproduces canine visceral leishmaniasis that occurs naturally.(AU)

Complement activation-related pseudoallergy in dogs following intravenous administration of a liposomal formulation of meglumine antimoniate / Pseudoalergia relacionada à ativação do complemento em cães após administração intravenosa de uma formulação lipossomal de antimoniato de meglumina

The increasing use of nanotechnologies in advanced therapies has allowed the observation of specific adverse reactions related to nanostructures. The toxicity of a novel liposome formulation of meglumine antimoniate in dogs with visceral leishmaniasis after single dose has been investigated. Groups of 12 animals received by the intravenous route a single dose of liposomal meglumine antimoniate (group I [GI], 6.5 mg Sb/kg), empty liposomes (GII) or isotonic saline (GIII). Evaluation of hematological and biochemical parameters showed no significant changes 4 days after administration. No undesired effects were registered in the GIII. However, adverse reactions were observed in 67.7% of dogs from both groups that received liposomal formulations. The side effects began moments after bolus administration and disappeared during the first 15 minutes after treatment. Prostation, sialorrhea and defecation were the most frequent clinical signs, registered in 33.3% and 41.6 % of animals from the groups GI and GII, respectively. Tachypnea, mydriasis, miosis, vomiting and cyanosis were also registered in both groups. The adverse reactions observed in this study were attributed to the activation of the complement system by lipid vesicles in a phenomenon known as Complement Activation-Related Pseudoallergy (CARPA). The influence of the physical-chemical characteristics of liposomal formulation in the triggering of CARPA is discussed.(AU)

O crescente uso das nanotecnologias nas terapias avançadas tem permitido a observação de reações adversas específicas relacionadas às nanoestruturas. A toxicidade de uma nova formulação lipossomal de antimoniato de meglumina após dose única foi avaliada em cães com leishmaniose visceral. Grupos de 12 animais receberam por via intravenosa uma dose única de antimoniato de meglumina lipossomal (grupo I [GI], 6,5 mg Sb/kg), lipossomas vazios (GII) ou solução salina isotônica (GIII). A avaliação de parâmetros hematológicos e bioquímicos não revelou alterações significativas quatro dias após a administração. Nenhum efeito indesejável foi registrado no GIII. No entanto, reações adversas foram observadas em 67,7% dos cães de ambos os grupos que receberam formulações lipossomais. Os efeitos colaterais iniciaram momentos após a administração em "bolus" e desapareceram no decurso dos primeiros 15 minutos após o tratamento. Prostração, sialorréia e defecação foram os sinais clínicos mais frequentes, registrados em 33,3% e 41,6% dos animais dos grupos GI e GII, respectivamente. Taquipnéia, midríase, miose, vômitos e cianose também foram registrados em ambos os grupos. As reações adversas observadas neste trabalho foram atribuídas à ativação do sistema complemento pelas vesículas lipídicas em fenômeno conhecido como Pseudoalergia Relacionada à Ativação do Complemento (PARAC). A influência das características físico-químicas da formulação lipossomal no desencadeamento de PARAC é abordada.(AU)

Chronic pericarditis in a naturally Leishmania (Leishmania) chagasi infected dog

Visceral Leishmaniasis is an infection disease of chronic evolution caused by the protozoan Leishmania sp. The main clinical manifestations in dogs are anemia, progressive weight loss, lymphadenopathy, hepatomegaly, and cutaneous lesions. The heart involvement in visceral leishmaniasis has been rarely reported. The aim of this work was to describe the presence of amastigote forms of Leishmania sp. and associated lesions in the heart of naturally infected dog. For diagnosis analysis, serological tests for anti-Leishmania antibodies and fine-needle aspirative bone marrow cytology were used. The samples (right ventricle and ear skin) were histologically evaluated and processed for imunodetection of Leishmania sp. The most significant histological change was an intense, non-specific, chronic pericarditis associated with intracytoplasmatic amastigotes within macrophages. The tissue parasitism was confirmed through positive imunomarcation. This is a first report of pericardium compromisement of naturally Leishmania infected adult dog.

Histopathological and parasitological analysis of skin tissues biopsies from two distinct anatomical areas of the ears of dogs naturally infected with Leishmania (Leishmania) chagasi

Canine visceral leishmaniasis is an endemic disease in Latin America caused by Leishmania (Leishmania) chagasi and transmitted to man and animals by infected blood-sucking sandflies) of the genus Lutzomyia. Dogs are considered to be the primary domestic reservoir of disease because they present an intense cutaneous parasitism. The aim of this study was to evaluate the intensity of the inflammatory process and to compare it to the parasite load of tissue from two different sites of the ear skin of dogs naturally infected with Leishmania chagasi. We think that exist a specific anatomical region that exhibits a relatively higher rate of parasitism. For diagnostic analysis, serological tests were carried out using the indirect fluorescence antibody test (IFAT) and the enzyme-linked immunosorbent assay (ELISA). Twelve animals naturally infected with Leishmania chagasi were euthanatized with a lethal dose of Sodium Thiopental™ and T61™ During the necropsy, fragments of the extremity and middle anatomical regions of the ear were collected. All tissues were fixed in a 10% formalin solution and then paraffin-embedded for histopathological (HE) and immunohistochemical analysis. The streptavidin-peroxidase immunohistochemistry method was used to detect tissue amastigotes using optical microscopy. Our results indicated a chronic inflammatory reaction, ranging from discrete to an intense magnitude. The inflammatory process was more frequently observed in the extremity of the ear than in the middle portion of the ear (p<0.05). The presence of parasites in the ear extremity was higher than in other evaluated regions. A positive correlation between the tissue inflammation, parasitism, and serological data was confirmed at both ear positions (p<0.05). Skin biopsies are an important tool for CVL diagnosis and the ear extremity represents an appropriated area to perform the assays.