The hearts of 30 dogs naturally infected with Leishmania infantum chagasi were evaluated histologically and immunohistochemically. Myocardial lesions were detected in all dogs, including lymphoplasmacytic myocarditis (27/30), myonecrosis (24/30), increased interstitial collagen (22/30), lepromatous-type granulomatous myocarditis (7/30), fibrinoid vascular change (3/30), and vasculitis (1/30). The parasite was detected in the hearts of 20 of 30 dogs. The number of parasitized cells correlated with the intensity of the inflammation and with the number of granulomas. The results indicate that cardiac lesions are prevalent in dogs with naturally occurring leishmaniasis even in the absence of clinical signs of cardiac disease.

The PTEN, AR, MDM2 and p53 protein network plays a central role in the development of many human cancers, thus eliciting the development of targeted cancer therapeutics. Dogs spontaneously develop tumours, and they are considered a good model for comparative oncology initiatives. Due to the limited information on these proteins in canine tumours, this study aimed to investigate gene and protein alterations in PTEN, AR, MDM2 and p53 in canine prostate cancer (PC). Protein expression was evaluated by immunohistochemistry (15 normal, 22 proliferative inflammatory atrophy (PIA) and 19 PC samples) and Western blotting (2 normal prostate tissue, 2 BPH, 2 PIA samples and 2 PC samples) and gene expression by RT-qPCR (10 normal, 10 PIA and 15 PC samples) of formalin-fixed tissue. We identified nuclear and cytoplasmic expression of PTEN and p53 in all samples, with only nuclear staining found for MDM2 and AR. Our results revealed high expression of MDM2 in PC and PIA samples compared to normal samples, whereas PTEN, P53 and AR expression was down-regulated in PC compared to normal tissue. All tumour samples (n=19) showed loss of nuclear PTEN expression, and all cancer mimickers showed positive nuclear staining. Therefore, nuclear PTEN staining could be a good diagnostic marker for differentiating between malignant lesions and mimickers. Canine prostate carcinogenesis involves increased expression of MDM2 in association with decreased expression of PTEN, p53 and AR, such as occurs in hormone refractory PC in men. Thus, dogs may be an important model for studying advanced stage PC.

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In dogs, there is an association of chronic visceral leishmaniasis with neurological symptoms, and very few publications have investigated whether these neurological manifestations correlate with specific alterations in brain. A total of 42 mixed-breed adult dogs were selected from the Veterinary Hospital of UNESP-Araçatuba and the Control Zoonosis Center in Araçatuba, São Paulo State, Brazil, which is an endemic area for visceral leishmaniasis. Animals presenting positive ELISA and/or positive parasitological diagnosis of Leishmania were enrolled in the group of infected dogs (n=32). Animals with negative ELISA results and parasitological tests for Leishmania, including a negative immunofluorescence test for toxoplasmosis and neosporosis, were included as the control group (n=10). Brain samples were collected, stored in 10% buffered formalin and subjected to routine histological procedures, following by staining with haematoxylin-eosin (HE) and immunohistochemical examination for T and B lymphocytes and phagocytic cells. Cerebrospinal fluid was collected to determine the anti-Leishmania antibody titers. Histological examination of HE stains demonstrated intense inflammatory infiltrate, primarily in the choroid plexus, which was composed of mononuclear cells with no detectable parasites. Immunohistochemistry revealed that CD3(+) T lymphocytes were the major components of the inflammatory infiltrate at the choroid plexus and in the brain. Infected dogs had more CD3(+) T cells than uninfected animals (P=0.0002). Cerebrospinal fluid from infected dogs contained high titers of anti-Leishmania antibodies in comparison with control animals (P<0.0001), which suggests a compromise of the blood-cerebrospinal fluid barrier. Leukocyte entry into the brain suggests the participation of these cells in the pathogenesis of neurological disorders during the advanced stages of leishmaniasis and confirms that the choroid plexus is an important structure for T cell influx.

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