Trypanosomiasis is caused by a pathogenic protozoan of the genus Trypanosoma , being Trypanosoma vivax the most important agent for cattle. The aim of the present study was to demonstrate the expansion of T. vivax infection in different mesoregions of Minas Gerais, Brazil, and describe the clinicopathological findings of trypanosomiasis in cattle. The diagnosis was based on visualization of the parasite in blood smears and DNA detection of T. vivax in the blood of live cows and tissues of necropsied animals by the polymerase chain reaction (PCR). Thirty suspected herds were tested, of which 11 were positive for T. vivax . The most frequent clinical signs were anemia, apathy, drop in milk production, weight loss, reproductive disorders, and nervous signs. Concomitant diseases, such as malignant edema, pneumonia and increased cases of mastitis were associated with T. vivax infection. Three cows were necropsied and the most significant findings were low body condition score, pale mucous and spleen with white pulp hyperplasia. The results demonstrated the expansion of T. vivax infection in Minas Gerais, that PCR-associated blood smears are promising for diagnosis, and that other diseases often occur concomitantly to T. vivax infection in regions with trypanosomiasis in cattle.

Although much has been published since the first cases of COVID-19, there remain unanswered questions regarding SARS-CoV-2 impact on testes and the potential consequences for reproductive health. We investigated testicular alterations in deceased COVID-19-patients, the precise location of the virus, its replicative activity, and the molecules involved in the pathogenesis. We found that SARS-CoV-2 testicular tropism is higher than previously thought and that reliable viral detection in the testis requires sensitive nanosensoring or RT-qPCR using a specific methodology. Macrophages and spermatogonial cells are the main SARS-CoV-2 lodging sites and where new virions form inside the Endoplasmic Reticulum Golgi Intermediate Complex. Moreover, we showed infiltrative infected monocytes migrating into the testicular parenchyma. SARS-CoV-2 maintains its replicative and infective abilities long after the patient infection, suggesting that the testes may serve as a viral sanctuary. Further, infected testes show thickening of the tunica propria, germ cell apoptosis, Sertoli cell barrier loss, evident hemorrhage, angiogenesis, Leydig cell inhibition, inflammation, and fibrosis. Finally, our findings indicate that high angiotensin II levels and activation of mast cells and macrophages may be critical for testicular pathogenesis. Importantly, our data suggest that patients who become critically ill exhibit severe damages and may harbor the active virus in testes.

Pure human and canine mammary invasive micropapillary carcinoma is a rare malignant epithelial tumor accounting for 0.9 to 2% of all invasive mammary carcinomas and present a high rate of lymphatic invasion and metastasis, with unfavorable prognosis. Surgery and chemotherapy are standard treatments for almost all mammary cancer in both species, as well as hormonal and target therapies available for human patients. However, depending on the patient's clinical staging, satisfactory therapeutic results for invasive micropapillary carcinoma are a challenge due to its high capacity of invasion and metastasis. Cyclooxygenase-2 (COX-2) isoform is an important enzyme stimulated by cytokines, growth factors and oncogenes activation to synthetizes prostaglandins in inflammatory process. COX-2 overexpression is associated with angiogenesis and invasion and contributes to cancer development, disease progression, tumor recurrence and regional lymph node metastasis in human and canine mammary carcinomas. This enzyme can be targeted by non-steroidal anti-inflammatory drugs and its inhibition can reduce tumor growth and metastasis in several cancer types. Given the similarity between both species, the present study aims to elucidate the involvement of COX-2 mRNA and protein expression in canine (cIMPC) and human (hIMPC) pure invasive mammary micropapillary carcinoma, with clinicopathological and survival data. Twenty-nine cases of cIMPC and 17 cases of hIMPC were analyzed regarding histologic type, grade, age, tumor size, lymph node condition, extracapsular extension, inflammatory infiltrate and immunophenotype. When available, information on adjuvant treatment, recurrence, metastasis and overall survival were collected. The present study demonstrated COX-2 protein expression in 65.5% of cIMPC and 92.3% of hIMPC, and an association with more advanced histological grades in bitches and higher Ki67 in women. COX-2 mRNA expression was significantly higher in cIMPC than in hIMPC, and its expression was not associated with COX-2 protein expression in both species. COX-2 mRNA expression was associated with negative-ER hIMPC as well as higher Ki67. cIMPC demonstrated proportional early development, more regional metastasis, and a prevalence of negative estrogen receptor, than hIMPC. This is the first time COX-2 expression is associated with negative prognostic factors in both cIMPC and hIMPC, besides the overexpression of COX-2 protein in such unfavorable histological type, which suggests that COX-2 can act as a potential target in IMPC.

BACKGROUNDNutritional intervention with the use of phytochemicals is an important method for the treatment and prevention of a metabolic syndrome. The objective of this study was to chemically characterize Moro orange juice. The influence of juice intake on metabolic parameters of rats that were obese, diabetic or both by means of body mass management after the activation of anthocyanins during refrigerated storage was also assessed.RESULTSJuice intake reversed most of the metabolic abnormalities exhibited by obese rats, including reduction of body mass and improvement of the biochemical profile. The loss of body mass by diabetic animals and obese and diabetic animals was not attributed to juice intake, but to type I diabetes mellitus. In these animals, no improvement was observed in the biochemical profile, liver enzymes and glycemia, so this treatment model was deemed unfeasible.CONCLUSIONThe beneficial effects cannot be explained only by the anthocyanin C3G present in the juice, but rather, by the synergism between all the components. Studies in humans are needed to determine whether the ingestion of this orange can be recommended as an effective strategy to prevent or ameliorate complications of obesity. © 2020 Society of Chemical Industry

Exosome–liposome hybrid nanocarriers containing chemotherapeutic agents have been developed to enhance drug delivery, improve the efficacy of the treatment of metastatic cancer, and overcome chemoresistance in cancer therapy. Thus, the objectives of this study were to investigate the toxicological profiles of exosomes fused with long-circulating and pH-sensitive liposomes containing doxorubicin (ExoSpHL-DOX) in healthy mice and the antitumor activity of ExoSpHL-DOX in Balb/c female mice bearing 4T1 breast tumors. The acute toxicity was determined by evaluating the mortality and morbidity of the animals and conducting hematological, biochemical, and histopathological analyses after a single intravenous administration of ExoSpHL-DOX. The results of the study indicated that the ExoSpHL-DOX treatment is less toxic than the free doxorubicin (DOX) treatment. ExoSpHL-DOX showed no signs of nephrotoxicity, even at the highest dose of DOX, indicating that the hybrid nanosystem may alter the distribution of DOX and reduce the kidney damage. Regarding the antitumor activity, ExoSpHL-DOX showed an antitumor effect compared to the control group. Furthermore, the hybrid nanocarrier of tumor-derived exosomes fused with long-circulating and pH-sensitive liposomes reduced the number of metastatic foci in the lungs. These results indicate that ExoSpHL-DOX may be a promising nanocarrier for the treatment of breast cancer, reducing toxicity and inhibiting metastasis, mainly in the lungs.

Animais de Produção/Livestock Diseases RESUMO.-[Intoxicação experimental por Brachiaria decumbens em coelhos.] Brachiaria ssp. são importantes fontes de forragem para ruminantes no Brasil, devido ao fácil cultivo, boa resistência a seca, boa adaptação a diferentes solos e baixo custo de manutenção. Entretanto, a ingestão desta gramínea está relacionada a surtos de fotossensibilização, em bovinos e ovinos, principalmente, ocasionando prejuízos econômicos significativos. Os efeitos hepatotóxicos relacionados à ingestão da gramínea são a formação de cristais e macrófagos espumosos causados pelo acúmulo de metabólitos tóxicos. A utilização de bovinos e ovinos em experimentos envolvendo a planta apresenta vários empecilhos, tanto no âmbito ético, econômico e no manejo dos animais. O objetivo do presente trabalho foi avaliar a sensibilidade de coelhos como modelo experimental para intoxicação por B. decumbens. No presente estudo foram realizados dois experimentos. O Experimento ABSTRACT.-Utiumi K.Brachiaria spp.are important sources of forage for ruminants in Brazil, due to the easy cultivation, good resistance to drought, good adaptation to different soils and low maintenance cost. However, the ingestion of this grass has been related to photosensitization outbreaks in cattle and sheep with significant economic losses. The hepatotoxic effects related to the ingestion of grass are the formation of crystals and foamy macrophages due to the accumulation of toxic metabolites. The use of cattle and sheep in experiments involving the plant presents several obstacles in the ethical, economic and animal management. The objective of this study was to evaluate the sensitivity of rabbits as an experimental model for B. decumbens poisoning. Two experiments were carried out. In Experiment 1 four rabbits received the fresh plant in daily doses of 10, 20, 40 and 80g/kg body weight for 120 days. In Experiment 2 three rabbits received the fresh plant in amounts of 500g daily with duration of 210 days. The animals of Experiment 1 showed no clinical signs and no macroscopic and microscopic changes characteristic of B. decumbens poisoning. In Experiment 2 the animals also showed no clinical signs or significant macroscopic alterations. Histological analysis showed isolated foamy macrophages or present in random groups of cells in the liver and mesenteric lymph nodes. Samples of liver and mesenteric lymph nodes of the rabbits of Experiment 2 were submitted to the lectin-histochemistry technique. The WGA, sWGA and RCA lectins showed reactivity in foamy macrophages in both organs. This is the first study of our knowledge that demonstrates histopathological lesions caused expetimentally by Brachiaria spp. in rabbits, demonstrating its potential as an animal model.INDEX TERMS: Experimental model, hepatogenic photosensitization, lectin histochemistry, foamy macrophages, toxicoses.

Background Cellular entry of SARS-CoV-2 has been shown to rely on angiotensin-converting enzyme 2 (ACE2) receptors, whose expression in the testis is among the highest in the body. Additionally, the risk of mortality seems higher among male COVID-19 patients, and though much has been published since the first cases of COVID-19, there remain unanswered questions regarding SARS-CoV-2 impact on testes and potential consequences for reproductive health. We investigated testicular alterations in non-vaccinated deceased COVID-19-patients, the precise location of the virus, its replicative activity, and the immune, vascular, and molecular fluctuations involved in the pathogenesis. Results We found that SARS-CoV-2 testicular tropism is higher than previously thought and that reliable viral detection in the testis requires sensitive nanosensors or RT-qPCR using a specific methodology. Through an in vitro experiment exposing VERO cells to testicular macerates, we observed viral content in all samples, and the subgenomic RNA’s presence reinforced the replicative activity of SARS-CoV-2 in testes of the severe COVID-19 patients. The cellular structures and viral particles, observed by transmission electron microscopy, indicated that macrophages and spermatogonial cells are the main SARS-CoV-2 lodging sites, where new virions form inside the endoplasmic reticulum Golgi intermediate complex. Moreover, we showed infiltrative infected monocytes migrating into the testicular parenchyma. SARS-CoV-2 maintains its replicative and infective abilities long after the patient’s infection. Further, we demonstrated high levels of angiotensin II and activated immune cells in the testes of deceased patients. The infected testes show thickening of the tunica propria, germ cell apoptosis, Sertoli cell barrier loss, evident hemorrhage, angiogenesis, Leydig cell inhibition, inflammation, and fibrosis. Conclusions Our findings indicate that high angiotensin II levels and activation of mast cells and macrophages may be critical for testicular pathogenesis. Importantly, our findings suggest that patients who become critically ill may exhibit severe alterations and harbor the active virus in the testes.

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