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Case series summary: Two cats, aged 13.5 and 14 years, presented with duodenal masses ultimately diagnosed as Brunner's gland (BG) adenomas. In the first cat, the lesion was a firm, pale tan, proximal duodenal polyp adjacent to the major duodenal papilla that was composed histologically of a well demarcated, expansile mass of well-differentiated BGs separated by fibrovascular septa and few adipocytes. This patient was euthanized for otitis-related vestibular signs, and the clinical significance of the duodenal polyp is unknown. The second cat presented with a 6-month history of vomiting. This cat had a mural duodenal mass in the region of the major duodenal papilla of approximately 2 cm, which was histologically composed of a dense population of variably ectatic BGs expanding the submucosa and lamina propria. This patient's mass was non-resectable, but the vomiting resolved after palliative gastroenterostomy loop surgery to allow ingesta to flow past the mass. The patient survived 35 months after the procedure. Relevance and novel information: BG adenoma is a rare, typically benign tumor in humans with non-specific clinical manifestations and no clear etiopathogenesis. This lesion, and the related condition BG hyperplasia, has been documented rarely in animals (one dog, two horses, and in mice and rats). This is the first description of the lesion in the cat. The comparative pathology, differential diagnoses and possible significance of these lesions are discussed.
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Several drug screening campaigns identified Calpeptin as a drug candidate against SARS-CoV-2. Initially reported to target the viral main protease (Mpro), its moderate activity in Mpro inhibition assays hints at a second target. Indeed, we show that Calpeptin is an extremely potent cysteine cathepsin inhibitor, a finding additionally supported by X-ray crystallography. Cell infection assays proved Calpeptin's efficacy against SARS-CoV-2. Treatment of SARS-CoV-2-infected Golden Syrian hamsters with sulfonated Calpeptin at a dose of 1 mg/kg body weight reduces the viral load in the trachea. Despite a higher risk of side effects, an intrinsic advantage in targeting host proteins is their mutational stability in contrast to highly mutable viral targets. Here we show that the inhibition of cathepsins, a protein family of the host organism, by calpeptin is a promising approach for the treatment of SARS-CoV-2 and potentially other viral infections.
Assuntos
COVID-19 , Humanos , SARS-CoV-2/metabolismo , Catepsinas , Antivirais/farmacologia , Antivirais/uso terapêutico , Antivirais/química , Inibidores de Proteases/farmacologia , Cisteína Endopeptidases/metabolismoRESUMO
Association between ovine ß-globin polymorphisms and resistance against haemonchosis was described and related to the mechanism of high oxygen affinity ßA â ßC switch during anaemia, but there are no studies regarding the involved local host responses. Phenotypic parameters and local responses were evaluated in sheep from two ß-globin haplotypes naturally infected with Haemonchus contortus. Morada Nova lambs were monitored at 63, 84 and 105 days of age for faecal egg counts and packed cell volume (PCV) under natural infection with H. contortus. At 210 days of age, lambs of Hb-AA and Hb-BB ß-globin haplotypes were euthanised, and the fundic region of abomasum was sampled for evaluation of microscopic lesions and relative expression of genes related to immune, mucin and lectin activities. Lambs harbouring the ßA allele presented an improved resistance/resilience against clinical haemonchosis, showing higher PCV during infection. Hb-AA animals presented increased eosinophilia in the abomasum compared to Hb-BB animals, accompanied by higher Th2 profile, mucin and lectin activity transcripts, while the inflammatory response was increased in Hb-BB animals. This is the first report to demonstrate an enhanced local response in the primary site of H. contortus infection related to ßA allele of ß-globin haplotype.
Assuntos
Hemoncose , Haemonchus , Doenças dos Ovinos , Animais , Ovinos , Haemonchus/genética , Hematócrito/veterinária , Mucinas/genética , Lectinas , Fezes , Contagem de Ovos de Parasitas/veterináriaRESUMO
Despite the known importance of Clostridioides (Clostridium) difficile infection (CDI) in animals, there are no published guidelines for the diagnosis of CDI. The performance of the available commercial methods, all standardized for human stool samples, can vary according to the animal species. Thus, the aim of the present study was to review the literature on the detection of C. difficile in pigs, horses, and dogs. The detection of toxins A and B using enzyme immunoassays seems to have low performance in piglet and dog samples, while it shows high sensitivity for the diagnosis of CDI in foals. On the other hand, tests for the detection of glutamate dehydrogenase (GDH) have a high sensitivity towards detection of C. difficile in animal samples, suggesting that it can be an adequate screening method. A few studies have evaluated real-time PCR or nucleic acid amplification tests in animal samples and, so far, these methods have also shown a low performance for the detection of C. difficile in animals. Although the intestinal lesions caused by CDI can vary among animal species, histopathology can be a useful auxiliary tool for postmortem diagnosis in animals.
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Toxinas Bacterianas , Clostridioides difficile , Infecções por Clostridium , Enterocolite Pseudomembranosa , Animais , Proteínas de Bactérias/análise , Toxinas Bacterianas/análise , Técnicas de Laboratório Clínico , Clostridioides , Clostridium , Infecções por Clostridium/diagnóstico , Infecções por Clostridium/veterinária , Cães , Enterocolite Pseudomembranosa/diagnóstico , Fezes/química , Glutamato Desidrogenase/análise , Cavalos , Sensibilidade e Especificidade , SuínosRESUMO
Nine cases of renal cell carcinoma were observed in a research of 586 tumors found at the necropsy of 6,706 cattle performed during 45 years (1964-2008). Of those, six cattle died due to complications related to the tumors and in three cattle the tumors were incidental findings. Clinical signs displayed by cattle affected by renal cell carcinoma were weight loss (5 cases), palpable abdominal masses (4 cases), respiratory distress (4 cases), cough (4 cases), partial (3 cases) or complete (2 cases) anorexia, abdominal pain (2 cases) and fever (1 case). The observed clinical signs were related to complications induced by metastasis that were present in all of the nine cases. Metastases were observed in the abdominal lymph nodes, peritoneum, liver and lung. Two cattle had bilateral renal tumors. Microscopically, tubular, solid, and mixed solid and tubulopapillary patterns were observed. The eosinophilic cellular type was predominant and only one solid tumor was basically formed by clear cells. Scirrhous reaction varied from mild to marked. Corpora amylaceae was a common finding. At immunohistochemistry, all tested tumors displayed variable degrees of positive reactivity to keratin AE1/AE3 and to CD10. CD10 was strongly positive in clear cells renal carcinomas and less intense in the other tumor types. Focal and weak reactivity for anti-PAX-2 was observed in three. Immunohistochemistry was negative for cytokeratin 34β12, c-KIT (CD117), S-100, chromogranine A and apoprotein A surfactant. The results obtained indicated that primary renal cell carcinoma are uncommon in cattle in southern Brazil with an average of cases of 1.3 cases per 1,000 necropsies and that anti-CD10 is a useful marker in the diagnosis of primary renal cell carcinoma in cattle.
Foram encontrados nove casos de carcinoma de células renais em uma pesquisa de 586 tumores em bovinos provenientes de 6.706 necropsias realizadas nessa espécie num período de 45 anos (1964-2008). Seis bovinos morreram por complicações do tumor e três foram achados incidentais. Os bovinos acometidos por carcinoma de células renais demonstraram os seguintes sinais clínicos: perda de peso (5 casos), massas abdominais palpáveis (4 casos), dificuldade respiratória (4 casos), tosse (4 casos), hiporexia (3 casos), anorexia (2 casos), dor abdominal (2 casos) e febre (1 caso). Os sinais clínicos observados estavam relacionados ao comprometimento induzido pelas metástases, que foram observadas nos nove casos. As metástases foram observadas nos linfonodos abdominais, superfícies serosas, fígado e pulmão. Dois bovinos tinham tumor renal bilateral. Microscopicamente, foi observado o padrão tubular, sólido e um misto de sólido e tubular e tubulopapilífero. O tipo celular eosinofílico foi predominante, apenas um tumor sólido era constituído basicamente por células claras. Reação cirrosa variou de discreta à acentuada. Corpora amylaceae foi um achado comum. Todos os tumores marcaram positivamente para citoceratina AE1/AE3 com diferentes graus de intensidade. A imunomarcação para CD10 foi observada em todos os casos testados. CD10 marcou intensamente no CCR de células claras, nos demais a marcação foi observada de forma isolada e menos intensa. Três tumores marcaram de forma isolada e discreta para o anticorpo anti-PAX-2. A avaliação foi negativa para citoceratina 34β12, c-KIT (CD117), S-100, cromogranina A e apoproteína A surfactante. Os resultados obtidos indicam que CCR são incomuns em bovinos no Sul do Brasil com uma média de 1.3 casos para cada mil necropsias realizadas e que o anticorpo anti-CD10 é útil no diagnóstico de CCR em bovinos.