Hydrogen sulfide formation in experimental model of acute pancreatitis

Acute pancreatitis (AP) is a disease defined as acute or chronic inflammatory process of the pancreas characterized by premature activation of digestive enzymes within the pancreatic acinar cells and causing pancreatic auto-digestion. In mammalian tissues, H2S is synthesized endogenously from L-cysteine in regulated enzymatic pathways catalyzed by pyridoxal phosphate-dependent enzymes: cystathionine beta-synthase (CBS), gammacystathionase (CTH) and cysteine aminotransferase (CAT) coupled with 3-mercaptopyruvate sulfurtransferase (MPST). In the mitochondria, hydrogen sulfide is oxidized to sulfite, which is then converted to thiosulfate (a sulfane sulfur-containing compound) by thiosulfate sulfurtransferase (rhodanese; TST). Activity and expression of CBS, CTH, MPST, and TST have been determined in vivo in pancreas of the control rats, rats with acute pancreatitis and a sham group. Levels of low-molecular sulfur compounds, such as the reduced and oxidized glutathione, cysteine, cystine and cystathionine, were also determined. This study revealed a significant role of MPST in H2S metabolism in the pancreas. Stress caused by the surgery (sham group) and AP cause a decrease in H2S production associated with a decrease in MPST activity and expression. Markedly higher level of cysteine in the AP pancreas may be caused by a reduced rate of cysteine consumption in a reaction catalyzed by MPST, but it can also be a sign of proteolytic processes occurring in the changed tissu

Deletion of Mcpip1 in Mcpip1fl/flAlbCreMcpip1^{fl/fl}Alb^{Cre} mice recapitulates the phenotype of human primary biliary cholangitis

Primary biliary cholangitis (PBC) is an autoimmune disease characterized by progressive destruction of the intrahepatic bile ducts. The immunopathology of PBC involves excessive inflammation; therefore, negative regulators of inflammatory response, such as Monocyte Chemoattractant Protein-1-Induced Protein-1 (MCPIP1) may play important roles in the development of PBC. The aim of this work was to verify whether Mcpip1 expression protects against development of PBC. Genetic deletion of Zc3h12a was used to characterize the role of Mcpip1 in the pathogenesis of PBC in 6–52-week-old mice. We found that Mcpip1 deficiency in the liver (Mcpip1fl/flAlbCre) recapitulates most of the features of human PBC, in contrast to mice with Mcpip1 deficiency in myeloid cells (Mcpip1fl/flLysMCre mice), which present with robust myeloid cell-driven systemic inflammation. In Mcpip1fl/flAlbCre livers, intrahepatic bile ducts displayed proliferative changes with inflammatory infiltration, bile duct destruction, and fibrosis leading to cholestasis. In plasma, increased concentrations of IgG, IgM, and AMA autoantibodies (anti-PDC-E2) were detected. Interestingly, the phenotype of Mcpip1fl/flAlbCre mice was robust in 6-week-old, but milder in 12–24-week-old mice. Hepatic transcriptome analysis of 6-week-old and 24-week-old Mcpip1fl/flAlbCre mice showed 812 and 8 differentially expressed genes, respectively, compared with age-matched control mice, and revealed a distinct set of genes compared to those previously associated with development of PBC. In conclusion, Mcpip1fl/flAlbCre mice display early postnatal phenotype that recapitulates most of the features of human PBC

First description of histopathological lesions associated with a fatal infection of moose (Alces alces) with the liver fluke Parafasciolopsis fasciolaemorpha Ejsmont, 1932

Parafasciolopsis fasciolaemorpha is a liver fluke typically parasitising moose in Central and Eastern Europe. The aim of our studies was to describe a case of fatal moose parafasciolopsosis, with special emphasis on the histopathological changes caused in the liver tissue by around 10,000 flukes

The occurrence of Fascioloides magna (Bassi, 1875) in the wild cervid population in the Lower Silesian Wilderness – epidemiological and pathological aspects

Fascioloides magna is a parasite of high veterinary importance due to its pathogenicity for wild and domestic ruminants. The aim of our study was to describe the presence of trematode infection in the red deer population in the Lower Silesian Wilderness, one of the established fascioloidosis foci in Central Europe, and to assess the overall prevalence of F. magna in the studied area. In order to achieve this, a coprological study of different cervid species was performed

Enalapril Diminishes the Diabetes-Induced Changes in Intestinal Morphology, Intestinal RAS and Blood SCFA Concentration in Rats

Evidence suggests that microbiota-derived metabolites, including short-chain fatty acids (SCFAs) and trimethylamine-oxide (TMAO), affect the course of diabetic multiorgan pathology. We hypothesized that diabetes activates the intestinal renin–angiotensin system (RAS), contributing to gut pathology. Twelve-week-old male rats were divided into three groups: controls, diabetic (streptozotocin-induced) and diabetic treated with enalapril. Histological examination and RT-qPCR were performed to evaluate morphology and RAS expression in the jejunum and the colon. SCFA and TMAO concentrations in stools, portal and systemic blood were evaluated. In comparison to the controls, the diabetic rats showed hyperplastic changes in jejunal and colonic mucosa, increased plasma SCFA, and slightly increased plasma TMAO. The size of the changes was smaller in enalapril-treated rats. Diabetic rats had a lower expression of Mas receptor (MasR) and angiotensinogen in the jejunum whereas, in the colon, the expression of MasR and renin was greater in diabetic rats. Enalapril-treated rats had a lower expression of MasR in the colon. The expression of AT1a, AT1b, and AT2 receptors was similar between groups. In conclusion, diabetes produces morphological changes in the intestines, increases plasma SCFA, and alters the expression of renin and MasR. These alterations were reduced in enalapril-treated rats. Future studies need to evaluate the clinical significance of intestinal pathology in diabetes