Autoři prezentují klinický obraz a terapeutické možnosti řešení u nepřímé karotido-kavernózní píštěle (K-K-P), která je častým zdrojemdiagnostických rozpaků. Zároveň referují o neobvyklé komplikaci - sekundárním glaukomu s uzavřeným úhlema venózní ischemické retinopatii při trombóze oftalmické vény a o možnostech léčby tohoto stavu.
The authors present clinical picture, diagnostic procedures and therapy of the dural shunt syndrome which is very often the cause of diagnostic difficulties. They report about unusual complication - secondary angle closure glaucoma and venous stasis retinopathy from thrombosis of ophthalmic vein and about the possibilities of the therapy.
- MeSH
- glaukom s uzavřeným úhlem diagnóza chirurgie MeSH
- ischemie MeSH
- karotido-kavernózní píštěl diagnóza komplikace MeSH
- lidé MeSH
- retina krevní zásobení MeSH
- senioři MeSH
- Check Tag
- lidé MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
The aim of this study was to investigate the use of a standardized animal model subjected to antibiotic treatment, and the effects of this treatment on the course of dextran sodium sulphate (DSS)-induced colitis in mice. By decontamination with selective antibiotics and observation of pathogenesis of ulcerative colitis (UC) induced chemically by exposure of mice to various concentrations of DSS, we obtained an optimum animal PGF model of acute UC manifested by mucin depletion, epithelial degeneration and necrosis, leading to the disappearance of epithelial cells, infiltration of lamina propria and submucosa with neutrophils, cryptitis, and accompanied by decreased viability of intestinal microbiota, loss of body weight, dehydration, moderate rectal bleeding, and a decrease in the selected markers of cellular proliferation and apoptosis. The obtained PGF model did not exhibit changes that could contribute to inflammation by means of alteration of the metabolic status and the induced dysbiosis did not serve as a bearer of pathogenic microorganisms participating in development of ulcerative colitis. The inflammatory process was induced particularly by exposure to DSS and its toxic action on compactness and integrity of mucosal barrier in the large intestine. This offers new possibilities of the use of this animal model in studies with or without participation of pathogenic microbiota in IBD pathogenesis.
- MeSH
- antibakteriální látky farmakologie MeSH
- apoptóza fyziologie MeSH
- epitelové buňky patologie MeSH
- modely nemocí na zvířatech MeSH
- myši inbrední BALB C MeSH
- myši MeSH
- proliferace buněk fyziologie MeSH
- síran dextranu farmakologie MeSH
- střevní mikroflóra účinky léků fyziologie MeSH
- střevní sliznice mikrobiologie patologie MeSH
- ulcerózní kolitida chemicky indukované farmakoterapie patologie MeSH
- zánět farmakoterapie patologie MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
The development of inflammatory bowel disease (IBD) is associated with alterations in the gut microbiota. There is currently no universal treatment for this disease, thus emphasizing the importance of developing innovative therapeutic approaches. Gut microbiome-derived metabolite butyrate with its well-known anti-inflammatory effect in the gut is a promising candidate. Due to increased intestinal permeability during IBD, butyrate may also reach the liver and influence liver physiology, including hepatic drug metabolism. To get an insight into this reason, the aim of this study was set to clarify not only the protective effects of the sodium butyrate (SB) administration on colonic inflammation but also the effects of SB on hepatic drug metabolism in experimental colitis induced by dextran sodium sulfate (DSS) in mice. It has been shown here that the butyrate pre-treatment can alleviate gut inflammation and reduce the leakiness of colonic epithelium by restoration of the assembly of tight-junction protein Zonula occludens-1 (ZO-1) in mice with DSS-induced colitis. In this article, butyrate along with inflammation has also been shown to affect the expression and enzyme activity of selected cytochromes P450 (CYPs) in the liver of mice. In this respect, CYP3A enzymes may be very sensitive to gut microbiome-targeted interventions, as significant changes in CYP3A expression and activity in response to DSS-induced colitis and/or butyrate treatment have also been observed. With regard to medications used in IBD and microbiota-targeted therapeutic approaches, it is important to deepen our knowledge of the effect of gut inflammation, and therapeutic interventions were followed concerning the ability of the organism to metabolize drugs. This gut-liver axis, mediated through inflammation as well as microbiome-derived metabolites, may affect the response to IBD therapy.
- Publikační typ
- časopisecké články MeSH
Inflammatory bowel disease is an idiopathic autoimmune disorder that is mainly divided into ulcerative colitis and Crohn's disease. Probiotics are known for their beneficial effect and used as a treatment option in different gastrointestinal problems. The aim of our study was to find suitable bacterial vectors for gene therapy of inflammatory bowel disease. Salmonella enterica serovar Typhimurium SL7207 and Escherichia coli Nissle 1917 were investigated as potential vectors. Our results show that the growth of Escherichia coli Nissle 1917 was inhibited in the majority of samples collected from dextran sodium sulphate-treated animals compared with control growth in phosphate-buffered saline. The growth of Salmonella enterica serovar Typhimurium SL7207 in all investigated samples was enhanced or unaffected in comparison with phosphate-buffered saline; however, it did not reach the growth rates of Escherichia coli Nissle 1917. Dextran sodium sulphate treatment had a stimulating effect on the growth of both strains in homogenates of distant small intestine and proximal colon samples. The gastrointestinal tract contents and tissue homogenates did not inhibit growth of Salmonella enterica serovar Typhimurium SL7207 in comparison with the negative control, and provided more suitable environment for growth compared to Escherichia coli Nissle 1917. We therefore conclude that Salmonella enterica serovar Typhimurium SL7207 is a more suitable candidate for a potential bacterial vector, even though it has no known probiotic properties.
- MeSH
- Escherichia coli účinky léků růst a vývoj MeSH
- gastrointestinální trakt účinky léků mikrobiologie MeSH
- hmotnostní úbytek MeSH
- myši inbrední C57BL MeSH
- Salmonella enterica účinky léků růst a vývoj MeSH
- síran dextranu farmakologie MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Several studies have indicated the beneficial anti-inflammatory effect of butyrate in inflammatory bowel disease (IBD) therapy implying attempts to increase butyrate production in the gut through orally administered dietary supplementation. Through the gut-liver axis, however, butyrate may reach directly the liver and influence the drug-metabolizing ability of hepatic enzymes, and, indirectly, also the outcome of applied pharmacotherapy. The focus of our study was on the liver microsomal cytochrome P450 (CYP) 2A5, which is a mouse orthologue of human CYP2A6 responsible for metabolism of metronidazole, an antibiotic used to treat IBD. Our findings revealed that specific pathogen-free (SPF) and germ-free (GF) mice with dextran sulfate sodium (DSS)-induced colitis varied markedly in enzyme activity of CYP2A and responded differently to butyrate pre-treatment. A significant decrease (to 50%) of the CYP2A activity was observed in SPF mice with colitis; however, an administration of butyrate prior to DSS reversed this inhibition effect. This phenomenon was not observed in GF mice. The results highlight an important role of gut microbiota in the regulation of CYP2A under inflammatory conditions. Due to the role of CYP2A in metronidazole metabolism, this phenomenon may have an impact on the IBD therapy. Butyrate administration, hence, brings promising therapeutic potential for improving symptoms of gut inflammation; however, possible interactions with drug metabolism need to be further studied.
- MeSH
- antibakteriální látky škodlivé účinky farmakologie terapeutické užití MeSH
- antiflogistika farmakologie MeSH
- butyráty * farmakologie MeSH
- metronidazol farmakologie MeSH
- modely nemocí na zvířatech MeSH
- myši inbrední C57BL MeSH
- myši MeSH
- síran dextranu škodlivé účinky MeSH
- střevní mikroflóra * MeSH
- systém (enzymů) cytochromů P-450 metabolismus MeSH
- ulcerózní kolitida * chemicky indukované farmakoterapie MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Neurotrophins are present in the gastrointestinal tract where they participate in the survival and growth of enteric neurons, augmentation of enteric circuits, elevation of colonic myoelectrical activity and also in different aspects of colitis. Previous studies largely focused on the role of neural and mucosal neurotrophins in gut inflammation. The expression of neurotrophins in colonic smooth muscle cells (SMCs) and the interactions of this potential source with colitis has not been studied in the gut. The expression of NGF, BDNF, NT-3 and NT-4 in SMCs from longitudinal and circular muscle layers of rat colon from normal and dextran sodium sulphate (DSS)-induced colitis rats was measured by ELISA. NGF, BDNF, NT-3 and NT-4 are differentially expressed in both longitudinal and circular SMCs, where the expressions of BDNF and NT-4 proteins were greater in SMCs from the longitudinal muscle layer than from the circular muscle layer, while NGF protein expression was greater in circular SMCs and NT-3 expression was equal in cells from both muscle layers. Induction of colitis with DSS significantly alters neurotrophins expression pattern in colonic SMCs. NGF levels upregulated in circular SMCs. BDNF level was increased in DSS-induced colitis in longitudinal SMCs. NGF, NT-3 and NT-4 levels were downregulated in longitudinal SMCs of DSS-induced colitis rats' colon. Disturbances of neurotrophins expression in SMCs resulted from colitis might account for the structural and functional changes in inflammatory bowel disease (IBD) such as loss of innervation and characteristic hypercontractility of longitudinal muscle in IBD.
- MeSH
- hladké svalstvo metabolismus patologie MeSH
- kolitida chemicky indukované metabolismus patologie MeSH
- kolon metabolismus patologie MeSH
- modely nemocí na zvířatech MeSH
- mozkový neurotrofický faktor metabolismus MeSH
- myocyty hladké svaloviny metabolismus patologie MeSH
- nervový růstový faktor metabolismus MeSH
- neurotrofin 3 metabolismus MeSH
- neurotrofní faktory metabolismus MeSH
- potkani Sprague-Dawley MeSH
- síran dextranu * MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- srovnávací studie MeSH
A decrease in the abundance and biodiversity of intestinal bacteria within the Firmicutes phylum has been associated with inflammatory bowel disease (IBD). In particular, the anti-inflammatory bacterium Faecalibacterium prausnitzii, member of the Firmicutes phylum and one of the most abundant species in healthy human colon, is underrepresented in the microbiota of IBD patients. The aim of this study was to investigate the immunomodulatory properties of F. prausnitzii strain A2-165, the biofilm forming strain HTF-F and the extracellular polymeric matrix (EPM) isolated from strain HTF-F. For this purpose, the immunomodulatory properties of the F. prausnitzii strains and the EPM were studied in vitro using human monocyte-derived dendritic cells. Then, the capacity of the F. prausnitzii strains and the EPM of HTF-F to suppress inflammation was assessed in vivo in the mouse dextran sodium sulphate (DSS) colitis model. The F. prausnitzii strains and the EPM had anti-inflammatory effects on the clinical parameters measured in the DSS model but with different efficacy. The immunomodulatory effects of the EPM were mediated through the TLR2-dependent modulation of IL-12 and IL-10 cytokine production in antigen presenting cells, suggesting that it contributes to the anti-inflammatory potency of F. prausnitzii HTF-F. The results show that F. prausnitzii HTF-F and its EPM may have a therapeutic use in IBD.
- MeSH
- antigeny povrchové metabolismus MeSH
- cytokiny genetika metabolismus MeSH
- dendritické buňky imunologie metabolismus MeSH
- extracelulární matrix metabolismus MeSH
- fenotyp MeSH
- forkhead transkripční faktory genetika metabolismus MeSH
- genetická transkripce MeSH
- idiopatické střevní záněty etiologie metabolismus patologie MeSH
- kolitida chemicky indukované genetika imunologie metabolismus mikrobiologie MeSH
- lymfatické uzliny imunologie metabolismus MeSH
- mediátory zánětu metabolismus MeSH
- modely nemocí na zvířatech MeSH
- myši MeSH
- Ruminococcus metabolismus ultrastruktura MeSH
- síran dextranu škodlivé účinky MeSH
- slezina imunologie metabolismus MeSH
- střevní sliznice metabolismus mikrobiologie patologie MeSH
- toll-like receptor 2 genetika metabolismus MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
