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

BACKGROUND AND AIMS: There are limited comparative data for infliximab and vedolizumab in inflammatory bowel disease patients. METHODS: We conducted a systematic review and meta-analysis to compare the efficacy and safety of infliximab and vedolizumab in adult patients with moderate-to-severe Crohn's disease or ulcerative colitis. RESULTS: We identified six eligible Crohn's disease and seven eligible ulcerative colitis trials that randomised over 1900 participants per disease cohort to infliximab or vedolizumab. In the Crohn's disease and ulcerative colitis cohorts, infliximab yielded better efficacy than vedolizumab for all analysed outcomes (CDAI-70, CDAI-100 responses, and clinical remission for Crohn's disease and clinical response and clinical remission for ulcerative colitis) during the induction phase, with non-overlapping 95% confidence intervals. In the maintenance phase, similar proportions of infliximab- or vedolizumab-treated patients achieved clinical response, clinical remission, or mucosal healing in both Crohn's disease and ulcerative colitis. For the safety outcomes, rates of adverse events, serious adverse events, and discontinuations due to adverse events were similar in infliximab- and vedolizumab-treated patients in both diseases. The infection rate was higher in infliximab for Crohn's disease and higher in vedolizumab when treating patients with ulcerative colitis. There was no difference between the treatments in the proportions of patients who reported serious infections in both indications. CONCLUSIONS: Indirect comparison of infliximab and vedolizumab trials in adult patients with moderate-to severe Crohn's disease or ulcerative colitis demonstrated that infliximab has better efficacy in the induction phase and comparable efficacy during the maintenance phase and overall safety profile compared to vedolizumab.

• MeSH
• Crohnova nemoc * chemicky indukované   farmakoterapie   MeSH
• dospělí MeSH
• gastrointestinální látky škodlivé účinky   MeSH
• humanizované monoklonální protilátky MeSH
• idiopatické střevní záněty * chemicky indukované   farmakoterapie   MeSH
• infliximab škodlivé účinky   MeSH
• lidé MeSH
• ulcerózní kolitida * chemicky indukované   farmakoterapie   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• metaanalýza MeSH
• systematický přehled MeSH

Ulcerative colitis is caused by various external factors and is an inflammatory disease that causes decreased intestinal function. Tenebrio molitor larvae contain more than 30 % fat, and the fat component consists of 45 % oleic acid, 20 % linoleic acid and 20 % polyunsaturated fatty acids. In this study, after administering Tenebrio molitor larva oil (TMLO) in a dextran sodium sulphate (DSS)-induced ulcerative colitis mouse model, the pathological findings and inflammatory markers of colitis were analysed to assess whether a colitis mitigation effect was achieved. In the TMLO-administered group, the colon length increased, the spleen weight decreased, and the body weight increased compared with that in the DSS group. In addition, the disease activity index level decreased, the mRNA expression level of inflammatory cytokines in the colon decreased, and the myeloperoxidase activity level significantly decreased. Also, the activity of the NF-κB pathway involved in the regulation of the inflammatory response was lower in the TMLO group than in the DSS group. Taken together, these results suggest that TMLO suppresses occurrence of acute ulcerative colitis in the DSS mouse model. Therefore, TMLO has the potential to be developed as a health food for the prevention and treatment of ulcerative colitis.

• MeSH
• antiflogistika farmakologie   terapeutické užití   MeSH
• kolitida * chemicky indukované   farmakoterapie   patologie   MeSH
• larva MeSH
• modely nemocí na zvířatech MeSH
• myši MeSH
• síran dextranu toxicita   MeSH
• Tenebrio * MeSH
• ulcerózní kolitida * chemicky indukované   farmakoterapie   patologie   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články 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

Intestinal inflammation induced with dextran sodium sulfate (DSS) is used to study acute or chronic ulcerative colitis in animal models. Decreased gut tissue anti-inflammatory cytokine IL-10 concentration and mRNA abundance are associated with the development of chronic bowel inflammation. Twelve piglets of 3 days old were fitted with an intragastric catheter and randomly allocated into control and DSS groups by administrating either sterile saline or 1.25 g of DSS/kg body weight (BW) in saline per day, respectively, for 10 days. Growth rate and food conversion efficiency were reduced (p<0.05) in the DSS piglets compared with the control group. Quantitative histopathological grading of inflammation in the jejunum and colon collectively showed that the DSS treatment resulted in 12 fold greater (p<0.05) inflammation severity scoring in the colon than in the jejunum, indicative of chronic ulcerative colitis in the colon. Upper gut permeability endpoint was 27.4 fold higher (p<0.05) in the DSS group compared with the control group. The DSS group had higher concentrations and mRNA abundances (p<0.05) of TNF-alpha and IL-6 in the jejunal and colonic tissues compared with the control group. Colonic concentration and mRNA abundance of IL-10 were reduced (p<0.05), however, jejunal IL-10 mRNA abundance was increased (p<0.05) in the DSS group compared with the control group. In conclusion, administration of DSS at 1.25 g/kg BW for 10 days respectively induced acute inflammation in the jejunum and chronic inflammation and ulcerative colitis in the colon with substantially decreased colonic concentration and mRNA abundance of IL-10 in the young pigs, mimicking the IL-10 expression pattern in humans Associated with chronic bowel inflammation.

• MeSH
• exprese genu MeSH
• interleukin-10 biosyntéza   genetika   MeSH
• kolon účinky léků   metabolismus   patologie   MeSH
• novorozená zvířata MeSH
• prasata MeSH
• síran dextranu toxicita   MeSH
• tenké střevo účinky léků   metabolismus   patologie   MeSH
• ulcerózní kolitida chemicky indukované   metabolismus   patologie   MeSH
• zánět chemicky indukované   metabolismus   patologie   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND: Daclizumab is a humanized monoclonal antibody against CD25 that modulates interleukin 2 signaling. The SELECT TRILOGY of clinical studies (SELECT/SELECTION/SELECTED) evaluated the safety and efficacy of daclizumab in patients with relapsing-remitting multiple sclerosis (RRMS). We report the long-term safety and efficacy of daclizumab 150 mg subcutaneous every 4 weeks in patients with RRMS in the SELECTED open-label extension study. METHODS: An interim intent-to-treat analysis of all enrolled patients was performed in January 2014 for this ongoing study. RESULTS: The SELECTED study enrolled 90% of patients who completed SELECTION. In the safety and efficacy analysis (N = 410), median treatment time in SELECTED was 25 months (range, <1-45). Adverse events (AEs) were reported in 76% of patients, serious AEs (SAEs) excluding MS relapse in 16%, and treatment discontinuation due to AEs including multiple sclerosis (MS) relapse in 12%. AEs were primarily of mild to moderate severity, and common AEs (≥10%), excluding MS relapse, were nasopharyngitis (12%) and upper respiratory tract infection (12%). Most commonly reported SAEs (in ≥3 patients), excluding MS relapses, were increased serum hepatic enzymes, pneumonia, ulcerative colitis, and urinary tract infection (<1% each). Incidences of AE groups of interest include cutaneous events (28%), cutaneous SAEs (2%), gastrointestinal SAEs (2%), hepatic SAEs, (1%) and malignancies (1%). The incidence of AEs, SAEs, and treatment-related study discontinuations did not increase over time and no deaths were reported. The adjusted annualized relapse rate (95% confidence interval (CI)) analyzed at 6-month intervals was 0.15 (0.10-0.22) for weeks 97-120 and 0.15 (0.10-0.21) for weeks 121-144. In year 3, the adjusted mean (95% CI) number of new/newly enlarging T2 hyperintense lesions was 1.26 (0.93-1.72) and the mean (median) annualized change in brain volume was -0.32% (-0.34%). CONCLUSIONS: The AE incidence did not increase with extension of therapy into year 3 in SELECTED; the safety profile was similar to that previously observed. The clinical efficacy of daclizumab was sustained over the 3 years comprising the SELECT TRILOGY, although potential selection bias cannot be excluded. TRIAL REGISTRATION: Clinicaltrials.gov NCT01051349; first registered January 15, 2010.

• MeSH
• alanintransaminasa účinky léků   MeSH
• analýza podle původního léčebného záměru MeSH
• aspartátaminotransferasy účinky léků   MeSH
• bezpečnost MeSH
• dospělí MeSH
• humanizované monoklonální protilátky aplikace a dávkování   škodlivé účinky   terapeutické užití   MeSH
• imunoglobulin G aplikace a dávkování   škodlivé účinky   terapeutické užití   MeSH
• imunosupresiva aplikace a dávkování   škodlivé účinky   terapeutické užití   MeSH
• infekce dýchací soustavy chemicky indukované   MeSH
• infekce močového ústrojí chemicky indukované   MeSH
• injekce subkutánní MeSH
• kohortové studie MeSH
• léková dermatitida etiologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• longitudinální studie MeSH
• mozek účinky léků   MeSH
• následné studie MeSH
• nazofaryngitida chemicky indukované   MeSH
• pneumonie chemicky indukované   MeSH
• receptor interleukinu-2 - alfa-podjednotka aplikace a dávkování   terapeutické užití   MeSH
• recidiva MeSH
• relabující-remitující roztroušená skleróza farmakoterapie   MeSH
• ulcerózní kolitida chemicky indukované   MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH

One of the promising approaches in the therapy of ulcerative colitis is administration of butyrate, an energy source for colonocytes, into the lumen of the colon. This study investigates the effect of butyrate producing bacterium Clostridium tyrobutyricum on dextran sodium sulphate (DSS)-induced colitis in mice. Immunocompetent BALB/c and immunodeficient severe combined immunodeficiency (SCID) mice reared in specific-pathogen-free (SPF) conditions were treated intrarectally with C. tyrobutyricum 1 week prior to the induction of DSS colitis and during oral DSS treatment. Administration of DSS without C. tyrobutyricum treatment led to an appearance of clinical symptoms - bleeding, rectal prolapses and colitis-induced increase in the antigen CD11b, a marker of infiltrating inflammatory cells in the lamina propria. The severity of colitis was similar in BALB/c and SCID mice as judged by the histological damage score and colon shortening after 7 days of DSS treatment. Both strains of mice also showed a similar reduction in tight junction (TJ) protein zonula occludens (ZO)-1 expression and of MUC-2 mucin depression. Highly elevated levels of cytokine tumour necrosis factor (TNF)-α in the colon of SCID mice and of interleukin (IL)-18 in BALB/c mice were observed. Intrarectal administration of C. tyrobutyricum prevented appearance of clinical symptoms of DSS-colitis, restored normal MUC-2 production, unaltered expression of TJ protein ZO-1 and decreased levels of TNF-α and IL-18 in the descending colon of SCID and BALB/c mice, respectively. Some of these features can be ascribed to the increased production of butyrate in the lumen of the colon and its role in protection of barrier functions and regulation of IL-18 expression.

• MeSH
• akutní nemoc MeSH
• antigeny CD11b biosyntéza   genetika   MeSH
• aplikace rektální MeSH
• bakteriální translokace MeSH
• butyráty metabolismus   MeSH
• Clostridium tyrobutyricum fyziologie   MeSH
• fosfoproteiny biosyntéza   genetika   MeSH
• imunokompetence MeSH
• interleukin-18 biosyntéza   genetika   MeSH
• kolon metabolismus   mikrobiologie   patologie   MeSH
• mastné kyseliny metabolismus   MeSH
• membránové proteiny biosyntéza   genetika   MeSH
• mucin 2 biosyntéza   genetika   MeSH
• muciny biosyntéza   MeSH
• myši inbrední BALB C MeSH
• myši SCID MeSH
• myši MeSH
• organismy bez specifických patogenů MeSH
• probiotika terapeutické užití   MeSH
• síran dextranu toxicita   MeSH
• těžká kombinovaná imunodeficience genetika   imunologie   MeSH
• TNF-alfa biosyntéza   genetika   MeSH
• ulcerózní kolitida chemicky indukované   genetika   imunologie   mikrobiologie   patologie   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

U 32leté ženy byl ve 20. týdnu gravidity diagnostikován Hodgkinův lymfom. Pacientka uváděla třítýdenní anamnézu celkové slabosti a nevysvětlitelného nočního pocení. Při fyzikálním vyšetření byly zjištěny zvětšené pravostranné krční uzliny velikosti 2,5 x 1,2 cm a 1,0 x 0,5 cm. Zobrazení magnetickou rezonancí ukázalo navíc masu velikosti 17 x 9 x 8 cm v mediastinu. Ultrazvukové vyšetření břicha a pánve a vyšetření kostní dřeně neprokázalo další postižení nádorovou masou. Histologické vyšetření z pravé krční uzliny potvrdilo podezření na Hodgkinův lymfom – typ nodulární sklerózy. Pacientka byla léčena vinblastin sulfátem v dávce 6 mg/m2 i. v. každé 2 týdny a kortikosteroidy (pro protinádorový účinek a podporu dozrávání plicní tkáně plodu). Došlo k významné parciální remisi (mediastinum po této léčbě bylo velikosti 7 x 9 x 8 cm). Během gravidity nebyl pegfilgrastim podáván. Ve 32. týdnu gravidity pacientka císařským řezem porodila zdravé dítě o hmotnosti 1 300 gramů. Skóre Apgarové bylo 9-9-10.

• MeSH
• dospělí MeSH
• faktor stimulující kolonie granulocytů aplikace a dávkování   MeSH
• Hodgkinova nemoc diagnóza   farmakoterapie   komplikace   MeSH
• klostridiové infekce farmakoterapie   MeSH
• lidé MeSH
• metronidazol aplikace a dávkování   MeSH
• nádorové komplikace v těhotenství diagnóza   farmakoterapie   MeSH
• narození živého dítěte MeSH
• neutropenie farmakoterapie   chemicky indukované   komplikace   MeSH
• protokoly antitumorózní kombinované chemoterapie aplikace a dávkování   škodlivé účinky   MeSH
• těhotenství MeSH
• ulcerózní kolitida farmakoterapie   chemicky indukované   mikrobiologie   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• kazuistiky MeSH

Autori popisujú prípad 47ročnej ženy s reumatoidnou artritídou, ktorá dlhodobo užívala nesteroidné antireumatiká. Počas kompletnej reumatologickej liečby sa stav komplikoval sideropenickou anémiou s vysokou zápalovou aktivitou. Bola vyšetrená gastroenterológom. Kolonoskopia odhalila závažnú kolitídu, ktorá bola predbežne hodnotená ako Crohnova choroba. Pacientke bola aplikovaná kompletná gastroenterologická liečba, vrátane infliximabu. Pre nezlepšovanie stavu bola realizovaná kontrolná kolonoskopia, ktorá ukázala zhoršenie nálezu so závažnými kontinuálnymi ulceráciami hrubého čreva. Diagnóza bola prehodnotená na kolopatiu indukovanú nesteroidovými antireumatikami. Pôvodná liečba bola ukončená a realizovaná kolektómia s ileosigmoanastomózou. Po operácii bola pacientka bez ťažkostí, krvný obraz sa upravil, klesla zápalová aktivita. Autori podávajú prehľad o kolopatii indukovanej nesteroidovými antireumatikami, ktorá môže imitovať Crohnovu chorobu.

The authors describe the case of a 47-year-old woman with rheumatoid arthritis who took, in the long term, nonsteroidal anti-inflammatory drugs (NSAID). Her state was complicated by sideropenic anaemia with high inflammatory humoral response during complete rheumatological therapy. She was examined by a gastroenterologist. Colonoscopy revealed severe colitis, which was preliminarily evaluated as a Crohn's disease and a complete therapy including infliximab was administered. However, her condition did not improve and repeated colonoscopy was carried out. This investigation revealed a worse finding with severe continuous ulcerationsof the large bowel. The diagnosis was re-evaluated for NSAID induced colopathy. The previous therapy was stopped and colectomy with ileosigmoideostomy was performed. After surgery the patient was feeling well, had no anaemia, and the humoral anti-inflammatory response decreased. The authors present a review of NSAID induced colopathy which can mimic Crohn's disease.

• MeSH
• antiflogistika nesteroidní aplikace a dávkování   škodlivé účinky   MeSH
• Crohnova nemoc diagnóza   MeSH
• lidé středního věku MeSH
• lidé MeSH
• revmatoidní artritida farmakoterapie   MeSH
• ulcerózní kolitida farmakoterapie   chemicky indukované   patologie   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• kazuistiky MeSH

• MeSH
• finanční podpora výzkumu jako téma MeSH
• gnotobiologické modely MeSH
• histologie MeSH
• kolon mikrobiologie   patologie   MeSH
• myši MeSH
• syndromy imunologické nedostatečnosti komplikace   MeSH
• ulcerózní kolitida chemicky indukované   imunologie   patologie   MeSH
• zánět etiologie   patologie   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• srovnávací studie MeSH