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Background Comparative data regarding different regimens of oral mesalazine (mesalamine) for maintaining remission in ulcerative colitis are limited. Aim To evaluate whether 3.0 g mesalazine once-daily (OD) is superior to the standard treatment of 0.5 g mesalazine three times daily (t.d.s.) and to prove the therapeutic equivalence of OD vs. t.d.s. dosing of total 1.5 g mesalazine for remission maintenance in patients with ulcerative colitis. Methods A 1-year, multicentre, double-blind, double-dummy study was undertaken in patients with endoscopically and histologically confirmed ulcerative colitis in remission. Patients were randomised to oral mesalazine 3.0 g OD, 1.5 g OD or 0.5 g t.d.s. The primary efficacy endpoint was the proportion of patients still in clinical remission at the final visit, with clinical relapse being defined as CAI score >4 and an increase of ≥3 from baseline. Results The primary efficacy endpoint occurred in 162/217 3.0 g OD patients (75%), 129/212 1.5 g OD patients (61%) and 150/218 0.5 g t.d.s. patients (69%) in the intention-to-treat population, and in 152/177 (86%), 121/182 (67%) and 144/185 (78%) in the per protocol population respectively; 3.0 g OD was superior to both low-dose regimens for the primary endpoint (i.e. P < 0.001, 3.0 g OD vs. 1.5 g OD; P = 0.024, 3.0 g OD vs. 0.5 g t.d.s.; superiority test, per protocol population). Safety analysis, including comprehensive renal monitoring, revealed no concern in any treatment group. Conclusion Mesalazine 3.0 g once daily was the most effective dose for maintenance of remission in ulcerative colitis of the three regimens assessed, with no penalty in terms of safety. [ABSTRACT FROM AUTHOR]

Background There are no comparative studies of coated mesalazine. Aim To compare the efficacy and tolerability of Eudragit-L- and ethylcellulose-coated mesalazine tablets in patients with mild to moderately active ulcerative colitis. Methods A double-blind, double-dummy, randomized parallel group trial was performed across 18 centres in Australia, and 20 in Eastern Europe. Patients were treated with 3 g mesalazine for 8 weeks with the primary efficacy end point being clinical remission. Results Of 215 patients, 69% achieved clinical remission in both treatment groups ( P < 0.001; chi-square test) with no differences in frequency of adverse events. In the Australian cohort ( n = 63), the Eudragit-L group had a higher remission rate (73% vs. 36%) and responded 13 days faster, compared with those in the European group (67% vs. 84%, and 2 days respectively). No clear reasons for differences in treatment responses were identified. Conclusions Eudragit-L and ethylcellulose-coated mesalazine tablets are well tolerated and equally effective in achieving remission in mild-moderately active ulcerative colitis over 8 weeks. [ABSTRACT FROM AUTHOR]

: Mesalazineas the treatment standard for ulcerative colitis can be applied in different galenical preparations.: A novel formulation of mesalazine pellets with delayed and prolonged release characteristics was compared with conventional Eudragit L-coated tablets. Furthermore, the effect of mesalazine dose escalation on nonresponders was evaluated in both treatment groups.: A total of 233 patients with mild to moderately active ulcerative colitis were randomized to receive either mesalazine (1.5 g/day in three doses) as pellets (n = 115) or tablets (n = 118) for 8 weeks. At insufficient response, the dose was increased to 3.0 g.: The clinical remission rate (clinical activity index ≤ 4) for pellets was 67% vs. 68% for tablets which statistically proved to be not inferior (significance levelα = 2.5%). In patients without dose increase, the remission rate was 47% (pellets) vs. 42% (tablets). Endoscopic improvement was observed in 80% (pellets) vs. 83% (tablets), and histological improvement in 48% (pellets) vs. 52% (tablets) of patients.: Mesalazine pellets are as effective as tablets in the treatment of mild to moderately active ulcerative colitis. Dose escalation to 3.0 g/day is a valid option for nonresponders to a starting dose of 1.5 g/day. [ABSTRACT FROM AUTHOR]

Bile acids (BAs) and bilirubin, primarily known for their role in lipid metabolism and as heme catabolite, respectively, have been found to have diverse effects on various physiological processes, including oxidative stress and inflammation. Indeed, accumulating evidence showed that the interplay between BAs and bilirubin in these processes involves intricate regulatory mechanisms mediated by specific receptors and signaling pathways under certain conditions and in specific contexts. Oxidative stress plays a significant role in the development and progression of cardiovascular diseases (CVDs) due to its role in inflammation, endothelial dysfunction, hypertension, and other risk factors. In the cardiovascular (CV) system, recent studies have suggested that BAs and bilirubin have some opposite effects related to oxidative and inflammatory mechanisms, but this area of research is still under investigation. This review aims to introduce BAs and bilirubin from a biochemical and physiological point of view, emphasizing their potential protective or detrimental effects on CVDs. Moreover, clinical studies that have assessed the association between BAs/bilirubin and CVD were examined in depth to better interpret the possible link between them. [ABSTRACT FROM AUTHOR]

OBJECTIVE: The goal of our research was to determine the impact of clinical nutrition in the form of home parenteral nutrition (HPN) in patients with nutritional disorders, most often caused by diseases of the digestive tract, with the risk of developing malnutrition. PATIENTS AND METHODS: We retrospectively evaluated 39 patients from the Gastroenterology Clinic and the Home Parenteral Nutrition Center of the University Hospital Bratislava, whose nutritional status was evaluated based on the determination of the body mass index (BMI), the completed nutritional risk screening (NRS) questionnaire and the determination of performance status. Subsequently, after fulfilling the criteria for HPN, the initiation of parenteral nutrition (PN) followed, implemented in a domestic environment for the following two years as HPN. During this period, we did a monthly check-up of the objective condition and laboratory parameters of the enrolled patients, which were the basis for adjusting the nutritional treatment. We also evaluated the occurrence of infectious and thrombotic complications clinically and on the basis of laboratory parameters focused on culture and hemocoagulation examination. After two years, we performed control exit examinations, which we compared with the entrance examinations and statistically evaluated the success of the treatment. We evaluated the obtained data using standard statistical methods. RESULTS: During HPN, there was a statistically significant elevation of the individual monitored values ​​(BMI, absolute lymphocytes count, cholesterol, cholinesterase, total proteins, albumins), which clearly proves correctly indicated and managed HPN. We recorded vein thrombosis in v. subclavia and v. jugularis in 6 (15 %) patients. Subsequent catheter extraction was necessary after unsuccessful catheter insertion. In 13 (33 %) patients, tunneled catheter replacement was required due to infection. The mortality rate in our group was 8 % (3 patients). These were female patients aged 39, 42, and 66 years. The cause of death in all of these patients was the underlying diagnosis (oncohematological disease, systemic connective tissue disease, and repeated resections of the digestive tract for inflammatory GIT disease with the development of severe malnutrition). We recorded a positive effect of applied HPN in all three patients until death. We did not register any factors that would have a relevant influence on the success of administered HPN. CONCLUSION: Based on our results, we can conclude that the patients included in the HPN were correctly indicated, and all of them, based on the monitored parameters (regardless of gender, age, initial diagnosis, or BMI value), benefited from the applied treatment, which was correctly chosen based on their individual needs. Our results clearly document the irreplaceable role of HPN in the management of patients with nutritional intake disorders leading to the development of malnutrition. [ABSTRACT FROM AUTHOR]

The main aim of this paper is to summarise the roles of m SP 6 sp A RNA methylation in post-TBI BGA to further highlight the possible regulatory mechanisms of m SP 6 sp A modification in TBI-induced BGA dysfunction, and, finally, to discuss the outcome of considering m SP 6 sp A as a therapeutic target to improve the recovery of the brain and gut dysfunction caused by TBI. Keywords: m6A RNA modification; brain-gut axis; traumatic brain injury EN m6A RNA modification brain-gut axis traumatic brain injury N.PAG N.PAG 26 08/29/22 20220801 NES 220801 1. Multiple lines of evidence from studies have shown that m SP 6 sp A modification influences almost all aspects of RNA metabolism, including RNA expression, splicing, nuclear output, translation, decay and RNA protein interactions [[73], [75]]. [Extracted from the article]

In the article, we point out the volume training indicators that determined the sports performance of the race walker at 20 and 50 km. The basis of the analysis were the training volume indicators and the annual sport performance. Nonparametric procedures were chosen according to the assessment of the normality of file layout. Differences between the completed volume were evaluated statistically (Z) and substantively ("r"). The nonparametric algorithm CHAID was used for the construction of the regression trees. By the trees method were selected training indicators which showed in the individual training cycles high tightness with race walking performance. The regression model in training cycles YTC 2017/2018 introduced the indicator of intense tempo endurance (walking 4:41-5:00 min.km-1), extensive aerobic endurance (walking 6:00 and more min.km-1) and the running volume indicator. Extended aerobic endurance (walking 5:41-6:00 min.km-1), extensive tempo endurance (walking 5:01-5:20 min.km-1), intense special endurance (walking 4:06-4:20 min.km-1), number of starts and regeneration have been enforced between the predictors of the walking performance in training cycles YTC 2018/2019. The analysis points to the training resources which were most involved in the improvement of the sport performance. Their exact identification will allow the rationalization of the training process in the future, coordinate the conceptual bases of sport preparation and to improve the system of shaping the top condition towards the 2021 Olympics in Tokyo. [ABSTRACT FROM AUTHOR]

Objectives: Useful indices to determine whether to reduce the dose of 5-aminosalicylic acid (5-ASA) in patients with ulcerative colitis (UC) during remission remain unclear. We aimed to analyze the rate and risk factors of relapse after reducing the dose of oral 5-ASA used for maintenance therapy of UC. Methods: UC patients whose 5-ASA dose was reduced in clinical remission (partial Mayo score of ≤ 1) at our institution from 2012 to 2017 were analyzed. Various clinical variables of patients who relapsed after reducing the dose of oral 5-ASA were compared with those of patients who maintained remission. Risk factors for relapse were assessed by univariate and multivariate logistic regression analyses. Cumulative relapse-free survival rates were calculated using the Kaplan–Meier method. Results: A total of 70 UC patients were included; 52 (74.3%) patients maintained remission and 18 (25.7%) patients relapsed during the follow-up period. Multivariate analysis indicated that a history of acute severe UC (ASUC) was an independent predictive factor for clinical relapse (p = 0.024, odds ratio: 21, 95% confidence interval: 1.50–293.2). Based on Kaplan–Meier survival analysis, the cumulative relapse-free survival rate within 52 weeks was 22.2% for patients with a history of ASUC, compared with 82.0% for those without. the log-rank test showed a significant difference in a history of ASUC (p < 0.001). Conclusions: Dose reduction of 5-ASA should be performed carefully in patients who have a history of ASUC. [ABSTRACT FROM AUTHOR]

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Background: Efficacy of maintenance therapy in ulcerative colitis (UC) in the remission stage has been reported to depend on release profile or dosing regimen of oral 5-aminosalicylic acid (5-ASA) products used. Aim of this study is to investigate real life results in using oral 5-ASA products for maintaining mild to moderate UC patients in Japan.Methods: Adult UC outpatients treated with oral 5-ASA products were enrolled from 379 sites in Japan between July 2012 and July 2013, and followed for 52 weeks. Remission maintenance rate was evaluated by products and dosages. Factors affecting recurrence were also examined.Results: A total of 5695 UC patients were registered. Among the 4677 patients in whom remission maintenance was observed, remission maintenance rate at week 52 was 80.2%. As for disease duration and dosage, Pentasa® 4000 mg/day in 2 divided doses was administered to 480 (21.0%) patients in remission and 341 (46.6%) patients in active stage, and Asacol® 3600 mg/day in 3 divided doses was administered to 696 (46.4%) patients in remission and 473 (67.3%) patients in active stage. The remission maintenance rate at week 52 by dosage and frequency did not significantly differ between Pentasa® Tablets at 4000 mg/day in 2 divided doses (76.5%) and Asacol® Tablets at 3600 mg/day in 3 divided doses (76.1%, P = 0.7868). Factors affecting the risk of relapse in UC were identified. Significantly persistent remission maintenance was noted in patients in whom duration of remission maintenance until enrollment was 12 to <24 months or ≥24 months relative to the reference category of <3 months (12 to <24 months: HR 0.600 [0.486-0.740], p < 0.0001]; ≥24 months: HR 0.352 [0.289-0.431], p < 0.0001).Conclusions: Efficacy of real life results in using oral 5-ASA products for maintaining mild to moderate UC patients was favorable. Maintaining remission for 12 months or longer after induction therapy was shown to reduce recurrence risk thereafter.Trial Registration: UMIN 000008563 (the date of registration: July 30, 2012), ClinicalTrials.gov NCT01654783 (the date of registration: July 30, 2012). [ABSTRACT FROM AUTHOR]

Presents an subject index for a 2005 issue of the "Alimentary Pharmacology and Therapeutics".

Inflammatory bowel diseases (IBD) have developed to become a major global health problem. Ulcerative colitis (UC) is one of two main types of IBD, and >90% of patients suffering from mild or moderate forms of UC are treated with mesalazine, a well-tolerated and cost-effective drug. To allow oral administration, the drug has to be protected from resorption before it can reach the affected sites in the colon. The drug is therefore released from most currently used medications either constantly slow (time-dependent) or triggered by an increased pH during gastrointestinal transition. Both variants are widely used in clinical practice and it is surprising that they have not yet been compared directly in a large clinical study. In this overview, the evidence that may suggest preferential use of one type of mesalazine formulation over the other in general or for defined subgroups of patients is summarized and evaluated. Data from in vitro modelling of drug release and measurements of drug concentrations in colonic mucosa suggest that in many cases, constant release and pH-dependent formulations are of similar therapeutic efficiency; however, pH-triggered release may be superior in patients with proctitis-type UC or sites of inflammation in the proximal colon. Additionally, patients with a long gastric residence time, slow small intestinal transition, disease-related diarrhea or sensitivity to systemic adverse effects may benefit more from pH-dependent release formulations. In general, medications based on both concepts show similar efficacies, but the pH-dependent release formulations seem to be more robust in the treatment of a not further classified group of patients with UC. Future comparative clinical studies are required to clearly define the subgroups of patients that should be treated preferably with constant or pH-dependent release formulations of mesalazine. [ABSTRACT FROM AUTHOR]

Background and aim: Oral mesalazine and sulfasalazine (SASP) are key drugs for treating ulcerative colitis (UC). The efficacy of switching from one of the several mesalazine formulations to another is largely unknown. This study assessed the efficacy of switching among three types of mesalazine formulation and SASP for UC therapy. Methods: UC patients receiving high-dose mesalazine/SASP who switched to other formulations due to disease activity were considered eligible. Efficacy was evaluated 2, 6, and 12 months after switching. Results: A total of 106 switches in 88 UC patients were analyzed. The efficacy at 2 months after switching was observed in 23/39 (59%) cases from any mesalazine formulation to SASP, in 18/55 (33%) cases from one mesalazine to another, and in 2/12 (17%) cases from SASP to any mesalazine formulation. Nine of 43 effective cases showed inefficacy or became intolerant post-switching. Delayed efficacy more than two months after switching was observed in four cases. Steroid-free remission was achieved in 42/106 (39%) cases—within 100 days in 35 of these cases (83%). Conclusions: Switching from mesalazine to SASP was effective in more than half of cases. The efficacy of switching between mesalazine formulations was lower but may be worth attempting in clinical practice from a safety perspective. [ABSTRACT FROM AUTHOR]