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Objectives: Bilirubin is a potent endogenous antioxidant and immunomodulating substance, which is also implicated in both cell signalling and various metabolic pathways. Mild elevation of systemic bilirubin concentrations provides substantial protection against many diseases of civilization. Rare published reports have suggested that serum bilirubin might also be relevant to sports performance. The purpose of the current study was to evaluate serum bilirubin concentrations and the prevalence of Gilbert syndrome (GS) in elite athletes., Methods: The study was carried out in 536 consecutive healthy elite athletes and in 2594 individuals of the Czech post-MONICA study representing the general Czech population. Serum bilirubin concentrations, the prevalence of benign hyperbilirubinemia > 17 µmol/L (1 mg/dL, a phenotypic sign of GS), and a variant of the UGT1A1 gene promoter responsible for GS manifestation in Caucasians (rs81753472) were evaluated in study subjects., Results: Compared to the general Czech population, significantly higher serum bilirubin concentrations were found in elite athletes (9.6 vs. 11.6 µmol/L, p < 0.001), both in men (11.3 vs. 12.6 µmol/L, p < 0.001) and women (8.3 vs. 10.5 µmol/L, p < 0.001). Furthermore, the prevalence of GS was also significantly higher in elite athletes (9.6 vs. 22%, p < 0.001) together with the tendency to higher frequencies of the genotypes (TA) 7/7 and (TA) 6/7 UGT1A1., Conclusion: Elite athletes have significantly higher concentrations of serum bilirubin, the most potent endogenous antioxidant substance known. Simultaneously, the prevalence of GS syndrome is also much higher in elite athletes, suggesting that a mild elevation of serum bilirubin might predispose to better sports performance., (© 2022. The Author(s).)

Background: The aim of this study was to examine the diurnal and exercise-related changes in red blood cell variables which serve as indirect markers of doping in sports., Methods: Ten men and 7 women, all undoped highly trained endurance athletes aged 19-34 years, were included in the study. Before and on the day with single and repeated bouts of exercise, blood samples were collected at 07:00, 09:00, 13:00, 18:00, and 21:00, at least 2 hours after exercise. Hemoglobin (Hb), hematocrit (Hct), and the reticulocytes % (Ret%) were determined by flow cytometry. Changes in OFF-hr score were also calculated and repeated-measures ANOVA was used to compare diurnal differences., Results: In overall, the mean Hb decreased continuously by 4.5 and 3.3% (all P<0.001) over the day with single and repeated bouts of exercise, respectively. Corresponding values for the decline in Hct were 4.2 and 5.9% (all P<0.001). In contrast, the Ret% showed no apparent diurnal rhythm but single and repeated bouts of exercise increased the relative Ret% in the evening by 12.4 and 16.7% (P<0.01), respectively. Then the calculated OFF-hr score was reduced by 6.2 and 9.8% (all P<0.01) at the end of the day., Conclusions: These results confirmed the normal diurnal pattern in the examined red blood cell variables in response to exercise in highly trained athletes. Furthermore, they showed noticeable between-subject variability and the possible risk of a false suspicion of blood doping in undoped athletes after repeated bouts of exercise.

Background: Unwarranted administration of antibiotics in acute pancreatitis presents a global challenge. The clinical reasoning behind the misuse is poorly understood. Our aim was to investigate current clinical practices and develop recommendations that guide clinicians in prescribing antibiotic treatment in acute pancreatitis., Methods: Four methods were used. 1) Systematic data collection was performed to summarize current evidence; 2) a retrospective questionnaire was developed to understand the current global clinical practice; 3) five years of prospectively collected data were analysed to identify the clinical parameters used by medical teams in the decision making process, and finally; 4) the UpToDate Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system was applied to provide evidence based recommendations for healthcare professionals., Results: The systematic literature search revealed no consensus on the start of AB therapy in patients with no bacterial culture test. Retrospective data collection on 9728 patients from 22 countries indicated a wide range (31-82%) of antibiotic use frequency in AP. Analysis of 56 variables from 962 patients showed that clinicians initiate antibiotic therapy based on increased WBC and/or elevated CRP, lipase and amylase levels. The above mentioned four laboratory parameters showed no association with infection in the early phase of acute pancreatitis. Instead, procalcitonin levels proved to be a better biomarker of early infection. Patients with suspected infection because of fever had no benefit from antibiotic therapy., Conclusions: The authors formulated four consensus statements to urge reduction of unjustified antibiotic treatment in acute pancreatitis and to use procalcitonin rather than WBC or CRP as biomarkers to guide decision-making., (Copyright © 2019 IAP and EPC. Published by Elsevier B.V. All rights reserved.)

Background & Aims: Comparative data on budesonide vs mesalamine for the treatment of mild-to-moderately active Crohn's disease (CD) are sparse. We assessed the efficacy and safety of each therapy in patients with mildly to moderately active CD., Methods: We performed a randomized, double-blind, double-dummy, 8-week, multicenter study in which 309 patients with mildly to moderately active CD received pH-modified-release oral budesonide (9 mg/day once daily or 3 mg/day 3 times daily) or Eudragit-L-coated oral mesalamine (4.5 g/day)., Results: The primary efficacy variable, clinical remission (defined as Crohn's Disease Activity Index ≤150), at the final visit occurred in 69.5% (107 of 154) of patients given budesonide vs 62.1% (95 of 153) of patients given mesalamine (difference, 7.4%; 95% repeated confidence interval, -4.6% to 18.0%; P = .001 for noninferiority). Clinical remission rates did not differ significantly between the 2 budesonide groups. Treatment response, defined as Crohn's Disease Activity Index of 150 or less and/or a decrease of 70 or more (Δ70) or 100 or more (Δ100) points from baseline to final visit, did not differ significantly between patients given budesonide vs mesalamine (Δ70, P = .11; Δ100, P = .15), or between the 2 budesonide groups (Δ70, P = .38; Δ100, P = .78). No other efficacy end points differed significantly between groups. Discontinuation because of adverse events occurred in 3% and 5% of budesonide- and mesalamine-treated patients, respectively. There were no clinically relevant differences in adverse events between the 2 budesonide groups., Conclusions: Budesonide (9 mg/day) was numerically, but not statistically, more effective than Eudragit-L-coated mesalamine (4.5 g/day) in patients with mildly to moderately active CD. Budesonide (9 mg/day), administered once daily, was as effective as the standard (3 times daily) regimen., (Copyright © 2011 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Involvement of genetic factors in the aetiology of inflammatory bowel disease (IBD) has been known for a long time. Our aim was to investigate the prevalence of polymorphisms in NOD2, ICAM-1 and CCR5 genes in Czech and Slovak patients with IBD in comparison with healthy controls. The frequency of well-known mutations (R702W, G908W and 1007fs in the NOD2 gene; K469E in the ICAM-1 gene, and Delta32 in the CCR5 gene) involved in IBD was tested in 45 patients with CD and 22 patients with UC. The allele frequency of these mutations was determined and genotype-phenotype correlation was specified. Isolated DNA was genotyped, and allele frequency was counted and statistically verified. Significant differences between the healthy control group and CD patients were observed in mutation 1007fs of the NOD2 gene (P = 0.0203). We also associated allele E469 of the ICAM-1 gene with CD (P = 0.0024). No significant association between other alleles and CD was found, and no gene variation was linked to UC. The number of mutations and mutated genes was higher among patients with CD than among patients with UC. Our results support previous findings about participation of mutations of NOD2 and ICAM-1 genes in IBD. We confirmed that both CD and UC are polygenic diseases with a genedosage effect. This observation strengthens the opinion that genetic factors play a more important role in CD than in UC.

Most colon carcinomas are preceded by an adenomatous polyp--adenoma-carcinoma sequence. Active oxygen species (AOS) can play a role in the pathogenesis of this process. Antioxidant enzymes (AE) are the primary defense against the deleterious effect of AOS. Activities of AE in 56 individuals with colorectal adenoma (CA), 29 individuals with colorectal carcinoma (CC) and in 24 control subjects were examined. Biopsy specimens from the non-neoplastic colonic mucosa and from the CA and CC were taken during colonoscopy for histological and enzymological analysis. Activities of following AE were estimated: CuZn-superoxide dismutase (CuZn-SOD), catalase (CAT) and glutathione peroxidase (GPx). It was found that individuals with CA and CC were characterized by: (1) increased activities of CAT and GPx in non-neoplastic mucosa, that persisted in some of the patients even after removal of tumors; (2) increased activities of CuZn-SOD, CAT and PGx in CA and CC tissues. It can be inferred that the accumulation of peroxides in the non-neoplastic colonic mucosa induced higher activities of CAT and GPx. The reasons of high activities of all AE in the tissues of CA and CC and their relation to carcinogenesis are not clear and require further studies.

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]

The authors present their experience with the outcome of gastrofibroscopic sclerotherapy of oesophageal varices, performed in a total of 70 patients with portal hypertension. All patients were classified in classes B and C according to Child's criteria, and 68 of them had variceal bleeding before receiving sclerotherapy. Acute bleeding was successfully arrested in seven cases, and elective sclerotherapy in between bleeding episodes was carried out in 60 cases. To date, complete obliteration has been noted in 34 patients. An effect of previous sclerotherapy was observed during the next therapeutic session in 18, and eight patients died from progressive hepatic insufficiency. In the discussion section, the authors analyse current concepts on the technique of sclerotherapy related to complications, on instrumentarium and sclerosing solutions, and on the significance of prophylactic, acute and elective sclerotherapy, with the importance of endoscopic sclerotherapy of oesophageal varices perceived mainly in comparison with the results of surgery from the point of view of long-term patient survival.

The authors report on their experience with endoscopic treatment of choledocholithiasis. Out of a total of 363 successful procedures of endoscopic papillosphincterotomy (EPS), choledocholithiasis was the indication for EPS in 270 patients (74.4%). Most often, EPS and extraction were performed in patients after cholecystectomy (79.6%) and those with choledocholithiasis and an in situ gallbladder, but free of stones (13.4%). In patients with concomitant cholecystolithiasis, EPS was carried out only in those cases in which surgery was contraindicated. EPS was performed in four cases of acute biliary pancreatitis. Removal of stones from the choledochus was successful in 95.5%. Of the total of 363 successful EPS's, complications were observed in 17 cases (4.7%), with a mortality of 1.1% (4 deaths). Most frequently, the causes included bleeding (1.9%) and perforation (1.1%). Of other complications, the authors noted acute pancreatitis, acute cholangitis and impaction of stone in the hepatocholedochus in two cases each. The complications required emergency surgery in six patients (35.3%).

The authors performed a total of 288 successful endoscopic gastroduodenal polypectomy procedures in 129 patients. Drawing on literary data and the results of follow-up of their own patients, they regard endoscopic gastroduodenal polypectomy as a successful and relatively low-risk method for secondary prevention of gastric cancer. Recurrence of adenomas, with malignant degeneration in 6-75%, was noted, only in the first year after primary polypectomy, in 8% of patients. Four percent of patients after adenoma polypectomy developed gastric carcinoma. Removal of gastroduodenal adenomas by endoscopy represents a final therapeutic procedure significantly reducing the possibility of these originally benign variants transforming into malignant ones. Even polyps smaller than 10 mm in diameter may be adenomas possessing a rather high malignant potential. The authors regard endoscopic polypectomy of hyperplastic polyps as a justified procedure since the literary data compiled and their own experience suggest polyp susceptibility to development of dysplasia. While this tendency gets manifest only rarely, it would be medically wrong to dismiss it as negligible. In case of removal of an early polypoid gastric carcinoma, endoscopic polypectomy is a therapeutic procedure only in clearly defined and histologically well classified cases. In other cases involving prominence of the gastroduodenal mucosa, it is an invaluable diagnostic method whose benefit is that it removes an entire polyp for histologic examination.

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]

Background: Studies about the association between bilirubin and migraine were few. Therefore, the purpose of this study was to investigate the association between serum total bilirubin and the prevalence of severe headaches or migraine., Methods: A multivariable logistic regression was used to assess the association between serum total bilirubin concentration and severe headaches or migraine. We also performed stratified analyses, interaction analyses and multiple interpolations in the sensitivity analysis., Results: This cross-sectional study included 12,552 adults from the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2004. The overall incidence of migraine was 19.99% (2,509/12,552). With every 1 mg/dl increase in bilirubin, the prevalence of migraine decreased by 23% (95% CI: 0.64, 0.93) after adjustment of all related covariates. Similarly, the risk of migraine was reduced by 17% (95% CI: 0.72, 0.97) in the Q4 group (the fourth quartile, highest serum total bilirubin level) compared with the Q1 group (the lowest level). Furthermore, interaction effects by age groups were significant in this relationship (P for interaction = 0.0004). In the Q4 group compared with Q1, inverse associations were observed in those aged ≥40 years (OR: 0.71,95% CI: 0.59, 0.85) in the stratified analysis., Conclusion: These findings support an association between serum total bilirubin and severe headaches or migraine, revealing an inverse association between serum total bilirubin quartiles and severe headaches or migraine in American adults. Age could play an important role in this association., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

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]

Severe acute pancreatitis represents about 20% of all pancreatitis diagnosis and it has a high mortality rate when associated with a lung dysfunction. The aim of this research was to investigate the use of a wild spectrum metabolic drug (Cytoflavin®) for the treatment of acute lung injury in experimental pancreatitis. A l-arginine-induced acute pancreatitis (groups II and III) was simulated experimentally in a rat population. A combined metabolic drug was used as treatment. We determined the levels of amylase, medium molecules (MM 254 and 280), malonic aldehyde (MA), diene conjugates (DC), interleukin-8 (IL-8), interleukin-10 (IL-10), and tumor necrosis factor-α (TNF-α) in the blood and we performed a histologic examination of the lungs and pancreas of the rat population. The activation of lipid peroxidation peaks at 24–48 h from the onset of the disease. The level of malonic aldehyde in groups II and III was higher (39.09% and 30.99%, respectively) than that in the control group I (p < 0.02; p < 0.01), the diene conjugates level was higher by 43.66% and 42.03% respectively (p < 0.01). With medical correction after 72 h (group III), the level of malonic aldehyde and diene conjugates decreased by 17.0% and 30.5% when compared with group II (no medical correction) (p < 0.05). The level of medium molecules peaked after 72 h of the disease induction (p < 0.001). A correlation was established between the level of endogenous intoxication with the membrane-destructive processes in the lung tissue 48 h after modeling of acute experimental pancreatitis. The use of the proposed medicament correction reduces the manifestations of endogenous intoxication. [ABSTRACT FROM AUTHOR]

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]

Purposes: Patients affected by Crohn's disease (CD) require lifelong medical therapy, but they can also often require abdominal surgery. The effect of CD therapy on postoperative course is still unclear. The aim of this study was to evaluate the effect of preoperative medical therapy on the outcome of intestinal surgery in these patients. Methods: Data from a consecutive series of 167 patients with CD operated on at the University of Padova Hospital from 2000 to 2013 were retrieved. Data of preoperative therapy during the 6 months before surgery were available for 146 patients who were enrolled in this retrospective study. Clinical data and surgical details were retrieved and postoperative complications and reoperation were considered outcome measures. Univariate and multivariate analysis were performed. Results: No significant difference was observed between patients without data about their preoperative therapy and those with them. Eight patients underwent reoperation in the first 30 postoperative days: two of them for anastomotic leak, three for bleeding, one for obstruction and two for abdominal wound dehiscence. At multivariate analysis, preoperative adalimumab and budesonide resulted to be an independent predictor of reoperation (OR = 7.67 (95% CI = 1.49-39.20), p = 0.01 and OR = 6.7749 (95% CI = 0.98-46.48), p = 0.05, respectively). At multivariate analysis neither pharmacological nor clinical variables resulted to predict anastomotic leak. Conclusions: In our series, adalimumab seemed to be associated to early reoperation after intestinal surgery. This may be due to a worst disease severity in patients who needed surgery in spite of biological therapy. Preoperative tapering of budesonide dose seems a safe option before elective abdominal surgery for CD. © 2015 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: In recent years, many achievements have been realized in the therapy of inflammatory bowel disease (IBD) although its etiology remains unknown. Thus IBD treatment is symptomatic and targets general inflammatory mechanisms. Oral formulations containing 5-aminosalicylic acid (5-ASA) have become the standard therapy for mild-to-moderate IBD. Objective: This article is a review of recently published research dealing with new 5-ASA dosage forms. Thus promising candidates for IBD treatment evaluated in vitro are reported; systems tested in vivo in trinitrobenzene sulfonic acid (TNBS)-induced colitis in rats are mentioned; and 5-ASA formulations used in clinical studies are presented. Moreover, all oral dosage forms containing 5-ASA or its prodrugs are reviewed; their characteristics and utilization in IBD treatment are discussed. Conclusion: In several clinical studies, it has been shown that multiparticulates such as pellets offer more advantages as compared with single unit forms, that is, coated tablets. Prolonged presence close to the site of the action, improved drug bioavailability, and easier administration of large drug doses belong to the benefits of pellets. [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]

When looking at different treatment guidelines the topics most debated for Crohn's disease are the following: (a) the use of mesalamine for remission induction and maintenance in mild to moderate Crohn's disease; (b) the early use of anti-TNF antibodies in Crohn's disease with or without classical immunomodulators for remission induction, and (c) remission induction in steroid-refractory disease with anti-TNF antibodies or calcineurin inhibitors. The topics mentioned above will be discussed with regard to the statements of the German Gastroenterology Association (DGVS) on the basis of the underlying evidence. © 2013 S. Karger AG, Basel [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]