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Purpose: To determine the curative impact of mesalazine (MSZ)-BTVCs combination on ulcerative colitis (UC), and its influence on inflammation and oxidative stress in the patients.Methods: 100 UC patients were randomely assigned to a control group given MSZ capsule treatment only, and a combination group treated with BTVCs and MSZ. Treatment effectiveness, inflammatory response, and oxidative stress in the two groups before and after treatment were compared.Results: The combination group had higher total effectiveness than the control group. The serum levels of MDA, high-sensitivity C-reactive protein (hs-CRP), TNF-α and interleukin-6 (IL-6) were lower, while serum levels of superoxide dismutase (SOD) and interleukin-10 (IL-10) were markedly increased in patients given combination treatment, when compared with controls. Pre-drug exposure UC disease activity index (UC-DAI) and clinical symptom scores were similar in both cohorts of patients, but the post-treatment scores were statistically decreased, especially in the combination group.Conclusion: The combined use of MSZ and BTVCs was more effective against UC than monotherapy, as it effectively relieved inflammation and oxidative stress in patients, resulting in better clinical efficacy.

In this study, a new, fast and sensitive HPLC method with fluorometric detection was developed for the determination of mesalazine in human plasma and applied to a pharmacokinetic study. Mesalazine was precolumn derivatized with NBD-Cl and the fluorescent derivative was separated on a C18 (150 x 4.6 mm x 2.6 mu m) analytical column at 30 oC using a mobile phase composed of acetonitrile-0.1% o-phosphoric acid in water (70:30, v/v) by isocratic elution with flow rate of 1.0 mL min(-1). The method was based on the measurement of the derivative using fluorescence detection (lambda(ex) = 280 nm, lambda(em) = 325 nm). The retention time of mesalazine is 3.08 +/- 0.06 min. Nortriptiline was used as internal standard. This currently developed method was validated according to ICH criteria by evaluating the specificity, linearity, precision, accuracy and robustness. The method was determined to be linear in a concentration range of 0.25-1.5 mu g mL(-1) with the correlation coefficient of 0.9997. LOD and LOQ were found to be 0.075 and 0.25 mu g mL(-1), respectively. Intraday and interday RSD values were less than 5.92%. The plasma concentration-time profile and pharmacokinetic parameters such as AUC(0-t), AUC(0-infinity), C-max, t(max), t(1/2), were calculated according to the assays. The presented method can certainly be used for bioequivalence and bioavailability investigations and routine analysis of the drug in plasma.

The prevalence of the chronic inflammatory bowel diseases (CIBD) Crohn's disease (CD) and ulcerative colitis (UC) is on the rise worldwide. In Germany CIBDs are also a significant healthcare problem. The pathogenesis is complex and involves genetic factors, environmental aspects and changes in the immunological constitution. Furthermore, the gut microbiota plays a role in the maintenance of intestinal inflammation. Fortunately, several new drugs, in particular biologicals, have been approved for the treatment of CIBDs. The treatment of UC is mainly based on 5‑aminosalicylic acid formulations, preferably as a topical form for distal colitis and proctitis as well as local budesonide formulations. In the case of extensive spread, high disease activity and refractory disease antibodies (biologicals) are successfully used, similar to CD. In addition to anti-tumor necrosis factor antibodies (infliximab, adalimumab, golimumab), vedolizumab, an anti-integrin antibody and the interleukin 12/23 antibody ustekinumab can be successfully used. The intravenous and also subcutaneous administration of antibodies are increasing in importance and are now available for all forms. Furthermore, the Janus kinase inhibitor tofacitinib is an orally administered option for UC. Clinical scores, endoscopy, ultrasound, laboratory parameters and calprotectin determination in stool are employed to evaluate treatment response (treat to target approach). Ultimately, the long-term goal is mucosal healing. Despite advances in the pharmaceutical treatment, a significant number of patients with CIBD still suffer from treatment refractory courses and need surgery at some time during the disease.Die Prävalenzen der chronisch-entzündlichen Darmerkrankungen (CED) Morbus Crohn (MC) und Colitis ulcerosa (CU) steigen weltweit an. Auch in Deutschland stellen die CED ein großes gesundheitspolitisches Problem dar. Die Pathogenese ist komplex und involviert genetische Faktoren, Umweltaspekte und Veränderungen in der immunologischen Konstitution. Weiterhin spielt das Darmmikrobiom eine Rolle bei der Aufrechterhaltung der Entzündung. In den letzten Jahren sind erfreulicherweise weitere Medikamente für die Behandlung der CED zugelassen worden, vor allem Biologika. Die Therapie der CU stützt sich hauptsächlich auf 5‑Aminosalicylsäure-Präparate, bevorzugt auch in topischer Form bei distaler Kolitis und Proktitis, sowie lokale Budesonidformulierungen. Bei ausgedehntem Befall, hoher Krankheitsaktivität oder refraktärem Verlauf kommen ähnlich wie beim MC auch Antikörper (Biologika) mit gutem Erfolg zum Einsatz. Neben Anti-Tumor-Nekrose-Faktor-Antikörpern (Infliximab, Adalimumab, Golimumab) werden der Integrinantikörper Vedolizumab sowie der Interleukin-12/23-Antikörper Ustekinumab erfolgreich verwendet. Einen zunehmenden Stellenwert erhält neben der intravenösen auch die subkutane Anwendung der Antikörpertherapien, die mittlerweile für alle Präparate zur Verfügung steht. Des Weiteren ist bei CU der Januskinaseinhibitor Tofacitinib eine orale Option. Der Therapieerfolg wird multimodal anhand von Endoskopie, Sonographie, Laborparametern, Calprotectinbestimmung im Stuhl und klinischen Scores beurteilt („treat-to-target approach“). Langfristig gilt das Ziel einer mukosalen Heilung. Trotz der Fortschritte in der medikamentösen Therapie leidet immer noch ein signifikanter Teil der Patienten mit CED unter therapierefraktären Verläufen und benötigt im Verlauf eine chirurgische Therapie.

Mesalazine is a widely prescribed drug, used for the treatment of ulcerative colitis to both induce and maintain remissions in disease. Mesalazine therapy has been associated with a low rate of serum enzyme elevations and a with rare instances of clinically apparent acute liver injury.A 51-year-old Caucasian woman with ulcerative colitis was treated with mesalazine. Two weeks later, the patient presented severe liver cholestatic injury. No symptoms of generalized hypersensitivity were seen. She had no history of liver disease and was known to have normal routine liver tests before starting treatment. The liver biopsy revealed mild periportal necroinflammatory lesions with no fibrosis, suggestive of drug-induced liver injury. The patient's symptoms were resolved by discontinuing the mesalazine treatment; within 6 months, all her liver panels returned to normal. After extensively excluding other potential causes of liver injury and with clinical and lab resolution after discontinuing the drug, we assumed mesalazine as the cause of hepatic toxicity.We describe a patient with ulcerative colitis who developed severe but fully reversible liver cholestatic injury following the prescription of mesalazine. This case reinforces the possibility of a causal relationship between mesalazine therapy and toxic hepatic injury without systemic hypersensitivity. Although it is a usually well-tolerated drug, clinicians should be alert and discontinue therapy when liver dysfunction occurs to avoid the development of chronic hepatitis and liver fibrosis.

A growing number of healthy dietary ingredients in fruits and vegetables have been shown to exhibit diverse biological activities. Phloretin, a dihydrochalcone flavonoid that is abundant in apples and pears, has anti-inflammatory effects on ulcerative colitis (UC) mice. The gut microbiota and metabolism are closely related to each other due to the existence of the food-gut axis in the human colon. To investigate the interplay of faecal metabolites and the microbiota in UC mice after phloretin treatment, phloretin (60 mg/kg) was administered by gavage to ameliorate dextran sulfate sodium (DSS)-induced UC in mice. Gut microbes and faecal metabolite profiles were detected by high-throughput sequencing and liquid chromatography mass spectrometry (LC-MS) analysis, respectively. The correlations between gut microbes and their metabolites were evaluated by Spearman correlation coefficients. The results indicated that phloretin reshaped the disturbed faecal metabolite profile in UC mice and improved the metabolic pathways by balancing the composition of faecal metabolites such as norepinephrine, mesalazine, tyrosine, 5-acetyl-2,4-dimethyloxazole, and 6-acetyl-2,3-dihydro-2-(hydroxymethyl)-4(1H)-pyridinone. Correlation analysis identified the relations between the gut microbes and their metabolites. Proteus was negatively related to many faecal metabolites, such as norepinephrine, L-tyrosine, laccarin, dopamine glucuronide, and 5-acetyl-2,4-dimethyloxazole. The abundance of unidentified Bacteriodales_S24-7_group was positively related to ecgonine, 15-KETE and 6-acetyl-2,3-dihydro-2-(hydroxymethyl)-4(1H)-pyridinone. The abundance of Christensenellaceae_R-7_group was negatively related to the levels of 15-KETE and netilmicin. Stenotrophomonas and 15-KETE were negatively related, while Intestinimonas and alanyl-serine were positively related. In conclusion, phloretin treatment had positive impacts on faecal metabolites in UC mice, and the changes in faecal metabolites were closely related to the gut microbiota.

Introduction.Ulcerative colitis (UC) is one of the severe therapeutic diseases. High doses of oral granular mesalazine are required to maintain clinical and endoscopic remission of UC, which may be sufficient and supposedly more acceptable for patients, as some studies showed that adherence to topical therapy is significantly lower than to oral 5-ASA drugs.Objective of the study. To evaluate the efficacy of therapy of patients with moderate left-sided ulcerative colitis (UC) and pancolitis receiving prolonged-release ethylcellulose-coated mesalazine.Materials and methods. The evaluation of the outcomes of treatment of UC patients who received prolonged-release mesalazine was carried out. We examined 87 patients with UC who received granular ethylcellulose-coated mesalazine, of those 38 (43.7%) men and 49 (56.3%) women. The average age of the enrolled patients was 38.3 ± 12.6 years.Results and discussion. After 2 weeks from the beginning of therapy with prolonged-release mesalazine, the majority of patients – 71 (81.6%) responded to the therapy. After 12 weeks, 71 (81.6%) of 87 UC patients, who responded to therapy with prolongedrelease mesalazine, remained in clinical remission. On average, the Mayo score in the group decreased from 7.6 ± 0.99 to 2.6 ± 0.25 points. There was a significant decrease in CRP, ESR, leukocytosis, and fecal calprotectin. After 26 weeks, Mayo score in the group of patients remained on average at the level of 2.2–2.3 points. The number of UC patients with colon mucosal healing was 32 (36.8%) patients. A year after the start of therapy with prolonged-release mesalazine, 69 (79.3%) UC patients who responded to therapy had a clinical remission, of those 32 (36.8%) patients had a clinical and endoscopic remission. During the year of observation, no case of surgical intervention or re-hospitalization due to exacerbation of the disease was recorded in patients with UC who achieved remission.Conclusions.Treatment of moderate active UC should begin with oral mesalazine ≥ 3 g per day in combination with topical mesalazine. The prolonged-release mesalazines are the most preferred

The 2021 National report from IBD UK included responses from over 10 000 patients with inflammatory bowel disease, over 70% of whom reported having at least one flare in the last 12 months. As the first-line treatment for patients with mild and moderate ulcerative colitis, the action and delivery mechanisms of mesalazine are crucial for successful management of the disease. The choice of the most appropriate formulation of mesalazine and securing patient concordance and adherence to treatment remains a challenge for healthcare professionals. This article details the outcome of a roundtable discussion involving a group of gastroenterology consultants and specialist nurses which considered the importance of ensuring that patients have individualised mesalazine therapy before escalation to other treatments and gives recommendations for the management of patients with mild or moderate ulcerative colitis.

The article presents data on the mechanism of action of sulfasalazine and 5-ASA preparations. The latest meta-analysis and polish and ECCO recommendations for the treatment of patients with ulcerative colitis are also included.

Стаття присвячена порівняльній характеристиці різних похідних 5-аміносаліцилової кислоти. Дослідження останніх десятиліть змінили уявлення про можливості застосування аміносаліцилатів у терапії різних запальних захворювань кишечника. У зв’язку з невідомою етіологією хвороби Крона та неспецифічного виразкового коліту етіотропної терапії цих захворювань немає. Сутність лікування зводиться до гальмування активності запалення при загостреннях і проведенні курсів протирецидивної терапії. Численні дослідження, проведені протягом останніх 20 років, показали, що основу базисної терапії хронічних неспецифічних запальних захворювань кишечника становлять препарати 5-аміносаліцилової кислоти, або саліцилати. При виборі лікарської форми слід ураховувати відмінності між препаратами месалазину залежно від типу оболонки. Показано, що з точки зору фармакокінетики найбільш ефективними лікарськими формами месалазину для лікування неспецифічного виразкового коліту та хвороби Крона з ураженням товстої кишки є таблетки з кишковорозчинним покриттям, що забезпечує рН-залежне поступове вивільнення 5-аміносаліцилової кислоти на протязі усієї товстої кишки. Наявні на сьогодні на фармацевтичному ринку препарати 5-аміносаліцилової кислоти здатні контролювати перебіг виразкового коліту та хвороби Крона з ураженням товстої кишки в переважної більшості пацієнтів. Застосування препаратів 5-аміносаліцилової кислоти не обмежується терапією неспецифічного виразкового коліту та хвороби Крона. Препарат широко застосовується при інших захворюваннях кишечника, таких як дивертикулярна хвороба товстої кишки, банальні коліти, променеві ураження ободової кишки, а також для лікування такої поширеної хвороби, як синдром подразненого кишечника. Результати дослідження, що було проведено у відділенні захворювань кишечника ДУ «Інститут гастроентерології НАМН України» упродовж 2 років, показали позитивний ефект 20-денного лікування Месаколом неускладненої дивертикулярної хвороби. Месакол у дозі 1600 мг на добу призвів до повного купірування абдомінальної симптоматики у 68,7 % хворих.

Pentasa (prolonged-release mesalazine [5-ASA]) has been available for30 years as an effective treatment for mild-to-moderate ulcerative colitis (UC). A systematic literature review and meta-analysis was undertaken to provide an up-to-date evaluation of oral Pentasa efficacy and safety for induction and maintenance of remission.Literature searches were conducted in PubMed, Embase and Cochrane databases, from inception to 02 December 2020. Unpublished studies were also sourced. Meta-analyses using a random-effects model and Bayesian inference compared Pentasa (tablets, granules, capsules) against placebo and other 5-ASAs.Twelve studies involving 3674 patients treated with Pentasa were identified. Pentasa 2-4 g/day was superior to placebo at inducing (absolute risk difference [ARD] at 8 weeks 0.14, 95% CI 0.07‒0.21;This study confirms oral Pentasa is efficacious and well-tolerated in treating active UC and maintaining remission. The availability of multiple forms of Pentasa supports physicians' ability to individualize treatment and optimize dosing to improve outcomes.

Skin fibrosis is a complex biological remodeling process occurring in disease like systemic sclerosis, morphea, or eosinophilic fasciitis. Since the knowledge about the underlying pathomechanisms is still incomplete, there is currently no therapy, which prevents or reverses skin fibrosis sufficiently. The present study investigates the role of polo-like kinase 2 (PLK2) and the pro-fibrotic cytokine osteopontin (OPN) in the pathogenesis of cutaneous fibrosis and demonstrates the antifibrotic effects of systemic mesalazine treatment in vivo. Isolated primary dermal fibroblasts of PLK2 wild-type (WT) and knockout (KO) mice were characterized invitro. Skin thickness and histoarchitecture were studied in paraffin-embedded skin sections. The effects of mesalazine treatment were examined in isolated fibroblasts and PLK2 KO mice, which were fed 100 µg/g mesalazine for 6 months via the drinking water. Compared to WT, PLK2 KO fibroblasts displayed higher spontaneous myofibroblast differentiation, reduced proliferation rates, and overexpression of the fibrotic cytokine OPN. Invitro, 72 h of treatment with 10 mmol/L mesalazine induced phenotype conversion in PLK2 KO fibroblasts and attenuated OPN expression by inhibiting ERK1/2. In vivo, dermal myofibroblast differentiation, collagen accumulation, and skin thickening were prevented by mesalazine in PLK2 KO. Plasma creatinine levels indicated good tolerability of systemic long-term mesalazine treatment. The current study reveals a spontaneous fibrotic skin phenotype and ERK1/2-dependent OPN overexpression in PLK2 KO mice. We provide experimental evidence for the antifibrotic effectiveness of systemic mesalazine treatment to prevent fibrosis of the skin, suggesting further investigation in experimental and clinical settings.

Mesalazine, also known as 5-aminosalicylic acid (5-ASA), is a synthetic drug from the family of nonsteroidal anti-inflammatory drugs (NSAIDs) used for inflammatory diseases of the gastrointestinal tract. However, 5-ASA has also been used for various other diseases due to its pharmacological effects, but they are usually scattered across various publications, which may limit further research and clinical use of this drug. This review is a summary of published information on the biological and pharmacological effects of 5-ASA with the aim of identifying its anti-oxidant role and medicinal use. 5-ASA data have been collected from 1987 to February 2021 using major databases such as Web of Science, PubMed, Elsevier, Wiley Online Library, Springer, Google Scholar, etc. According to research, the pharmacological and biological effects of 5-ASA include treatment of inflammatory bowel disease, and anti-oxidant, anti-inflammatory, antibacterial, antifungal, anticancer, anti-amyloid, gastric protection (gastroprotective), and antidiverticulosis properties. Numerous pharmacological studies have shown that 5-ASA is an anti-oxidant and anti-ulcer compound with high therapeutic potential that, if the appropriate dose is discovered, its chemical structure changes and its effectiveness is optimized, 5-ASA has been used experimentally for other diseases.

Background This case report presents a case of Vulvar Crohn’s disease (VCD) in an adolescent, that is an uncommon manifestation of Crohn’s disease (CD) without gastrointestinal symptoms. Before treating CD itself with proper medication, vulvar abscess continued to recur without improvement. Case presentation We report the case of an 18-year-old woman with VCD. After treatment with azathioprine 50 mg daily and mesalazine 1 g three times daily, vulvar lesions resolved after 6 weeks. We collected electronic medical data on patient characteristics, and evaluated findings of physical examinations, pelvic MRI, and biopsy specimen obtained from gastroduodenoscopy/colonoscopy. Conclusions VCD is a rare manifestation of CD that may be misdiagnosed in the absence of gastrointestinal symptoms leading to delayed treatment. If a patient has an unexplained vulvar inflammatory lesion and with repeated failed surgical treatment, gynecologists should consider the possibility of a VCD.

Introduction: Pyoderma Gangrenosum (PG) manifests as recurrent deep ulceration of the skin and PG is often associated with a variety of systemic diseases, such as Inflammatory Bowel Diseases (IBD), inflammatory arthropathies, hematologic malignancies and hepatitis. There has been neither laboratory finding nor histological feature diagnostic of PG, and diagnosis of PG is mainly made based on the exclusion criteria. Patient and methods: A male patient 21 years old, complained of rectal bleeding of 3 weeks duration. He presented with a large, painful and rapidly progressive cutaneous ulcer in the right flank. Laboratory and microbiological investigations, colonoscopic biopsy and a skin biopsy from the ulcer were performed. Results: An atypical presentation of PG with Ulcerative Colitis (UC) was diagnosed. The PG rapidly resolved after starting treatment with prednisolone and mesalazine and the ulcer healed with scar. After successful treatment the patient suddenly stopped all his treatment and he came back again with rectal bleeding and a rounded, painful and rapidly progressive cutaneous ulcer in each cheek. One month after starting prednisolone and mesalazine treatment, complete healing of both ulcers has occurred. Conclusion: A rare atypical presentation of PG with risk of misdiagnosis and the rapid healing of PG with combination of prednisolone and mesalazine therapy were concluded.

Background and purpose. The aim of this work is to evaluate the efficacy of treatment patients with moderate left-sided and total ulcerative colitis (UC) with prolonged-release ethylcellulose-coated mesalazine. Materials and methods. The clinical analyses of results of treatment UC patients with prolonged-release ethylcellulose-coated mesalazine was performed. Eighty-seven patients with UC, treated with ethylcellulose coated microgranules of mesalazine, were examined: 38 (43,7%) men and 49 (56,3%) women. The age of patients was from 26 to 49 years, median age 38,3±12,6 year. Results. After 2 weeks prolonged-release ethylcellulose coated mesalazine treatment the response to therapy was demonstrated in majority of UC patients -71 (81,6%). After 12 weeks treatment prolonged remission persisted in 71 (81,6%) UC patients. Mayo score decreased from 7,6±0,99 to 2,6±0,25 points. Significant decrease of inflammation markers (CRP, ESR, leukocytosis, fecal calprotectin etc) was determined. After 26 weeks of treatment Mayo score was 2,2-2,3 points. Thirty-two (36,8%) UC patients showed healing of colon mucosa. After 1 year of prolonged-release ethylcellulose-coated mesalazine treatment clinical remission was determined in 69 (79,3%) UC patients with response to therapy, clinical-endoscopic remission — in 32 (36,8%) patients. During 1 year follow-up no cases of surgical procedure and readmission because of UC reccurence were noted. Conclusion. Treatment of moderate active UC should be started with oral mesalazine > 3 gr per day and rectal mesalazine. The most appropriate effective and high compliance forms of mesalazine are prolonged-release forms of meselazine. For citation: Knyazev OV, Kagramanova AV, Veselov AV, Shkurko TV. Effectiveness of treatment moderate ulcerative colitis with prolonged-release ethylcellulose-coated mesalazine in real clinical practice in Moscow. City Healthсare. 2021; 2(2): 65-74. doi: 10.47619/2713-2617.zm.2021.v2i2;65-74

BACKGROUND Glycogen storage disease type Ib (GSD-Ib) is a glycogen metabolism disorder that leads to the manifestations of inflammatory bowel disease (IBD), especially Crohn’s disease (CD)-like colitis. Although biological agents are effective for treating CD, their application in the treatment of GSD-Ib with CD-like colitis has been rarely reported. CASE SUMMARY A 13-year-old Han male was diagnosed with GSD-Ib with CD. The patient was treated with granulocyte colony-stimulating factor. When he had symptoms of CD-like colitis, he was continuously pumped with enteral nutrition and administered oral mesalazine for 2 wk; however, the symptoms did not improve significantly. Hence, infliximab (IFX) was administered. Hitherto, the patient has been followed up for 1 year, and no clinical manifestations have been observed. After 6 mo of treatment (fifth IFX treatment), the disease activity index and all inflammatory indexes decreased, and a review of the colonoscopy data showed that the ulcers appeared smooth. CONCLUSION In this study, the patient was successfully treated with IFX. In cases of GSD-Ib, IBD should be highly considered.

Objective: to study the causes of pancreatitis. Materials and methods: a clinical case of acute pancreatitis during the treatment of ulcerative colitis with 5-aminosalicylic acid-containing drugs. Methods: clinical, laboratory and instrumental (biochemical blood analysis, standard coprological examination, Ultrasound examination of the abdominal cavity, Esophagogastroduodenoscopy). Results: based on the data of the clinic, laboratory and instrumental studies, a diagnosis was made: drug-induced pancreatitis associated with mesalazine intake. Ulcerative colitis, total form, high degree of activity. Duodenal ulcer disease associated with Helicobacter pylori, unstable remission. Erosive bulbitis. The indicated therapy with polyenzyme drugs, proton pump inhibitors, antispasmodics, and glucocorticosteroids resulted in the resolution of clinical manifestations and the normalization of altered laboratory parameters. Conclusions: the use of 5-aminosalicylic acid preparations for the treatment of ulcerative colitis may be associated with the development of pancreatitis, which must be taken into account in clinical practice.

Introduction: Ulcerative colitis is a chronic disease affecting large intestine, characterized by rectal bleeding, diarrhea, abdominal pain, and could be accompanied by extraintestinal manifestation such as fever, anemia, and weight loss. Ulcerative colitis is causing an inflammation even ulceration of the rectum which can extend to proximal colon. The incidence of this disease is increasing worldwide and its frequency is variable depend on age, race and geographic area. Thorough history and examination are needed in diagnosing ulcerative colitis, since its symptoms are similar to many other gastrointestinal diseases. Definitive diagnosis of ulcerative colitis can be obtained by colonoscopy and histopathology. Case Report: We reported a case of 53 years old man who suffered from diarrhea and weight loss for one month before admission. There were also blood and mucus in his stool. The result of colonoscopy was hyperemia and ulcers along the rectum to the caecum. Histopathology examination showed pieces of intestinal mucosal tissue covered by columnar epithelium, with goblet cell and round-oval core. The lamina propria is densely packed with lymphocyte cells, plasma cells and PMN leukocytes. This result represents chronic colitis with acute exacerbation. Conclusion: Patient was treated with mesalazine 3x1000 mg per oral, methyl prednisolone 3x16 mg per oral, and low fiber diet to achieve remission.

A 78-year-old man with a history of pancolitis, after the treatment of dental abscess with oral antibiotics and local application of camphorated and mentholated chlorophenol (CMCP), presented with abdominal pain of 4-day duration, as well as hair loss in the area of moustache and finger nail lifting. He was already treated with rectal application of budesonide because of pancolitis, diagnosed 6 weeks ago and interpreted as an allergic reaction to clindamycin. For further investigation, we performed gastroscopy and colonoscopy, which showed the edematous mucosa with polypus-like changes of the whole mucosa of the stomach, duodenum, first part of the jejunum, distal ileum, complete colon, and rectum. The diagnosis was complicated and was achieved in synopsis with anamnestic details, such as endodontic application of camphorated chlorophenol. The patient symptoms abated after he commenced on mesalazine therapy.

Interferon (IFN) is a multifaceted immunomodulator that is effective against many diseases, including chronic hepatitis B and chronic hepatitis C infection. IFN defends against viral infection, but may also cause various side effects, such as ulcerative colitis (UC). Herein, we present a case of UC triggered by pegylated interferon alpha-2b (PEG-IFN-α-2b) therapy in a patient with concurrent chronic hepatitis B (CHB) infection. The diagnosis was based on typical clinical symptoms, colonoscopy findings, colonic mucosal biopsy, and histopathology. Accordingly, treatment with mesalazine was initiated without stopping PEG-IFN-α-2b. Fortunately, UC relieved gradually without compromising the effects of treatment. Simultaneously, we conducted a literature review of previously published case reports on the side effect of UC in patients with underlying chronic hepatitis. Various reactions have been reported, including induction, exacerbation, and no change. This is the first report of UC triggered by PEG-IFN-α-2b in a CHB patient. We recommend that physicians pay attention to the rare side effect of UC during administration of PEG-IFN-α-2b. Mesalazine can relieve UC with sustained use of PEG-IFN-α-2b.

The case of a toddler with long-channel cloaca, mild chronic kidney disease (CKD) due to renal dysplasia, and early onset of ulcerative colitis (UC) is herein reported. The patient underwent definitive repair of cloaca, that included vaginal elongation with colon, at 5 months of age and was admitted for episodes of vaginal bleeding at 22 months of age. A vaginoscopy revealed a severe inflammation of the colonic neovagina. As rectal bleeding was also noticed, she underwent a colonscopy that showed the same macroscopic inflammatory picture. Neovaginal and colonic biopsies confirmed UC. The mother turned out to be affected by UC since adolescence. The patient is now on oral therapy with mesalazine and topical steroid and mesalazine in the neovagina. The association between cloaca and inflammatory bowel disease (IBD) is anecdotal, but the family history of IBD should be considered when planning the surgical reconstruction of patients with cloaca. In this patient, the occurrence of UC may require a new neovagina in the future and the concomitance of CKD may complicate the overall management due to the potential nephrotoxicity of drugs used for UC therapy.

Mesalazine (5-aminosalicylic acid, 5-ASA) has been widely used to treat inflammatory bowel disease (IBD). However, it remains unclear about the underlying biological mechanisms of IBD pathogenesis and mesalazine treatment, which could be partially clarified by exploring the profiling of circular RNAs (circRNAs) using RNA-seq. A total of 15 mice (C57BL/6) were randomly assigned to three equally sized groups: control, dextran sulfate sodium (DSS, using DSS to induce IBD), and DSS+5-ASA (using mesalazine to treat IBD). We randomly selected three mice of each group to collect colon tissues for RNA-seq and then performed bioinformatic analysis for two comparisons: DSS vs. control and DSS+5-ASA vs. DSS. Comparisons of a series of indicators (e.g., body weight) verified the establishment of DSS-induced IBD mouse model and the effectiveness of mesalazine in treating IBD. We identified 182 differentially expressed circRNAs, including 55 up-regulated and 47 down-regulated circRNAs when comparing the DSS+5-ASA with the DSS group. These 102 circRNA-associated genes were significantly involved in the N-Glycan biosynthesis and lysine degradation. The network analysis of circRNA-miRNA-mRNAs identified an important pathway, i.e., chr10:115386962-115390436+/mmu-miR-6914-5p/Atg7, which is related to autophagy. The findings provide new insights into the biological mechanisms of IBD pathogenesis and mesalazine treatment, particularly highlighting the circRNA-miRNA-mRNA pathway.

ObjectiveOur aim was to explore the risk of infection with all classes of inflammatory bowel disease (IBD) medications and the impact of these medications on the disease course in a nationwide cohort of patients with IBD.DesignThis was a retrospective national cohort study of patients with IBD in the Veterans Affairs Healthcare System. We categorised IBD medication use immediately prior to the COVID-19 pandemic and used survival analysis methods to study associations with SARS-CoV-2 infection, as well as a combined secondary outcome of COVID-19 hospitalisation or COVID-19-related mortality.ResultsThe analytical cohort of 30 911 patients was primarily male (90.9%), white (78.6%) and with ulcerative colitis (58.8%). Over a median follow-up of 10.7 months, 649 patients (2.1%) were diagnosed with SARS-CoV-2 infection and 149 (0.5%) met the combined secondary outcome. In adjusted models, vedolizumab (VDZ) use was significantly associated with infection relative to mesalazine alone (HR 1.70, 95% CI 1.16 to 2.48, p=0.006). Patients on no IBD medications had increased risk of the combined secondary outcome relative to mesalazine alone (sub-HR 1.64, 95% CI 1.12 to 2.42, p=0.01), however, no other IBD medication categories were significantly associated with this outcome, relative to mesalazine alone (each p>0.05). Corticosteroid use was independently associated with both SARS-CoV-2 infection (HR 1.60, 95% CI 1.23 to 2.09, p=0.001) and the combined secondary outcome (sub-HR 1.90, 95% CI 1.14 to 3.17, p=0.01).ConclusionVDZ and corticosteroid were associated with an increased risk of SARS-CoV-2 infection. Except for corticosteroids no medications including mesalazine were associated with an increased risk of severe COVID-19.

Purpose Studies of patients with ulcerative colitis (UC) report that reduced clinical symptoms and endoscopic activity predict better health-related quality of life (HRQoL). However, no study has examined the joint and unique associations of clinical and endoscopic activity with HRQoL, nor of histologic inflammation and HRQoL. These post hoc analyses evaluated whether reduced clinical, endoscopic, and histologic disease activity were uniquely associated with improved HRQoL for adults with active mild-to-moderate UC receiving once-daily 4.8 g/day multimatrix mesalazine for 8 weeks. Methods Assessments at baseline and week 8 (i.e., treatment completion) included clinical and endoscopic activity (modified UC-Disease Activity Index), histology (Geboes scoring), and HRQoL (Short Inflammatory Bowel Disease Questionnaire [SIBDQ]; SF-12v2® Health Survey [SF-12v2]). Associations among each type of disease activity and HRQoL were examined by correlations and by mean changes in SIBDQ and SF-12v2 scores between disease activity subgroups (e.g., achievement of clinical remission; mucosal healing). Regression models estimated unique variance in HRQoL accounted by each type of disease activity. Results Within the analysis sample (n = 717), patients with reduced clinical and endoscopic activity had significantly larger improvements in all HRQoL domains (p p p Conclusions Clinical symptoms and mucosal health have separable, distinct impacts on UC patients’ HRQoL.

Ulcerative colitis (UC) is an inflammatory disease affecting the mucosa in the colon. Despite significant progress and expansion of the therapeutic armamentarium for UC, there are currently no curative medications available and some cases require colectomy. In this communication, we report the case of a 38 years old male patients with a five-year history of UC who had involvement of the entire colon and was medically refractory. The patient had received treatment with steroids, mesalazine, infliximab, and adalimumab, but failed to achieve remission in the process. He had non-remitting symptoms with endoscopic and histologic evidence of severe disease, and experienced episodes of significant lower gastrointestinal bleeding. Ultimately, the patient was advised to undergo colectomy, but he refused; instead, he adopted a lifestyle modification approach—the health triangle method. In short, this approach emphasizes three aspects of nutrition, use of herbal medicines, and interventions (called aamal-e-yadavi in Traditional Iranian Medicine) like oiling, cupping, and phlebotomy (hejamat). These interventions can improve the cellular energy balance and truly cure the autoimmune disease if adopted over the long term. After three years, the patient reported substantial improvement in symptoms, and the colonoscopy and histology showed evidence of remission. This case indicated the potential efficacy and safety of complementary and alternative approaches in patients with UC; however, the health triangle method needs to be investigated in randomized controlled trials.

Mesalazine is a main medicine for treatment of ulcerative colitis. Most patience of left-sides and total colitis receive oral mesalazine for many years. Currently, there is a little information about the tolerability and safety of long-term use of mesalazine. The eosinophilic pneumonia, organizing pneumonia, and nonspecific interstitial pneumonia are very rare adverse effects of ulcerative colitis treatment with mesalazine. The article presents case of the development interstitial lung disease induced by mesalazine under long-term maintenance treatment for three years in the young patient with ulcerative colitis. It shows the difficulties in diagnosing this disease due to the work-long low-grade fever in manifestation of pneumonitis, the similarity of clinical and radiological manifestations (diffuse bilateral pattern in chest imaging). The article demonstrates the limitations of modern laboratory and instrumental diagnostic methods for the differentiation of disseminated lesions of the lung tissue, and shows the importance of elimination treatment of mesalazine-induced pneumonitis.

We aimed to develop a 5-aminosalicylic acid (5-ASA, mesalazine)-based anti-colitic drug with higher efficacy than sulfasalazine (SSZ), a colon-targeted prodrug of 5-ASA, for the treatment of inflammatory bowel disease (IBD). To this end, we synthesized a colon-targeted mutual prodrug (ASA-azo-NA) consisting of 5-ASA and the GPR109A agonist nicotinic acid, 5-[(3-carboxy-4-hydroxyphenyl)diazenyl] nicotinic acid. In our previous study, oral gavage of ASA-azo-NA delivered 5-ASA and 5-aminonicotinic acid specifically to the large intestine in a 2,4-dinitrobenzene sulfonic acid (DNBS)-induced rat colitis model and ameliorated colonic damage and inflammation more effectively than oral SSZ. To increase the therapeutic convincibility of ASA-azo-NA for the treatment of IBD with multifactorial pathologies, the colon targetability and therapeutic activity of ASA-azo-NA were examined using a dextran sulfate sodium (DSS)-induced colitis mouse model with a different pathogenesis from that of DNBS-induced colitis in rats. ASA-azo-NA liberated 5-ASA in the cecal contents of mice while remaining stable in the small intestinal contents, with a cecal conversion rate and extent comparable to those of SSZ. Oral ASA-azo-NA and SSZ accumulated similar concentrations of 5-ASA in the cecum, indicating that ASA-azo-NA was delivered to and activated in the large intestine as efficiently as SSZ. In mice with DSS-induced colitis, oral ASA-azo-NA mitigated colonic damage and inflammation, as assessed using macroscopic and molecular indices, and was therapeutically superior to SSZ. ASA-azo-NA acted as a colon-targeted mutual prodrug against DSS-induced mouse colitis. Thus, ASA-azo-NA may be therapeutically applicable to patients with IBD who are resistant to SSZ treatment.

Objectives Roxithromycin, a macrolide antibiotic, has been shown to ameliorate acetic acid induced colitis in rats by suppressing inflammation and oxidative stress. The aim of this study was to evaluate the effect of roxithromycin on small intestinal transit and cholinergic responsiveness of the colonic smooth muscles of colitic rats. Methods Colitis was induced in rats by acetic acid and the small intestinal transit was determined by measuring the distance traversed by charcoal meal from the gastro-duodenal junction in 1 h. The test drug roxithromycin, reference drug mesalazine and anti-inflammatory drug diclofenac were administered orally before inducing colitis and their effect on intestinal transit was compared with colitic control group. The effect on cholinergic responsiveness of colonic smooth muscles was evaluated in vitro by plotting a dose-response curve using different concentrations of acetylcholine. The concentration producing 50% of maximal response (EC50) was calculated for all the treatment groups. Results The small intestinal transit was enhanced in colitic rats as compared to normal rats (86.00 ± 1.36 vs. 57.00 ± 1.34 cm; pin vitro experiment show that colitis increased cholinergic responsiveness of the colonic smooth muscles that was not affected by roxithromycin and mesalazine while diclofenac significantly decreased it. Conclusions This study shows that like mesalazine, roxithromycin affords protection in colitis mainly by normalizing propulsive movement of the small intestine than by affecting cholinergic responsiveness of the colonic smooth muscles.

Barriers to drug adherence in the developing world are multifactorial and under evaluated. We aimed to evaluate predictive factors of medication adherence in Indian patients with inflammatory bowel disease (IBD) and association of adherence with quality of life (QOL) and relapse free remission.Adherence was assessed in consecutive IBD patients using a self-administered survey questionnaire including Morisky Medication Adherence Scale together with interview and Short Inflammatory Bowel Disease Questionnaire (SIBDQ) to assess QOL. Logistic regression analysis was used to identify variables correlating with adherence, Cox proportional hazards method used for variables associated with relapse and Kaplan-Meier survival curve used for comparing relapse free remission in adherent and nonadherent.A total of 467 consecutive outpatients (279 ulcerative colitis, 188 Crohn's disease, mean age 38.6 y) were mostly on mesalazine 439 (94%) or thiopurines 213 (46%). Self-reported nonadherence was noted in 236/467 (51%). Disease remission was associated with medication adherence [P=0.003, odds ratio (OR): 1.75, 95% confidence interval (CI): 1.21-2.52]. Medication-related factors like high dosing frequency (3/d) (OR: 0.39, P=0.005) and concomitant non-IBD medications (OR: 0.44, P=0.007) were associated with nonadherence. Psychosocial factors associated with nonadherence were lack of drug information (OR: 0.30, P0.001), feeling depressed (OR: 0.43, P0.001), comorbidities (OR: 0.47, P=0.005), doubts about efficacy (OR: 0.49, P=0.001) and perceived poor QOL (OR: 0.61, P=0.01). High-cost perception was associated with nonadherence in univariate analysis (OR: 0.47, P0.001) but lost significance on multivariate analysis (OR: 0.68, P=0.07). Physician imparting disease information (OR: 2.5, P=0.14) and physician reinforcement (OR: 1.8, P=0.049) were associated with adherence.Adherence was associated with improved QOL (SIBDQ, R=0.724). Nonadherence was associated with3-fold risk of recurrence within 2 years (hazard ratio: 3.89, 95% CI: 2.74-5.52, P0.001).Nonadherence is common in Indian IBD patients but adherence is associated with improved QoL and lower probability of relapse. Psychosocial and medication-related factors are important determinants of adherence compared with demographic or clinical variables and should be addressed.

Concentrations of 16 metals in the scalp hair of male Crohn’s disease (CD) patients (n = 28) were compared to those of male control subjects (n = 25). The majority of patients (n = 20) took an anti-inflammatory agent (mesalazine), and several patients underwent colectomy. A low concentration of serum ferritin was observed in approximately 50% of CD patients due to Fe-deficiency anemia. The concentrations of Fe, Cr, and Co in the hair of CD patients were significantly higher than those of control subjects, and particularly high concentrations were found in CD patients with low serum ferritin. Significant correlations were found among the concentrations of Fe, Cr, and Co in the hair of CD patients, but not in control subjects. In agreement with previous reports, a significant negative correlation was found between ferritin and transferrin concentrations in serum, although the available data in this study was limited (n = 8). Transferrin not only binds to Fe3+ but also to Cr3+ and Co3+, and the amount of transferrin is increased in Fe-deficiency anemia. Thus, the majority of the Fe3+, Cr3+, and Co3+ in the serum of CD patients is likely to bind to transferrin, which may be associated with the higher concentrations of those metals, as well as the significant correlations among those metals in the scalp hair of CD patients. In addition, colectomy may alter the intestinal absorption rate of some metals, while mesalazine may increase the concentrations of Mn and some metals in the scalp hair by chelate formation.

Background: We aimed to evaluate the therapeutic effect of additional ursodeoxycholic acid (UDCA) with mesalazine, compared to mesalazine alone in patients with ulcerative colitis (UC). The mechanism was evaluated by monitoring the changes of IL-23-IL-17 axis and the intestinal microflora. Methods: In this prospective, single center study, patients with UC were randomly assigned to the Mesalazine group (n=20) or the UDCA + Mesalazine group (n=20). Mayo score and Inflammatory Bowel Disease Questionnaire (IBDQ), and fecal samples for 16S rRNA sequencing and blood samples for IL-23 and IL-17 ELISA were collected for analysis. Results: Mayo scores and IBDQ score of the UDCA + Mesalazine group were significantly better than those of the Mesalazine group (P = 0.015 and P < 0.001, respectively). At post-treatment week 4, IL-23 and IL-17 levels were significantly lower in the UDCA + Mesalazine group compared to those in the Mesalazine group (both P < 0.038). In patients with UC after treatment, Firmicutes in the UDCA + Mesalazine group was higher than those in the Mesalazine group (P < 0.001). The UDCA + Mesalazine group showed lower percentage of Proteobacteria compared to those in the Mesalazine group (P < 0.001). Conclusion: Additional UDCA could provide better therapeutic effects than mesalazine alone, possibly due to the change of IL-23 and IL-17 and the proportional distribution of intestinal microflora.