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Aim of this work is to study the effect of pectin content on the physicochemical, morphological, swelling and releasing properties of composite hydrogel beads based on pectin and sodium metasilicate (SM). Synthesis of pectin–silica composite beads was carried out using the ionotropic gelation method and sol–gel reaction of SM as a silica precursor. The entrapment efficiency of mesalazine (66–88%) and gel strength (0.86–2.10 N) increased in the pectin–silica hydrogels compared to pectin–Ca hydrogels. These parameters increased with the increase in concentration of pectin. Energy-dispersive X-ray analysis showed that the silicon content was higher in the beads with an increased SM/pectin ratio (2:1). Fourier transform infrared spectroscopy revealed the formation of an organic/inorganic composite, the presence of H–bonds in pectin–silica hydrogel and the loading of mesalazine into the composite gel. Composite hydrogels with the lowest amount of pectin (an organic component) showed the highest thermal stability. Pectin–silica hydrogels were less sensitive to the adsorption of gastrointestinal fluids and released mesalazine very slowly compared to pectin–Ca gels. Mesalazine release from composite gels decreased with the increase in pectin concentration and gel strength. The gel formulations with high gel strength and a low SM/pectin ratio had the lowest mesalazine release rate in the gastrointestinal environment. Mesalazine was released slowly in gastrointestinal fluids and more rapidly in colonic fluid. Synthesized pectin–silica hydrogels based on callus culture pectin, appear to be a promising composite system for targeted drug delivery to the colon. [ABSTRACT FROM AUTHOR]

Background: Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by relapsing inflammation of the colon. Tanshinone IIA, a compound derived from traditional Chinese medicine, has demonstrated anti-inflammatory properties and may enhance treatment outcomes when combined with mesalazine. This study aims to determine the overall response rate of Tanshinone IIA in combination with mesalazine for the treatment of UC. Methods: We reviewed articles from the establishment of the databases until April 2023 in the PubMed, Embase, Cochrane Library, CNKI, Wanfang, CQVIP, and CBM databases. They included a randomized controlled trial in which the intervention group was given tanshinone IIA plus mesalazine (T + M), while the comparative group was given only mesalazine (M). We removed duplicates or similar papers; papers with no available full text or incomplete data; animal research; and review and systematic review articles. STATA 15.1 was used to analyze the data. Results: The perceived total effectiveness rate of T + M was found to be higher than M and the difference was found to be significant (P = 0.000). Additionally, pooled results show that TNF-α (P = 0.000) and CRP (P = 0.000) levels in the T + M group were all significantly lower than that in the M group. Furthermore, MHC-II expression in the T + M group was minors compared to that of the M group (P = 0.001). However, there was no significant difference in the incidence of adverse events between the T + M and M groups (P = 0.700). Conclusion: This meta-analysis demonstrates that combining tanshinone IIA with mesalazine significantly enhances the overall treatment efficacy for ulcerative colitis compared to mesalazine alone. Tanshinone IIA also exhibits anti-inflammatory effects by reducing TNF-α, CRP levels, and MHC-II expression without notably increasing adverse events. Despite some limitations, these findings suggest that tanshinone IIA can be a promising adjunctive therapy for ulcerative colitis. Further large-scale, multi-center studies are needed to confirm these results and establish the long-term safety and effectiveness of this combination therapy. [ABSTRACT FROM AUTHOR]

Aim(s): This article explores the application of mesalazine-loaded nanoparticles (MLZ-NPs) encapsulated in Abelmoschus esculentus plant polysaccharide-based pellets (MLZ-NPs-Pellets) for ulcerative colitis. Methods: MLZ-NPs were prepared and evaluated for diameter, PDI, and entrapment efficiency. In-vitro efficacy study was conducted on Caco-2 cells. MLZ-NPs were encapsulated in polysaccharides to form MLZ-NPs-Pellets and characterised for efficacy in animals and targeting efficiency in human volunteers. Results: Optimised batch of MLZ-NPs were characterised for diameter, PDI, zeta potential and entrapment efficiency which was found to be 145.42 ± 6.75 nm, 0.214 ± 0.049, −31.63 mV and 77.65 ± 2.33(%w/w) respectively. ROS, superoxide and NF-kβ were well controlled in Caco-2 cells when treated with MLZ-NPs. In-vivo data revealed that some parameters (body weight, colon length, lipid peroxidase, and glutathione) recovered significantly in the DSS-induced mice model treated with oral MLZ-NPs-Pellets. Gamma scintigraphy revealed that the formulation can effectively target the colon within 600 min. Conclusion: MLZ-NPs-Pellets can be effectively used for microbial-triggered colon targeting approach in treating ulcerative colitis. [ABSTRACT FROM AUTHOR]

In this study, a zinc/aluminium layered double hydroxide (LDH) was synthesized and characterized using FESEM, EDX, and FT-IR spectroscopy. The LDH was incorporated into carbon paste to create an electrochemical sensor for mesalazine detection. This sensor was employed as the working electrode in voltammetric determination of mesalazine. Experimental conditions were optimized, with 5 mg of modifier and pH 6. Electrochemical parameters were set at 50 mV pulse amplitude, 30 ms pulse time, and 40 mV s−1 scan rate. The sensor displayed linear anodic peak current responses for mesalazine concentrations ranging from 5 to 100 and 100 to 600 μM, with a detection limit of 2.5 μM. Reproducibility was assessed through inter- and intra-day relative standard deviations of 2.2% and 2.9%, respectively. Selectivity was tested against potential interferences like ascorbic acid, oxalic acid, glucose, sucrose, and folic acid. The successful mesalazine detection in real samples highlighted the sensor's potential as an efficient analytical tool. [ABSTRACT FROM AUTHOR]

Radiation-induced morphea (RIM) is a rare complication of radiotherapy presenting as inflammatory fibrosis, most commonly reported in breast cancer patients. As underlying disease mechanisms are not well understood, targeted therapies are lacking. Since fibroblasts are the key mediators of all fibroproliferative diseases, this study aimed to characterize patient-derived fibroblasts to identify therapeutic targets. We studied primary human control and RIM-fibroblasts on a functional and molecular basis, analyzed peripheral blood and tissue samples and conducted, based on our findings, a treatment attempt in one patient. In RIM, we identified a distinct myofibroblast phenotype reflected by increased alpha-smooth-muscle-actin (αSMA) expression, reduced proliferation and migration rates, and overexpression of osteopontin (OPN). Our RNA sequencing identified aberrant Myc activation as a potential disease driver in RIM fibroblasts, similar to previous findings in systemic sclerosis. Treatment with the anti-inflammatory drug mesalazine reversed the myofibroblast phenotype by targeting Myc. Based on these findings, a patient with RIM was successfully treated with mesalazine, resulting in reduced inflammation and pain and tissue softening, while serum OPN was halved. The present study provides a comprehensive characterization of RIM fibroblasts, suggests a disease-driving role for Myc, demonstrates promising antifibrotic effects of mesalazine and proposes OPN as a biomarker for RIM. [ABSTRACT FROM AUTHOR]

Colonic drug delivery offers numerous pharmaceutical opportunities, including direct access to local therapeutic targets and drug bioavailability benefits arising from the colonic epithelium's reduced abundance of cytochrome P450 enzymes and particular efflux transporters. Current workflows for developing colonic drug delivery systems involve time-consuming, low throughput in vitro and in vivo screening methods, which hinder the identification of suitable enabling materials. Polysaccharides are useful materials for colonic targeting, as they can be utilised as dosage form coatings that are selectively digested by the colonic microbiota. However, polysaccharides are a heterogeneous family of molecules with varying suitability for this purpose. To address the need for high-throughput material selection tools for colonic drug delivery, we leveraged machine learning (ML) and publicly accessible experimental data to predict the release of the drug 5-aminosalicylic acid from polysaccharide-based coatings in simulated human, rat, and dog colonic environments. For the first time, Raman spectra alone were used to characterise polysaccharides for input as ML features. Models were validated on 8 unseen drug release profiles from new polysaccharide coatings, demonstrating the generalisability and reliability of the method. Further, model analysis facilitated an understanding of the chemical features that influence a polysaccharide's suitability for colonic drug delivery. This work represents a major step in employing spectral data for forecasting drug release from pharmaceutical formulations and marks a significant advancement in the field of colonic drug delivery. It offers a powerful tool for the efficient, sustainable, and successful development and pre-ranking of colon-targeted formulation coatings, paving the way for future more effective and targeted drug delivery strategies. [Display omitted] • A new Raman spectrum processing pipeline for effective Machine Learning. • Raman spectra of polysaccharide coatings can successfully predict 5-ASA release. • ML model is robust in human, rat and dog IBD-simulated colonic environments. • Model interpretation revealed coating molecular properties influencing 5-ASA release. [ABSTRACT FROM AUTHOR]

Objective: We took advantage of a single-center cross-sectional study to investigate the effect of different drugs on intestinal microbiota and function in Crohn's disease. Methods: We studied the difference in fecal microbiota of Crohn's disease patients treated with mesalazine, azathioprine, and infliximab, as well as untreated patients, by metagenome and screened for differential microbiota. Further, we investigated functional differences in intestinal microbiota among the four groups. Results: Through metagenomic sequencing, we found that there was no difference between the four groups in ACE and Chao1 indices, but IFX and mesalazine improved species diversity and homogeneity compared to the untreated group, as evidenced by statistically significant differences in the Shannon index, Simpson index, and pielou_evenness. In addition, beta diversity suggested a difference between groups, but the difference was not significant. Non-parametric tests revealed differences between the four groups at the phylum level, class level, and genus level. Further analysis by LEfSe analysis revealed that the level of short-chain fatty acid-producing microbiota was increased in the treated groups, while there was no difference between the treated groups when compared to each other. Finally, the KEGG database and EggNOG database revealed that there were functional differences in intestinal microbiota among the four groups, including microbial metabolism pathway, cysteine and methionine metabolism pathway, cytoskeleton, etc. Conclusions: Mesalazine, azathioprine, and infliximab can all affect the intestinal microbiota and function in patients with Crohn's disease, and the drugs may alleviate intestinal inflammation in patients with Crohn's disease by modulating the intestinal microbiota. [ABSTRACT FROM AUTHOR]

Abstract Background Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by relapsing inflammation of the colon. Tanshinone IIA, a compound derived from traditional Chinese medicine, has demonstrated anti-inflammatory properties and may enhance treatment outcomes when combined with mesalazine. This study aims to determine the overall response rate of Tanshinone IIA in combination with mesalazine for the treatment of UC. Methods We reviewed articles from the establishment of the databases until April 2023 in the PubMed, Embase, Cochrane Library, CNKI, Wanfang, CQVIP, and CBM databases. They included a randomized controlled trial in which the intervention group was given tanshinone IIA plus mesalazine (T + M), while the comparative group was given only mesalazine (M). We removed duplicates or similar papers; papers with no available full text or incomplete data; animal research; and review and systematic review articles. STATA 15.1 was used to analyze the data. Results The perceived total effectiveness rate of T + M was found to be higher than M and the difference was found to be significant (P = 0.000). Additionally, pooled results show that TNF-α (P = 0.000) and CRP (P = 0.000) levels in the T + M group were all significantly lower than that in the M group. Furthermore, MHC-II expression in the T + M group was minors compared to that of the M group (P = 0.001). However, there was no significant difference in the incidence of adverse events between the T + M and M groups (P = 0.700). Conclusion This meta-analysis demonstrates that combining tanshinone IIA with mesalazine significantly enhances the overall treatment efficacy for ulcerative colitis compared to mesalazine alone. Tanshinone IIA also exhibits anti-inflammatory effects by reducing TNF-α, CRP levels, and MHC-II expression without notably increasing adverse events. Despite some limitations, these findings suggest that tanshinone IIA can be a promising adjunctive therapy for ulcerative colitis. Further large-scale, multi-center studies are needed to confirm these results and establish the long-term safety and effectiveness of this combination therapy.

Abstract Radiation-induced morphea (RIM) is a rare complication of radiotherapy presenting as inflammatory fibrosis, most commonly reported in breast cancer patients. As underlying disease mechanisms are not well understood, targeted therapies are lacking. Since fibroblasts are the key mediators of all fibroproliferative diseases, this study aimed to characterize patient-derived fibroblasts to identify therapeutic targets. We studied primary human control and RIM-fibroblasts on a functional and molecular basis, analyzed peripheral blood and tissue samples and conducted, based on our findings, a treatment attempt in one patient. In RIM, we identified a distinct myofibroblast phenotype reflected by increased alpha-smooth-muscle-actin (αSMA) expression, reduced proliferation and migration rates, and overexpression of osteopontin (OPN). Our RNA sequencing identified aberrant Myc activation as a potential disease driver in RIM fibroblasts, similar to previous findings in systemic sclerosis. Treatment with the anti-inflammatory drug mesalazine reversed the myofibroblast phenotype by targeting Myc. Based on these findings, a patient with RIM was successfully treated with mesalazine, resulting in reduced inflammation and pain and tissue softening, while serum OPN was halved. The present study provides a comprehensive characterization of RIM fibroblasts, suggests a disease-driving role for Myc, demonstrates promising antifibrotic effects of mesalazine and proposes OPN as a biomarker for RIM.

Objective: To discuss the anti-inflammatory and antioxidant effect of mesalazine (MSZ) in the RAW264. 7 cell model, and to elucidate its therapeutic effect on periodontitis in the rats. Methods: The proliferation rates of RAW264. 7 cells stimulated by different concentrations (0, 62. 5, 125. 0, 250. 0, 500. 0, 1 000. 0, and 2 000. 0 mg·L-1 )of MSZ were detected by CCK-8 method to determine the optimal concentration of MSZ for cell treatment. Porphyromonas gingivalis lipopolysaccharide (P. g-LPS) and MSZ were used to treat the RAW264. 7 cells, and the cells were divided into control group, P. g-LPS group, and MSZ+P. g-LPS group. The levels of reactive oxygen species (ROS) in the cells in various groups were detected by the DCFH-DA fluorescent probe assay; the malondialdehyde (MDA) levels, glutathione (GSH) levels and superoxide dismutase (SOD) activities in the cells in various groups were detected by ELISA method; the expression levels of inflammatory factors interleukin-8 (IL-8) and interleukin-1β (IL-1β) mRNA in the cells in various groups were detected by real-time fluorescence quantitative PCR (RT-qPCR) method. The periodontitis rat model was established by the ligation method combined with the injection of P. g bacterial fluid. A total of 18 rats were randomly divided into control group (without treatment), model group (making periodontits model), and drug administration group (making periodontits model and given MSZ), and there were 6 rats in each group. Micro-CT was used to assess the alveolar bone destruction of the rats in various groups; HE staining was used to observe the morphology of periodontal tissue of the rats in various groups. Results: Compared with control group, the proliferation rate of the cells in 500. 0 mg·L-1 MSZ group was significantly increased (P<0. 01), so 500. 0 mg·L-1 MSZ was subsequently selected to treat the cells. Compared with control group, the levels of ROS and MDA in the cells in P. g-LPS group were significantly increased (P<0. 01), and the level of GSH and activity of SOD were significantly decreased (P<0. 01), and the expression levels of IL-1β and IL-8 mRNA were significantly increased (P<0. 01); compared with P. g-LPS group, the levels of ROS and MDA in the cells in MSZ+P. g-LPS group were significantly decreased (P<0. 01), the level of GSH and activity of SOD were significantly increased (P<0. 01), and the expression levels of IL-1β and IL-8 mRNA were significantly decreased (P<0. 01). The micro-CT assay results showed that compared with control group, the distance from the cemento-enamel junction to alveolar bone crest (CEJ-ABC) of the rats in model group was significantly increased (P<0. 01), and the bone volume fraction (BV/TV) was significantly decreaced (P<0. 05); compared with model group; the CEJ-ABC of the rats in drug administration group was decreased (P<0. 01), and the BV/TV was increased (P<0. 05). The HE staining results showed that the inflammatory cell infiltration in periodontal tissue of the rats in drug administration group was reduced, and epithelial attachment was restored. Conclusion: MSZ effectively inhibits the production of pro-inflammatory factors and peroxides in the P. g-LPS-induced RAW264. 7 cells, improves the cellular anti-inflammatory and antioxidant capacity, inhibits the alveolar bone resorption, and alleviates the inflammation of periodontal tissues in the periodontitis rats. [ABSTRACT FROM AUTHOR]

Background Mesalazine is an established first-line therapy for inflammatory bowel disease (IBD) and remains the mainstay of treatment for mild to moderate ulcerative colitis (UC). Both mesalazine and UC are rare but recognized causes of myopericarditis. Cardiac magnetic resonance (CMR) is a non-invasive method of assessing for myopericarditis. This case reports highlights the importance of early CMR in diagnosis, and management of myocarditis in a patient with IBD. Case summary A 28-year-old male was admitted with a 2-day history of chest pain. Three weeks prior to this presentation, the patient was initiated on mesalazine for UC. Serum troponin T and C-reactive protein were elevated. An echocardiogram showed borderline low left ventricular systolic function (LVEF = 50–55%). A CMR showed extensive patchy late gadolinium enhancement (LGE) in the mid to epicardial basal and mid lateral wall. The findings were consistent with acute myocarditis, and a working diagnosis of mesalazine-induced myocarditis was made. Mesalazine was stopped and guideline-directed anti-inflammatories initiated. Oral prednisolone was also introduced for IBD control. Follow-up CMR at four months showed near complete resolution of LGE. Discussion Myocarditis in the context of IBD may be infective, immune-mediated or due to mesalazine hypersensitivity. Histological conformation was not available in this case. This case report highlights the importance of access to early CMR in order establish the diagnosis and withdrawal of the culprit medication. In the majority of cases, CMR will replace the need for endomyocardial biopsy; however, this may still be required in the most severe cases. [ABSTRACT FROM AUTHOR]

Ulcerative colitis (UC) is a chronic inflammatory bowel disease mainly affecting the colon and remains a challenging disease to manage clinically with its relapsing-remitting course. Traditional treatments for this disease showed some drawbacks, including systemic toxicity and ineffective targeting of the affected colon areas. This article introduces a unique treatment method that uses mesalazine (MSZ)-loaded TPP/Chitosan nanoparticles (MSZNP)-embedded into bovine serum albumin (BSA) hydrogels (MSZNPH) for targeted intrarectal medication delivery. Additionally, conventional MSZ was integrated into BSA hydrogel (MSZH), and then, MSZH, MSZNP, and MSZNPH were characterized and compared with an emphasis on encapsulation efficiency, drug release profile, and hydrogel swelling behavior. Our findings show that MSZNPH composite technology may improve targeted administration and prolonged release of MSZ, indicating a promising new route for UC therapy with the potential to improve patient adherence and outcomes. [ABSTRACT FROM AUTHOR]

The treatment of inflammatory bowel disease (IBD) remains challenging and significantly impacts both patients and their families. This study evaluated the role of Bifidobacterium animalis subsp. lacti XLTG11 (XLTG11) in combination with mesalazine (5-ASA) in the improvement of IBD. The results demonstrated that the XLTG11+5-ASA group exhibited superior recovery compared to both the XLTG11-only group and the 5-ASA-only group. The XLTG11+5-ASA group significantly reduced myeloperoxidase activity (MPO), attenuated colonic tissue damage, lowered the levels of lipopolysaccharides (LPS) and D-lactic acid (D-LA), and decreased intestinal permeability. Furthermore, it upregulated the mRNA expression of Claudin-1, Occludin, ZO-1, and MUC2, which contributed to the protective effect on intestinal barrier function. Additionally, the XLTG11+5-ASA group significantly increased the levels of anti-inflammatory cytokines while decreasing pro-inflammatory cytokine levels. Notably, treatment with the XLTG11+5-ASA group significantly increased levels of acetic, propionic, and butyric acids, as well as the relative abundance of beneficial bacteria such as Bifidobacterium and Lactobacillus, while decreasing the relative abundance of Enterococcus, Enterobacteriaceae, and Clostridium perfringens. The results indicate that the combination of XLTG11 and 5-ASA was more effective in treating IBD than either treatment alone, significantly improving IBD-related symptoms and providing a scientific basis for future clinical applications.

IntroductionUlcerative colitis (UC), a common gastrointestinal disorder in affluent nations, involves chronic intestinal mucosal inflammation. This research investigated the effects of combined probiotic treatment of Lactobacillus casei (L. casei) and mesalazine on disease activity index and inflammatory factors in the UC model.Methods20 male BALB/c mice were utilized and divided into four groups. To induce UC, all groups received 100 μL of 4% acetic acid (AA) intra-rectally. The first group received phosphate-buffered saline (PBS) (as a control group), the second group was treated with L. casei, the third group was treated with mesalazine and, the fourth group was treated with L. casei and mesalazine. Treatment with L. Casei and mesalazine commenced after the manifestation of symptoms resulting from UC induction. Finally, the mice were euthanized and the disease activity index, myeloperoxidase activity, nitric oxide rate, cytokines level (IL-1β, IL-6, TNF-α) and, gene expression (iNOS, COX-2, and cytokines) were evaluated.ResultsThe combined treatment of L. casei and mesalazine led to a significant decrease in the levels of NO, MPO and inflammatory cytokines. In addition, the expression of cytokines, iNOS and COX-2 genes decreased in mice treated with the combination.DiscussionThis study shows that combined treatment of L. casei and mesalazine improves of experimental UC, which can be attributed to the anti-inflammatory properties of L. casei and mesalazine. In conclusion, this combination therapy can be considered a suitable option for the management of UC.

Purpose: Current pharmacological treatments for Ulcerative Colitis (UC) have limitations. Therefore, it is important to elucidate any available alternative or complementary treatment, and Chinese herbal medicine shows the potential for such treatment. As a traditional Chinese herbal medicine, Danshenrelated preparations have been reported to be beneficial for UC by improving coagulation function and inhibiting inflammatory responses. In spite of this, the credibility and safety of this practice are incomplete. Therefore, in order to investigate whether Danshen preparation (DSP) is effective and safe in the treatment of UC, we conducted a systematic review and meta-analysis. Methods: PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure, Wanfang Database and CQVIP Database were searched for this review. The main observation indexes were the effect of DSP combined with mesalazine or DSP on the effective rate, platelet count (PLT), mean platelet volume (MPV) and C-reactive protein (CRP) of UC. The Cochrane risk of bias tool was used to assess the risk of bias. The selected studies were evaluated for quality and data processing using RevMan5.4 and Stata17.0 software. Results: A total of 37 studies were included. Among them, 26 clinical trials with 2426 patients were included and 11 animal experimental studies involving 208 animals were included. Meta-analysis results showed that compared with mesalazine alone, combined use of DSP can clearly improve the clinical effective rate (RR 0.86%, 95% CI:0.83-0.88, p < 0.00001) of UC. Furthermore it improved blood coagulation function by decreasing serum PLT and increasing MPV levels, and controlled inflammatory responses by reducing serum CRP, TNF-α, IL-6, and IL-8 levels in patients. Conclusion: Combining DSP with mesalazine for UC can enhance clinical efficacy. However, caution should be exercised in interpreting the results of this review due to its flaws, such as allocation concealment and uncertainty resulting from the blinding of the study. [ABSTRACT FROM AUTHOR]

Background: Diverticular disease (DD) represents a common gastrointestinal condition that poses a heavy burden on healthcare systems worldwide. A high degree of uncertainty surrounds the therapeutic approaches for the control of symptoms in patients with symptomatic uncomplicated diverticular disease (SUDD) and primary and secondary prevention of diverticulitis and its consequences. Objectives: To review the current knowledge and discuss the unmet needs regarding the management of SUDD and the prevention of acute diverticulitis. Eligibility criteria: Randomized trials, observational studies, and systematic reviews on lifestyle/dietary interventions and medical treatment (rifaximin, mesalazine, and probiotics) of SUDD or prevention of acute diverticulitis. Sources of evidence: The literature search was performed from inception to April 2023, without language restriction, following the modified Preferred Reporting Items for Systematic review and Meta-Analyses (PRISMA) reporting guidelines. References of the papers selected were checked to identify additional papers of potential interest. The final list of references was evaluated by a panel of experts, who were asked to check for any lack of relevant studies. Charting methods: Information on patient population, study design, intervention, control group, duration of the observation, and outcomes assessed was collected by two authors independently. Results: The review shows a high degree of uncertainty about therapeutic interventions, both dietary/lifestyle and pharmacological, in patients with SUDD, because of the scarcity and weakness of existing evidence. Available studies are generally of low quality, heterogeneous, and outdated, precluding the possibility to draw robust conclusions. Similarly, acute diverticulitis prevention has been seldom investigated, and there is a substantial lack of evidence supporting the role of dietary/lifestyle or pharmacological approaches to reduce the risk of diverticulitis. Conclusion: The lack of robust evidence regarding therapeutic options for gastrointestinal symptoms in SUDD patients and for primary and secondary prevention of acute diverticulitis remains an important unmet need in the management of DD. [ABSTRACT FROM AUTHOR]

Key Clinical Message: This case report describes the clinical course of a 64‐year‐old male with intermittent abdominal pain attributed to recurrent ulcers at the appendiceal orifice. Initial investigations in November 2019 revealed chronic gastritis and ulcers at the appendiceal orifice, prompting consideration of ulcerative colitis (UC). The patient responded well to mesalazine therapy, experiencing relief from symptoms and improved colonoscopy findings in May 2020. Despite discontinuing medication, a recurrence of symptoms in August 2021 led to a repeat colonoscopy showing renewed ulcers. Mesalazine was reinstated, resulting in symptom resolution and improved colonoscopy findings by December 2021. However, in May 2023, a subsequent recurrence of abdominal pain and colonoscopy‐confirmed mucosal changes at the appendiceal orifice prompted reintroduction of mesalazine. The patient remains under regular monitoring on mesalazine therapy. This case highlights the challenges in managing recurrent appendiceal ulcers and the importance of long‐term therapeutic vigilance in suspected UC cases. [ABSTRACT FROM AUTHOR]

Mesalazine represents a key treatment for intestinal bowel diseases and only in rare cases produces cardiac toxicity, with a not completely known mechanism. We report a case of a 25-year-old man with a first episode of myocarditis after 2 weeks from the first mesalazine intake, documented also by a characteristic cardiac magnetic resonance pattern. Then, after less than 1 month, he suffered myocarditis recurrence and so, guided by a multidisciplinary team evaluation, in the suspicion of mesalazine-induced myocarditis, the drug was promptly stopped, with consequent recovery of cardiac damage. In our patient, the recurrence of myocarditis because of the non-interruption of the drug is very peculiar (only three cases described in literature) and definitively confirms the diagnosis. This paper reports an exemplary case of cardiac toxicity induced by mesalazine, a key treatment for inflammatory bowel diseases such as Crohn's disease and ulcerative colitis. In rare cases, this drug can lead to cardiac impairment, with a mechanism not yet clarified. The young patient described experiencing a first episode of myocarditis (inflammation of the heart muscle cells) after 2 weeks of starting mesalazine. The diagnosis was possible thanks to cardiac magnetic resonance, a noninvasive exam providing high-definition images associated with tissue characterization. Mesalazine was not discontinued because drug-induced etiology was not suspected, due to its rarity. Consequently, the patient suffered a second episode of myocarditis, diagnosed by endomyocardial biopsy, an invasive technique that can accurately assess the etiology of myocardial damage, leading to prompt cessation of treatment. Since myocarditis can have various causes, diagnosis was also facilitated through a multidisciplinary team, which ruled out other possible causes for this condition. This case report is highly educational and underscores the importance of clinicians being vigilant about this side effect and considering it in patients taking mesalazine who present with myocarditis, to promptly discontinue the treatment. Mesalazine interruption is otherwise the only effective therapy for this condition, in addition to anti-inflammatory and analgesic drugs. Furthermore, this paper highlights the increasing importance of multidisciplinary teams, comprising various specialists, for accurate diagnosis and therapeutic decisions. The authors also propose an algorithm for diagnosing mesalazine-induced myocarditis, with certainty derived from recurrence after drug rechallenge, either voluntarily or accidentally, as demonstrated in this case. Article highlights 5-aminosalicylic acid (5-ASA) is an important treatment for inflammatory bowel diseases, and its cardiac toxicity is reported in 0.3% of cases. The mechanism of mesalazine-induced myocarditis is not completely understood. The clinical, instrumental, and laboratory presentation is similar to common forms of myocarditis (e.g., chest pain, troponin increase, electrocardiogram abnormalities). The use of imaging techniques is useful, particularly cardiac magnetic resonance, which has acquired increasing importance because of its potential for tissue characterization. The gold standard for confirming the diagnosis of myocarditis is endomyocardial biopsy, although a certain etiological definition is not always possible. The diagnosis of 5-ASA-induced myocarditis must be made first by ruling out other causes of myocarditis. Two main findings support the suspicion: clinical manifestation within 2–4 weeks after the first drug intake and improvement of the patient's condition immediately after discontinuation of therapy, which represents the only effective treatment for this condition. We report the case of a 25-year-old patient who experienced a first episode of myocarditis 2 weeks after the first mesalazine intake, with a characteristic cardiac magnetic resonance pattern. Then, after less than one month, he experienced myocarditis recurrence due to the non-interruption of 5-ASA. Endomyocardial biopsy, associated with laboratory tests, excluded other possible causes (e.g., infectious, autoimmune). Through multidisciplinary team evaluation, in suspicion of mesalazine-induced myocarditis, the drug was promptly stopped, leading to the recovery of cardiac damage. This case raises awareness about myocardial inflammation as a side effect of 5-ASA, and clinicians should always suspect this condition in patients taking this drug who present with cardiac impairment. In our patient, the recurrence of myocarditis due to the non-interruption of the drug is very peculiar (only 3 cases described in the literature) and definitively confirms the diagnosis, associated with the ex juvantibus criterion. In the end, we propose a diagnostic algorithm for 5-ASA-induced myocarditis; it starts from myocarditis diagnosis and exclusion of other possible causes, reaching progressive levels of likelihood by considering symptoms onset within 2–4 weeks of first drug intake (diagnosis possible), recovery after 5-ASA interruption (diagnosis likely) and myocarditis recurrence after rechallenging/non-stopping 5-ASA (diagnosis certain). [ABSTRACT FROM AUTHOR]

Objective: We took advantage of a single-center cross-sectional study to investigate the effect of different drugs on intestinal microbiota and function in Crohn’s disease. Methods: We studied the difference in fecal microbiota of Crohn’s disease patients treated with mesalazine, azathioprine, and infliximab, as well as untreated patients, by metagenome and screened for differential microbiota. Further, we investigated functional differences in intestinal microbiota among the four groups. Results: Through metagenomic sequencing, we found that there was no difference between the four groups in ACE and Chao1 indices, but IFX and mesalazine improved species diversity and homogeneity compared to the untreated group, as evidenced by statistically significant differences in the Shannon index, Simpson index, and pielou_evenness. In addition, beta diversity suggested a difference between groups, but the difference was not significant. Non-parametric tests revealed differences between the four groups at the phylum level, class level, and genus level. Further analysis by LEfSe analysis revealed that the level of short-chain fatty acid-producing microbiota was increased in the treated groups, while there was no difference between the treated groups when compared to each other. Finally, the KEGG database and EggNOG database revealed that there were functional differences in intestinal microbiota among the four groups, including microbial metabolism pathway, cysteine and methionine metabolism pathway, cytoskeleton, etc. Conclusions: Mesalazine, azathioprine, and infliximab can all affect the intestinal microbiota and function in patients with Crohn’s disease, and the drugs may alleviate intestinal inflammation in patients with Crohn’s disease by modulating the intestinal microbiota.

A key challenge for the effective treatment of intestinal diseases, including inflammatory bowel disease (IBD), is to develop an oral drug delivery system that can resist gastric acid erosion and efficiently release drugs after rapid entry into the intestine. In the present work, we developed oral composite nanoparticles (MSZ@PRHS) consisting of a rough mesoporous silica (RHS) loaded with Mesalazine (MSZ) and a CAP polymer membrane for targeted relief of inflammation in colitis. At the pH values of the simulated stomach and small intestine, the release rate of MSZ from MSZ@PRHS was low, while at the pH values of the simulated colon, the release rate of MSZ was high. In dextran sulfate sodium salt (DSS)-induced acute colitis mouse model, compared with oral administration of the drug Mesalazine in the equivalent solution form, oral administration of PRHS loaded with drug-loaded nanoparticles can significantly alleviate the symptoms of inflammatory bowel disease, and improve the therapeutic effect. We propose that the intestinal microenvironment provides an interface for nanocomposites switch and a promising drug delivery platform for the management and treatment of many intestinal diseases, where controlled drug release and prolonged residence time are required. [ABSTRACT FROM AUTHOR]

Herein, a metal–organic framework-derived NiS/Ni3S4 heterostructure embedded in N, S co-doped carbon (NiS/Ni3S4/NSC) was successfully prepared and applied in electrochemical detection of anti-inflammatory drug mesalazine (MSZ). The exposed sulfur atoms of the NiS/Ni3S4/NSC composite could efficiently recognize and trap MSZ targets through the S–π interaction. Meanwhile, the active metal centers of NiS/Ni3S4/NSC revealed a high-performance catalytic property for the oxidation of MSZ on the working electrode surface. The highly efficient adsorption and electrocatalytic abilities of the NiS/Ni3S4/NSC composite enhanced the electrochemical signals for MSZ detection. Markedly, the glassy carbon electrode modified by NiS/Ni3S4/NSC (NiS/Ni3S4/NSC/GCE) featured a low limit of detection (LOD, 4.4 nM) for the electrochemical analysis of MSZ in the 0.05–100 μM concentration range. Moreover, the sensor could avoid the interference of the coexisting species during detection of MSZ and also revealed satisfactory reproducibility, repeatability, and stability. Particularly, the NiS/Ni3S4/NSC/GCE sensor was used to monitor the contents of MSZ in practical drug, human serum, and urine samples with satisfactory recoveries. The remarkable performance demonstrated that the NiS/Ni3S4/NSC/GCE sensor could be a prospective candidate for the accurate detection of MSZ in the biomedical fields. [ABSTRACT FROM AUTHOR]

Objective: To investigate effects of mesalazine (MS) on proliferation, apoptosis and inflammatory injury of cell model of ulcerative colitis (UC) induced by lipopolysaccharide (LPS), as well as transforming growth factor-β1 (TGF-β)/Smad signaling pathway effect in this study. Methods: Human colonic epithelial cells NCM-460 cultured in vitro were induced UC model by LPS, and divided into Con group (no treatment, LPS group (l mg/L LPS, MS group (0.1, 0.2, 0.4 mg/L MS+1 mg/L LPS) and inhibitor group (10 µmol/L TGF-β1/Smad signaling pathway inhibitor LY2109761+0.2 mg/L MS+1 mg/L LPS). Cell morphology, proliferation, apoptosis and levels of inflammatory factors and TGF-β1/Smad pathway-related markers were examined by inverted microscope, EdU assay, Hoechst 33258 staining, ELISA and Western blot. Results: LPS treatment highly induced cell proliferation rate and Smad7 protein level compared with Con group, while apoptotic cells, inflammatory factors TNF-α and IL-6, soluble interleukin-2 receptor (sIL-2R) release, as well as TGF-β1, p-Smad2, p-Smad3 protein expressions were increased; the above effects induced by LPS was reversed by MS in a dose-dependent manner (P<0.05). Compared with 0.2 mg/L MS group, NCM-460 cells proliferation rate and Smad7 expression were increased, while apoptotic cells, TNF-α and IL-6, sIL-2R releases, and TGF-β1, p-Smad2, p-Smad3 protein expressions were decreased (P<0.05). Conclusion: MS can attenuate LPS-induced apoptosis and inflammatory injury in NCM-460 cells, and this protection was possibly through suppressing TGF-β1/Smad signaling pathway. [ABSTRACT FROM AUTHOR]

Objective To observe the clinical efficacy of acupuncture at Front Mu point in the treatment of ulcerative colitis. Methods Sixty patients with ulcerative colitis treated at the Traditional Chinese Medicine Hospital in Kunming from August 2022 to June 2023 were collected. Using a random number table method, 30 cases were assigned to each of the control group and the combined group. The treatment method involved administering oral mesalazine to the control group for a continuous period of 8 weeks, while the combined group received both oral mesalazine and acupuncture at front Mu points. The clinical efficacy, colonoscopy results score (Baron score), and colonic mucosal healing score (Geboes) before and after treatment were compared. Follow-up was conducted at 3 months to calculate the recurrence rate in the combination and control groups. Results The total effective rate in the combination group was higher than that in the control group (P < 0.05), with rates of 93.33% and 67.67%, respectively. After treatment, the disease activity index, Baron score, and Geboes score decreased compared to before treatment (P<0.05), and the combination group had a lower disease activity index, Baron score, and Geboes score than the control group after treatment (P<0.05). Comparing the recurrence rates at 3 months posttreatment, the combination group was lower than the control group. Conclusion Acupuncture at Front Mu Point can significantly improve the clinical symptoms of ulcerative colitis, reduce the recurrence rate compared to patients in the control group, and is safe and reliable without serious adverse reactions. [ABSTRACT FROM AUTHOR]

Chronic rhinosinusitis (CRS) is a disease characterised by the inflammation of the nasal and paranasal cavities. It is a widespread condition with considerable morbidity for patients. Current treatment for chronic rhinosinusitis consists of appropriate medical therapy followed by surgery in medically resistant patients. Although oral steroids are effective, they are associated with significant morbidity, and disease recurrence is common when discontinued. The development of additional steroid sparing therapies is therefore needed. Mesalazine is a commonly used therapeutic in inflammatory bowel disease, which shares a similar disease profile with chronic rhinosinusitis. This exploratory in vitro study aims to investigate whether mesalazine could be repurposed to a nasal wash, which is safe on human nasoepithelial cells, and retains its anti-inflammatory effects. CRS patients' human nasal epithelial cells (HNECs) were collected. HNECs were grown at an air-liquid interface (ALIs) and in a monolayer and challenged with mesalazine or a non-medicated control. Transepithelial electrical resistance, paracellular permeability, and toxicity were measured to assess epithelial integrity and safety. The anti-inflammatory effects of mesalazine on the release of interleukin (IL)-6 and tumour necrosis factor alpha (TNF-α) were analysed using human leukemia monocytic cell line (THP-1). mesalazine did not impact the barrier function of HNEC-ALIs and was not toxic when applied to HNECs or THP-1 cells at concentrations up to 20 mM. mesalazine at 0.5 and 1 mM concentrations significantly inhibited TNF-α release by THP-1 cells. mesalazine effectively decreases TNF-α secretion from THP-1 cells, indicating the possibility of its anti-inflammatory properties. The safety profile of mesalazine at doses up to 20 mM suggests that it is safe when applied topically on HNECs. [ABSTRACT FROM AUTHOR]

Background: Mesalazine, a preparation of 5-aminosalicylic acid, is a medication widely used in clinical practice as a first-line therapy in the treatment of mild and moderate inflammatory bowel disease. However, the long-term safety of mesalazine in large sample population was unknown. The current study was to assess mesalazine -related adverse events of real-world through data mining of the US Food and Drug Administration Adverse Event Reporting System (FAERS). Methods: Disproportionality analyses, including the reporting odds ratio (ROR), the proportional reporting ratio the Bayesian confidence propagation neural network and the multi-item gamma Poisson shrinker (MGPS) algorithms were employed to quantify the signals of mesalazine -associated AEs. Results: Out of 14,149,980 reports collected from the FDA Adverse Event Reporting System database, 24,284 reports of mesalazine -associated AEs were identified. A total of 170 significant disproportionality preferred terms conforming to the four algorithms simultaneously were retained. The most common AEs included colitis ulcerative, diarrhoea, condition aggravated, crohn's disease, fatigue, abdominal pain, nausea, haematochezia, which were corresponding to those reported in the specification and clinical trials. Unexpected significant AEs as dizziness, drug ineffective, drug hypersensitivity, infection, off label use, weight decreased, decreased appetite, arthralgia, rash might also occur. The median onset time of mesalazine -related AEs was 1,127 days (interquartile range [IQR] 1,127-1,674 days), and most of the cases occurred 2 years later (n = 610, 70.93%) and within the first 1 month (n = 89, 10.35%) after mesalazine initiation. Conclusion: Results of our study were consistent with clinical observations. We also found potential new and unexpected AEs signals for mesalazine, suggesting prospective clinical studies were needed to confirm these results and illustrate their relationship. Our results could provide valuable evidence for further safety studies of mesalazine. [ABSTRACT FROM AUTHOR]

Key Clinical Message This case report describes the clinical course of a 64‐year‐old male with intermittent abdominal pain attributed to recurrent ulcers at the appendiceal orifice. Initial investigations in November 2019 revealed chronic gastritis and ulcers at the appendiceal orifice, prompting consideration of ulcerative colitis (UC). The patient responded well to mesalazine therapy, experiencing relief from symptoms and improved colonoscopy findings in May 2020. Despite discontinuing medication, a recurrence of symptoms in August 2021 led to a repeat colonoscopy showing renewed ulcers. Mesalazine was reinstated, resulting in symptom resolution and improved colonoscopy findings by December 2021. However, in May 2023, a subsequent recurrence of abdominal pain and colonoscopy‐confirmed mucosal changes at the appendiceal orifice prompted reintroduction of mesalazine. The patient remains under regular monitoring on mesalazine therapy. This case highlights the challenges in managing recurrent appendiceal ulcers and the importance of long‐term therapeutic vigilance in suspected UC cases.

A novel green, straightforward, and precise spectrophotometric method for determination of mesalazine drug has been developed. This method relies on an oxidative coupling reaction between mesalazine and the environmentally friendly phenoxazine reagent in an acidic medium within the presence of potassium iodate as an oxidizing agent. The resulting colored product exhibits maximum absorbance at 549 nm. The calibration graph was rectilinear over the range of 0.2-30 µg mL-1 (1.31×10-6-1.96×10-4 mol L-1) with determination Coefficient (R2) of 0.9994 and molar absorptivity of 4.8×103 L mol-1 cm-1. The limits of detection and quantitation were found to be 0.191 and 0.638 µg mL-1, respectively. The average recovery percentage was 100.9 with a relative standard deviation less than 3.1. The proposed method was effectively applied to determine mesalazine in tablet dosage forms from three different sources, yielding highly satisfactory results that closely align with the standard method outlined in the British Pharmacopeia.

Abstract Background The introduction of biological drugs has led to great expectations and growing optimism in the possibility that this new therapeutic strategy could favourably change the natural history of Inflammatory Bowel Disease (IBD) and, in particular, that it could lead to a significant reduction in surgery in the short and long term. This study aims to assess the impact of biological versus conventional therapy on surgery-free survival time (from the diagnosis to the first bowel resection) and on the overall risk of surgery in patients with Crohn’s disease (CD) who were never with the surgical option. Methods This is a retrospective, double-arm study including CD patients treated with either biological or conventional therapy (mesalamine, immunomodulators, antibiotics, or steroids). All CD patients admitted at the GI Unit of the S. Salvatore Hospital (L’Aquila. Italy) and treated with biological therapy since 1998 were included in the biological arm. Data concerning the CD patients receiving a conventional therapy were retrospectively collected from our database. These patients were divided into a pre-1998 and post-1998 group. Our primary outcome was the evaluation of the surgery-free survival since CD diagnosis to the first bowel resection. Surgery-free time and event incidence rates were calculated and compared among all groups, both in the original population and in the propensity-matched population. Results Two hundred three CD patients (49 biological, 93 conventional post-1998, 61 conventional pre-1998) were included in the study. Kaplan-Meier survivorship estimate shows that patients in the biological arm had a longer surgery-free survival compared to those in the conventional arm (p = 0.03). However, after propensity matching analysis, conducted on 143 patients, no significant difference was found in surgery-free survival (p = 0.3). A sub-group analysis showed shorter surgery-free survival in patients on conventional therapy in the pre-biologic era only (p = 0.02; Hazard Ratio 2.9; CI 1.01–8.54) while no significant difference was found between the biologic and conventional post-biologic groups (p = 0.15; Hazard Ratio 2.1; CI 0.69–6.44). Conclusion This study shows that the introduction of biological therapy has only a slight impact on the eventual occurrence of surgery in CD patients over a long observation period. Nevertheless, biological therapy appears to delay the first intestinal resection.

Abstract Bickerstaff’s brainstem encephalitis is a rare autoimmune disorder that presents with ataxia, ophthalmoplegia, disturbance of consciousness and quadriplegia. A 45-year-old man with a history of ulcerative colitis (UC) taking mesalazine (5-aminosalicylic acid) visited the emergency room presenting with ataxia, ophthalmoplegia and a progressively worsening cognitive impairment. Cerebrospinal fluid analysis showed mild elevation in protein and white blood cell count and increased intracranial pressure. Anti-GQ1b autoantibodies were found positive in the patient’s serum and contrast-enhanced brain magnetic resonance imaging showed diffuse leptomeningeal enhancement and pontine lesions. Based on these findings and the patient’s clinical course and history, he was diagnosed with Bickerstaff’s brainstem encephalitis. Mesalazine was discontinued and high-dose steroid pulse therapy was started, followed by intravenous immunoglobulin, which resulted in gradual improvement of the neurologic symptoms. When an ulcerative colitis patient presents with progressive cognitive impairment, quadriplegia and disturbance of consciousness and gait, Bickerstaff brainstem encephalitis should be considered in the differential diagnosis and prompt immunotherapy may lead to favorable prognosis.

Background: The introduction of biological drugs has led to great expectations and growing optimism in the possibility that this new therapeutic strategy could favourably change the natural history of Inflammatory Bowel Disease (IBD) and, in particular, that it could lead to a significant reduction in surgery in the short and long term. This study aims to assess the impact of biological versus conventional therapy on surgery-free survival time (from the diagnosis to the first bowel resection) and on the overall risk of surgery in patients with Crohn's disease (CD) who were never with the surgical option. Methods: This is a retrospective, double-arm study including CD patients treated with either biological or conventional therapy (mesalamine, immunomodulators, antibiotics, or steroids). All CD patients admitted at the GI Unit of the S. Salvatore Hospital (L'Aquila. Italy) and treated with biological therapy since 1998 were included in the biological arm. Data concerning the CD patients receiving a conventional therapy were retrospectively collected from our database. These patients were divided into a pre-1998 and post-1998 group. Our primary outcome was the evaluation of the surgery-free survival since CD diagnosis to the first bowel resection. Surgery-free time and event incidence rates were calculated and compared among all groups, both in the original population and in the propensity-matched population. Results: Two hundred three CD patients (49 biological, 93 conventional post-1998, 61 conventional pre-1998) were included in the study. Kaplan-Meier survivorship estimate shows that patients in the biological arm had a longer surgery-free survival compared to those in the conventional arm (p = 0.03). However, after propensity matching analysis, conducted on 143 patients, no significant difference was found in surgery-free survival (p = 0.3). A sub-group analysis showed shorter surgery-free survival in patients on conventional therapy in the pre-biologic era only (p = 0.02; Hazard Ratio 2.9; CI 1.01–8.54) while no significant difference was found between the biologic and conventional post-biologic groups (p = 0.15; Hazard Ratio 2.1; CI 0.69–6.44). Conclusion: This study shows that the introduction of biological therapy has only a slight impact on the eventual occurrence of surgery in CD patients over a long observation period. Nevertheless, biological therapy appears to delay the first intestinal resection. [ABSTRACT FROM AUTHOR]

Background: Diverticular disease (DD) is a common condition in Western countries. The role of microbiota in the pathogenesis of DD and its related symptoms has been frequently postulated since most complications of this disease are bacteria‐driven and most therapies rely on microbiota modulation. Preliminary data showed fecal microbial imbalance in patients with DD, particularly when symptomatic, with an increase of pro‐inflammatory and potentially pathogenetic bacteria. In addition, bacterial metabolic markers can mirror specific pathways of the disease and may be even used for monitoring treatment effects. All treatments currently suggested for DD can affect microbiota structure and metabolome compositions. Purpose: Sparse evidence is available linking gut microbiota perturbations, diverticular disease pathophysiology, and symptom development. We aimed to summarize the available knowledge on gut microbiota evaluation in diverticular disease, with a focus on symptomatic uncomplicated DD, and the relative treatment strategies. [ABSTRACT FROM AUTHOR]

The active season of hibernators corresponds to rapid adiposity in preparation for the next hibernation season. We have previously shown that this dramatic increase in adipose mass is associated with metabolic inflammation similar to what is seen in obesity and metabolic disease. We next sought to determine whether curbing this inflammation at its source (i.e., the gut) would attenuate weight gain in fattening 13-lined ground squirrels (Ictidomys tridecemlineatus). We fed active yearling ground squirrels a diet containing the gut-specific nonsteroidal anti-inflammatory drug mesalazine (5-aminosalicylic acid) for 10 wk. Mesalazine treatment had slight effects on microbial community diversity in the cecum and colon. Not surprisingly, mesalazine treatment decreased inflammatory cytokine levels in the ileum and colon. Mesalazine also decreased proinflammatory and increased antiinflammatory cytokines in omental white adipose tissue (oWAT). Despite this, body mass was unaffected, and caloric intake increased in mesalazine-treated squirrels, mainly in males. Mass of the primary WAT depot, intra-abdominal WAT (iaWAT), or the highly metabolic oWAT were unaltered by treatment, as was adiposity index. Together, these results suggest that mesalazine treatment has some effects on adiposity in fattening ground squirrels, but this treatment needs to be modified to overcome the strong drive to fatten in this species. NEW & NOTEWORTHY Adiposity and obesity are caused, at least in part, by inflammation of metabolic tissues. Hibernators, like ground squirrels, undergo this same metabolic inflammation during their summer fattening period. We attempted to curb this inflammation, and thus fattening, using mesalazine. We found that mesalazine did curb the inflammation but did not affect fattening, likely due to the strong drive to fatten in hibernators. [ABSTRACT FROM AUTHOR]

The prevalence of ulcerative colitis (UC) in the Middle East is increasing, impacting the economic and healthcare burden. The management of patients with mild to moderate UC is still a challenge as several factors can affect optimal care, including drug choice, induction and maintenance dose, treatment optimization and de-escalation, therapy duration, monitoring, and safety profile. We conducted an expert consensus to standardize the management of patients with mild to moderate UC. Sixteen experts in inflammatory bowel diseases, through a well-established and accepted Delphi methodology, voted and approved eight statements in order to provide practical guidance to clinicians in the Middle East. [ABSTRACT FROM AUTHOR]

Bickerstaff's brainstem encephalitis is a rare autoimmune disorder that presents with ataxia, ophthalmoplegia, disturbance of consciousness and quadriplegia. A 45-year-old man with a history of ulcerative colitis (UC) taking mesalazine (5-aminosalicylic acid) visited the emergency room presenting with ataxia, ophthalmoplegia and a progressively worsening cognitive impairment. Cerebrospinal fluid analysis showed mild elevation in protein and white blood cell count and increased intracranial pressure. Anti-GQ1b autoantibodies were found positive in the patient's serum and contrast-enhanced brain magnetic resonance imaging showed diffuse leptomeningeal enhancement and pontine lesions. Based on these findings and the patient's clinical course and history, he was diagnosed with Bickerstaff's brainstem encephalitis. Mesalazine was discontinued and high-dose steroid pulse therapy was started, followed by intravenous immunoglobulin, which resulted in gradual improvement of the neurologic symptoms. When an ulcerative colitis patient presents with progressive cognitive impairment, quadriplegia and disturbance of consciousness and gait, Bickerstaff brainstem encephalitis should be considered in the differential diagnosis and prompt immunotherapy may lead to favorable prognosis. [ABSTRACT FROM AUTHOR]

Mesalazine is a drug used to treat ulcerative colitis and Crohn's disease, and is known to rarely cause lung injury. We show herein a unique case who developed this drug-induced injury. A 17-year-old boy presented with fever and anorexia after administration of mesalazine. Computed tomography showed extensive ground-glass opacities with peripheral distribution in both lungs. He had general weakness, but had no respiratory symptoms such as cough and dyspnea. With prednisolone, which is primarily aimed at controlling ulcerative colitis, the extensive opacity in both lungs were improved. All patients with this drug-induced lung injury reported to date have had respiratory symptoms, but this patient had no subjective respiratory symptoms and had no abnormalities in respiratory rate and oxyhaemoglobin saturation. Although very rare, we do believe that this clinical course will provide some suggestive information on treatment for patients with similar course in the future. [ABSTRACT FROM AUTHOR]

Michal Gorzkiewicz,1,2 Monika Marcinkowska,1 Maciej Studzian,3,4 Iwona Karwaciak,4,5 Lukasz Pulaski,3,4 Barbara Klajnert-Maculewicz1 1Department of General Biophysics, Faculty of Biology and Environmental Protection, University of Lodz, Lodz, Poland; 2Department of Molecular Medicine II, Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf, Germany; 3Department of Oncobiology and Epigenetics, Faculty of Biology and Environmental Protection, University of Lodz, Lodz, Poland; 4Laboratory of Transcriptional Regulation, Institute of Medical Biology PAS, Lodz, Poland; 5Laboratory of Epigenetics, Institute of Medical Biology PAS, Lodz, PolandCorrespondence: Michal Gorzkiewicz, Department of General Biophysics, Faculty of Biology and Environmental Protection, University of Lodz, 141/143 Pomorska Street, Lodz, 90-236, Poland, Tel +48 42 635 41 47, Email michal.gorzkiewicz@biol.uni.lodz.plBackground: Mesalazine is one of the main drugs used to treat inflammatory bowel diseases. However, its applicability is limited by its rapid inactivation and removal from the organism, as well as the need for its membrane transporter-dependent cellular uptake to exert therapeutic effect. The present study involved the development of an innovative nanocarrier, based on poly(amidoamine) (PAMAM) dendrimer of the 4th generation, to obtain higher concentrations of the drug in the intestinal epithelial cells, thus increasing its anti-inflammatory potential. The work involved synthesis and in vitro characterization of covalent PAMAM-mesalazine conjugate with succinic linker.Results: PAMAM-mesalazine conjugate was synthesized and characterized by 1H NMR, 13C NMR, FTIR and MALDI-TOF MS. This allowed to confirm the purity of the obtained compound and intermediates. Based on the analyses, it was found that ~45 drug molecules were successfully attached to one molecule of PAMAM dendrimer. The conjugate was then characterized in terms of hydrodynamic diameter, zeta potential, spectral properties, drug release from the carrier, as well as cellular uptake and cytotoxicity in two in vitro models of gastrointestinal epithelium (CaCo-2 and HT-29 human cell lines). Analyzing cellular parameters related to the specific mechanism of action of mesalazine (inhibition of NF-κB signaling, decrease in interleukin and prostaglandin synthesis, and ROS scavenging), we showed that such a dendrimer-based carrier may enhance cellular uptake of the drug, which translated into its improved anti-inflammatory efficacy.Conclusion: The use of PAMAM macromolecule as a carrier for mesalazine increases the bioavailability of the drug, ensuring enhanced cellular uptake and bypassing the need to utilize mesalazine-specific membrane transporters. All these characteristics translate into an improved anti-inflammatory activity of mesalazine in vitro. In conjunction with appropriately designed in vivo studies, such a compound may prove to be a promising alternative to the therapeutics currently used in inflammatory bowel diseases.Graphical Abstract: Keywords: PAMAM dendrimer, mesalazine, inflammatory bowel disease, drug delivery

Two straightforward, fast, easy, accurate, and sensitive spectrophotometric methods were developed to measure mesalazine either in its pure form or in tablet dosage form The proposed procedures, specifically, rely on a condensation reaction between mesalazine and aromatic aldehydes, (method A) and (method B), to produce yellow color Schiff's bases. For methods A and B, the concentration ranges where Beer's relationship was observed were 0.4–10 µg mL-1 with a limit of detection of 0.1070 µg mL-1 and a limit of quantification of 0.1323 µg mL-1, and 2–15 µg mL–1 with a limit of detection of 0.3244 µg mL–1 and 0.4010 µg mL–1, respectively. The recovery percentage was 97.82% to 102.1% and 98.15% to 99.91% for the two proposed methods. The proposed methods have been used successfully to determine mesalazine in their tablet formulations.

Determining the actual amounts of active ingredients in various pharmaceutical commercial forms is still receiving a lot of attention. Two flow injection analysis (FIA) methods were suggested for determination of mesalazine (MES) in pharmaceutical forms. Normal and reverse FIA systems (nFIA and rFIA) combined with UV-Vis spectrophotometric technique were used for the analysis. The methods involved using two mods of FIA systems for measuring a colored product result from coupling of MES with 2,2'-dihydroxybiphenyl after oxidized with sodium periodate in alkaline medium. The absorbance of the red colored dye was measured at maximum wavelength of 500 nm. The calibration graphs for MES were linear in the ranges 2.5-200 and 0.5-60 µg/mL with RSD of best than 3% for both methods respectively. Also the limits of detection were 1.2 and 0.2 µg/mL and limits of quantitation were 3.6 and 0.7 µg/mL of MSL for nFIA and rFIA systems respectively. All physical and chemical conditions of flow systems such as flow rate, reaction coil length and reagent concentrations were carefully studied. The proposed methods were applied for determining MES in four commercial tablets without any interferences.

Objectives: Myocardial infarction (MI) initiates a complex reparative response during which damaged cardiac muscle is replaced by connective tissue. While the initial repair is essential for survival, excessive fibrosis post‐MI is a primary contributor to progressive cardiac dysfunction, and ultimately heart failure. Currently, there are no approved drugs for the prevention or the reversal of cardiac fibrosis. Therefore, we tested the therapeutic potential of repurposed mesalazine as a post‐MI therapy, as distinct antifibrotic effects have recently been demonstrated. Methods: At 8 weeks of age, MI was induced in male C57BL/6J mice by LAD ligation. Mesalazine was administered orally at a dose of 100 μg/g body weight in drinking water. Fluid intake, weight development, and cardiac function were monitored for 28 days post intervention. Fibrosis parameters were assessed histologically and via qPCR. Results: Compared to controls, mesalazine treatment offered no survival benefit. However, no adverse effects on heart and kidney function and weight development were observed, either. While total cardiac fibrosis remained largely unaffected by mesalazine treatment, we found a distinct reduction of perivascular fibrosis alongside reduced cardiac collagen expression. Conclusions: Our findings warrant further studies on mesalazine as a potential add‐on therapy post‐MI, as perivascular fibrosis development was successfully prevented. [ABSTRACT FROM AUTHOR]

Two straightforward, fast, easy, accurate, and sensitive spectrophotometric methods were developed to measure mesalazine either in its pure form or in tablet dosage form The proposed procedures, specifically, rely on a condensation reaction between mesalazine and aromatic aldehydes, (method A) and (method B), to produce yellow color Schiff's bases. For methods A and B, the concentration ranges where Beer's relationship was observed were 0.4-10 μg mL-1 with a limit of detection of 0.1070 μg mL-1 and a limit of quantification of 0.1323 μg mL-1, and 2-15 μg mL-1 with a limit of detection of 0.3244 μg mL-1 and 0.4010 μg mL-1, respectively. The recovery percentage was 97.82% to 102.1% and 98.15% to 99.91% for the two proposed methods. The proposed methods have been used successfully to determine mesalazine in their tablet formulations. [ABSTRACT FROM AUTHOR]

Background Inflammatory bowel diseases (IBD) are characterized by chronic inflammation of the gastrointestinal tract but can have multiorgan involvement. Mesalazine (5-ASA) is a key therapeutic agent in IBD. Mesalazine has rare but potentially life-threatening side effects such as cardiac injury. Case summary We present two cases of myopericarditis, documented also with cardiac magnetic resonance, that we attributed to 5-ASA hypersensitivity: the first is a young woman with ulcerative colitis who developed myopericarditis after the initiation of 5-ASA, with a good clinical response after discontinuation; the second is a 79-year-old man who developed symptoms of heart failure after the diagnosis of IBD and the introduction of 5-ASA. Discussion Mesalazine may cause rare but potentially life-threatening cardiac injury, which can be difficult to distinguish from acute IBD-induced cardiac inflammation. [ABSTRACT FROM AUTHOR]

Chemoprevention is one of the ways to fight colorectal cancer, which is a huge challenge in oncology. Numerous pieces of evidence indicate that chronic inflammation in the course of Crohn's disease or ulcerative colitis (UC) is a significant cancer risk factor. Epidemiologic studies suggest that long-term use of non-steroidal anti-inflammatory drugs (NSAIDs), including mesalazine, has beneficial effects on colitis-associated colorectal cancer. Mesalazine is a first-line therapy for UC and is also widely used for maintaining remission in UC. Data showed that mesalazine has antiproliferative properties associated with cyclooxygenase (COX) inhibition but can also act through COX-independent pathways. This review summarizes knowledge about mesalazine's molecular mechanisms of action and chemopreventive effect by which it could interfere with colorectal cancer cell proliferation and survival. [ABSTRACT FROM AUTHOR]

Amyloid formation due to protein aggregation is associated with several amyloid diseases (amyloidosis). The use of small organic ligands as inhibitors of protein aggregation is an attractive strategy for the treatment of these diseases. In the present study, we evaluated the in vitro inhibitory and destabilizing effects of Mesalazine on human insulin fibrillation. To induce fibrillation, human insulin was incubated in 50 mM glycine buffer (pH 2.0) at 50 °C. The effect of Mesalazine on insulin amyloid aggregation was studied using spectroscopic, imaging, and computational approaches. Based on the results, the Mesalazine in a concentration-dependent manner (different ratios (1:0.1, 1:0.5, 1:1, and 1:5) of the insulin to Mesalazine) prevented the formation of amyloid fibrils and destabilized pre-formed fibrils. In addition, our molecular docking study confirmed the binding of Mesalazine to insulin through hydrogen bonds and hydrophobic interactions. Our findings suggest that Mesalazine may have therapeutic potential in the prevention of insulin amyloidosis and localized amyloidosis. [ABSTRACT FROM AUTHOR]

Abstract Objectives Myocardial infarction (MI) initiates a complex reparative response during which damaged cardiac muscle is replaced by connective tissue. While the initial repair is essential for survival, excessive fibrosis post‐MI is a primary contributor to progressive cardiac dysfunction, and ultimately heart failure. Currently, there are no approved drugs for the prevention or the reversal of cardiac fibrosis. Therefore, we tested the therapeutic potential of repurposed mesalazine as a post‐MI therapy, as distinct antifibrotic effects have recently been demonstrated. Methods At 8 weeks of age, MI was induced in male C57BL/6J mice by LAD ligation. Mesalazine was administered orally at a dose of 100 μg/g body weight in drinking water. Fluid intake, weight development, and cardiac function were monitored for 28 days post intervention. Fibrosis parameters were assessed histologically and via qPCR. Results Compared to controls, mesalazine treatment offered no survival benefit. However, no adverse effects on heart and kidney function and weight development were observed, either. While total cardiac fibrosis remained largely unaffected by mesalazine treatment, we found a distinct reduction of perivascular fibrosis alongside reduced cardiac collagen expression. Conclusions Our findings warrant further studies on mesalazine as a potential add‐on therapy post‐MI, as perivascular fibrosis development was successfully prevented.

Neonatal anemia is an important cause of newborn morbimortality. Its causes fall into three categories: hemorrhagic, hemolytic or hypoplastic. Prompt recognition and acute care are crucial for good outcomes. Its etiological investigation is also essential to prevent further complications for the newborn and its mother. We report a case of a full-term neonate born after an uneventful pregnancy of a mother with a significant medical history of ulcerative colitis under mesalazine treatment. He was delivered by an emergency c-section for a non-reassuring fetal status with an Apgar score of 5-8-9. Investigation revealed severe neonatal anemia with high reticulocyte count and a positive Kleihauer-Betke test. After an effective blood transfusion, he was discharged home under iron supplementation and later reevaluations showed normalization of blood parameters and regular growth and neurodevelopment. Many causes of neonatal anemia have been described. The presence of fetal erythrocytes in maternal blood occurs in nearly all term pregnancies, but massive fetomaternal hemorrhage occurs only in 0.5% of cases. Active inflammatory bowel disease is also associated with adverse pregnancy outcomes and, in recent years, mesalazine, one of its main treatments, has been linked to neonatal anemia and hydrops fetalis. Regardless of the patient’s clinical presentation and predicted anemia etiology, we highlight the importance of identifying and acting on further possible causes.

COVID-19 infection may present with gastrointestinal lesions in up to 25% of patients. One of the target organs of the SARS-CoV-2 virus is the intestine. The pathogenesis of intestinal damage in a new coronavirus infection remains unclear and requires further in-depth study. Possible mechanisms include a direct cytotoxic effect of the virus, a persistent reduction in butyrate-producing bacteria, side effects of drugs, Clostridioides difficile infection, microvascular thrombosis, and the immune-mediated inflammatory reactions in the intestine. The most common symptom of intestinal damage during coronavirus infection, both in the acute phase and in the post-COVID period, is diarrhea. The impact of many aggressive factors on the intestines can form both long-term functional disorders and be the cause of the onset of organic diseases. Treatment should be aimed at possible causes of intestinal damage (Clostridioides difficile), as well as reducing inflammation, restoring intestinal permeability, cytoprotection of mucosal cells, replenishing butyric acid deficiency. When choosing a therapy for intestinal disorders, preference should be given to drugs with a pleiotropic effect in order to influence various possible pathogenetic mechanisms.

Resumen: Introducción y objetivos: Los 5-aminosalicilatos, principalmente la mesalazina, es la primera opción de tratamiento para la colitis ulcerosa crónica idiopática (CUCI) con actividad de leve a moderada. Con la nueva formulación de mesalazina multimatrix (MMX) se observan altas tasas de inducción y mantenimiento de la remisión clínica, principalmente en pacientes con enfermedad distal. Nuestro objetivo es describir la experiencia de la vida real en pacientes con CUCI y mesalazina MMX en dos hospitales de tercer nivel. Material y métodos: Es un estudio de cohorte retrospectivo donde participaron un total de 142 pacientes con diagnóstico confirmado de CUCI los cuales se analizaron en tres grupos de estudio: 1) Mesalazina MMX vía oral en monoterapia para inducción a la remisión. 2) Mesalazina MMX vía oral en monoterapia para mantenimiento de la remisión y grupo. 3) Inducción a la remisión con mesalazina MMX vía oral y terapia tópica. Resultados: En el grupo 1 se presentó una frecuencia de inducción a la remisión clínica del 80.3% con 74.2% de remisión bioquímica. En el grupo 2 se mantuvo la remisión clínica y bioquímica en el 100%. En el grupo 3 la frecuencia de inducción a la remisión clínica fue del 88.6% y 85.7% de remisión bioquímica, con un 87.3% de suspensión de terapia tópica al final del seguimiento. No se documentó ningún efecto adverso. Conclusiones: Se presentaron altos porcentajes de remisión clínica y bioquímica en ambos grupos de estudio, con suspensión de terapia tópica en la mayoría de los pacientes en un corto tiempo de seguimiento. Abstract: Introduction and aims: The 5-aminosalicylates, especially mesalazine, are the first option in the treatment of mild-to-moderate ulcerative colitis (UC). High rates of remission induction and maintenance have been observed with the new multimatrix (MMX) mesalazine formulation, mainly in patients with distal disease. Our aim was to describe the real-world experience with MMX mesalazine in patients with UC at two tertiary care centers. Materials and methods: A retrospective cohort study was conducted that included 142 patients with confirmed UC diagnosis, analyzed in three study groups: 1) oral MMX mesalazine as monotherapy for remission induction, 2) oral MMX mesalazine as monotherapy for remission maintenance, and 3) oral MMX mesalazine plus topical therapy for remission induction. Results: The frequency of clinical remission induction in group 1 was 80.3%, with biochemical remission of 74.2%. Group 2 had 100% clinical and biochemical remission maintenance. The frequency of clinical remission induction in group 3 was 88.6%, biochemical remission was 85.7%, and topical therapy was suspended in 87.3% at the end of follow-up. No adverse events were documented. Conclusions: There were high percentages of clinical and biochemical remission in the two corresponding study groups and topical therapy was suspended in the majority of patients in a short follow-up period.