Search

AbstractAim(s)MethodsResultsConclusionThis article explores the application of mesalazine-loaded nanoparticles (MLZ-NPs) encapsulated in Abelmoschus esculentus plant polysaccharide-based pellets (MLZ-NPs-Pellets) for ulcerative colitis.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.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.MLZ-NPs-Pellets can be effectively used for microbial-triggered colon targeting approach in treating ulcerative colitis. [ABSTRACT FROM AUTHOR]

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]

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]

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]

Mesalazine, often referred to as mesalamine or 5-aminosalicylic acid (5-ASA), and its derivatives are some of the first medications to be approved for treating digestive tract inflammations, including ulcerative colitis and mild to moderate Crohn’s disease. Sulfasalazine, discovered in 1938 for therapeutic use, was the first mesalazine derivative. High yields of four different mesalazine derivatives were synthesized, including two Schiff bases and two azo compounds. The present study involved the synthesis of Schiff bases through the reaction of mesalazine with pyrrole-2-carbaldehyde or indole-2-carbaldehyde, resulting in the formation of 5-(((1H-pyrrol-2-yl)methylene)amino)-2-hydroxybenzoic acid (1) or 5-(((1H-indol-2-yl)methylene)amino)-2hydroxybenzoic acid (2), respectively. The synthesis of azo compounds involved the coupling of mesalazine with sulfamethoxazole or pyridoxine, resulting in the formation of 5-amino-2-hydroxy-3-((4-(N-(5-methylisoxazol-3-yl)sulfamoyl)phenyl)diazenyl)benzoic acid (3) or 2-hydroxy-5-((5-hydroxy-3,4-bis(hydroxymethyl)-6-methylpyridin-2-yl)diazenyl)benzoic acid (4), respectively. The identification of the synthesized compounds was carried out using IR and 1H-NMR spectroscopy. Antibacterial assessment of the synthetic compounds was performed in vitro against gram-negative bacteria (such as Escherichia coli and Pseudomonas aeruginosa) and gram-positive bacteria (Staphylococcus aureus). The antibacterial activity studies demonstrated that against Escherichia coli and Staphylococcus aureus, the Schiff base compounds are more active than azo compounds. Compound 1 showed the highest activity, resulting in a 23 mm inhibition zone against E. coli at 1000 ug/mL. In contrast, the antibacterial activity of compound 2 was observed to be 25 mm against S. aureus at the same highest concentration.

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

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]

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.

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]

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 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.

Background: Mesalazine is among the medications most prescribed by gastroenterologists, with variable and controversial use in different settings. We aimed to explore the use of mesalazine in the clinical practice of young gastroenterologists. Methods: A web-based electronic survey was distributed to all participants of the National Meeting of the Italian Young Gastroenterologist and Endoscopist Association. Results: A total of 101 participants took part in the survey, with a majority (54.4%) being aged >30 years, 63.4% of whom were trainees in academic hospitals, and 69.3% of whom were involved in the clinical management of inflammatory bowel disease (IBD). While both non-dedicated and IBD physicians generally agreed on the appropriate dose of mesalazine for mild ulcerative colitis (UC), significant differences were observed between the two groups for moderate-severe ulcerative colitis (UC). Additionally, in IBD patients who were starting immuno-modulators and/or biologics, 80% of IBD-dedicated physicians continued to prescribe mesalazine, compared to 45.2% of non-dedicated physicians (p = 0.002). Indeed, 48.4% of non-dedicated IBD physicians did not acknowledge mesalazine for colorectal cancer chemoprevention. With regards to Crohn's disease, it is mainly used by 30.1% of IBD physicians for preventing postoperative recurrence of Crohn's disease. Finally, 57.4% used mesalazine for symptomatic uncomplicated diverticular disease, and 84.2% did not recommend its use for irritable bowel syndrome. Conclusions: This survey showed heterogeneous behaviors in the daily use of mesalazine, mainly in the management of IBD. Educational programs and novel studies are needed to clarify its use. [ABSTRACT FROM AUTHOR]

Background: Two major types of 5-aminosalicylic acid (5-ASA)-containing preparations, namely, mesalazine/5-ASA and sulfasalazine (SASP), are currently used as first-line therapy for ulcerative colitis. Recent reports show that optimization of 5-ASA therapy is beneficial for both patient outcomes and healthcare costs. Although 5-ASA and SASP have good efficacy and safety profiles, clinicians occasionally encounter patients who develop 5-ASA intolerance. Summary: The most common symptoms of acute 5-ASA intolerance syndrome are exacerbation of diarrhea, fever, and abdominal pain. Patients who discontinue 5-ASA therapy because of intolerance have a higher risk of adverse clinical outcomes, such as hospital admission, colectomy, need for advanced therapies, and loss of response to anti-tumor necrosis factor (TNF) biologics. When patients develop symptoms of 5-ASA intolerance, the clinician should consider changing the type of 5-ASA preparation. Recent genome-wide association studies and meta-analyses have shown that 5-ASA allergy is associated with certain single-nucleotide polymorphisms. Although there are no modalities or biomarkers for diagnosing 5-ASA intolerance, the drug-induced lymphocyte stimulation test can be used to assist in the diagnosis of acute 5-ASA intolerance syndrome with high specificity and low sensitivity. This review presents a general overview of 5-ASA and SASP in the treatment of inflammatory bowel disease and discusses the latest insights into 5-ASA intolerance. Key Messages: 5-ASA is used as first-line therapy for ulcerative colitis. Optimization of 5-ASA may be beneficial for patient outcomes and healthcare systems. Acute 5-ASA intolerance syndrome is characterized by diarrhea, fever, and abdominal pain. Periodic renal function monitoring is recommended for patients receiving 5-ASA. [ABSTRACT FROM AUTHOR]

A sensitive, quick and easy visible spectrophotometry method has been developed for the determination of a widely used anti-inflammatory drug Mesalazine (MSZ) in pure form as well as in pharmaceutical preparations. In this method, oxidation of MSZ was accompanied by the reduction of Fe(III) to Fe(II) and further complexation of Fe(II) with DMG and pyridine instantly in a pH range of 6 – 8. The resultant complex was imperial red in color that could be easily seen with naked eye, spectrophotometrically showing maximum absorption at 515 nm. To achieve the maximum intensity of absorption, different variables affecting the reaction were studied and optimum conditions were established. Linear relationship was found between the absorbance and drug concentration over a range of 0.2 – 1.6 μg/mL with a correlation coefficient (r) of 0.998. The limit of detection (LOD) and limit of quantification (LOQ) were found to be 0.769 and 2.332 μg/mL, respectively. Statistical results obtained by the proposed method and reported methods were compared by t-test and F-test, which showed good agreement in both accuracy and precision. Spectrofluorimetric studies using the proposed method gave information about changes in the fluorescent behaviour of MSZ before and after oxidation. Cyclic voltammetry studies have also been done for understanding the electrochemical behavior of reactions involved. The proposed method has been successfully applied to the quantification of MSZ in pure form and pharmaceutical compositions. [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 Background Ulcerative colitis (UC) is an idiopathic inflammatory bowel disease that limits to colon mucosa, which characterised by relapsing and remitting abdominal pain and diarrhea. Neurological complications in UC patients are usually underestimated. The most frequently reported neurological disorders associated with UC are peripheral neuropathy, cerebrovascular disease and demyelinating disease. However, acute transverse myelitis (TM) is rarely reported in UC patients. Case presentation We report a case of a 39-year-old man presented with fatigue, muscle weakness, numbness in the lower limbs and fingers with underlying UC. Laboratory results revealed elevated neutrophil count, high-sensitivity C-reactive protein and erythrocyte sedimentation rate. Strip-shaped high signal intensity was identified in the cervical and thoracic spinal cord on T2-weighted magnetic resonance imaging. Acute TM was diagnosed. Significant improvements after intravenous high-dose methylprednisolone were observed. Conclusion We speculate that acute TM may be the extraintestinal manifestation of UC, which may be related to the abnormalities of cell-mediated and humoral immunity rather than the side effect of mesalazine.

Copyright of Farmacia is the property of Societatea de Stiinte Farmaceutice Romania and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

• Solubility study of mesalazine in ternary mixture of ethanol, propylene glycol, and water at different temperatures. • Correlation/back-calculation of the solubility data by some mathematical models. • Calculation of thermodynamic parameters by using the van't Hoff and Gibbs equations. Mesalazine is a low-permeable and low-soluble drug, which makes it a class IV drug in the Biopharmaceutics Classification System. Hence, its solubilization can be helpful for various stages of formulation development. The purpose of this study was to investigate the solubilization manner and thermodynamics of mesalazine in ternary solvent combinations of {ethanol (1) + propylene glycol (2) + water (3)} using the shake-flask technique at (298.2–313.2) K. In the following, the mathematical representation of the acquired solubility data using some popular models was evaluated. The accuracies of the applied models were described by percentages of mean relative deviation (MRD%). Based on obtained results (MRD % < 10.0), it can be concluded that the trained models can adequately predict the solubility of mesalazine in the investigated ternary solvent combinations. The findings also revealed that the solution composition and temperatures greatly influence the solubility of mesalazine. In addition, the thermodynamic characteristics of the mesalazine dissolution process indicate that the mesalazine dissolution process is endothermic and entropy-driven. The generating data in the current work also expands the available solubility database for mesalazine in the solvent mixtures. [ABSTRACT FROM AUTHOR]

Targeted drug delivery systems into the colon to cure different local diseases like ulcerative colitis, cancer, and irritable bowel diseases have gained attention. These drug delivery systems are more effective for local inflammation and have limited side effects. The purpose of the present study is to formulate a controlled-release system of mesalazine, an anti-inflammatory agent by fluidized bed coating. The formulation was prepared using hydroxyl propyl methylcellulose as sustained delivery and cellulose acetate phthalate for enteric-coated behavior. The prepared granules were evaluated for particles size, moisture content, friability, dissolution test. The granules made with wet granulation had a suitable size and free flowability with carr's index lower than 20. It was concluded that the prepared granules could be successfully formulated with the use of release retarding polymers. The formulation showed appropriate release retardation of the drug, indicating the potential of a delivery system. A further investigation like capsule preparation and microbial count examination is needed for better evaluation of the formulation. Please cite this article as: Sanaz Mehdi-alamdarlou, Negin Mozafari, Saeid Daneshamouz, Hajar Ashrafi. Preparation and in vitro evaluation of controlled release granules of mesalazine for colon targeted drug delivery system. Trends in Pharmaceutical Sciences. 2022;8(1):37-42 .doi: 10.30476/TIPS.2021.92954.1116

Background and Objective: Irritable bowel syndrome is one of the common gastrointestinal complaints that is often resistant to standard treatment. Since mesalazine reduces abdominal pain and diarrhea through its anti-inflammatory effects, this study was conducted to investigate the effect of mesalazine on pain management in patients with diarrhea-predominant irritable bowel syndrome (IBS-D). Methods: This case-control study was conducted among 100 patients diagnosed with diarrhea-predominant irritable bowel syndrome referred to Ayatollah Rouhani Hospital in Babol. Patients were randomly divided into two groups of 50, receiving standard treatment (amitriptyline 25 mg) and a group that received mesalazine at a dose of 500 mg for 4 weeks three times a day in addition to standard treatment. Subjects were examined and compared in terms of pain intensity and frequency of discharge and recovery. Findings: The intensity of pain after treatment in the case group was lower than before treatment (4.66±2.29 vs. 7.80±2.01) (p=0.004). Out of 50 patients, 38 people (76.0%) in the case group and only 20 people (40%) in the control group recovered (p

Background: Nonspecific terminal ileal ulcers are one of the common ulcerative diseases in terminal ileum. However, the studies about treatment efficacy are scarce. We aimed to investigate the efficacy of mesalazine in the treatment of this disease. Methods: Eighty-two patients with nonspecific terminal ileal ulcers who sought outpatient medical treatment in the Division of Gastroenterology, Wuhan Union Hospital, from April 2016 to January 2019 were enrolled and randomly divided into two groups. The experimental group took mesalazine orally, 4.0 g/d, once a day for 3 months. The control group was followed up without special intervention. The primary endpoint was the endoscopic remission rate at the 6th and 12th month. Secondary endpoints included the clinical remission rate at the 1st, 6th and 12th month and adverse events (ChiCTR1900027503). Results: About the endoscopic efficacy, the remission rate of the experimental group and control group was 73.2 versus 61.0% at the 6th month (RR = 1.20, 95% CI 0.88~1.63, p = 0.24) and 87.8 versus 78.0% at the 12th month (RR = 1.13, 95% CI 0.92~1.37, p = 0.24). About the clinical efficacy, the remission rate was 70.3 versus 43.8% at the 1st month (RR = 1.61, 95%CI 1.03~2.51, p = 0.03), 83.8 versus 68.8% at the 6th month (RR = 1.22, 95%CI 0.93~1.60, p = 0.14) and 91.9 versus 81.3% at the 12th month (RR = 1.13, 95%CI 0.93~1.37, p = 0.34). During follow-up, no patients were diagnosed with Crohn's disease or intestinal tuberculosis, and no patients developed significant complications. Conclusion: For patients with nonspecific terminal ileal ulcers, there is no disease progression over a short term. In addition, there is no significant difference in clinical or endoscopic efficacy between patients who received mesalazine and patients who are followed up without special intervention. [ABSTRACT FROM AUTHOR]

Background: Mesalazine is the first-line inflammatory bowel disease (IBD) treatment. However, it can cause fatal cardiotoxicity. We aimed to analyze the clinical characteristics of mesalazine-induced cardiotoxicity and provide evidence for clinical diagnosis, treatment, and prevention. Methods: We collected Chinese and English literature on mesalazine-induced cardiotoxicity from 1970 to 2021 for retrospective analysis. Results: A total of 52 patients (40 males and 12 females) were included, with a median age of 24.5 years (range 9-62) and a median onset time of 14 days (range 2-2880). Cardiotoxicity manifested as myocarditis, pericarditis, and cardiac pericarditis. The main clinical manifestations are chest pain (82.7%), fever (46.2%), and respiratory symptoms such as dyspnea and cough (40.4%). The levels of troponin T, creatine kinase, C-reactive protein, leukocyte count, erythrocyte sedimentation rate, and other biochemical markers were significantly increased. Cardiac imaging often suggests myocardial infarction, pericardial effusion, myocardial necrosis, and other symptoms of cardiac injury. It is essential to discontinue mesalamine immediately in patients with cardiotoxicity. Although corticosteroids are a standard treatment option, the benefits remain to be determined. Re-challenge of mesalamine should be carefully considered as cardiotoxic symptoms may reoccur. Conclusion: Mesalazine may cause cardiotoxicity in patients with inflammatory bowel disease, which should be comprehensively diagnosed based on clinical manifestations, biochemical indicators, and cardiac function imaging examinations. Mesalazine should be immediately discontinued, and corticosteroids may be an effective treatment for cardiotoxicity. [ABSTRACT FROM AUTHOR]

Copyright of Farmacia is the property of Societatea de Stiinte Farmaceutice Romania and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: Various systemic agents have been assessed for treatment of alopecia areata; however, there is a paucity of comparative studies. Aim: To compare the efficacy of azathioprine versus mesalazine in the treatment of severe alopecia areata. Methods: Our study was carried out in 30 patients with severe alopecia areata divided into two groups, group A: fifteen patients were treated by azathioprine in an oral dose of 1–2 mg/kg/day and group B: fifteen patients were treated by mesalazine in an oral dose of 15–30 mg/kg/day in two divided doses. The treatment was considered effective if percentage regrowth of hair was determined by change in SALT score >50 from base line after 6 months of treatment. The treatment was continued for 3–6 months after complete remission to minimize the risk of relapse. The dose was gradually tapered during this time. Results: The study found that there is statistically significant difference between mean SALT scores before treatment and after 6 months of treatment in both groups. In group A, SALT score at base line was 84.42 ± 17.41, after 6 months it was 35.95 ± 35.79 (p value 0.04). In group B, SALT score at base line was 73.06 ± 22.10, after 6 months it was 23.04± 12.27 (p value 0.037). Changes in SALT score after 6 months were −27.74 ± 20.66 in group A and −60.42±38.41 in group B (p value 0.055). Conclusion: Mesalazine may be considered as effective as azathioprine with lesser side effects. Azathioprine is also considered safe. However, a large group study should be performed to confirm these findings. [ABSTRACT FROM AUTHOR]

The aim is to unravel the mechanism of mesalazine (5-ASA) on proinflammatory cytokines in PBMCs of patients with HLA-B27 +and HLA-B27 -acute anterior uveitis (AAU), and whether this may explain the different effects of 5-ASA in both disoders. PBMCs from 12 HLA-B27+ and 4 HLA-B27- AAU patients were preincubated with 5-ASA and stimulated with LPS. As mesalazine (5-ASA) could be involved in ER stress, proinflammatory and ER stress-associated cytokines and markers were measured. Mesalazine (5-ASA) suppressed IL-6 mRNA in healthy donors and in HLA-B27+ and HLA-B27- patients but did not lead to induction and secretion of IL-1β. In HLA-B27 + or – patients the ER stress-associated markers CHOP (DDIT3) and ATF6 were suppressed. Here we show that mesalazine (5-ASA) inhibits the transcription of proinflammatory and (ER) stress associated cytokines and markers, independently of the HLA-B27 status. Results show the similarities of both AAU types but do not decipher the mechanism why the HLA-B27 status determines the therapeutic response to mesalazine in AAU. [ABSTRACT FROM AUTHOR]

Myocarditis is a rare extra-intestinal complication of inflammatory bowel disease (IBD), in particular, ulcerative colitis. We report a case of acute myocarditis as first manifestation of severe ulcerative colitis. A 22-year-old man was admitted with fever, bloody diarrhea, and fatigue. He had suffered from frequent bloody diarrhea, abdominal pain, fatigue, and weight loss for one month. A 12-lead-electrocardiogram showed sinus rhythm with QRS fragmentation and T waves inversion. High sensitivity troponin-I was elevated and the echocardiogram showed a mild pericardial effusion and inferior hypokinesia with normal ejection fraction. Cardiac magnetic resonance disclosed late enhancement in the inferior wall, corroborating the hypothesis of myocarditis. One week later, a colonoscopy revealed severe ulcerative extensive colitis (Mayo subscore 3). 5-aminosalicylic acid (mesalazine) and systemic steroid were started with good clinical and biochemical response. The following days the patient developed mesalazine hepatic and pancreatic induced toxicity requiring drug discontinuation and strict multi-disciplinary follow-up. At 7 months follow-up intestinal symptoms were well controlled with complete normalization of liver and pancreatic enzymes. Transthoracic echocardiography showed normal biventricular function and pericardial effusion resolution. This case underscores the importance of a high suspicion for extra intestinal involvement in patients with IBD. These complications may be multifactorial and need multidisciplinary management. • When a patient was first-time diagnosed with a severe form of inflammatory bowel disease or has a disease relapse, bear in mind myocarditis as possible extra intestinal manifestation. • Multidisciplinary management is crucial to ensure the best level of care and follow-up in a such challenging and insidious clinical picture. [ABSTRACT FROM AUTHOR]

Aim: Colorectal cancer is an extremely aggressive form of cancer that often leads to death. Lactoferrin shows potential for targeting and treating colorectal cancer; however, oral delivery faces hurdles hampering clinical applications. We engineered dual-responsive lactoferrin nanostructured microbeads to overcome delivery hurdles and enhance drug targeting., Methods: The hydrophobic drug mesalazine (MSZ) was coupled to lactoferrin to form amphiphilic conjugate nanoparticles, dispersed in water. The lipid-soluble polyphenolic drug resveratrol (RSV) was then encapsulated into the hydrophobic core of LF-MSZ nanoparticles. To impart thermoresponsive properties, the dual-payload NPs were coupled with a PNIPAAm shell; finally, to further endow the nanoparticles with gastrointestinal resistance and pH responsiveness, the nanoparticles were microencapsulated into ionically cross-linked pectin-alginate beads., Results: The nanoparticles showed enhanced internalization and cytotoxicity against HCT colon cancer cells via LF-receptor-mediated endocytosis. Thermal triggering and tuned release were conferred by the temperature-sensitive polymer. The coatings protected the drugs from degradation. Orally delivered microbeads significantly reduced tumor burden in a mouse colon cancer model, lowering carcinoembryonic antigen and elevating antioxidant enzymes. Apoptotic pathways were stimulated, indicated by heightened Bax/Bcl2 ratio and caspase-3/9 expression., Conclusion: Overall, we propose the innovative lactoferrin nanostructured microbeads as a paradigm shift in oral colorectal cancer therapeutics.

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., Competing Interests: Declaration of competing interest This work was funded by University College London Research Excellence Scholarship and the University College London Centre for Digital Innovation Scholarship (Youssef Abdalla)., (Copyright © 2024. Published by Elsevier B.V.)