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A dioxomolybdenum(VI) complex has been successfully prepared by the reaction of an ONO donor Schiff base, derived by condensing 3-methoxysalicylaldehyde and 4-amino-2-hydroxybenzohydrazide, with Mo...

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

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

Background The kidney function monitoring is recommended in routine practice to detect 5-aminosalicylic acid (5-ASA) related nephrotoxicity, although is not standardized. The optimal monitoring is unknown, especially the best timing and which tests to perform. We summarized why, how, and when to perform the monitoring for patients treated with 5-ASA and provided an overview of the current guidelines on this topic. Method Relevant studies on this topic were searched in PubMed, Embase, and Web of Science databases from July to August 2020. Results Serum creatinine, the estimated glomerular filtration rate, and 24-h proteinuria are the 3 main tests used for the monitoring in daily practice. Regarding the timing, several monitoring strategies have been proposed and guidelines are available too, but they provide conflicting information. To date, there is no medical evidence-based that one strategy is better than another. Comorbidities, chronic renal disease, use of nephrotoxic drugs or concomitant steroid therapy also impact the nephrotoxicity risk. Based on the literature review we proposed a kidney function monitoring strategy to guide physicians in clinical practice. Conclusion A baseline assessment should be performed in all patients treated with 5-ASA. The monitoring should be carried out according to the other nephrotoxic factors. A tight monitoring may reduce morbidity and mortality of drug nephrotoxicity.

Solubility and density profiles for 3-aminosalicylic acid (3-ASA) in the mixed solvents of 2-propanol and water is determined by a shake-flask method at 293.2–313.2 K. The obtained numerical data i...

Five-aminosalicylic acid (5-ASA) is an anti-inflammatory drug indicated in the treatment of inflammatory bowel diseases such as ulcerative colitis and Crohn's disease. Among the analytical methods of quantification of 5-ASA described in the literature, the High Efficiency Liquid Chromatography stands out, a sensitive technique but with a high cost. In recent years, alternative methods have been developed, presenting efficiency and reduced cost, such as UV/visible spectrophotometric, spectrofluorescent, and electrochemical methods, techniques recommended for the application in quality control and quantification of 5-ASA in pharmaceutical forms and biological fluids. This article aims to review the physicochemical characteristics, pharmacokinetics, mechanisms of action, controlled release systems, and the different analytical and bioanalytical methods for the quantification of 5-ASA.

Despite several recent advances in therapy in inflammatory bowel disease (IBD), 5-aminosalicylic acid (5-ASA) therapy has retained its place especially in ulcerative colitis. This consensus on 5-ASA is obtained through a modified Delphi process, and includes guiding statements and recommendations based on literature evidence (randomized trials, and observational stud ies), clinical practice, and expert opinion on use of 5-ASA in IBD by Indian gastroenterologists. The aim is to aid practitioners in selecting appropriate treatment strategies and facilitate optimal use of 5-ASA in patients with IBD. (Intest Res 2020;18:355-378)

Behçet's disease (BD) is a recurrent, multisystemic, inflammatory blood vessel disorder that can result in mouth, genital, and skin ulcers; arthritis; and eye and intestinal inflammation. We describe a 21-year-old Korean female patient with intestinal BD refractory to conventional medical treatment and biologic drugs. The patient was initially treated with high-dose steroids and sulfasalazine. Two months later, a skin rash occurred as a side effect of sulfasalazine. Therefore, infliximab (IFX) was administered, and disease activity decreased. However, IFX also induced a skin rash; hence, the patient was switched to adalimumab. After 12 months, the patient experienced a relapse of intestinal BD. Hence, treatment was initiated using a combination of methotrexate and adalimumab; however, this treatment was ineffective. Methotrexate was discontinued and replaced with 5‑aminosalicylic acid while maintaining adalimumab, and no recurrence has been observed to date. We report this novel strategy involving the use of anti-tumor necrosis factor‑α agents for patients with resistant BD; however, further large cohort studies are required to verify its usefulness.

5-Aminosalicylic acid (5-ASA) is used as first line therapy for symptom remission and maintenance of inflammatory bowel disease (IBD). Because 5-ASA is well absorbed from the small intestine when orally administered, several 5-ASA formulations for selective delivery to the colon have been developed and used in clinical practice. However, its delivery efficiency to local inflamed colonic sites remains low. Intestinal H+-coupled oligopeptide transporter 1 (PEPT1) expression in the colon is low, whereas its expression is induced in the colon under chronic inflammation conditions, such as IBD. Therefore, we considered that PEPT1 would be a target transporter to improve 5-ASA delivery efficiency to local colonic lesions. We evaluated the transport characteristics of dipeptide-like 5-ASA derivatives, which were coupling glycine (Gly), lysine, glutamic acid (Glu), valine (Val) and tyrosine to amino or carboxyl group of 5-ASA, in Caco-2 cells. [3H]Glycylsarcosine (Gly-Sar) uptake into Caco-2 cells was inhibited by all 5-ASA derivatives. In addition, 5-ASA derivatives (Gly-ASA, Glu-ASA and Val-ASA), which were coupled by glycine, glutamic acid and valine to amino group of 5-ASA, were taken up in a pH- and concentration-dependent manner and their uptake was inhibited by excess Gly-Sar. Two-electrode voltage-clamp experiment using human PEPT1 expressing Xenopus oocytes showed that Gly-ASA, Glu-ASA and Val-ASA induced marked currents at pH 6.0. Taken together, these results showed that these 5-ASA derivatives are transportable substrates for PEPT1.

The article discusses the possible relationships between intestinal microbiota and the therapeutic efficacy of 5-aminosalicylic acid (5-ASA) in inflammatory bowel diseases. Intestinal microbiota may be involved in 5-ASA enzymatic biotransformation, but the metabolism of drugs by the intestinal microbiota has been studied in less detail, and little is known about the relationships between anti-inflammatory efficacy of 5-ASA with bacterial viability, quantity and activity. It remains unclear whether 5-ASA affects the microbiota depending on the different segments of gastrointestinal tract. Drugs and diet can both improve and worsen the composition of the intestinal microbiota. However, it is not known whether drugs affect the intestinal microbiota regardless of diet. Further research is needed to answer these questions.

We regret that this article is behind a paywall., BACKGROUND: Treatment of multidrug-resistant tuberculosis requires long-term therapy with a combination of multiple second-line drugs. These drugs are associated with numerous adverse events that can cause severe morbidity, such as deafness, and in some instances can lead to death. Our aim was to estimate the absolute and relative frequency of adverse events associated with different tuberculosis drugs to provide useful information for clinicians and tuberculosis programmes in selecting optimal treatment regimens. METHODS: We did a meta-analysis using individual-level patient data that were obtained from studies that reported adverse events that resulted in permanent discontinuation of anti-tuberculosis medications. We used a database created for our previous meta-analysis of multidrug-resistant tuberculosis treatment and outcomes, for which we did a systematic review of literature published between Jan 1, 2009, and Aug 31, 2015 (updated April 15, 2016), and requested individual patient-level information from authors. We also considered for this analysis studies contributing patient-level data in response to a public call made by WHO in 2018. Meta-analysis for proportions and arm-based network meta-analysis were done to estimate the incidence of adverse events for each tuberculosis drug. FINDINGS: 58 studies were identified, including 50 studies from the updated individual patient data meta-analysis for multidrug-resistant tuberculosis treatment. 35 of these studies, with 9178 patients, were included in our analysis. Using meta-analysis of proportions, drugs with low risks of adverse event occurrence leading to permanent discontinuation included levofloxacin (1·3% [95% CI 0·3-5·0]), moxifloxacin (2·9% [1·6-5·0]), bedaquiline (1·7% [0·7-4·2]), and clofazimine (1·6% [0·5-5·3]). Relatively high incidence of adverse events leading to permanent discontinuation was seen with three second-line injectable drugs (amikacin: 10·2% [6·3-16·0]; kanamycin: 7·5% [4·6-11·9]; capreomycin: 8·2% [6·3-10·7]), aminosalicylic acid (11·6% [7·1-18·3]), and linezolid (14·1% [9·9-19·6]). Risk of bias in selection of studies was judged to be low because there were no important differences between included and excluded studies. Variability between studies was significant for most outcomes analysed. INTERPRETATION: Fluoroquinolones, clofazimine, and bedaquiline had the lowest incidence of adverse events leading to permanent drug discontinuation, whereas second-line injectable drugs, aminosalicylic acid, and linezolid had the highest incidence. These results suggest that close monitoring of adverse events is important for patients being treated for multidrug-resistant tuberculosis. Our results also underscore the urgent need for safer and better-tolerated drugs to reduce morbidity from treatment itself for patients with multidrug-resistant tuberculosis.

Therapeutic targeting of folate biosynthetic pathway has recently been explored as a viable strategy in the treatment of tuberculosis. The bioactive metabolite substrate of Para-amino salicyclic acid (PAS-M) reportedly dual-targets dihydrofolate reductase (DHFR) and flavin-dependent thymidylate synthase (FDTS), two essential enzymes in folate biosynthetic pathway. However, the molecular mechanisms and structural dynamics of this dual inhibitory activity of the PAS-M remain elusive. Molecular dynamics simulations revealed that binding of PAS-M towards DHFR is characterized by a recurrence of strong conventional hydrogen bond interactions between a peculiar DHFR binding site residue (Asp27) and the 2-amino-decahydropteridin-4-ol group of PAS-M. Similarly, the binding of PAS-M towards FDTS also involved consistent strong conventional hydrogen bond interactions between some specific residues (Tyr101, Arg172, Thr4, Gln103, Arg87 and Gln106) and, the 2-amino-decahydropteridin-4-ol group, thus establishing the cruciality of the group. Structural dynamics of the bound complexes of both enzymes revealed that, upon binding, PAS-M is anchored at the entrance of hydrophobic pockets by strong hydrogen bond interactions while the rest of the structure gains access to deeper hydrophobic residues to engage in favorable interactions. Further analysis of atomistic changes of both enzymes showed increased C-α atom deviations as well as an increase C-α atoms radius of gyration consistent with structural disorientations. These conformational changes possibly interfered with the biological functions of the enzymes and hence their inhibition as experimentally reported. Structural Insights provided could open up a novel paradigm of structure-based design of multi-targeting inhibitors of biological targets in the folate biosynthetic pathway toward tuberculosis therapy.

Background/Aims: 5-Aminosalicylic acid (ASA) causes intolerance reactions in some patients. This study was performed to examine the prognosis of patients with ulcerative colitis (UC) and 5-ASA intolerance, and to evaluate the potential interaction between 5-ASA intolerance and the intestinal microbiota. Methods: We performed a retrospective cohort study of patients with UC who visited participating hospitals. The primary endpoint was to compare the incidence of hospitalization within 12 months between the 5-ASA intolerance group and the 5-ASA tolerance group. The secondary endpoint was to compare the risk of adverse clinical outcomes after the start of biologics between the 2 groups. We also assessed the correlation between 5-ASA intolerance and microbial change in an independently recruited cohort of patients with UC. Results: Of 793 patients, 59 (7.4%) were assigned to the 5-ASA intolerance group and 734 (92.5%) were assigned to the 5-ASA tolerance group. The admission rate and incidence of corticosteroid use were significantly higher in the intolerance than tolerance group (P

Background: Pyoderma gangrenosum (PG) in inflammatory bowel disease (IBD) is a rare cutaneous condition and its treatment remains controversial due to limited data. Aims and Objectives: The purpose of this study was to investigate the characteristics and treatment response to specific therapies of IBD-associated PG. Methods: In this retrospective study, we reviewed a series of cases of IBD-associated PG patients who presented at our institution, and collected clinical data, such as demographics, characteristics, subtype, and disease activity of IBD and specific therapies used and their treatment response. Results: In total, 42 cases were identified: 69% female and 92.9% with ulcerative colitis (UC). At PG diagnosis, 93% had active and 7% inactive IBD. PG ulcers occurred predominantly on the legs (33.3%); 14.3% had multiple lesions. In total, 20/39 UC patients received the combination therapy of systemic corticosteroids and 5-aminosalicylic acid (5-ASA) with a good response in 19 patients (95%). Seven patients received the monotherapy of 5-ASA with a response rate of 43%. Five patients were successfully treated with systemic corticosteroids alone. Other patients were treated with intravenous immunoglobulin, infliximab, or cyclophosphamide alone or in combination with corticosteroids and all showed a good response. Conclusion: Our study indicates the therapeutic efficacy of corticosteroids in combination with 5-ASA, which may be considered as the first-line therapy for UC-associated PG.

Tuberculosis (TB), caused by Mycobacterium tuberculosis (M. tuberculosis), is one of the most fatal diseases in the world. Methylenetetrahydrofolate reductase (MTHFR) catalyzes the production of 5-methyltetrahydrofolate (5-CH3-THF), which is required for the de novo biosynthesis of methionine in bacteria. In this study, we identified Rv2172c as an MTHFR in M. tuberculosis through in vitro and in vivo analyses and determined that the protein was essential for the in vitro growth of the bacterium. Subsequently, we constructed rv2172c R159N and L214A mutants in M. tuberculosis, and found that these mutants were more sensitive to the antifolates para-aminosalicylic acid (PAS) and sulfamethoxazole (SMX). Combining biochemical and genetic methods, we found that rv2172c R159N or L214A mutation impaired methionine production, leading to increased susceptibility of M. tuberculosis to PAS, which was largely restored by adding exogenous methionine. Moreover, overexpression of rv2172c in M. tuberculosis could increase methionine production and lead to PAS resistance. This research was the first to identify an MTHFR in M. tuberculosis and revealed that the activity of this enzyme was associated with susceptibility to antifolates. These findings have particular value for anti-tubercular drugs design for the treatment of drug-resistant TB.

Despite immunosuppression is critical for reducing immune overactivation, existing immunosuppressive agents are largely restricted by low inhibition efficiencies and unpredictable off‐target toxicities. Here, the use of the dopaminergic system is reported to suppress hyperactive immune responses in local inflamed tissues. A polydopamine nanoparticular immunosuppressant (PDNI) is synthesized to stimulate regulatory T (Treg) cells and directly inhibit T helper 1 (Th1), Th2, and Th17 cells. Moreover, PDNI can inhibit the activation of dendritic cells to upregulate the ratio of Treg/Th17, which assists the reversion of inflammatory responses. The application of dopaminergic immunoregulation is further disclosed by combining with gut microbiota modulation for treating inflammations. The combination is implemented by coating living beneficial bacteria with PDNI. Following oral delivery, coated bacteria not only suppress the hyperactive immune responses but also positively modulate the gut microbiome in mice characterized with colitis. Strikingly, the combination demonstrates enhanced treatment efficacies in comparison with clinical aminosalicylic acid in two murine models of colitis. The use of the dopaminergic system opens a window to intervene immune responses and provides a versatile platform for the development of new therapeutics for treating inflammatory diseases., The dopaminergic system is reported to suppress hyperactive immune responses in local inflamed tissues by a polydopamine nanoparticular immunosuppressant, which can stimulate regulatory T lymphocytes and dendritic cells, while directly inhibit T helper cells. The application of dopaminergic immunoregulation is further disclosed by combining with oral probiotics that can modulate the gut microbiota for treating colitis.

To develop a 5-aminosalicylic acid (5-ASA)-based anticolitic drug with enhanced therapeutic activity, a colon-targeted codrug constituting 5-ASA and a GPR109A agonist was designed. 5-ASA azo-coupled with nicotinic acid (ASA-azo-NA) was synthesized, and the colon specificity and anticolitic effects were evaluated. Approximately 89% of ASA-azo-NA was converted to 5-aminonicotinic acid (5-ANA) and 5-ASA after 24 h of incubation in the cecal contents. 5-ANA was identified as a GPR109A agonist (concentration that gives half-maximal response (EC50): 18 μM) in a cell-based assay. Upon oral gavage of ASA-azo-NA (oral ASA-azo-NA) and sulfasalazine (oral SSZ), a colon-targeted 5-ASA prodrug, cecal accumulation of 5-ASA was comparable, and 5-ANA was barely detectable in the blood, while it was detected up to 62.7 μM with oral 5-ANA. In parallel, oral ASA-azo-NA did not elicit an adverse skin response. In murine macrophage and human colon carcinoma cells, activation of GPR109A by 5-ANA elevated the level of the anti-inflammatory cytokine IL-10, suppressed NF-κB activation, and potentiated the inhibitory activity of 5-ASA on NF-κB. Oral ASA-azo-NA ameliorated rat colitis and was more effective than oral SSZ, which were substantially blunted following cotreatment with the GPR109A antagonist, mepenzolate. In conclusion, ASA-azo-NA is a colon-targeted anticolitic codrug with a reduced risk of skin toxicity induced by the GPR109A agonist, therapeutically surpassing a current 5-ASA-based anti-inflammatory bowel disease drug in a rat colitis model.

Para-aminosalicylic acid (PAS), often the last drug remaining for treatment of drug-resistant tuberculosis, is notorious for causing gastrointestinal intolerance; however, the cause of PAS intolerance is uncertain. The objective of this study was to assess relationships between peak concentrations of PAS administered as a granular slow-release enteric coated formulation, and its metabolites acetyl-PAS and glycine-PAS, and intolerance. PAS and its metabolites were measured in 29 adult patients with drug-resistant tuberculosis at Brooklyn Hospital, Cape Town, randomized to receive granular slow-release enteric-coated PAS 4 g twice daily or 8 g once daily for 1 week, followed by the alternative regimen. Concentrations of PAS and its metabolites were determined by liquid chromatography and tandem mass spectrometry, and a visual analogue scale evaluated intolerance. Spearman's correlation test assessed the relationship between maximum plasma concentrations (Cmax ) and intolerance scores. A large interindividual variability was observed for the PAS Cmax (40.42-68.55 mg/L) following 4 g twice daily; (62.69-102.41 mg/L) for 8 g once daily and a similar wide Cmax range found for the metabolites acetyl-PAS and glycine-PAS. Twenty-six patients reported at least 1 intolerance episode, but most visual analogue scale scores clustered around 0. Significant inverse associations were found between acetyl-PAS Cmax and bloating (rho = -0.448; P = .025) and diarrhea (rho = -0.407; P = .044) for the twice-daily regimen and a similar inverse association found for glycine-PAS and diarrhea (rho = -0.412; P = .041). Plasma concentrations of the metabolites did not correlate with the occurrence of gastrointestinal symptoms, but higher metabolite concentrations correlated with lower intolerance scores; slow metabolism of PAS and its continued presence in the intestinal tract may be the main cause of intolerance.

Interfacial charge transfer (ICT) complexes between wide-band-gap metal oxides and small colorless organic molecules have promising use in a variety of applications. The possibility to control opti...

Compound 5-{[(2E)-3-bromo-3-carboxyprop-2-enoyl]amino}-2-hydroxybenzoic acid (C1), a new 5-aminosalicylic acid (5-ASA) derivative, has proven to be an antioxidant in vitro and an anti-inflammatory agent in mice. The in vivo inhibition of myeloperoxidase was comparable to that of indomethacin. The aim of this study was to take another step in the preclinical evaluation of C1 by examining acute toxicity with the up-and-down OECD method and pharmacokinetic profiles by administration of the compound to Wistar rats through intravenous (i.v.), oral (p.o.), and intraperitoneal (i.p.) routes. According to the Globally Harmonized System, C1 belongs to categories 4 and 5 for the i.p. and p.o. routes, respectively. An RP-HPLC method for C1 quantification in plasma was successfully validated. Regarding the pharmacokinetic profile, the elimination half-life was approximately 0.9 h with a clearance of 24 mL/min after i.v. administration of C1 (50 mg/kg). After p.o. administration (50 mg/kg), the maximum plasma concentration was reached at 33 min, the oral bioavailability was about 77%, and the compound was amply distributed to all tissues evaluated. Therefore, C1 administered p.o. in rats is suitable for reaching the colon where it can exert its effect, suggesting an important advantage over 5-ASA and indomethacin in treating ulcerative colitis and Crohn’s disease.

Background: Due to the increased incidence of colorectal cancer in inflammatory bowel diseases (IBDs), the value of chemoprevention for this patient group has been repeatedly debated in the past decade. This review describes available evidence and the current recommendations for chemoprevention in national and international guidelines IBD guidelines. Summary: 5-Aminosalicylic acid (5-ASA) compounds are the preferred therapeutic option for mild to moderate ulcerative colitis (UC). Aside from the known anti-inflammatory effects, their chemopreventive abilities have been described in vitro and in vivo. Pooling the increasing number of retrospective and population-based clinical studies over the last 15 years, 7 consecutive meta-analyses revealed partially conflicting results for the chemopreventive efficacy of 5-ASA, and thus, not all IBD guidelines currently recommend chemoprevention with mesalamine compounds. Accumulating evidence for decreasing the colorectal cancer (CRC) risk in support of thiopurines more recently shows a protective effect. This effect seems solely mediated by control of intestinal inflammation since, for this drug class, another mechanistic interference in IBD-associated CRC pathogenesis is not known. The results regarding chemopreventive efficacy for ursodeoxycholic acid or folic acid are equivocal, and the use of these medications to prevent CRC is not firmly established. Like UC, the risk of CRC is also significantly increased in patients with Crohn’s disease (CD), especially Crohn’s colitis. However, no published studies exclusively assess the effects of surveillance on the early detection of cancer or CRC chemoprevention in CD patients. In meta-analyses, which predominantly included UC patients, 5-ASA or thiopurines were not beneficial in small CD subgroups. The level of evidence for anti-TNFα agents, anti-integrin (e.g., vedolizumab), or anti-IL-12/IL-23 agents (e.g., ustekinumab) and Janus kinase inhibitors is currently too low or nonexistent to use them solely for chemoprevention in UC or CD patients. Key Message: Intestinal inflammation is one of the main risk factors for developing CRC in IBD, and all drugs that induce and maintain mucosal healing most likely also decrease the IBD-associated CRC risk. Thus, a therapeutic strategy of adding a 5-ASA therapy to a successfully mucosal healing-inducing therapy, for example, with a biologic or a small molecule merely to prevent CRC appears to be obsolete.

Background and Aims. The efficacy of 5-aminosalicylic acid (5-ASA) in the long-term outcome of Crohn’s disease (CD) patients was uncertain. This study aimed to evaluate the efficacy of the 5-ASA in preventing disease behavior progression and intestinal resection in CD patients. Methods. CD patients were prospectively enrolled from January 2008 to September 2019 in Xijing Hospital. Disease behavior progression was defined as the development of stricturing (B2) or penetrating disease (B3) in patients with nonstricturing/nonpenetrating disease (B1) at diagnosis. Cox regression analyses were used to investigate the associations between disease location progression, disease behavior progression, and intestinal resection and multiple covariates. Results. In total, 122 CD patients were followed up for 4.3 years. At the time of diagnosis, disease location was ileal in 19.7% (24/122), colonic in 41.0% (50/122), and ileocolonic in 39.3% (48/122). A total of 87 (71.3%) patients had B1 at diagnosis. The disease behavior progression and intestinal resection rates were 42.5% (37/87) and 29.5% (36/122). The use of 5-ASA reduced the risk of disease behavior progression (HR 0.30, 95% CI 0.14–0.61, P = 0.001) and intestinal resection (HR 0.33, 95% CI 0.17–0.90, P = 0.027) in colonic and ileocolonic CD patients. Patients who presented with ileal disease at diagnosis did not have the same protective effects when taking 5-ASA ( P > 0.05). Conclusions. The use of 5-ASA could improve the long-term outcome of CD patients with colon involvement. The result emphasized the importance of early use of 5-ASA in the daily management of colonic involved CD.

Background: Oral 5-aminosalicylic acid (5-ASA) is the mainstay treatment of ulcerative colitis (UC) and therapy with oral 5-ASA is associated with beneficial outcomes. We have examined factors associated with the persistence of oral 5-ASA treatment in a national cohort of UC patients. Methods: Patients with newly diagnosed UC from 2010 to 2014 using oral 5-ASA monotherapy were identified by combining data from the Norwegian Patient Registry and the Norwegian Prescription Database. The median follow-up time was 1029 days. Drug persistence was defined as duration of oral 5-ASA preparation as monotherapy. Non-persistence of a oral 5-ASA preparation as monotherapy was defined as stopping oral 5-ASA, initiation of any further anti-inflammatory treatment including a course of glucocorticoids and a change to another oral 5-ASA preparation. Drug persistence was analyzed using the Kaplan–Meier method and influence of covariates on drug persistence was analyzed with the Cox proportional hazard model. Results: A total of 3421 patients were identified. The overall median 5-ASA drug persistence was 179 days. In univariate analyses, persistence was associated with preparation type and high-dose treatment, while oral glucocorticoid use or hospitalization around the start of oral 5-ASA were associated with shorter 5-ASA persistence. In multivariate analyses, oral glucocorticoids [HR 1.67 (1.54–1.80), p Conclusion: High-dose treatment with oral 5-ASA was associated with longer persistence of oral 5-ASA monotherapy, whereas the presence of factors indicating more severe disease around initiation of 5-ASA monotherapy was associated with a shorter persistence.

Background: The drug 5-aminosalicylic acid (5-ASA) is the first-line therapy for the treatment of patients with mild-to-moderate ulcerative colitis (UC). However, in some cases, 5-ASA cannot achieve the desired therapeutic effects. Therefore, patients have to undergo therapies that include corticosteroids, monoclonal antibodies or immunosuppressants, which are expensive and may be accompanied by significant side effects. Synergistic drug combinations can achieve greater therapeutic effects than individual drugs while contributing to combating drug resistance and lessening toxic side effects. Thus, in this study, we sought to identify synergistic drugs that can act synergistically with 5-ASA.Methods: We started our study with protein-metabolite analysis based on peroxisome proliferator-activated receptor gamma (PPARG), the therapeutic target of 5-ASA, to identify more additional potential drug targets. Then, we further evaluated the possibility of their synergy with PPARG by integrating Kyoto Encyclopedia of Genes and Genome (KEGG) pathway enrichment analysis, pathway-pathway interaction analysis, and semantic similarity analysis. Finally, we validated the synergistic effects with in vitro and in vivo experiments.Results: The combination of 5-ASA and vorinostat (SAHA) showed lower toxicity and mRNA expression of p65 in human colonic epithelial cell lines (Caco-2 and HCT-116), and more efficiently alleviated the symptoms of dextran sulfate sodium (DSS)-induced colitis than treatment with 5-ASA and SAHA alone.Conclusion: SAHA can exert effective synergistic effects with 5-ASA in the treatment of UC. One possible mechanism of synergism may be synergistic inhibition of the nuclear factor kappa B (NF-kB) signaling pathway. Moreover, the metabolite-butyric acid may be involved.

Polyfluorinated analogues of salicylamide and p-aminosalicylic acid have been synthesized based on methyl polyfluorosalicylates. Polyfluorosalicylamides were obtained by the reaction with aqueous ammonia, while 4-aminopolyfluorosalicylic acids were prepared in two steps via regio-oriented nucleophilic replacement of para-positioned fluorine atom with azido group followed by its reduction. 3,4,5-Trifluorosalicylamide showed pronounced analgesic in vivo activity in hot plate test while 4-amino-3,5-difluorosalicylic acid revealed high tuberculostatic activity.

BACKGROUND: Knowing patients' ulcerative colitis history is essential to selecting the appropriate therapy according to risk stratification. OBJECTIVE: To evaluate and identify predictive factors of non-response to aminosalicylates judged as the need for a step-up approach over time. METHODS: A case-control study of ulcerative colitis patients treated with aminosalicylates after the diagnosis of disease flare included in the ENEIDA single-centre registry from 1997 to 2017. Long-term treatment maintenance with aminosalicylates and higher therapeutic requirements were recorded. The cumulative incidence of treatment escalation was estimated using Kaplan-Meier curves and compared by the log-rank test. Cox regression analysis was performed to identify predictive factors of treatment with immunomodulators, biological agents or surgery. RESULTS: A total of 457 patients were included, of whom 28% (n = 126) were non-responders to aminosalicylates. The cumulative probability for a step-up approach within 20 years of follow up was 35%, mainly due to steroid-dependent colitis. Risk factors for treatment escalation were age ≤27 years (hazard ratio 2.31, 95% confidence interval 1.36–3.92), extensive colitis (hazard ratio 1.65, 95% confidence interval 1.04–2.60), Mayo endoscopic subscore ≥2 (hazard ratio 1.45, 95% confidence interval 1.02–2.06) and extraintestinal manifestations (hazard ratio 2.04, 95% confidence interval 1.03–4.05). CONCLUSIONS: Aminosalicylates represent an effective maintenance therapy. Younger age, extensive colitis, endoscopic disease severity and extraintestinal manifestations are risk factors for higher therapeutic requirements.

The current study is devoted to the synthesis of Schiff base ligand, HL, by condensation of 5-aminosalicylic acid with o-vanillin, followed by preparing its Cu(II), Co(II), Mn(II), and Zn(II) complexes, and their characterization. The Schiff base behaves as a bidentate ligand which forms tetrahedral complexes with Cu(II) and Zn(II), unlike Co(II) and Mn(II) that give octahedral complexes. The Schiff base ligand and its complexes with Cu2+, Co2+, Mn2+, and Zn2+ exhibit considerable antibacterial activity against some drug resistant reference strains and local isolates of S. aureus, E. Coli, P. aersginosa. Overall, the metal complexes exhibit more potent antibacterial activity than the ligand HL alone.

Background Sodium para-aminosalicylic acid (PAS-Na), an anti-tuberculosis drug, has been demonstrated its function in facilitating the Mn elimination in manganism patients and Mn-exposed models in vivo and improving the symptoms of Mn poisoning. But whether it can improve the growth retardation and inflammatory responses induced by Mn have not been reported. Objectives This study was designed to investigate the preventive effects of PAS-Na on the development of retardation and inflammatory responses in Mn-exposed rats. Methods Male Sprague Dawley (SD) rats (8 weeks old, weighing 180 ± 20 g) were randomly divided into normal control group and Mn-exposed group in the 4 weeks experiment observation and normal control group, Mn-exposed group, PAS-Na preventive group and PAS-Na control group in the 8 weeks experiment observation. The Mn-exposed group received an intraperitoneal injection (i.p.) of 15 mg/kg MnCl2 and the normal control group i.p. physiological Saline in the same volume once a day for 4 or 8 weeks, 5 days per week. The PAS-Na preventive group i.p. 15 mg/kg MnCl2 along with back subcutaneous (s.c.) injection of 240 mg/kg PAS-Na once a day for 8 weeks, 5 days per week. PAS-Na control group received s.c. injection of 240 mg/kg PAS-Na along with i.p. injection of saline once daily. The body weight was determined once a week until the end of the experiment. The manganese contents in the blood were detected by graphite furnace atomic absorption spectrometry. The inflammatory factor levels (TNF-α, IL-1β, IL-6, and PGE2) in the blood were detected by using enzyme-linked immunosorbent assay (Elisa) and each organ taking from rats were weighed and recorded. Results Mn exposure significantly suppressed the growth in rats and increased heart, liver, spleen and kidney coefficients as compared with the control group. The whole blood Mn level and serum levels of IL-1β, IL-6, PGE2, and TNF-α in sub-chronic Mn-exposure group were markedly higher than those in the control group. However, preventive treatment with PAS-Na obviously reduced the whole blood Mn level, the spleen and liver coefficients of the Mn-exposed rats. And serum levels of IL-1β and TNF-α were significantly reduced by 33.9% and 14.7% respectively in PAS-Na prevention group. Conclusions PAS-Na could improve the growth retardation and alleviate inflammatory responses in Mn-exposed rats.

Background and aim Oral 5-aminosalicylic acid (5-ASA) is recommended for the therapy of mild to moderate intestinal Behcet's disease (BD). However, the induction remission efficacy and endoscopic outcomes of 5-ASA are unknown. We investigated remission induction at 8 weeks, endoscopic outcomes until 52 weeks, and event-free survival at 52 weeks in patients with intestinal BD treated with 5-ASA. Methods Forty-one patients with intestinal BD were treated with oral 5-ASA. Clinical remission was evaluated with the Crohn's disease activity index (CDAI). The endoscopic response was evaluated using the modified global gastrointestinal endoscopic assessment scores. Rescue therapy-free survival and surgery-free survival at 52 weeks were estimated, and predictive factors for a clinical response at weeks 8 and 52 were identified. Results Seven patients (17%) withdrew 5-ASA early (≤ 8 weeks) because of adverse events. At week 8, clinical efficacy could be accurately evaluated in 28 patients, and the response and remission rates were 61% and 57%, respectively, using the CDAI. Endoscopic evaluation was achieved in 17 patients up to 52 weeks, and the endoscopic response and remission rates were 71% and 35%, respectively. The probabilities of rescue therapy-free survival and surgery-free survival were 73% and 100%, respectively, at 52 weeks in all 41 patients. The predictive factors for therapeutic effectiveness at week 8 were a higher baseline C-reactive protein level and CDAI, but they were negative predictive factors for a 52-week response. Conclusions 5-ASA is effective for clinical and endoscopic induction and maintaining a response in patients with mild to moderate intestinal BD.

The repurposing of existing FDA-approved non-cancer drugs is a potential source of new treatment options for cancer patients. An anti-inflammatory drug, 5-aminosalicylic acid (5-ASA), has been clinically used to treat inflammatory bowel disease. Hyperthermia (HT) is widely applicable addendum therapy with the existing cancer treatment modalities. Here, we addressed how 5-ASA combined with HT induces lethal effects in human oral squamous cell carcinoma (OSCC) HSC-3 cells. We found that 5-ASA/HT combination significantly inhibited the viability of HSC-3 cells, while cytotoxic effects in primary human dermal fibroblast cells were minor. Apoptotic endpoints were significantly increased by the 5-ASA/HT combined treatment, as evidenced by presence of Annexin V-FITC/PI positive cells, loss of MMP, Bcl-2/Bax ratio alteration, and increased Fas, cleaved Bid, and caspase expression. Interestingly, the enhancement of apoptosis was reversed in the presence of ON/ONOO− scavengers. These findings indicate that the combination treatment enhances apoptosis via ON/ONOO− mediated ER stress-Ca2+-mitochondria signaling and caspase-dependent apoptotic pathways. Our findings provide novel evidence that the combination of 5-ASA and HT is a promising approach for the enhancement of apoptosis; it may serve as an effective strategy for treating human OSCC.

The interaction of the oxidized fraction of polyvinyl alcohol (OF of PVA) with 4- and 5-aminosalicylic acids (4- and 5-ASA) in aqueous solutions was examined by ultraviolet spectroscopy. OF of PVA is obtained by oxidation of polyvinyl alcohol in an aqueous medium affected by hydrogen peroxide (363 K, [PVA] = 3.5% wt., [H2O2] = 1 mol/l, toxid. = 45 min), further separated from the solution by acetone addition. The average molecular weight of the oxidized fraction of PVA, calculated from the experimentally found value of the characteristic viscosity using the Mark-Kun-Houwink equation, amounted to 4.5 kDa. It was found that the addition of the original (non-oxidized) polyvinyl alcohol to aqueous solutions of 4- and 5-ASA does not change their UV spectra. At the same time, the introduction of an oxidized fraction of polyvinyl alcohol into aqueous solutions of aminosalicylic acids leads to spectral changes, indicating intermolecular interactions and complexation. By the method of molar ratios, it was shown that in dilute aqueous solutions OF of PVA forms complex 1 : 1 compounds with 4-ASA and 5-ASA, i.e., one molecule of 4- or 5-aminosalicylic acid accounts for one carboxyl group of the oxidized PVA fraction. Using this method, in the 291-316 K temperature range, the stability constants (K) of the resulting complex compounds were calculated. The results analised demonstrated that the oxidized fraction of polyvinyl alcohol forms strong enough complexes with 4- and 5-aminosalicylic acids: the K values in the temperature range under study vary within (1-7)∙104 l/mol. It was found out that with increasing temperature, the values of stability constants of complex compounds decrease. The study of the temperature dependence of K made it possible to determine the standard values of the changes in the Gibbs energy (ΔG°), enthalpy (ΔH°), and entropy (ΔS°) of complexing. Negative values of thermodynamic parameters indicate a spontaneous process of formation of complexes, their exothermicity and the resulting constraints of the movements of molecules.

The effect of sodium para-aminosalicylate (PAS-Na) on litchi pericarp browning and the potential regulating mechanism was investigated in this study. Results showed that 0.3 g L−1 PAS-Na significantly inhibited the development of pericarp browning and reduced respiration rate of litchi fruit. PAS-Na inhibited the production of reactive oxygen species (ROS) and decreased the expression level of senescence-related genes. Additionally, PAS-Na treatment enhanced the activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX), which might contribute to the scavenging of ROS. Meanwhile, PAS-Na treatment maintained membrane integrity as indicated by reduced relative membrane leakage rate and malondialdehyde (MDA) content, as well as lower activities of membrane lipids-degrading enzymes: lipase and lipoxygenase (LOX). Amino acids, especially GABA, Glu, Met contents were also significantly affected by PAS-Na treatment. Taken together, we postulated that PAS-Na treatment might be a promising method for controlling postharvest browning and prolonging shelf-life of harvested litchi fruit.

Background 5‐aminosalicylic acid (5‐ASA) is the first‐line therapy for ulcerative colitis (UC). 5‐ASA acts locally in the colonic mucosa by numerous proposed mechanisms, and is metabolised by N‐acetyltransferase (NAT). Large variations in mucosal 5‐ASA concentrations have been reported, but the underlying mechanisms are not understood. Aim To study the relationship between 5‐ASA concentration, 5‐ASA formulation, NAT genotype and bacterial microbiome in patients with UC. Methods Patients with quiescent UC, using monotherapy of Mezavant (n = 18), Asacol (n = 14) or Pentasa (n = 10), 4.0‐4.8 g/day were included. 5‐ASA was measured in colonic mucosal biopsies and serum by ultra‐high performance liquid chromatography. NAT genotypes were determined by Sanger sequencing. Bacterial microbiome was sequenced from faeces and mucosa by 16S rRNA sequencing using Illumina Miseq. Results Mezavant provided the highest mucosal 5‐ASA levels (geometric mean 2.39 ng/mg), followed by Asacol (1.60 ng/mg, 33% lower, P = 0.50) and Pentasa (0.57 ng/mg, 76% lower, P = 0.033). Mucosal 5‐ASA concentration was not associated with NAT genotype, but serum 5‐ASA concentration and NAT1 genotype was associated (P = 0.044). Mucosal 5‐ASA concentration was positively associated with mucosal bacterial diversity (P = 0.0005) and bacterial composition. High mucosal 5‐ASA concentration was related to reduced abundance of pathogenic bacteria such as Proteobacteria, and increased abundance of several favourable bacteria such as Faecalibacterium. Conclusions Mucosal 5‐ASA concentration is positively associated with bacterial diversity and a mucosal bacterial composition that are perceived favourable in UC. Mezavant yielded higher mucosal 5‐ASA concentrations than Pentasa. 5‐ASA may have beneficial effects on the mucosal microbiome, and high concentrations possibly amend dysbiosis in UC. © 2019 The Authors. Alimentary Pharmacology & Therapeutics Published by John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

Intelligent drug delivery systems are growing and changing too fast, these systems usually show a proper response at the proper time to one or several environmental factors. In the current research a biodegradable drug delivery system (pectin-g-PMA-co-PAAm) was designed and synthesized to release 5 aminosalicylic acid (5-ASA). The synthesized hydrogel is based on natural pectin and is in the form of simultaneous graft copolymerization of synthesized acryl-acid and acryl-amid. Using vinylized bovine serum albumin (VBSA) as cross linker agent is amongst important characteristics of this hydrogel. VBSA was synthesized through BSA modification with methylene-bis-acrylamide (MBA). In addition to having high water absorption, this hydrogel is pH-sensitive. In vitro tests under acid and base conditions of stomach show that this hydrogel is an appropriate option to release drugs through mouth. SEM analysis images show that synthesized hydrogel has a porous surface composed of nano and micro cavities.

A library of novel 4-{[(benzyloxy)carbonyl]amino}-2-hydroxybenzoic acid amides was designed and synthesized in order to provide potential acetyl- and butyrylcholinesterase (AChE/BChE) inhibitors, the in vitro inhibitory profile and selectivity index were specified. Benzyl (3-hydroxy-4-{[2-(trifluoromethoxy)phenyl]carbamoyl}phenyl)carbamate was the best AChE inhibitor with the inhibitory concentration of IC50 = 36.05 µM in the series, while benzyl {3-hydroxy-4-[(2-methoxyphenyl)carbamoyl]phenyl}-carbamate was the most potent BChE inhibitor (IC50 = 22.23 µM) with the highest selectivity for BChE (SI = 2.26). The cytotoxic effect was evaluated in vitro for promising AChE/BChE inhibitors. The newly synthesized adducts were subjected to the quantitative shape comparison with the generation of an averaged pharmacophore pattern. Noticeably, three pairs of fairly similar fluorine/bromine-containing compounds can potentially form the activity cliff that is manifested formally by high structure–activity landscape index (SALI) numerical values. The molecular docking study was conducted for the most potent AChE/BChE inhibitors, indicating that the hydrophobic interactions were overwhelmingly generated with Gln119, Asp70, Pro285, Thr120, and Trp82 aminoacid residues, while the hydrogen bond (HB)-donor ones were dominated with Thr120. π-stacking interactions were specified with the Trp82 aminoacid residue of chain A as well. Finally, the stability of chosen liganded enzymatic systems was assessed using the molecular dynamic simulations. An attempt was made to explain the noted differences of the selectivity index for the most potent molecules, especially those bearing unsubstituted and fluorinated methoxy group.

Pulmonary fibrosis is one of the most common complications of paraquat (PQ) poisoning, which becomes the focus of treatment. More and more studies have found that 5-Aminosalicylic acid (5-ASA) may be a prospective therapy against fibrotic diseases. In the present study, we observed whether 5-ASA could attenuate the pulmonary fibrosis in PQ-treated rats and human lung fibroblasts (WI38VA13) cells, and subsequently explored the possible underlying mechanisms. Wistar rats were divided into control group, 5-ASA group, PQ group and PQ + 5-ASA group. Rats were sacrificed on 3, 7, 14, and 28 days after PQ treatment. We observed pulmonary histopathological changes and fibrosis formation among different groups through hematoxylin and eosin (H&E) and Masson staining and TGF-β1, p-Smad3 and the peroxisome proliferator activated receptor γ (PPARγ) pulmonary content via immunohistochemical staining and Western blot. In addition, human lung fibroblasts WI38VA13 were also divided into control group, PQ group, 5-ASA group and PQ + 5-ASA group. And the role of TGF-β1 signaling pathway regulated factors (TGF-β1, p-Smad3 and PPARγ) were explored. Treatment with 5-ASA significantly inhibited the PQ-induced activation of TGF-β1 signaling pathway in human lung fibroblasts WI38VA13 cells. In conclusion, the results of this study suggested that 5-ASA has potential value in the treatment of PQ-induced pulmonary fibrosis via suppressing the activation of TGF-β1 signaling pathway.

An expansion of Enterobacterales in the fecal microbiota is a microbial signature of dysbiosis that is linked to many noncommunicable diseases, including ulcerative colitis. Here, we used Escherichia coli, a representative of the Enterobacterales, to show that its dysbiotic expansion during colitis can be remediated by modulating host epithelial metabolism., 5-Aminosalicylic acid (5-ASA), a peroxisome proliferator-activated receptor gamma (PPAR-γ) agonist, is a widely used first-line medication for the treatment of ulcerative colitis, but its anti-inflammatory mechanism is not fully resolved. Here, we show that 5-ASA ameliorates colitis in dextran sulfate sodium (DSS)-treated mice by activating PPAR-γ signaling in the intestinal epithelium. DSS-induced colitis was associated with a loss of epithelial hypoxia and a respiration-dependent luminal expansion of Escherichia coli, which could be ameliorated by treatment with 5-ASA. However, 5-ASA was no longer able to reduce inflammation, restore epithelial hypoxia, or blunt an expansion of E. coli in DSS-treated mice that lacked Pparg expression specifically in the intestinal epithelium. These data suggest that the anti-inflammatory activity of 5-ASA requires activation of epithelial PPAR-γ signaling, thus pointing to the intestinal epithelium as a potential target for therapeutic intervention in ulcerative colitis.

Bullo Saifullah,1,2 Palanisamy Arulselvan,3,4 Mohamed E El Zowalaty,3,5 Woan Sean Tan,3 Sharida Fakurazi,6 Thomas J Webster,7 Rabia Baby,1 Mohd Zobir Hussein1 1Materials Synthesis and Characterization Laboratory, Institute of Advanced Technology (ITMA), Universiti Putra Malaysia, Serdang, Selangor, Malaysia; 2Department of Management Sciences and Technology, The Begum Nusrat Bhutto Women University Sukkur, Sukkur, Sindh, 65170, Pakistan; 3Laboratory for Vaccine and Immunotherapeutics, Institute of Biosciences, University Putra Malaysia, Serdang, Selangor, 43400, Malaysia; 4Muthayammal Centre for Advanced Research, Muthayammal College of Arts and Science, Namakkal, Tamil Nadu, 637408, India; 5Zoonosis Science Center, Department of Microbiology and Immunology, Uppsala University, Uppsala, Sweden; 6Department of Human Anatomy, Faculty of Medicine and Health Science, Universiti Putra Malaysia, Serdang, Selangor, Malaysia; 7Department of Chemical Engineering, Northeastern University, Boston, MA, USACorrespondence: Mohd Zobir HusseinMaterials Synthesis and Characterization Laboratory, Institute of Advanced Technology, (ITMA), Universiti Putra Malaysia, Serdang, Selangor, MalaysiaTel +60 397698092Email mzobir@upm.edu.myIntroduction: Mycobacterium tuberculosis infections are associated with severe local inflammatory reactions, which may be life-threatening and lead to tuberculosis pathogenesis and associated complications. Inorganic nanolayers have been vastly exploited for biomedical applications (especially in drug delivery) because of their biocompatible and biodegradable nature with the ability to release a drug in a sustained manner. Herein, we report a new nanodelivery system of inorganic nanolayers based on magnesium layered hydroxides (MgLH) and a successfully intercalated anti-tuberculosis drug para-aminosalicylic acid (PAS).Methods: The designed anti-tuberculosis nanodelivery composite, MgLH-PAS, was prepared by a novel co-precipitation method using MgNO3 as well MgO as starting materials.Results: The designed nano-formulation, PAS-MgLH, showed good antimycobacterial and antimicrobial activities with significant synergistic anti-inflammatory effects on the suppression of lipopolysaccharide (LPS) stimulated inflammatory mediators in RAW 264.7 macrophages. The designed nano-formulation was also found to be biocompatible with human normal lung cells (MRC-5) and 3T3 fibroblast cells. Furthermore, the in vitro release of PAS from PAS-MgLH was found to be sustained in human body simulated phosphate buffer saline (PBS) solutions of pH 7.4 and pH 4.8.Discussion: The results of the present study are highly encouraging for further in vivo studies. This new nanodelivery system, MgLH, can be exploited in the delivery of other drugs and in numerous other biomedical applications as well.Keywords: Mycobacterium tuberculosis, magnesium layered hydroxides, biomaterial, sustained release, anti-tuberculosis, anti-inflammatory

Herein, a novel ratio fluorescence method based on N/P-doped carbon dots (NPCDs) for detecting 5-aminosalicylic acid (5-ASA) in mesalazine enteric coated tablets and blood were reported for the first time. NPCDs were successfully prepared through a simple one-step hydrothermal strategy by employing adenosine triphosphate (ATP) and p-toluidine as raw materials. NPCDs exhibit bright blue emissions with excitation/emission peaks at 340/423 nm with moderate quantum yield (20.75%). In addition, 5-ASA has a certain weak fluorescence emission peak at 487 nm. Adding 5-ASA into NPCDs significantly enhanced the fluorescence intensity, which may result from aggregation induced emission (AIE) of 5-ASA on the surface of NPCDs. Therefore, NPCDs only provide self-calibration signals, and their fluorescence remains almost unchanged when co-existing with 5-ASA. Therefore, the ratio of fluorescence at F487/F423 was used for detection of 5-ASA. For the fluorometric determination assay, there was a good linear relationship between F487/F423 and 5-ASA concentration between 0.50 and 130 μM (R2 = 0.9979). The detection limit was about 0.13 μM. Therefore, this method is simple, sensitive and low cost, and will be successfully applied to the detection of 5-ASA in drugs.

BACKGROUND AND AIM 5-Aminosalicylic acid (5-ASA) nephrotoxicity is a rare and idiosyncratic condition in patients with inflammatory bowel disease (IBD), which may lead to end-stage kidney failure. Kidney function monitoring is recommended in clinical practice to prevent this complication. However, no data is available regarding the knowledge and adherence of patients with IBD to this monitoring. METHODS As a part of routine practice, patients with IBD under treatment or previously treated with 5-ASA were systematically interviewed about knowledge of 5-ASA nephrotoxicity and adherence to kidney function monitoring. We reported here the experience among the first 103 consecutive patients seen in a French referral center. RESULTS A total of 103 patients (93.2% ulcerative colitis, 5.8% Crohn's disease, and 1% unclassified colitis) were analyzed. Among them, 70% were informed about the need for kidney function monitoring, and in most cases, information was provided by their gastroenterologist (94.4%). The adherence rate to monitoring was very high (84.7%). Monitoring consisted of serum creatinine and estimated glomerular filtration rate in most cases (97.2%), while 24-h proteinuria was less frequently used (69.4%). These tests were performed twice or ≥3 times per year by 44.4 and 41.7% of patients, respectively. One case of isolated elevation of proteinuria related to 5-ASA treatment was observed. CONCLUSION We reported for the first time that patients with IBD are well informed and adherent to kidney function monitoring of treatment with 5-ASA. The monitoring performed by their treating physician was generally in accordance with current recommendations.

In this study, drug nanocarriers were designed using linear copolymers with different contents of cholinium-based ionic liquid units, i.e., [2-(methacryloyloxy)ethyl]trimethylammonium chloride (TMAMA/Cl: 25, 50, and 75 mol%). The amphiphilicity of the copolymers was evaluated on the basis of their critical micelle concentration (CMC = 0.055&ndash, 0.079 mg/mL), and their hydrophilicities were determined by water contact angles (WCA = 17&deg, &ndash, 46&deg, ). The chloride anions in the polymer chain were involved in ionic exchange reactions to introduce pharmaceutical anions, i.e., p-aminosalicylate (PAS&minus, ), clavulanate (CLV&minus, ), piperacillin (PIP&minus, ), and fusidate (FUS&minus, ), which are established antibacterial agents for treating lung and respiratory diseases. The exchange reaction efficiency decreased in the following order: CLV&minus, &gt, PAS&minus, PIP&minus, FUS&minus, The hydrophilicity of the ionic drug conjugates was slightly reduced, as indicated by the increased WCA values. The major fraction of particles with sizes ~20 nm was detected in systems with at least 50% TMAMA carrying PAS or PIP. The influence of the drug character and carrier structure was also observed in the kinetic profiles of the release processes driven by the exchange with phosphate anions (0.5&ndash, 6.4 &mu, g/mL). The obtained polymer-drug ionic conjugates (especially that with PAS) are promising carriers with potential medical applications.

Surface decoration of living cells by exogenous substances offers a unique tool for understanding and tuning cell behaviors, which plays a critical role in cell-based therapy. Here, a facile yet versatile approach for decorating individual living cells with multimodal coatings is reported. By simply co-depositing with dopamine under a cytocompatible condition, various functional small molecules and polymers can be encoded to form a multifunctional coating on a cell's surface. The accessibility and versatility of this method to decorate diverse cells, including bacteria, fungi, and mammalian cells is demonstrated. With the ability to tune surface functions, ligand co-deposited gut microbiota is prepared as oral therapeutics for targeted treatment of colitis. Given the dual cytoprotective and targeting effects of the coating, decorated cells show more than 30-times higher bioavailability in the gut and fourfold higher accumulation in the inflamed tissue in comparison with those of uncoated bacteria. Multimodal therapeutic cells further validate strikingly increased treatment efficacy over clinical aminosalicylic acid in colitis mice. Decorating with multifunctional coatings proposes a robust platform for developing multimodal cells for enhanced cell-based therapy.