AIM： To investigate whether microproteinuria in patients with inflammatory bowel disease （IBD） is associated with the disease activity or the treatment with 5-aminosalicylic acid （5-ASA）. METHODS： We prospective...AIM： To investigate whether microproteinuria in patients with inflammatory bowel disease （IBD） is associated with the disease activity or the treatment with 5-aminosalicylic acid （5-ASA）. METHODS： We prospectively studied microproteinuria in 86 consecutive patients with IBD, 61 with ulcerative colitis （UC） and 25 with Crohn＇s disease （CD）, before as well as 2 and 6 months after their inclusion in the study. Forty-six patients received 5-ASA for a period of 28.8 months （range 1-168 too）. Microalbuminuria （mALB） and urine levels of the renal tubular proteins β2-microglobulin （β2mGLB） and β-N-acetyI-D-glucosamidase （β-NAG） as well as the creatinine clearance were determined in a 12-h overnight urine collection. Tumor necrosis factor-α （TNF-α） serum levels were also measured. RESULTS： A total of 277 measurements （194 in UC patients and 83 in CD patients） were performed. The prevalence of abnormal microoproteinuria in UC and CD patients was 12.9% and 6.0% for mALB, 22.7% and 27.7% for B2mGLB, and 11.3% and 8.4% for β-NAG, respectively, mALB was not associated with IBD activity. β2mGLB and B-NAG urine levels were correlated to UC activity （UCAI： P〈0.01; UCEI： P〈0.005）. mALB in UC patients and β-NAG urine levels in CD patients were related to TNF-α serum levels. An association was noticed between microproteinuria and smoking habit. Treatment with 5-ASA was not correlated to the severity of microproteinuria or to the changes of creatinine clearance.CONCLUSION： Microproteinuria is mainly associated with UC and its activity but not affected by 5-ASA.展开更多
Severe reactions to mesalamine products are rarely seen in pediatric patients. We report a case of a 12-year-old boy who had a severe cardiac reaction to a mesalamine product Asacol. Past medical history is significan...Severe reactions to mesalamine products are rarely seen in pediatric patients. We report a case of a 12-year-old boy who had a severe cardiac reaction to a mesalamine product Asacol. Past medical history is significant for ulcerative colitis (UC) diagnosed at 9 years of age. Colo- noscopy one week prior to admission revealed pancoli- tis. He was treated with Asacol 800 mg three times per day and prednisone 20 mg/d. He was subsequently ad- mitted to the hospital for an exacerbation of his UC and started on intravenous solumedrol. He had improvement of his abdominal pain and diarrhea. The patient com- plained of new onset of chest pain upon initiating Asacol therapy. Electrocardiogram (ECG) revealed non-specific ST-T wave changes with T-wave inversion in the lateral leads. Echocardiogram (ECHO) revealed low-normal to mildly depressed left ventricular systolic function. The left main coronary artery and left anterior descending artery were mildly prominent measuring 5 mm and 4.7 mm, respectively. His chest pain completely resolved within 24-36 h of discontinuing Asacol. A repeat echo- cardiogram performed two days later revealed normal left ventricular function with normal coronary arteries (< 3.5 mm). Onset of chest pain after Asacol and im- mediate improvement of chest pain, as well as improve- ment of echocardiogram and ECG findings after discon- tinuing Asacol suggests that our patient suffered from a rare drug-hypersensitivity reaction to Asacol.展开更多
AIM: To investigate the effects of 5-aminosalicylic acid (5-ASA) in combination with nimesulide on the proliferation of HT-29 colon carcinoma cells and its potential mechanisms. METHODS: Inhibitory effects of drugs (5...AIM: To investigate the effects of 5-aminosalicylic acid (5-ASA) in combination with nimesulide on the proliferation of HT-29 colon carcinoma cells and its potential mechanisms. METHODS: Inhibitory effects of drugs (5-ASA,nimesulide and their combination) on HT-29 colon carcinoma cells were investigated by thiazolyl blue tetrazolium bromide (MTT) assay. Cellular apoptosis and proliferation were detected by TUNEL assay and immunocytochemical staining,respectively. RESULTS: Pretreatment with 5-ASA or nimesulide at the concentration of 10-1000 μmol/L inhibited proliferation of HT-29 colon carcinoma cells in a dose-dependent manner in vitro (t = 5.122,P < 0.05; t = 3.086,P < 0.05,respectively). The inhibition rate of HT-29 colon carcinoma cell proliferation was also increased when pretreated with 5-ASA (100 μmol/L) or nimesulide (100 μmol/L) for 12-96 h,which showed an obvious time-effect relationship (t = 6.149,P < 0.05; t = 4.159,P < 0.05,respectively). At the concentration of 10-500 μmol/L,the apoptotic rate of HT-29 colon carcinoma cells significantly increased (t = 18.156,P < 0.001; t = 19.983,P < 0.001,respectively),while expression of proliferating cell nuclear antigen (PCNA) was remarkably decreased (t = 6.828,P < 0.05; t = 14.024,P < 0.05,respectively). 5-ASA in combination with nimesulide suppressed the proliferation of HT-29 colon carcinoma cells more than either of these agents in a dose-dependent and time-dependent manner (t = 5.448,P < 0.05; t = 4.428,P < 0.05,respectively). CONCLUSION: 5-ASA and nimesulide may inhibit the proliferation of HT-29 colon carcinoma cells and coadministration of these agents may have additional chemopreventive potential.展开更多
The development of 5-aminosalicylic acid (5-ASA) therapy as a life long treatment for ulcerative colitis is reviewed from its origins in the 1940s to the present day. The drug was designed to treat rheumatoid arthriti...The development of 5-aminosalicylic acid (5-ASA) therapy as a life long treatment for ulcerative colitis is reviewed from its origins in the 1940s to the present day. The drug was designed to treat rheumatoid arthritis,but was found helpful in the management of nine patients with ulcerative colitis. This discovery preceded the emergence of the clinical trial as a tool for assessing a new drug's efficacy; as a result it lacked scientific rigour and was selective in its presentation of results. Nevertheless it identified the future cornerstone of therapy in ulcerative colitis. In 1962,the first double blind controlled trial of sulphasalazine was conducted on 40 patients. Outcome measures were subjective and included symptoms and an assessment of the rectal mucosa. In 1973,the first two papers on the role of sulphasalazine in maintenance of remission were published. Both used placebo controls and had a stratified design. Outcomes were measured using "an intention to treat" approach. The British study of 64 patients used both subjective and objective criteria to assess outcomes. Patients on placebo had a relapse rate four times patients on active treatment and this founded the basis for a life long approach to therapy with 5-ASA compounds in ulcerative colitis. However,in 1985,a small "on demand" study of 32 patients suggested this approach might be as effective as continuous treatment. Some support for this view came from an Italian study which showed no benefit to continued treatment for those in remission for two years or more. The central problem these studies identify is that of adherence to treatment in the long-term. Few studies have considered patients' attitudes to continuous therapy and it is an area that needs further investigation.展开更多
AIM： To investigate the release of cyclodextrin-S-amino- salicylic acid （CyD-S-ASA） in cecum and colon. METHODS： An anti-inflammatory drug 5-ASA was conjugated onto the hydroxyl groups of α-, β- and γ-cydodextr...AIM： To investigate the release of cyclodextrin-S-amino- salicylic acid （CyD-S-ASA） in cecum and colon. METHODS： An anti-inflammatory drug 5-ASA was conjugated onto the hydroxyl groups of α-, β- and γ-cydodextrins （CyDs） through an ester linkage, and the in vivo drug release behavior of these prodrugs in rat＇ s gastrointestinal tract after the oral administration was investigated. RESULTS： The 5-ASA concentration in the rat＇s stomach and small intestine after the oral administration of CyD- 5-ASA conjugate was much lower than that after the oral administration of 5-ASA alone. The lower concentration was attributable to the passage of the conjugate through the stomach and small intestine without significant degradation or absorption, followed by the degradation of the conjugate site-specific in the cecum and colon. The oral administration of CyD-S-ASA resulted in lower plasma and urine concentration of 5-ASA than that of 5-ASA alone. CONCLUSION： CyD-5-ASA conjugates may be used as prodrugs for colon-specific drug delivery system.展开更多
AIM: To investigate the effect of 5-aminosalicylic acid (5-ASA) suppositories on rectal band ligation-induced pain. METHODS: Sixty patients were randomized into two treatment groups. RESULTS: Our results showed that t...AIM: To investigate the effect of 5-aminosalicylic acid (5-ASA) suppositories on rectal band ligation-induced pain. METHODS: Sixty patients were randomized into two treatment groups. RESULTS: Our results showed that there was no difference between 5-ASA suppository group and the control group for pain control. CONCLUSION: 5-ASA may be an alternative treatment for hemorrhoids; however, it does not affect the rectal band ligation-induced pain.展开更多
AIM: To study anti-Epstein-Barr virus(EBV) Ig G antibodies in Crohn′s disease in relation to treatment, immune cells, and prior tonsillectomy/appendectomy.METHODS: This study included 36 CD patients and 36 healthy in...AIM: To study anti-Epstein-Barr virus(EBV) Ig G antibodies in Crohn′s disease in relation to treatment, immune cells, and prior tonsillectomy/appendectomy.METHODS: This study included 36 CD patients and 36 healthy individuals(controls), and evaluated different clinical scenarios(new patient, remission and active disease), previous mucosa-associated lymphoid tissue removal(tonsillectomy and appendectomy) and therapeutic regimens(5-aminosalicylic acid, azathioprine, anti-tumor necrosis factor, antibiotics, and corticosteroids). T and B cells subsets in peripheral blood were analyzed by flow cytometry(markers included: CD45, CD4, CD8, CD3, CD19, CD56, CD2, CD3, TCRαβ and TCRγδ) to relate with the levels of anti-EBV Ig G antibodies, determined by enzyme-linked immunosorbent assay.RESULTS: The lowest anti-EBV Ig G levels were observed in the group of patients that were not in a specific treatment(95.4 ± 53.9 U/m L vs 131.5 ± 46.2 U/m L, P = 0.038). The patients that were treated with 5-aminosalicylic acid showed the highest anti-EBV Ig G values(144.3 U/m L vs 102.6 U/m L, P = 0.045). CD19+ cells had the largest decrease in the group of CD patients that received treatment(138.6 vs 223.9; P = 0.022). The analysis of anti-EBV Ig G with respect to the presence or absence of tonsillectomy showed the highest values in the tonsillectomy group of CD patients(169.2 ± 20.7 U/m L vs 106.1 ± 50.3 U/m L, P = 0.002). However, in the group of healthy controls, no differences were seen between those who had been tonsillectomized and subjects who had not been operated on(134.0 ± 52.5 U/m L vs 127.7 ± 48.1 U/m L, P = 0.523).CONCLUSION: High anti-EBV Ig G levels in CD are associated with 5-aminosalicylic acid treatment, tonsillectomy, and decrease of CD19+ cells.展开更多
5-aminosalicylate(5-ASA)agents remain the mainstay treatment in ulcerative colitis(UC).A number of oral 5-ASA agents are commercially available,including azobond pro-drugs,as well as delayed-and controlledrelease form...5-aminosalicylate(5-ASA)agents remain the mainstay treatment in ulcerative colitis(UC).A number of oral 5-ASA agents are commercially available,including azobond pro-drugs,as well as delayed-and controlledrelease forms of mesalazine.However,poor adherence due to frequent daily dosing and a large number of tablets has been shown to be an important barrier to successful management of patients with UC.Recently, new,once-daily formulations of mesalazine,including the unique multi-matrix delivery system and mesalazine granules,were proven to be efficacious in inducing and maintaining remission in mild-to-moderate UC,with a good safety profile comparable to that of other oral mesalazine formulations.In addition,they offer the advantage of a low pill burden and might contribute to increased long-term compliance and treatment success in clinical practice.This editorial summarizes the available literature on the short-and medium-term efficacy and safety of the new once-daily mesalazine formulations.展开更多
New once daily mesalamine formulations may improve adherence to medication usage.Response to Asacol and other forms of 5-aminosalicyclic acid(5-ASA)is better correlated with tissue concentrations and best predicted by...New once daily mesalamine formulations may improve adherence to medication usage.Response to Asacol and other forms of 5-aminosalicyclic acid(5-ASA)is better correlated with tissue concentrations and best predicted by concentrations of the drug within the lumen of the colon.Our group used computer simulation to predict colonic 5-ASA levels after Asacol administration.In our study,the model simulated Asacol distribution in the healthy colon,and during quiescent and active ulcerative colitis.An Asacol dosage of 800 mg,threetimes a day,was compared to 2400 mg given once a day.Under ideal conditions,the predicted maximum drug in the total colon and individual colonic segments over 100 d differed by less than 3%between single and multiple doses.Despite changes in motility and defection rates,the predicted maximum and average 5-ASA concentrations in the total colon and individual colonic segments differed by less than 10%between dosing regimens.Asymmetric distribution of 5-ASA in the colon was influenced by frequency of bowel movements and colonic transit rate.In active colitis,sigmoid 5-ASA concentration becomes negligible.Our model supports once daily administration of Asacol as standard treatment for ulcerative colitis.展开更多
Inflammatory bowel disease (IBD) is classically subdivided into ulcerative colitis (UC) and Crohn's disease (CD). Patients with IBD have increased risk for colorectal cancer. Because the pathogenesis of colorectal...Inflammatory bowel disease (IBD) is classically subdivided into ulcerative colitis (UC) and Crohn's disease (CD). Patients with IBD have increased risk for colorectal cancer. Because the pathogenesis of colorectal carcinoma has not been entirely defined yet and there is no ideal treatment for colon cancer, cancer prevention has become increasingly important in patients with IBD. The two adopted methods to prevent the development of colon cancer in clinical practice include the prophylactic colectomy and colonoscopic surveillance.But patients and physicians seldom accept colectomy as a routine preventive method and most patients do not undergo appropriate colonoscopic surveillance. Chemoprevention refers to the use of natural or synthetic chemical agents to reverse, suppress, or to delay the process of carcinogenesis.Chemoprevention is a particularly useful method in the management of patients at high risk for the development of specific cancers based on inborn genetic susceptibility, the presence of cancer-associated disease, or other known risk factors. Prevention of colorectal cancer by administration of chemopreventive agents is one of the most promising options for IBD patients who are at increased risks of the disease. The chemopreventive efficacy of nonsteroidal antiinflammatory drugs (NSAIDs) against intestinal tumors has been well established. But with reports that NSAIDs aggravated the symptoms of colitis, their sustained use for the purpose of cancer chemoprevention has been relatively contraindicated in IBD patients. Another hopeful candidate chemoprevention drug for IBD patients is 5-aminosalicylic acid (5-ASA), which is well tolerated by most patients and has limited systemic adverse effects, and no gastrointestinal toxicity. 5-ASA lacks the well-known side effects of longterm NSAIDs use. Retrospective correlative studies have suggested that the long-term use of 5-ASA in IBD patients may significantly reduce the risk of development of colorectal cancer. According to the literature, this agent might well satisfy clinical expectations with respect to a safe and effective chemopreventive agent.展开更多
2,5-Furandicarboxylic acid(FDCA)is a promising biomass-derived polymeric monomer that serves as an attractive alternative to terephthalic acid derived from fossil resources.However,the green and efficient production o...2,5-Furandicarboxylic acid(FDCA)is a promising biomass-derived polymeric monomer that serves as an attractive alternative to terephthalic acid derived from fossil resources.However,the green and efficient production of FDCA through the oxidation of 5-hydroxymethylfurfural(HMF)and its derivatives is still rudimentary under base-free conditions.In this work,oxygen-vacancy-rich Mn Oxwas prepared and displayed a strong adsorption and anchoring ability to Ru species that mainly exposed the(210)plane of RuO_(2),bringing about highly dispersed and active interfacial Ru-O-Mn structures.Experimental results and density functional theory calculations confirm that these above features greatly facilitate the adsorption/activation of oxygen and the dehydrogenation-oxidation of HMF/5-methoxymethylfurfural(MMF),which enables an efficient FDCA production under base-free and mild conditions.Notably,a desirable FDCA yield of 86.56%was still obtained from concentrated HMF(10 wt%)under base-free conditions over oxygen-vacancy-rich Mn Oxsupported Ru Ox(1.0 MPaO_(2),120℃,6 h).This work delineates a facile catalyst preparation strategy for HMF/MMF oxidation,and might open a new avenue for the green synthesis of FDCA under base-free conditions.展开更多
Highly-efficient oxidation of 5-hydroxymethylfurtural(HMF) to 2,5-furandicarboxylic acid(FDCA) at low temperature with air as the oxidant is still challenging.Herein,inspired by the respirato ry electron transport cha...Highly-efficient oxidation of 5-hydroxymethylfurtural(HMF) to 2,5-furandicarboxylic acid(FDCA) at low temperature with air as the oxidant is still challenging.Herein,inspired by the respirato ry electron transport chain(ETC) of living cells mediated by electron carriers,we constructed artificial ETCs and transformed liquid flow fuel cells(LFFCs) to flexible reactors for efficient oxidation of HMF to produce FDCA under mild conditions.This LFFC reactor employed an electrodeposition modified nickel foam as an anode to promote HMF oxidation and(VO_(2))_(2)SO_(4) as a cathode electron carrier to facilitate the electron transfer to air.The reaction rate could be easily controlled by selecting the anode catalyst,adjusting the external loading and changing the cathodic electron carrier or oxidants.A maximal power density of 44.9 mW cm^(-2) at room temperature was achieved,while for FDCA production,short-circuit condition was preferred to achieve quick transfer of electrons.For a single batch operation with 0.1 M initial HMF,FDCA yield reached 97.1%.By fed-batch operation,FDCA concentration reached 144.5 g L^(-1) with a total yield of 96%.Ni^(2+)/Ni^(3+) redox couple was the active species mediating the electron transfer,while both experimental and DFT calculation results indicated that HMFCA pathway was the preferred reaction mechanism.展开更多
Pien Tze Huang(PZH),a class-1 nationally protected traditional Chinese medicine(TCM),has been used to treat liver diseases such as hepatitis;however,the effect of PZH on the progression of sepsis is unknown.Here,we re...Pien Tze Huang(PZH),a class-1 nationally protected traditional Chinese medicine(TCM),has been used to treat liver diseases such as hepatitis;however,the effect of PZH on the progression of sepsis is unknown.Here,we reported that PZH attenuated lipopolysaccharide(LPS)-induced sepsis in mice and reduced LPS-induced production of proinflammatory cytokines in macrophages by inhibiting the activation of mitogen-activated protein kinase(MAPK)and nuclear factor-kappa B(NF-κB)signalling.Mechanistically,PZH stimulated signal transducer and activator of transcription 3(STAT3)phosphorylation to induce the expression of A20,which could inhibit the activation of NF-κB and MAPK signalling.Knockdown of the bile acid(BA)receptor G protein-coupled bile acid receptor 1(TGR5)in macrophages abolished the effects of PZH on STAT3 phosphorylation and A20 induction,as well as the LPS-induced inflammatory response,suggesting that BAs in PZH may mediate its anti-inflammatory effects by activating TGR5.Consistently,deprivation of BAs in PZH by cholestyramine resin reduced the effects of PZH on the expression of phosphorylated-STAT3 and A20,the activation of NF-κB and MAPK signalling,and the production of proinflammatory cytokines,whereas the addition of BAs to cholestyramine resin-treated PZH partially restored the inhibitory effects on the production of proinflammatory cytokines.Overall,our study identifies BAs as the effective components in PZH that activate TGR5-STAT3-A20 signalling to ameliorate LPS-induced sepsis.展开更多
Strawberry Fusarium wilt (SFW) is a systematic soil-borne disease caused by Fusarium oxysporum f.sp.fragaria (Fof),which infects the vascular bundles,blocking water and nutrient transport from roots to the aboveground...Strawberry Fusarium wilt (SFW) is a systematic soil-borne disease caused by Fusarium oxysporum f.sp.fragaria (Fof),which infects the vascular bundles,blocking water and nutrient transport from roots to the aboveground.It is a severe pathogen which spreads rapidly and destroys strawberry production.Finding a way to control this disease is of great scientific value and practical importance.In this study,three fungi were isolated from the vascular tissues of sick strawberries in the field.After DNA sequencing,they were identified as Fof,Aspergillus fumigatus and Trichoderma harzianum,respectively,among which the first two are pathogens and the third is a probiotic.All fungi were controlled by thiophanate-methyl (TM),a commercial fungicide.On PDA medium,20 mg·L^(-1)5-aminolevulinic acid (ALA),a natural non-protein amino acid,promoted T.harzianum proliferation,but inhibited Fof and A.fumigatus.In confrontation test,the growth of Fof or A.fumigatus was inhibited by T.harzianum and exogenous ALA promoted T.harzianum growth but significantly inhibited the pathogen growth.When three species of fungi were separately or combinedly inoculated on healthy strawberry plants,T.harzianum promoted plant growth and development while Fof or A.fumigatus caused growth retardation,where Fof directly caused leaf yellowing and plant wilting.When the plants inoculated with different fungus were treated with ALA,the results turned out that ALA alleviated SFW symptoms by bidirectionally promoting T.harzianum proliferation and inhibiting Fof and A.fumigatus.Thus,ALA might be used in comprehensively controlling SFW in strawberry industry.展开更多
Despite the advent of biological products, such as anti-tumor necrosis factor-α monoclonal antibodies (infliximab and adalimumab), for treatment of moderate to severe cases of inflammatory bowel disease (I...Despite the advent of biological products, such as anti-tumor necrosis factor-α monoclonal antibodies (infliximab and adalimumab), for treatment of moderate to severe cases of inflammatory bowel disease (IBD), most patients depend upon aminosalicylates as the conventional treatment option. In recent years, the increased knowledge of complex pathophysiological processes underlying IBD has resulted in development of a number of newer pharmaceutical agents like low-molecular-weight heparin, omega-3 fatty acids, probiotics and innovative formulations such as high-dose, once-daily multi-matrix mesalamine, which are designed to minimize the inflammatory process through inhibition of different targets. Optimization of delivery of existing drugs to the colon using the prodrug approach is another attractive alternative that has been utilized and commercialized for 5-aminosalicylic acid (ASA) in the form of sulfasalazine, balsalazide, olsalazine and ipsalazine, but rarely for its positional isomer 4-ASA - a well-established antitubercular drug that is twice as potent as 5-ASA against IBD, and more specifically, ulcerative colitis. The present review focuses on the complete profile of 4-ASA and its advantages over 5-ASA and colon-targeting prodrugs reported so far for the management of IBD. The review also emphasizes the need for reappraisal of this promising but unexplored entity as a potential treatment option for IBD.展开更多
5-aminosalicylic acid（5-ASA） is drug of choice for the treatment of ulcerative colitis（UC）. In this study, the efficacy of topical versus oral 5-ASA for the treatment of UC was examined as well as the action mecha...5-aminosalicylic acid（5-ASA） is drug of choice for the treatment of ulcerative colitis（UC）. In this study, the efficacy of topical versus oral 5-ASA for the treatment of UC was examined as well as the action mechanism of this medication. A flexible tube was inserted into the rat cecum to establish a topical administration model of 2,4,6-trinitrobenzene sulfonic acid（TNBS）-induced UC. A total of 60 rats were divided into sham operation group（receiving an enema of 0.9% saline solution instead of the TNBS solution via the tube）, model group, topical 5-ASA group, oral Etiasa group（a release agent of mesalazine used as positive control） and oral 5-ASA group（n=12 each）. Different treatments were administered 1 day after UC induction. The normal saline（2 mL） was instilled twice a day through the tube in the sham operation group and model group. 5-ASA was given via the tube in the topical 5-ASA group（7.5 g/L, twice per day, 100 mg/kg）, and rats in the oral Etiasa group and oral 5-ASA group intragastrically received Etiasa（7.5 g/L, twice per day, 100 mg/kg） and 5-ASA（7.5 g/L, twice per day, 100 mg/kg）, respectively. The body weight was recorded every day. After 7 days of treatment, blood samples were drawn from the heart to harvest the sera. Colonic tissues were separated and prepared for pathological and related molecular biological examinations. The concentrations of 5-ASA were detected at different time points in the colonic tissues, feces and sera in different groups by using the high pressure liquid chromatography（HPLC）. The results showed that the symptoms of acute UC, including bloody diarrhea and weight loss, were significantly improved in topical 5-ASA-treated rats. The colonic mucosal damage, both macroscopical and histological, was significantly relieved and the myeloperoxidase activity was markedly decreased in rats topically treated with 5-ASA compared with those treated with oral 5-ASA or Etiasa. The mRNA and protein expression of IL-1β, IL-6, and TNF-α was down-regulated in the colonic tissue of rats topically treated with 5-ASA, significantly lower than those from rats treated with oral 5-ASA or Etiasa. The concentrations of 5-ASA in the colonic tissue were significantly higher in the topical 5-ASA group than in the oral 5-ASA and oral Etiasa groups. It was concluded that the topical administration of 5-ASA can effectively increase the concentration of 5-ASA in the colonic tissue, decrease the expression of proinflammatory cytokines, alleviate the colonic pathological damage and improve the symptoms of TNBS-induced acute UC in rats.展开更多
文摘AIM： To investigate whether microproteinuria in patients with inflammatory bowel disease （IBD） is associated with the disease activity or the treatment with 5-aminosalicylic acid （5-ASA）. METHODS： We prospectively studied microproteinuria in 86 consecutive patients with IBD, 61 with ulcerative colitis （UC） and 25 with Crohn＇s disease （CD）, before as well as 2 and 6 months after their inclusion in the study. Forty-six patients received 5-ASA for a period of 28.8 months （range 1-168 too）. Microalbuminuria （mALB） and urine levels of the renal tubular proteins β2-microglobulin （β2mGLB） and β-N-acetyI-D-glucosamidase （β-NAG） as well as the creatinine clearance were determined in a 12-h overnight urine collection. Tumor necrosis factor-α （TNF-α） serum levels were also measured. RESULTS： A total of 277 measurements （194 in UC patients and 83 in CD patients） were performed. The prevalence of abnormal microoproteinuria in UC and CD patients was 12.9% and 6.0% for mALB, 22.7% and 27.7% for B2mGLB, and 11.3% and 8.4% for β-NAG, respectively, mALB was not associated with IBD activity. β2mGLB and B-NAG urine levels were correlated to UC activity （UCAI： P〈0.01; UCEI： P〈0.005）. mALB in UC patients and β-NAG urine levels in CD patients were related to TNF-α serum levels. An association was noticed between microproteinuria and smoking habit. Treatment with 5-ASA was not correlated to the severity of microproteinuria or to the changes of creatinine clearance.CONCLUSION： Microproteinuria is mainly associated with UC and its activity but not affected by 5-ASA.
文摘Severe reactions to mesalamine products are rarely seen in pediatric patients. We report a case of a 12-year-old boy who had a severe cardiac reaction to a mesalamine product Asacol. Past medical history is significant for ulcerative colitis (UC) diagnosed at 9 years of age. Colo- noscopy one week prior to admission revealed pancoli- tis. He was treated with Asacol 800 mg three times per day and prednisone 20 mg/d. He was subsequently ad- mitted to the hospital for an exacerbation of his UC and started on intravenous solumedrol. He had improvement of his abdominal pain and diarrhea. The patient com- plained of new onset of chest pain upon initiating Asacol therapy. Electrocardiogram (ECG) revealed non-specific ST-T wave changes with T-wave inversion in the lateral leads. Echocardiogram (ECHO) revealed low-normal to mildly depressed left ventricular systolic function. The left main coronary artery and left anterior descending artery were mildly prominent measuring 5 mm and 4.7 mm, respectively. His chest pain completely resolved within 24-36 h of discontinuing Asacol. A repeat echo- cardiogram performed two days later revealed normal left ventricular function with normal coronary arteries (< 3.5 mm). Onset of chest pain after Asacol and im- mediate improvement of chest pain, as well as improve- ment of echocardiogram and ECG findings after discon- tinuing Asacol suggests that our patient suffered from a rare drug-hypersensitivity reaction to Asacol.
基金Supported by The Key Laboratory of Digestive Diseases of Anhui Province and colleagues from Department of Gastroenterology, The First Affiliated Hospital, Anhui Medical University, China
文摘AIM: To investigate the effects of 5-aminosalicylic acid (5-ASA) in combination with nimesulide on the proliferation of HT-29 colon carcinoma cells and its potential mechanisms. METHODS: Inhibitory effects of drugs (5-ASA,nimesulide and their combination) on HT-29 colon carcinoma cells were investigated by thiazolyl blue tetrazolium bromide (MTT) assay. Cellular apoptosis and proliferation were detected by TUNEL assay and immunocytochemical staining,respectively. RESULTS: Pretreatment with 5-ASA or nimesulide at the concentration of 10-1000 μmol/L inhibited proliferation of HT-29 colon carcinoma cells in a dose-dependent manner in vitro (t = 5.122,P < 0.05; t = 3.086,P < 0.05,respectively). The inhibition rate of HT-29 colon carcinoma cell proliferation was also increased when pretreated with 5-ASA (100 μmol/L) or nimesulide (100 μmol/L) for 12-96 h,which showed an obvious time-effect relationship (t = 6.149,P < 0.05; t = 4.159,P < 0.05,respectively). At the concentration of 10-500 μmol/L,the apoptotic rate of HT-29 colon carcinoma cells significantly increased (t = 18.156,P < 0.001; t = 19.983,P < 0.001,respectively),while expression of proliferating cell nuclear antigen (PCNA) was remarkably decreased (t = 6.828,P < 0.05; t = 14.024,P < 0.05,respectively). 5-ASA in combination with nimesulide suppressed the proliferation of HT-29 colon carcinoma cells more than either of these agents in a dose-dependent and time-dependent manner (t = 5.448,P < 0.05; t = 4.428,P < 0.05,respectively). CONCLUSION: 5-ASA and nimesulide may inhibit the proliferation of HT-29 colon carcinoma cells and coadministration of these agents may have additional chemopreventive potential.
文摘The development of 5-aminosalicylic acid (5-ASA) therapy as a life long treatment for ulcerative colitis is reviewed from its origins in the 1940s to the present day. The drug was designed to treat rheumatoid arthritis,but was found helpful in the management of nine patients with ulcerative colitis. This discovery preceded the emergence of the clinical trial as a tool for assessing a new drug's efficacy; as a result it lacked scientific rigour and was selective in its presentation of results. Nevertheless it identified the future cornerstone of therapy in ulcerative colitis. In 1962,the first double blind controlled trial of sulphasalazine was conducted on 40 patients. Outcome measures were subjective and included symptoms and an assessment of the rectal mucosa. In 1973,the first two papers on the role of sulphasalazine in maintenance of remission were published. Both used placebo controls and had a stratified design. Outcomes were measured using "an intention to treat" approach. The British study of 64 patients used both subjective and objective criteria to assess outcomes. Patients on placebo had a relapse rate four times patients on active treatment and this founded the basis for a life long approach to therapy with 5-ASA compounds in ulcerative colitis. However,in 1985,a small "on demand" study of 32 patients suggested this approach might be as effective as continuous treatment. Some support for this view came from an Italian study which showed no benefit to continued treatment for those in remission for two years or more. The central problem these studies identify is that of adherence to treatment in the long-term. Few studies have considered patients' attitudes to continuous therapy and it is an area that needs further investigation.
文摘AIM： To investigate the release of cyclodextrin-S-amino- salicylic acid （CyD-S-ASA） in cecum and colon. METHODS： An anti-inflammatory drug 5-ASA was conjugated onto the hydroxyl groups of α-, β- and γ-cydodextrins （CyDs） through an ester linkage, and the in vivo drug release behavior of these prodrugs in rat＇ s gastrointestinal tract after the oral administration was investigated. RESULTS： The 5-ASA concentration in the rat＇s stomach and small intestine after the oral administration of CyD- 5-ASA conjugate was much lower than that after the oral administration of 5-ASA alone. The lower concentration was attributable to the passage of the conjugate through the stomach and small intestine without significant degradation or absorption, followed by the degradation of the conjugate site-specific in the cecum and colon. The oral administration of CyD-S-ASA resulted in lower plasma and urine concentration of 5-ASA than that of 5-ASA alone. CONCLUSION： CyD-5-ASA conjugates may be used as prodrugs for colon-specific drug delivery system.
文摘AIM: To investigate the effect of 5-aminosalicylic acid (5-ASA) suppositories on rectal band ligation-induced pain. METHODS: Sixty patients were randomized into two treatment groups. RESULTS: Our results showed that there was no difference between 5-ASA suppository group and the control group for pain control. CONCLUSION: 5-ASA may be an alternative treatment for hemorrhoids; however, it does not affect the rectal band ligation-induced pain.
文摘AIM: To study anti-Epstein-Barr virus(EBV) Ig G antibodies in Crohn′s disease in relation to treatment, immune cells, and prior tonsillectomy/appendectomy.METHODS: This study included 36 CD patients and 36 healthy individuals(controls), and evaluated different clinical scenarios(new patient, remission and active disease), previous mucosa-associated lymphoid tissue removal(tonsillectomy and appendectomy) and therapeutic regimens(5-aminosalicylic acid, azathioprine, anti-tumor necrosis factor, antibiotics, and corticosteroids). T and B cells subsets in peripheral blood were analyzed by flow cytometry(markers included: CD45, CD4, CD8, CD3, CD19, CD56, CD2, CD3, TCRαβ and TCRγδ) to relate with the levels of anti-EBV Ig G antibodies, determined by enzyme-linked immunosorbent assay.RESULTS: The lowest anti-EBV Ig G levels were observed in the group of patients that were not in a specific treatment(95.4 ± 53.9 U/m L vs 131.5 ± 46.2 U/m L, P = 0.038). The patients that were treated with 5-aminosalicylic acid showed the highest anti-EBV Ig G values(144.3 U/m L vs 102.6 U/m L, P = 0.045). CD19+ cells had the largest decrease in the group of CD patients that received treatment(138.6 vs 223.9; P = 0.022). The analysis of anti-EBV Ig G with respect to the presence or absence of tonsillectomy showed the highest values in the tonsillectomy group of CD patients(169.2 ± 20.7 U/m L vs 106.1 ± 50.3 U/m L, P = 0.002). However, in the group of healthy controls, no differences were seen between those who had been tonsillectomized and subjects who had not been operated on(134.0 ± 52.5 U/m L vs 127.7 ± 48.1 U/m L, P = 0.523).CONCLUSION: High anti-EBV Ig G levels in CD are associated with 5-aminosalicylic acid treatment, tonsillectomy, and decrease of CD19+ cells.
文摘5-aminosalicylate(5-ASA)agents remain the mainstay treatment in ulcerative colitis(UC).A number of oral 5-ASA agents are commercially available,including azobond pro-drugs,as well as delayed-and controlledrelease forms of mesalazine.However,poor adherence due to frequent daily dosing and a large number of tablets has been shown to be an important barrier to successful management of patients with UC.Recently, new,once-daily formulations of mesalazine,including the unique multi-matrix delivery system and mesalazine granules,were proven to be efficacious in inducing and maintaining remission in mild-to-moderate UC,with a good safety profile comparable to that of other oral mesalazine formulations.In addition,they offer the advantage of a low pill burden and might contribute to increased long-term compliance and treatment success in clinical practice.This editorial summarizes the available literature on the short-and medium-term efficacy and safety of the new once-daily mesalazine formulations.
文摘New once daily mesalamine formulations may improve adherence to medication usage.Response to Asacol and other forms of 5-aminosalicyclic acid(5-ASA)is better correlated with tissue concentrations and best predicted by concentrations of the drug within the lumen of the colon.Our group used computer simulation to predict colonic 5-ASA levels after Asacol administration.In our study,the model simulated Asacol distribution in the healthy colon,and during quiescent and active ulcerative colitis.An Asacol dosage of 800 mg,threetimes a day,was compared to 2400 mg given once a day.Under ideal conditions,the predicted maximum drug in the total colon and individual colonic segments over 100 d differed by less than 3%between single and multiple doses.Despite changes in motility and defection rates,the predicted maximum and average 5-ASA concentrations in the total colon and individual colonic segments differed by less than 10%between dosing regimens.Asymmetric distribution of 5-ASA in the colon was influenced by frequency of bowel movements and colonic transit rate.In active colitis,sigmoid 5-ASA concentration becomes negligible.Our model supports once daily administration of Asacol as standard treatment for ulcerative colitis.
文摘Inflammatory bowel disease (IBD) is classically subdivided into ulcerative colitis (UC) and Crohn's disease (CD). Patients with IBD have increased risk for colorectal cancer. Because the pathogenesis of colorectal carcinoma has not been entirely defined yet and there is no ideal treatment for colon cancer, cancer prevention has become increasingly important in patients with IBD. The two adopted methods to prevent the development of colon cancer in clinical practice include the prophylactic colectomy and colonoscopic surveillance.But patients and physicians seldom accept colectomy as a routine preventive method and most patients do not undergo appropriate colonoscopic surveillance. Chemoprevention refers to the use of natural or synthetic chemical agents to reverse, suppress, or to delay the process of carcinogenesis.Chemoprevention is a particularly useful method in the management of patients at high risk for the development of specific cancers based on inborn genetic susceptibility, the presence of cancer-associated disease, or other known risk factors. Prevention of colorectal cancer by administration of chemopreventive agents is one of the most promising options for IBD patients who are at increased risks of the disease. The chemopreventive efficacy of nonsteroidal antiinflammatory drugs (NSAIDs) against intestinal tumors has been well established. But with reports that NSAIDs aggravated the symptoms of colitis, their sustained use for the purpose of cancer chemoprevention has been relatively contraindicated in IBD patients. Another hopeful candidate chemoprevention drug for IBD patients is 5-aminosalicylic acid (5-ASA), which is well tolerated by most patients and has limited systemic adverse effects, and no gastrointestinal toxicity. 5-ASA lacks the well-known side effects of longterm NSAIDs use. Retrospective correlative studies have suggested that the long-term use of 5-ASA in IBD patients may significantly reduce the risk of development of colorectal cancer. According to the literature, this agent might well satisfy clinical expectations with respect to a safe and effective chemopreventive agent.
基金the funding supported by the National Natural Science Foundation of China(22378338,22078275)the Natural Science Foundation of Fujian Province of China(2021H0009)the Fundamental Research Funds for the Central Universities(20720220065)。
文摘2,5-Furandicarboxylic acid(FDCA)is a promising biomass-derived polymeric monomer that serves as an attractive alternative to terephthalic acid derived from fossil resources.However,the green and efficient production of FDCA through the oxidation of 5-hydroxymethylfurfural(HMF)and its derivatives is still rudimentary under base-free conditions.In this work,oxygen-vacancy-rich Mn Oxwas prepared and displayed a strong adsorption and anchoring ability to Ru species that mainly exposed the(210)plane of RuO_(2),bringing about highly dispersed and active interfacial Ru-O-Mn structures.Experimental results and density functional theory calculations confirm that these above features greatly facilitate the adsorption/activation of oxygen and the dehydrogenation-oxidation of HMF/5-methoxymethylfurfural(MMF),which enables an efficient FDCA production under base-free and mild conditions.Notably,a desirable FDCA yield of 86.56%was still obtained from concentrated HMF(10 wt%)under base-free conditions over oxygen-vacancy-rich Mn Oxsupported Ru Ox(1.0 MPaO_(2),120℃,6 h).This work delineates a facile catalyst preparation strategy for HMF/MMF oxidation,and might open a new avenue for the green synthesis of FDCA under base-free conditions.
基金supported by the National Key R&D Program of China(2022YFA2105900)the National Natural Science Foundation of China(22178197)。
文摘Highly-efficient oxidation of 5-hydroxymethylfurtural(HMF) to 2,5-furandicarboxylic acid(FDCA) at low temperature with air as the oxidant is still challenging.Herein,inspired by the respirato ry electron transport chain(ETC) of living cells mediated by electron carriers,we constructed artificial ETCs and transformed liquid flow fuel cells(LFFCs) to flexible reactors for efficient oxidation of HMF to produce FDCA under mild conditions.This LFFC reactor employed an electrodeposition modified nickel foam as an anode to promote HMF oxidation and(VO_(2))_(2)SO_(4) as a cathode electron carrier to facilitate the electron transfer to air.The reaction rate could be easily controlled by selecting the anode catalyst,adjusting the external loading and changing the cathodic electron carrier or oxidants.A maximal power density of 44.9 mW cm^(-2) at room temperature was achieved,while for FDCA production,short-circuit condition was preferred to achieve quick transfer of electrons.For a single batch operation with 0.1 M initial HMF,FDCA yield reached 97.1%.By fed-batch operation,FDCA concentration reached 144.5 g L^(-1) with a total yield of 96%.Ni^(2+)/Ni^(3+) redox couple was the active species mediating the electron transfer,while both experimental and DFT calculation results indicated that HMFCA pathway was the preferred reaction mechanism.
基金supported by research funds from Zhangzhou Pien Tze Huang Pharmaceutical Co.Ltd(Grant Nos.:437b8f31,d6092dae,YHT-19064 to Chundong Yu)the National Natural Science Foundation of China(Grant Nos.:81970485,82173086 to Chundong Yu)the Natural Science Foundation of Fujian Province(Grant No.:2023J01249 to Shicong Wang).
文摘Pien Tze Huang(PZH),a class-1 nationally protected traditional Chinese medicine(TCM),has been used to treat liver diseases such as hepatitis;however,the effect of PZH on the progression of sepsis is unknown.Here,we reported that PZH attenuated lipopolysaccharide(LPS)-induced sepsis in mice and reduced LPS-induced production of proinflammatory cytokines in macrophages by inhibiting the activation of mitogen-activated protein kinase(MAPK)and nuclear factor-kappa B(NF-κB)signalling.Mechanistically,PZH stimulated signal transducer and activator of transcription 3(STAT3)phosphorylation to induce the expression of A20,which could inhibit the activation of NF-κB and MAPK signalling.Knockdown of the bile acid(BA)receptor G protein-coupled bile acid receptor 1(TGR5)in macrophages abolished the effects of PZH on STAT3 phosphorylation and A20 induction,as well as the LPS-induced inflammatory response,suggesting that BAs in PZH may mediate its anti-inflammatory effects by activating TGR5.Consistently,deprivation of BAs in PZH by cholestyramine resin reduced the effects of PZH on the expression of phosphorylated-STAT3 and A20,the activation of NF-κB and MAPK signalling,and the production of proinflammatory cytokines,whereas the addition of BAs to cholestyramine resin-treated PZH partially restored the inhibitory effects on the production of proinflammatory cytokines.Overall,our study identifies BAs as the effective components in PZH that activate TGR5-STAT3-A20 signalling to ameliorate LPS-induced sepsis.
基金funded by the Natural Science Foundation of China (Grant No.32172512)the Jiangsu Agricultural Science and Technology Innovation Fund[Grant No.CX(20)2023]+1 种基金the Jiangsu Special Fund for Frontier Foundation Research of Carbon Peaking and Carbon Neutralization (Grant No.BK20220005)a project funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions。
文摘Strawberry Fusarium wilt (SFW) is a systematic soil-borne disease caused by Fusarium oxysporum f.sp.fragaria (Fof),which infects the vascular bundles,blocking water and nutrient transport from roots to the aboveground.It is a severe pathogen which spreads rapidly and destroys strawberry production.Finding a way to control this disease is of great scientific value and practical importance.In this study,three fungi were isolated from the vascular tissues of sick strawberries in the field.After DNA sequencing,they were identified as Fof,Aspergillus fumigatus and Trichoderma harzianum,respectively,among which the first two are pathogens and the third is a probiotic.All fungi were controlled by thiophanate-methyl (TM),a commercial fungicide.On PDA medium,20 mg·L^(-1)5-aminolevulinic acid (ALA),a natural non-protein amino acid,promoted T.harzianum proliferation,but inhibited Fof and A.fumigatus.In confrontation test,the growth of Fof or A.fumigatus was inhibited by T.harzianum and exogenous ALA promoted T.harzianum growth but significantly inhibited the pathogen growth.When three species of fungi were separately or combinedly inoculated on healthy strawberry plants,T.harzianum promoted plant growth and development while Fof or A.fumigatus caused growth retardation,where Fof directly caused leaf yellowing and plant wilting.When the plants inoculated with different fungus were treated with ALA,the results turned out that ALA alleviated SFW symptoms by bidirectionally promoting T.harzianum proliferation and inhibiting Fof and A.fumigatus.Thus,ALA might be used in comprehensively controlling SFW in strawberry industry.
文摘Despite the advent of biological products, such as anti-tumor necrosis factor-α monoclonal antibodies (infliximab and adalimumab), for treatment of moderate to severe cases of inflammatory bowel disease (IBD), most patients depend upon aminosalicylates as the conventional treatment option. In recent years, the increased knowledge of complex pathophysiological processes underlying IBD has resulted in development of a number of newer pharmaceutical agents like low-molecular-weight heparin, omega-3 fatty acids, probiotics and innovative formulations such as high-dose, once-daily multi-matrix mesalamine, which are designed to minimize the inflammatory process through inhibition of different targets. Optimization of delivery of existing drugs to the colon using the prodrug approach is another attractive alternative that has been utilized and commercialized for 5-aminosalicylic acid (ASA) in the form of sulfasalazine, balsalazide, olsalazine and ipsalazine, but rarely for its positional isomer 4-ASA - a well-established antitubercular drug that is twice as potent as 5-ASA against IBD, and more specifically, ulcerative colitis. The present review focuses on the complete profile of 4-ASA and its advantages over 5-ASA and colon-targeting prodrugs reported so far for the management of IBD. The review also emphasizes the need for reappraisal of this promising but unexplored entity as a potential treatment option for IBD.
基金supported by grants from the National Natural Science Foundation of China(No.81072431)the Innova-tion Foundation of Huazhong University of Science and Tech-nology(No.2010MS027)
文摘5-aminosalicylic acid（5-ASA） is drug of choice for the treatment of ulcerative colitis（UC）. In this study, the efficacy of topical versus oral 5-ASA for the treatment of UC was examined as well as the action mechanism of this medication. A flexible tube was inserted into the rat cecum to establish a topical administration model of 2,4,6-trinitrobenzene sulfonic acid（TNBS）-induced UC. A total of 60 rats were divided into sham operation group（receiving an enema of 0.9% saline solution instead of the TNBS solution via the tube）, model group, topical 5-ASA group, oral Etiasa group（a release agent of mesalazine used as positive control） and oral 5-ASA group（n=12 each）. Different treatments were administered 1 day after UC induction. The normal saline（2 mL） was instilled twice a day through the tube in the sham operation group and model group. 5-ASA was given via the tube in the topical 5-ASA group（7.5 g/L, twice per day, 100 mg/kg）, and rats in the oral Etiasa group and oral 5-ASA group intragastrically received Etiasa（7.5 g/L, twice per day, 100 mg/kg） and 5-ASA（7.5 g/L, twice per day, 100 mg/kg）, respectively. The body weight was recorded every day. After 7 days of treatment, blood samples were drawn from the heart to harvest the sera. Colonic tissues were separated and prepared for pathological and related molecular biological examinations. The concentrations of 5-ASA were detected at different time points in the colonic tissues, feces and sera in different groups by using the high pressure liquid chromatography（HPLC）. The results showed that the symptoms of acute UC, including bloody diarrhea and weight loss, were significantly improved in topical 5-ASA-treated rats. The colonic mucosal damage, both macroscopical and histological, was significantly relieved and the myeloperoxidase activity was markedly decreased in rats topically treated with 5-ASA compared with those treated with oral 5-ASA or Etiasa. The mRNA and protein expression of IL-1β, IL-6, and TNF-α was down-regulated in the colonic tissue of rats topically treated with 5-ASA, significantly lower than those from rats treated with oral 5-ASA or Etiasa. The concentrations of 5-ASA in the colonic tissue were significantly higher in the topical 5-ASA group than in the oral 5-ASA and oral Etiasa groups. It was concluded that the topical administration of 5-ASA can effectively increase the concentration of 5-ASA in the colonic tissue, decrease the expression of proinflammatory cytokines, alleviate the colonic pathological damage and improve the symptoms of TNBS-induced acute UC in rats.
