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Sample records for aminosalicylic acid-para

  1. Synthesis of Chromium (Ⅲ) 5-aminosalicylate

    Institute of Scientific and Technical Information of China (English)

    LI Wei; HAO Er-jun; JIANG Yu-qin

    2004-01-01

    As we all known that diabetes is a chronic disease with major health consequences.Research has revealed that the occurrence of diabetes have great thing to do with the chromium deficient. Almost 40 years after the first report of glucose tolerance factor(GTF) [1], no conclusive evidence for an isolable ,biologically active form of chromium exited. Three materials have been proposed to be the biologically active form of chromium: "glucose tolerance factor", chromium Picolinate and low-molecular-weight chromium-binding substance (LWMCr) [2] . So there is potential for the design of new chromium drugs .5-Aminosalicylic acid (5-ASA) is identified as an active component in the therapy of inflammatory bowel disease (IBD) such as Crohn's disease and ulcerative colitis . The therapeutic action of 5-ASA is believed to be coupled to its ability to act as a free radical scavenger [3-4],acting locally on the inflamed colonic mucosa [5-7]. However, the clinical use of 5-ASA is limited, since orally administered 5-ASA is rapidly and completely absorbed from the upper gastrointestinal tract and therefore the local therapeutic effects of 5-ASA in the colon is hardly expected.In this paper, we report the synthesis of chromium(Ⅲ)5-aminosalicylate from 5-ASA and CrCl3. 6H2O.The synthesis route is as follow:The complex has been characterized by elemental analysis, IR spectra, X-ray powder diffractionand TG-DTA . They indicate that the structure is tris(5-ASA) Chromium . Experiments show that thecomplex has a good activity for supplement tiny dietary chromium, lowering blood glucose levels,lowering serum lipid levels and in creasing lean body mass .

  2. Preparation and study of rare earth 4-aminosalicylates

    International Nuclear Information System (INIS)

    p-Aminosalicylates of Y, La and lanthanides prepared in the reaction of the ammonium p-aminosalicylate and lanthanide chlorides in solutions have the general formula Ln(C7H6O3N)3.nH2O, where n = 3 for La, Ce; n = 2 for Pr, Nd, Sm, Eu; n = 0 for Y, Gd-Lu. Their solubilities in water are of the order of 10-3mol dm-3. Heating above 350-450K leads to dehydration and decomposition at the same time. The IR and X-ray spectra for the obtained complexes of La-Nd are crystalline compounds. The way of metal-ligand coordination is discussed. (Author)

  3. Synthesis of azo derivatives of 4-aminosalicylic acid

    Institute of Scientific and Technical Information of China (English)

    Zheng Bao Zhao; Hui Xia Zheng; Yuan Gui Wei; Jiang Liu

    2007-01-01

    For searching a better 4-aminosalicylic acid derivative with higher activity and less side effects against the inflammatory bowel disease, 4-aminosalicylic acid (4-ASA) was protected by benzyloxycarbonyl and acetyl, respectively.The resultant was hydrogenized to remove protective group of amino group, then the product was reacted with NaNO2 to give diazonium salt, which was conjugated with salicylic acid, hydroxybenzene, N-salicyloyl glycine acid to get azo derivatives of 4-ASA.The azo derivatives were hydrolyzed under the alkaline condition to get the target products.All compounds were characterized by FT-IR, 1H NMR, 13C NMR spectra in details.New derivatives of 4-ASA were characterized.The synthetic route was reasonable and feasible.

  4. Real-time in vitro dissolution of 5-aminosalicylic acid from single ethyl cellulose coated extrudates studied by UV imaging

    DEFF Research Database (Denmark)

    Gaunø, Mette Høg; Vilhelmsen, Thomas; Larsen, Crilles Casper; Bøtker, Johan Peter; Wittendorff, Jørgen; Rantanen, Jukka; Ostergaard, Jesper

    2013-01-01

    The purpose of this study was to investigate the in vitro release of 5-aminosalicylic acid from single extrudates by UV imaging and to explore the technique as a visualization tool for detecting film coating defects on extrudates coated with a thin ethyl cellulose layer. 5-Aminosalicylic acid ext...

  5. 5-Aminosalicylic acid dependency in Crohn's disease: A Danish Crohn Colitis Database study

    DEFF Research Database (Denmark)

    Duricova, D.; Pedersen, N.; Elkjaer, M.;

    2010-01-01

    Background and aims The role of 5 aminosalicylic acid (5 ASA) in Crohns disease is unclear The outcome of the first course of 5 ASA monotherapy with emphasis on 5 ASA dependency was retrospectively assessed in consecutive cohort of 537 Crohn s disease patients diagnosed 1953-2007 Methods Following...

  6. Synthesis and properties of bis(p-aminosalicyl)borates of the 2 group metals of periodic system

    International Nuclear Information System (INIS)

    Potassium, zinc and cadmium bis(n-aminosalicyl) borates of the Me[N2C14H10O6B]2xnH2O composition have been obtained. The densities and crystal lattice plane spacings have been determined and the IR absorption spectra have been recorded. A tentative structure of the bis(n-aminosalicyl) borates is suggested on the basis of analysis of the IR spectra

  7. Allopurinol and 5-aminosalicylic acid influence thiopurine-induced hepatotoxicity in vitro

    OpenAIRE

    Broekman, Mark M. T. J.; Roelofs, Hennie M. J.; Wong, Dennis R.; Kerstholt, Mariska; Leijten, Alex; Hoentjen, Frank; Peters, Wilbert H. M.; Geert J A Wanten; de Jong, Dirk J.

    2015-01-01

    Introduction The use of thiopurines is frequently accompanied by hepatotoxicity. Studies on hepatocyte cultures showed a time- and dose-dependent increase of thiopurine toxicity. 5-Aminosalicylic acid (5-ASA) and allopurinol can influence thiopurine metabolism; however, it is unknown whether this affects in vitro cytotoxicity. Methods Human hepatoma cells (Huh7, HepG2 and HepaRG) were incubated with increasing concentrations of thiopurines, 5-ASA or allopurinol. Water-soluble tetrazolium salt...

  8. Identification of major degradation products of 5-aminosalicylic acid formed in aqueous solutions and in pharmaceuticals

    DEFF Research Database (Denmark)

    Jensen, J.; Cornett, Claus; Olsen, C. E.;

    1992-01-01

    The formation of four major degradation products of 5-aminosalicylic acid (5-ASA) in buffered solutions at pH 7.0 was demonstrated by gradient HPLC analysis. The isolation and structural elucidation of the resulting degradation products showed that the degradation of 5-ASA led to the formation of......-containing pharmaceuticals, which had not been stored as prescribed, but in diffuse daylight for up to 2 years....

  9. A Novel Preparation Method for 5-Aminosalicylic Acid Loaded Eudragit S100 Nanoparticles

    OpenAIRE

    Sining Li; Yaping Zhao; Daode Hu; Wenjuan Chen; Liang Liu

    2012-01-01

    In this study, solution enhanced dispersion by supercritical fluids (SEDS) technique was applied for the preparation of 5-aminosalicylic acid (5-ASA) loaded Eudragit S100 (EU S100) nanoparticles. The effects of various process variables including pressure, temperature, 5-ASA concentration and solution flow rate on morphology, particle size, 5-ASA loading and entrapment efficiency of nanoparticles were investigated. Under the appropriate conditions, drug-loaded nanoparticles exhibited a spheri...

  10. Common misconceptions about 5-aminosalicylates and thiopurines in inflammatory bowel disease

    Institute of Scientific and Technical Information of China (English)

    Javier P Gisbert; María Chaparro; Fernando Gomollón

    2011-01-01

    Misconceptions are common in the care of patients with inflammatory bowel disease (IBD). In this paper, we state the most commonly found misconceptions in clinical practice and deal with the use of 5-aminosalicylates and thiopurines, to review the related scientific evidence, and make appropriate recommendations. Prevention of errors needs knowledge to avoid making such errors through ignorance. However, the amount of knowledge is increasing so quickly that one new danger is an overabundance of information. IBD is a model of a very complex disease and our goal with this review is to summarize the key evidence for the most common daily clinical problems. With regard to the use of 5-aminosalicylates, the best practice may to be consider abandoning the use of these drugs in patients with small bowel Crohn' s disease. The combined approach with oral plus topical 5-aminosalicylates should be the first-line therapy in patients with active ulcerative colitis; once-daily treatment should be offered as a first choice regimen due to its better compliance and higher efficacy. With regard to thiopurines, they seem to be as effective in ulcerative colitis as in Crohn' s disease. Underdosing of thiopurines is a form of undertreatment. Thiopurines should probably be continued indefinitely because their withdrawal is associated with a high risk of relapse. Mercaptopurine is a safe alternative in patients with digestive intolerance or hepatotoxicity due to azathioprine. Finally, thiopurine methyltransferase (TPMT) screening cannot substitute for regular monitoring because the majority of cases of myelotoxicity are not TPMT-related.

  11. Examination of coated tablet of 99Tcm-5-aminosalicylic acid for delivering drug in colon

    International Nuclear Information System (INIS)

    The radionuclide trace technique is used to examine and determine that 99Tcm-5-aminosalicylic acid coated table delivere drug in colon. 5-aminosalicylic acid labelled with 99Tcm is made to be coated tablet. Which character in artificial gastrointestinal liquid is observed by testing radioactivity leakage of the coated tablet, and in dogs vivo motor process by SPECT. Coated tablet is not dissolved in artificial gastric juice and outward appearance of which does not change. Coated table is take out after laid in artificial gastric juice for 1 h and placed in artificial intestinal liquid, partial coating is corroded and appears a great quantity of hole in a utensil at 3 h, and coating starts to burst and release at 3.5 h. The coated tablet starts to release drug in ascending colon and remain in colon for 6-7 h after taking orally. Therefore coated table of 99Tcm-5-aminosalicylic acid is able to release drug by location in colon. (authors)

  12. Five-Aminosalicylic Acid: An Update for the Reappraisal of an Old Drug

    Directory of Open Access Journals (Sweden)

    Cristiana Perrotta

    2015-01-01

    Full Text Available Inflammatory bowel disease (IBD comprises several conditions with chronic or recurring immune response and inflammation of the gastrointestinal apparatus, of which ulcerative colitis and Crohn’s disease are the commonest forms. This disease has a significant prevalence and it is of an unknown aethiology. Five-aminosalicylic acid (5-ASA and its derivatives are among the oldest drugs approved for the treatment of the IBD. In this review we reapprise aspects of 5-ASA mechanism of action, safety, and efficacy that in our opinion make it a valuable drug that can be fruitfully tailored in personalised treatments as a therapeutic option alongside other immune-modifying agents.

  13. Preparation and evaluation of magnetic microspheres of mesalamine (5-aminosalicylic acid) for colon drug delivery

    Institute of Scientific and Technical Information of China (English)

    Satinder Kakar; Deepa Batra; Ramandeep Singh

    2013-01-01

    Objective:To study magnetic microspheres of mesalamine(5-aminosalicylic acid) for colon drug delivery.Methods:Magnetic microspheres were prepared by solvent evaporation technique for use in the application of magnetic carrier technology.An attempt was made to target mesalamine (5-aminosalicylic acid) to its site of action i.e. to colon.EudragitS-100, ethylcellulose and chitosan were used in three different drug: polymer ratios i.e.1:1,1:2 and1:3.The microspheres were characterized in terms of particle size, percentage yield, drug content, encapsulation efficiency,in vitro release pattern andex vivo study.The microspheres were uniform in size and shape.Thein vitrorelease profile was studied in pH7.4 phosphate buffer medium usingUSP dissolution apparatus.Results:Chitosan microspheres were found to be better retained in terms of percentage release of the drug.Thus chitosan microspheres could be better retained at their target site.Conclustion:Flow characteristics are also better in case of chitosan magnetic microspheres. Thus reticuloendothelial clearance can be minimized and site specificity can be increased.

  14. Colon-specific prodrugs of 4-aminosalicylic acid for inflammatory bowel disease.

    Science.gov (United States)

    Dhaneshwar, Suneela S

    2014-04-01

    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. PMID:24707139

  15. Mutual azo prodrug of 5-aminosalicylic acid for colon targeted drug delivery: Synthesis, kinetic studies and pharmacological evaluation

    Directory of Open Access Journals (Sweden)

    Nagpal Deepika

    2006-01-01

    Full Text Available Mutual azo prodrug of 5-aminosalicylic acid with histidine, was synthesized by coupling L-histidine with salicylic acid, for targeted drug delivery to the inflamed gut tissue, in inflammatory bowel disease. In vitro kinetic studies in HCl buffer (pH 1.2 showed negligible release of 5-aminosalicylic acid, whereas in phosphate buffer (pH 7.4, only 14% release was observed over a period of 6h. In rat fecal matter, the release of 5-aminosalicylic acid was almost complete (85.6%, with a half life of 163 min, following zero order kinetics. The azo conjugate was evaluated for its ulcerogenic potential by Rainsford′s cold stress method. Therapeutic efficacy of the carrier system and the mitigating effect of the azo conjugate were evaluated in trinitrobenzenesulphonic acid- induced experimental colitis model. The synthesized prodrug was found to be equally effective in mitigating the colitis in rats, as that of sulfasalazine, without the ulcerogenicity of 5-aminosalicylic acid, and adverse effects of sulfasalazine.

  16. Synthesis and structural elucidation of glutathione and N-aceyl-cysteine conjugates of 5-aminosalicylic acid

    DEFF Research Database (Denmark)

    Jensen, J.; Cornett, Claus; Olsen, C. E.;

    1993-01-01

    The ability of 5-aminosalicylic acid (5-ASA) to be oxidized to a quinone monoimine compound capable of conjugating with nucleophilic compounds such as N-acetyl-cysteine (NAC) and glutathione (GSH) has been investigated in vitro. Three isomeric conjugates of 5-ASA and NAC as well as three isomeric...... conjugates of 5-ASA and GSH were found to be formed. 5-ASA was initially oxidized by PbO2 in a solution of TRIS-HCl buffer pH 9.3 followed by the in situ addition of N-acetyl-cysteine or glutathione to the oxidized 5-ASA at pH 7.5. The resulting conjugates were N-acetylated at the aromatic amino group in...

  17. A Novel Preparation Method for 5-Aminosalicylic Acid Loaded Eudragit S100 Nanoparticles

    Directory of Open Access Journals (Sweden)

    Sining Li

    2012-05-01

    Full Text Available In this study, solution enhanced dispersion by supercritical fluids (SEDS technique was applied for the preparation of 5-aminosalicylic acid (5-ASA loaded Eudragit S100 (EU S100 nanoparticles. The effects of various process variables including pressure, temperature, 5-ASA concentration and solution flow rate on morphology, particle size, 5-ASA loading and entrapment efficiency of nanoparticles were investigated. Under the appropriate conditions, drug-loaded nanoparticles exhibited a spherical shape and small particle size with narrow particle size distribution. In addition, the nanoparticles prepared were characterized by X-ray diffraction, Differential scanning calorimetry and Fourier transform infrared spectroscopy analyses. The results showed that 5-ASA was imbedded into EU S100 in an amorphous state after SEDS processing and the SEDS process did not induce degradation of 5-ASA.

  18. Relapsing tubulointerstitial nephritis in an adolescent with inflammatory bowel disease without aminosalicylate exposure.

    LENUS (Irish Health Repository)

    Shahrani Muhammad, H S

    2012-01-31

    A 14-year-old boy presented with ongoing constipation as a manifestation of newly diagnosed Crohn\\'s disease (CD) and a concomitant decline in renal function with biopsy-proven interstitial nephritis. Initiation of steroid therapy and mesalazine was associated with an improvement in symptoms and renal function. We describe a rare case of a 5-aminosalicylic acid (5-ASA)-naive patient who developed interstitial nephritis in association with CD with no evidence of other primary glomerulopathy. A unique feature of the case being a profound systemic inflammatory response at the time of diagnosis and a relapse in nephritis 2 months after cessation of mesalazine in the absence of any macroscopic colitis.

  19. Pharmacokinetics and tissue distribution of 14C-5-aminosalicylic acid (14C-5-ASA) in rats

    International Nuclear Information System (INIS)

    5-Aminosalicylic acid (5-ASA) is effective in the treatment of ulcerative colitis and Crohn's disease. As part of a preclinical metabolism profile with 5-ASA, we evaluated the tissue level and distribution of 14C-5-ASA in rats. Biodistribution of 14C-radioactivity was determined in the major organs of rats after a single oral dose (34 mg/kg; 15 uci/rat). Data from tissue area under the curve (AUC 0-72) indicated that the highest amounts of radioactivity were retained in cecum (481.1 hr.ug.equ/gm), colon-rectum (178.5 hr.ug.equ/gm), ileum (166.7 hr.ug.equ/gm), jejunum (65.5 hr.ug.equ/gm), followed by kidneys (58.0 hr.ug.equ/gm) and liver (14.8 hr.ug.equ/gm). The radioactivity retained in tissues at 72 hours postdose was wither nondetectable or less than 0.1 ppm. The radioactivity concentration in blood was highest at 0.5 hr (tmax) postdose and the terminal half-life (t1/2) of 14C-radioactivity (5-ASA + metabolite) was 2.7 hours. 14C-5-ASA is absorbed and distributed in the body. The greatest amount of 14C-radioactivity was found in the stomach and GI tract. 14C-5-ASA was eliminated completely (44.9% in the urine, 51.7% in the feces) 72 hours after administration without significant tissue retention

  20. Comparative electrochemical degradation of salicylic and aminosalicylic acids: Influence of functional groups on decay kinetics and mineralization.

    Science.gov (United States)

    Florenza, Xavier; Garcia-Segura, Sergi; Centellas, Francesc; Brillas, Enric

    2016-07-01

    Solutions of 100 mL with 1.20 mM of salicylic acid (SA), 4-aminosalicylic acid (4-ASA) or 5-aminosalicylic acid (5-ASA) have been comparatively degraded by anodic oxidation with electrogenerated H2O2 (AO-H2O2), electro-Fenton (EF) and photoelectro-Fenton (PEF). Trials were carried out with a stirred tank reactor with a BDD anode and an air-diffusion cathode for continuous H2O2 production. A marked influence of the functional groups of the drugs was observed in their decay kinetics, increasing in the order SA H2O2 and 5-ASA H2O2 H2O2 at 100 mA cm(-2). The mineralization rate in EF and PEF grew in the order: 4-ASA 98% mineralization for all the drugs at 100 mA cm(-2). Oxalic and oxamic acids were detected as final short-linear aliphatic carboxylic acids by ion-exclusion HPLC, allowing the fast photolysis of their Fe(III) complexes by UVA light to justify the high power of PEF. PMID:27045634

  1. Long-term Compliance with Oral 5-aminosalicylic Acid Therapy and Risk of Disease Recurrence in Patients with Ulcerative Colitis

    DEFF Research Database (Denmark)

    Prosberg, Michelle V; Vester-Andersen, Marianne K; Andersson, Mikael; Jess, Tine; Andersen, Jon T; Vind, Ida; Bendtsen, Flemming

    2016-01-01

    BACKGROUND: Noncompliance to long-term medical therapy is a well-known problem among patients treated for ulcerative colitis, but studies of long-term consequences in unselected patients are lacking. The authors aimed to determine the risk of recurrence according to long-term compliance with oral 5......-aminosalicylic acid among unselected patients with ulcerative colitis. METHODS: The authors conducted a 7-year follow-up study of a population-based inception cohort of 243 Danish patients with ulcerative colitis diagnosed from 2003 to 2004. Compliance was defined as consumption of ≥80% of prescribed oral 5...... treatment, or colectomy) in compliant versus noncompliant patients. RESULTS: In total, 182 patients(75%) experienced at least 1 recurrence during follow-up. For the first year after diagnosis, risk of recurrence did not differ significantly between compliant and noncompliant patients. For 1 to 3 years...

  2. The prophylactic effect of 5-aminosalicylic acid and salazosulphapyridine on degraded-carrageenan-induced colitis in guinea pigs

    DEFF Research Database (Denmark)

    Poulsen, Steen Seier

    1984-01-01

    placebo group, all guinea pigs developed many small punctiform ulcerations in the cecum (median, 30/cm2). In the 5-ASA group no protective effect was demonstrated, since the number of ulcerations was 37/cm2. The difference is not statistically significant. However, the SASP group presented significantly......Experimental colitis was induced in guinea pigs by administration of 5% degraded carrageenan for 5 days. The prophylactic effect of a slow-release preparation of 5-aminosalicylic acid (5-ASA; 13 mg/100 g/day) was compared with approximately equimolar amounts of salazosulphapyridine (SASP; 26 mg/100...... fewer ulcerations (4/cm2). The concentrations of 5-ASA and/or its acetylated metabolite were several times higher in the cecum content and twice as high in plasma in the SASP group, indicating a difference in the absorption patterns of 5-ASA and the two drugs. These results and the etiological...

  3. Inhibitory Effect of Flavonoids on the Efflux of -Acetyl 5-Aminosalicylic Acid Intracellularly Formed in Caco-2 Cells

    Directory of Open Access Journals (Sweden)

    Shin Yoshimura

    2009-01-01

    Full Text Available -acetyl 5-aminosalicylic acid (5-AcASA that was intracellularly formed from 5-aminosalicylic acid (5-ASA at 200 M was discharged 5.3, 7.1, and 8.1-fold higher into the apical site than into the basolateral site during 1, 2, and 4-hour incubations, respectively, in Caco-2 cells grown in Transwells. The addition of flavonols (100 M such as fisetin and quercetin with 5-ASA remarkably decreased the apically directed efflux of 5-AcASA. When 5-ASA (200 M was added to Caco-2 cells grown in tissue culture dishes, the formation of 5-AcASA decreased, and, in addition, the formed 5-AcASA was found to be accumulated within the cells in the presence of such flavonols. Thus, the decrease in 5-AcASA efflux by such flavonols was attributed not only to the inhibition of -acetyl-conjugation of 5-ASA but to the predominant cellular accumulation of 5-AcASA. Various flavonoids also had both of the effects with potencies that depend on their specific structures. The essential structure of flavonoids was an absence of a hydroxyl substitution at the C5 position on the A-ring of flavone structure for the inhibitory effect on the -acetyl-conjugation of 5-ASA, and a presence of hydroxyl substitutions at the C3 or C4 position on the B-ring of flavone structure for the promoting effect on the cellular accumulation of 5-AcASA. Both the decrease in 5-AcASA apical efflux and the increase in 5-AcASA cellular accumulation were also caused by MK571 and indomethacin, inhibitors of MRPs, but not by quinidine, cyclosporin A, P-glycoprotein inhibitors, and mitoxantrone, a BCRP substrate. These results suggest that certain flavonoids suppress the apical efflux of 5-AcASA possibly by inhibiting MRPs pumps located on apical membranes in Caco-2 cells.

  4. Mucoadhesive microparticulates based on polysaccharide for target dual drug delivery of 5-aminosalicylic acid and curcumin to inflamed colon.

    Science.gov (United States)

    Duan, Haogang; Lü, Shaoyu; Gao, Chunmei; Bai, Xiao; Qin, Hongyan; Wei, Yuhui; Wu, Xin'an; Liu, Mingzhu

    2016-09-01

    In this work, thiolated chitosan/alginate composite microparticulates (CMPs) coated by Eudragit S-100 were developed for colon-specific delivery of 5-aminosalicylic acid (5-ASA) and curcumin (CUR), and the use of it as a multi drug delivery system for the treatment of colitis. The physicochemical properties of the CMPs were evaluated. In vitro release was performed in gradually pH-changing medium simulating the conditions of different parts of GIT, and the results showed that the Eudragit S-100 coating has a pH-sensitive release property, which can avoid drug being released at a pH lower than 7. An everted sac method was used to evaluate the mucoadhesion of CMPs. Ex vivo mucoadhesive tests showed CMPs have excellent mucosa adhesion for the colonic mucosa of rats. In vivo treatment effect of enteric microparticulates systems was evaluated in colitis rats. The results showed superior therapeutic efficiency of this drug delivery system for the colitis rats induced by TNBS. Therefore, the enteric microparticulates systems combined the properties of pH dependent delivery, mucoadhesive, and control release, and could be an available tool for the treatment of human inflammatory bowel disease. PMID:27239905

  5. Protective effects of ebselen (Ebs) and para-aminosalicylic acid (PAS) against manganese (Mn)-induced neurotoxicity

    Energy Technology Data Exchange (ETDEWEB)

    Marreilha dos Santos, A.P., E-mail: apsantos@ff.ul.pt [I-Med.UL, Department of Toxicology and Food Sciences, Faculty of Pharmacy, University of Lisbon, Lisbon (Portugal); Lucas, Rui L.; Andrade, Vanda; Mateus, M. Luísa [I-Med.UL, Department of Toxicology and Food Sciences, Faculty of Pharmacy, University of Lisbon, Lisbon (Portugal); Milatovic, Dejan; Aschner, Michael [Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN 37232 (United States); Batoreu, M. Camila [I-Med.UL, Department of Toxicology and Food Sciences, Faculty of Pharmacy, University of Lisbon, Lisbon (Portugal)

    2012-02-01

    Chronic, excessive exposure to manganese (Mn) may induce neurotoxicity and cause an irreversible brain disease, referred to as manganism. Efficacious therapies for the treatment of Mn are lacking, mandating the development of new interventions. The purpose of the present study was to investigate the efficacy of ebselen (Ebs) and para-aminosalicylic acid (PAS) in attenuating the neurotoxic effects of Mn in an in vivo rat model. Exposure biomarkers, inflammatory and oxidative stress biomarkers, as well as behavioral parameters were evaluated. Co-treatment with Mn plus Ebs or Mn plus PAS caused a significant decrease in blood and brain Mn concentrations (compared to rats treated with Mn alone), concomitant with reduced brain E{sub 2} prostaglandin (PGE{sub 2}) and enhanced brain glutathione (GSH) levels, decreased serum prolactin (PRL) levels, and increased ambulation and rearing activities. Taken together, these results establish that both PAS and Ebs are efficacious in reducing Mn body burden, neuroinflammation, oxidative stress and locomotor activity impairments in a rat model of Mn-induced toxicity. -- Highlights: ► The manuscript is unique in its approach to the neurotoxicity of Mn. ► The manuscript incorporates molecular, cellular and functional (behavioral) analyses. ► Both PAS and Ebs are effective in restoring Mn behavioral function. ► Both PAS and Ebs are effective in reducing Mn-induced oxidative stress. ► Both PAS and Ebs led to a decrease in Mn-induced neuro-inflammation.

  6. Antimycobacterial, antimicrobial, and biocompatibility properties of para-aminosalicylic acid with zinc layered hydroxide and Zn/Al layered double hydroxide nanocomposites

    Directory of Open Access Journals (Sweden)

    Saifullah B

    2014-07-01

    Full Text Available Bullo Saifullah,1 Mohamed E El Zowalaty,2,3 Palanisamy Arulselvan,2 Sharida Fakurazi,2,4 Thomas J Webster,5,6 Benjamin M Geilich,5 Mohd Zobir Hussein1 1Materials Synthesis and Characterization Laboratory, Institute of Advanced Technology (ITMA, Universiti Putra Malaysia, Serdang, Selangor, Malaysia; 2Laboratory of Vaccines and Immunotherapeutics, Institute of Bioscience, Universiti Putra Malaysia, Serdang, Selangor, Malaysia; 3Department of Environmental Health, Faculty of Public Health and Tropical Medicine, Jazan University, Jazan, Saudi Arabia; 4Department of Human Anatomy, Faculty of Medicine and Health Science, Universiti Putra Malaysia, Serdang, Selangor, Malaysia; 5Department of Chemical Engineering and Program in Bioengineering, Northeastern University, Boston, MA, USA; 6Center of Excellence for Advanced Materials Research, King Abdulaziz University, Jeddah, Saudi Arabia Abstract: The treatment of tuberculosis by chemotherapy is complicated due to multiple drug prescriptions, long treatment duration, and adverse side effects. We report here for the first time an in vitro therapeutic effect of nanocomposites based on para-aminosalicylic acid with zinc layered hydroxide (PAS-ZLH and zinc-aluminum layered double hydroxides (PAS-Zn/Al LDH, against mycobacteria, Gram-positive bacteria, and Gram-negative bacteria. The nanocomposites demonstrated good antimycobacterial activity and were found to be effective in killing Gram-positive and Gram-negative bacteria. A biocompatibility study revealed good biocompatibility of the PAS-ZLH nanocomposites against normal human MRC-5 lung cells. The para-aminosalicylic acid loading was quantified with high-performance liquid chromatography analysis. In summary, the present preliminary in vitro studies are highly encouraging for further in vivo studies of PAS-ZLH and PAS-Zn/Al LDH nanocomposites to treat tuberculosis.  Keywords: Zn/Al-layered double hydroxides, zinc layered hydroxides, tuberculosis, para-aminosalicylic

  7. N-Acetyltransferase Genotypes and the Pharmacokinetics and Tolerability of para-Aminosalicylic Acid in Patients with Drug-Resistant Pulmonary Tuberculosis

    OpenAIRE

    Sherwin K. B. Sy; de Kock, Lizanne; Diacon, Andreas H.; Werely, Cedric J.; Xia, Huiming; Rosenkranz, Bernd; van der Merwe, Lize; Donald, Peter R.

    2015-01-01

    The aim of this study was to examine the relationships between N-acetyltransferase genotypes, pharmacokinetics, and tolerability of granular slow-release para-aminosalicylic acid (GSR-PAS) in tuberculosis patients. The study was a randomized, two-period, open-label, crossover design wherein each patient received 4 g GSR-PAS twice daily or 8 g once daily alternately. The PAS concentration-time profiles were modeled by a one-compartment disposition model with three transit compartments in serie...

  8. "Protective Effects of Some Azo Derivatives of 5-aminosalicylic Acid and Their Pegylated Prodrugs on Acetic Acid-induced Rat Colitis "

    OpenAIRE

    Alireza Garjani; Soodabeh Davaran; Mohamadreza Rashidi; Nasrin Malek

    2004-01-01

    The protective and anti-inflammatory effects of azo and azo-linked polymeric prodrugs of 5-aminosalicylic acid (5-ASA) on acetic acid induced colitis in rats were investigated. Three azo prodrugs; 4,4 -dihydroxy-azobenzene-3-carboxilic acid (azo compound I), 4-hydroxy-azobenzene-3,4-dicarboxilic acid (azo compound II), 4,4-dihydroxy-3-formyl-azobenzene-3-carboxylic acid (azo compound III) and their polyethylene glycol (PEG 6000) derivatives were synthesized. Rats were pretreated orally (1 hou...

  9. 5-aminosalicylic acid is an attractive candidate agent for chemoprevention of colon cancer in patients with inflammatory bowel disease

    Institute of Scientific and Technical Information of China (English)

    Yang Cheng; Pierre Desreumaux

    2005-01-01

    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

  10. A relative bioavailability study of 500 mg calcium p-aminosalicylate film coating tablet in healthy individuals

    Directory of Open Access Journals (Sweden)

    Chinhwa Cheng

    2014-06-01

    Full Text Available The purpose of this study is to evaluate the only available calcium p-aminosalicylate (Ca PAS commercial product, which is one of the most commonly prescribed non-surveillance products from the Bureau of National Health Insurance (BNHI database in Taiwan. An open-randomized, balanced, two-way crossover study was designed to evaluate the relative bioavailability (F of a 500 mg Ca PAS F.C. tablet with a 500 mg Ca PAS suspension in 13 healthy individuals. Blood samples were collected according to a planned time schedule. The plasma concentrations of PAS were measured by a validated liquid chromatography coupled with tandem mass spectrometry (LC/MS/MS method. Pharmacokinetic parameters of area under the plasma concentration-time curve from the time zero to the time of last quantifiable concentration (AUC0–t, area under the plasma concentration-time curve from time zero to infinity (AUC0–∞, maximum plasma concentration (Cmax, time to reach measured maximum plasma concentration (Tmax, elimination half-life (T1/2, and mean residence time (MRT were determined by non-compartment methods. F was calculated by [AUC0–∞] of the test drug divided by [AUC0–∞] of the reference drug. The mean geometric ratios of pharmacokinetic parameters, including AUC0–t, AUC0–∞, and Cmax obtained were 0.873, 0.874, and 0.569, respectively. The 90% confidence intervals of ln (AUC0–t, ln (AUC0–∞, and ln (Cmax after being back natural log-transformed were (74.0–103.0%, (74.1–103.0%, and (38.4–84.3%, respectively. The relative bioavailability of the Ca PAS tablet was 87.4%.

  11. The effect of probiotic Escherichia coli strain Nissle 1917 lipopolysaccharide on the 5-aminosalicylic acid transepithelial transport across Caco-2 cell monolayers.

    Science.gov (United States)

    Stětinová, Věra; Smetanová, Libuše; Kholová, Dagmar; Květina, Jaroslav; Svoboda, Zbyněk; Zídek, Zdeněk; Tlaskalová-Hogenová, Helena

    2013-09-01

    The object of this study was to investigate the effect of probiotic Escherichia coli strain Nissle 1917 (EcN) (i) EcN lipopolysaccharide (EcN LPS) and (ii) bacteria-free supernatant of EcN suspension (EcN supernatant) on in vitro transepithelial transport of mesalazine (5-aminosalicylic acid, 5-ASA), the most commonly prescribed anti-inflammatory drug in inflammatory bowel disease (IBD). Effect of co-administered EcN LPS (100 µg/ml) or EcN supernatant (50 µg/ml) on the 5-ASA transport (300 µmol/l) was studied using the Caco-2 monolayer (a human colon carcinoma cell line) as a model of human intestinal absorption. Permeability characteristics for absorptive and secretory transport of parent drug and its intracellularly-formed metabolite were determined. The quantification of 5-ASA and its main metabolite N-acetyl-5-amino-salicylic acid (N-Ac-5-ASA) was performed by high performance liquid chromatography. Obtained results suggest that neither EcN LPS nor EcN supernatant had effect on the total 5-ASA transport (secretory flux greater than absorptive flux) and on the transport of intracellularly formed N-Ac-5-ASA (preferentially transported in the secretory direction). The percent cumulative transport of the total 5-ASA alone or in combination with EcN LPS or EcN supernatant did not exceed 1%. PMID:23846256

  12. The Efficacy of Probiotic (Lactobacillus rhamnosus GG) and 5-ASA (Aminosalicylic Acid) in the Treatment of Experimental Radiation Proctitis in Rats.

    Science.gov (United States)

    Dandin, Özgür; Akin, Mehmet Levhi; Balta, Ahmet Ziya; Yücel, Ergün; Karakaş, Dursun Özgür; Demirbaş, Sezai; Özdemir, Sevim; Haholu, Apdullah

    2015-12-01

    The aims of the study are to demonstrate the effect of probiotic use on the healing of radiation proctitis (RP) and evaluate the efficiency of fecal biomarkers at follow-up of the treatment. Thirty-two male/female rats were randomly separated into four groups of eight rats. The first group (control) was not radiated. RP was created by 17.5 Gy single dose rectal irradiation. The second group (RP) was subjected to RP, but not treated. The third group (RP+ASA) was treated with 5-aminosalicylic acid (5-ASA) 250 mg/kg daily by gastric lavage for 14 days after the irradiation, and the forth group (RP+LGG) was treated with Lactobacillus GG (LGG) 25 × 100 million CFU daily. Feces samples were taken at the 7th and 14th day of the treatment for fecal biomarkers. Rectums of the rats were resected at the 14th day by laparotomy. Samples were evaluated both macroscopically and microscopically. RP was achieved both macroscopically and microscopically. Weight loss of RP group is statistically significant (p < 0.005) than other groups. The healing ratio of RP+ASA and RP+LGG groups was significantly better than the RP group (p < 0.005) both macroscopically and microscopically. But there was no significant difference between ASA and LGG groups. Biochemically, fecal calprotectin was found to be more effective than fecal myeloperoxidase and fecal lactoferrin to show the efficacy of treatment of radiation proctitis. The results of our study demonstrate that probiotic is as effective as 5-aminosalicylic in the treatment of radiation proctitis, and fecal calprotectin is a useful biomarker in determining the response to the treatment. PMID:26730065

  13. Pharmacokinetics of para-Aminosalicylic Acid in HIV-Uninfected and HIV-Coinfected Tuberculosis Patients Receiving Antiretroviral Therapy, Managed for Multidrug-Resistant and Extensively Drug-Resistant Tuberculosis

    OpenAIRE

    de Kock, Lizanne; Sy, Sherwin K.B.; Rosenkranz, Bernd; Diacon, Andreas H; Prescott, Kim; Hernandez, Kenneth R.; Yu, Mingming; Derendorf, Hartmut; Donald, Peter R.

    2014-01-01

    The emergence of multidrug-resistant (MDR) and extensively drug-resistant (XDR) Mycobacterium tuberculosis prompted the reintroduction of para-aminosalicylic acid (PAS) to protect companion anti-tuberculosis drugs from additional acquired resistance. In sub-Saharan Africa, MDR/XDR tuberculosis with HIV coinfection is common, and concurrent treatment of HIV infection and MDR/XDR tuberculosis is required. Out of necessity, patients receive multiple drugs, and PAS therapy is frequent; however, n...

  14. Novel pH-sensitive hydrogels for 5-aminosalicylic acid colon targeting delivery: in vivo study with ulcerative colitis targeting therapy in mice.

    Science.gov (United States)

    Bai, Xia Yan; Yan, Yan; Wang, Lin; Zhao, Lan Gui; Wang, Ke

    2016-07-01

    Current guidelines recommend patients with active and mild-to-moderate ulcerative colitis (UC), who have received initial therapy with 5-aminosalicylic acid (5-ASA). In this study, a novel drug delivery vehicle achieved by pH-sensitive hydrogels was applied to 5-ASA. In our previous work, a novel P(CE-MAA-MEG) pH-sensitive hydrogel was successfully synthesized by the heat-initiated free radical polymerization method. The aim of this study is to investigate its site-specific delivering of drugs to the colon and evaluate its colon-targeting characteristic in vivo. 5-ASA was chosen as a model drug and successfully loaded in the hydrogel. In vitro investigations were carried out to evaluate its release process. Above all, animal treatment results reveal an obvious effect on the UC healing. Therefore, all results suggested that the developed 5-ASA-P(CE-MAA-MEG) hydrogel (5-ASA-GEL) as a colon-targeting vector might have a great potential application in the UC therapy. PMID:25693641

  15. 5-Aminosalicylic Acid Azo-Linked to Procainamide Acts as an Anticolitic Mutual Prodrug via Additive Inhibition of Nuclear Factor kappaB.

    Science.gov (United States)

    Kim, Wooseong; Nam, Joon; Lee, Sunyoung; Jeong, Seongkeun; Jung, Yunjin

    2016-06-01

    To improve the anticolitic efficacy of 5-aminosalicylic acid (5-ASA), a colon-specific mutual prodrug of 5-ASA was designed. 5-ASA was coupled to procainamide (PA), a local anesthetic, via an azo bond to prepare 5-(4-{[2-(diethylamino)ethyl]carbamoyl}phenylazo)salicylic acid (5-ASA-azo-PA). 5-ASA-azo-PA was cleaved to 5-ASA and PA up to about 76% at 10 h in the cecal contents while remaining stable in the small intestinal contents. Oral gavage of 5-ASA-azo-PA and sulfasalazine, a colon-specific prodrug currently used in clinic, to rats showed similar efficiency in delivery of 5-ASA to the large intestine, and PA was not detectable in the blood after 5-ASA-azo-PA administration. Oral gavage of 5-ASA-azo-PA alleviated 2,4,6-trinitrobenzenesulfonic acid-induced rat colitis. Moreover, combined intracolonic treatment with 5-ASA and PA elicited an additive ameliorative effect. Furthermore, combined treatment with 5-ASA and PA additively inhibited nuclear factor-kappaB (NFκB) activity in human colon carcinoma cells and inflamed colonic tissues. Finally, 5-ASA-azo-PA administered orally was able to reduce inflammatory mediators, NFκB target gene products, in the inflamed colon. 5-ASA-azo-PA may be a colon-specific mutual prodrug acting against colitis, and the mutual anticolitic effects occurred at least partly through the cooperative inhibition of NFκB activity. PMID:27112518

  16. Antioxidant activities and radical scavenging activities of flavonoids studied by the electrochemical methods and ESR technique based on the novel paramagnetic properties of poly(aniline-co-5-aminosalicylic acid)

    International Nuclear Information System (INIS)

    Graphical abstract: ESR spectra of the PAASA/RGO/graphite electrodes: (1) in the buffer solution consisting of 0.20 M phosphate and methanol (80: 20, v/v), (2) in the buffer solutions containing 150 μM of (+)-catechin. -- Abstract: Four kinds of flavonoid, viz. flavanone naringenin, Flavone apigenin, flavonol kaempferol, and flavanol (+)-catechin, are used to investigate their antioxidant and radical scavenging activitis in the water-methanol solution of pH 6.3, using the electrochemical methods and electron spin resonance (ESR) technique. Poly(aniline-co-5-aminosalicylic acid) (PAASA) is first used as a radical source that was polymerized on a reduced graphene oxide (RGO)/glassy carbon (GC) disk or on the RGO/graphite fiber electrode. The assessment of the antioxidant activities is performed using both cyclic voltammetry and the open circuit potential measurement. On the basis of results from both electrochemical mathods, the order of the antioxidant actitvities of flavonoids is as follows: (+)-catechin > kaempferol > apigenin > naringenin However, the difference in the antioxidant activities between naringenin and apigenin is very small. On the basis of the ESR signal intensities of PAASA, the order of the radical scavenging activities of flavonoids is in good agreement with that of the above antioxdant activities.Three oxidation peaks on the cyclic voltammograms of (+)-catechin are first detected, which gives us a deep insight into the oxidation mechanism of (+)-catechin

  17. Crystal structures and hydrogen bonding in the co-crystalline adducts of 3,5-dinitrobenzoic acid with 4-aminosalicylic acid and 2-hydroxy-3-(1H-indol-3-ylpropenoic acid

    Directory of Open Access Journals (Sweden)

    Graham Smith

    2014-10-01

    Full Text Available The structures of the co-crystalline adducts of 3,5-dinitrobenzoic acid (3,5-DNBA with 4-aminosalicylic acid (PASA, the 1:1 partial hydrate, C7H4N2O6·C7H7NO3·0.2H2O, (I, and with 2-hydroxy-3-(1H-indol-3-ylpropenoic acid (HIPA, the 1:1:1 d6-dimethyl sulfoxide solvate, C7H4N2O6·C11H9NO3·C2D6OS, (II, are reported. The crystal substructure of (I comprises two centrosymmetric hydrogen-bonded R22(8 homodimers, one with 3,5-DNBA, the other with PASA, and an R22(8 3,5-DNBA–PASA heterodimer. In the crystal, inter-unit amine N—H...O and water O—H...O hydrogen bonds generate a three-dimensional supramolecular structure. In (II, the asymmetric unit consists of the three constituent molecules, which form an essentially planar cyclic hydrogen-bonded heterotrimer unit [graph set R32(17] through carboxyl, hydroxy and amino groups. These units associate across a crystallographic inversion centre through the HIPA carboxylic acid group in an R22(8 hydrogen-bonding association, giving a zero-dimensional structure lying parallel to (100. In both structures, π–π interactions are present [minimum ring-centroid separations = 3.6471 (18 Å in (I and 3.5819 (10 Å in (II].

  18. Pharmacokinetics in Wistar Rats of 5-[(4-Carboxybutanoyl)Amino]-2-Hydroxybenzoic Acid: A Novel Synthetic Derivative of 5-Aminosalicylic Acid (5-ASA) with Possible Anti-Inflammatory Activity

    Science.gov (United States)

    Correa-Basurto, José; Rosales Hernández, Martha Cecilia; Padilla Martínez, Itzia Irene; Mendieta-Wejebe, Jessica Elena

    2016-01-01

    5-[(4-carboxybutanoyl)amino]-2-hydroxybenzoic acid (C2) is a novel synthetic derivative of 5-aminosalicylic acid (5-ASA), which is currently being evaluated ex vivo as an anti-inflammatory agent and has shown satisfactory results. This study aimed to obtain the pharmacokinetic profiles, tissue distribution and plasma protein binding of C2 in Wistar Rats. Additionally, an HPLC method was developed and validated to quantify C2 in rat plasma. The pharmacokinetic profiles of intragastric, intravenous and intraperitoneal administration routes at singles doses of 100, 50, and 100 mg/kg, respectively, were studied in Wistar rats. The elimination half-life of intravenously administered C2 was approximately 33 min. The maximum plasma level of C2 was reached approximately 24 min after intragastric administration, with a Cmax value of 2.5 g/mL and an AUCtot value of 157 μg min-1/mL; the oral bioavailability was approximately 13%. Following a single intragastric or oral dose (100 mg/kg), C2 was distributed and detected in all examined tissues (including the brain and colon). The results showed that C2 accumulates over time. The plasma protein binding results indicated that the unbound fraction of C2 at concentrations of 1 to 20 μg/mL ranged from 89.8% to 92.5%, meaning that this fraction of C2 is available to cross tissues. Finally, the blood-plasma partitioning (BP ratio) of C2 in rat plasma was 0.71 and 0.6 at concentrations of 5 and 10 μg/mL, respectively, which indicates that C2 is free in the plasmatic phase and not inside blood cells. The results of this study suggest that a fraction of the administered C2 dose is absorbed in the stomach, and the fraction that is not absorbed reaches the small intestine and colon. This distribution constitutes the main advantage of C2 compared with 5-ASA for the treatment of ulcerative colitis (UC) and Crohn's disease (CD). PMID:27454774

  19. NEW METABOLITES OF THE DRUG 5-AMINOSALICYLIC ACID .2. N-FORMYL-5-AMINOSALICYLIC ACID

    DEFF Research Database (Denmark)

    Tjornelund, J.; Hansen, S. H.; Cornett, Claus

    1991-01-01

    rat liver homogenate when 5-ASA and N-formyl-L-kynurenine were added. Thus N-formyl-5-ASA might be formed by the actions of formamidase in vivo. 5. N-Formyl-5-ASA has been found in human plasma from healthy volunteers dosed i.v. with 5-ASA (250 mg). N-beta-D-glucopyranosyl-5-ASA, N-acetyl-5-ASA and N...

  20. Possible interactions between dietary fibres and 5-aminosalicylic acid [corrected

    DEFF Research Database (Denmark)

    Henriksen, Camilla; Hansen, Steen Honoré; Nordgaard-Lassen, Inge;

    2010-01-01

    fibres is related to disease activity in patients with ulcerative colitis (UC) treated with 5-ASA. METHODS: In vitro: 15 g of Ispaghula Husk, wheat bran, citrus-pectin, or wheat flour were incubated in a 37°C buffered solutions of 5-ASA (1 g/l) for 3 hours at pH 6 and 7. The concentrations of 5-ASA were...... Ispaghula Husk (5.3-10.0 mg/g) and wheat bran (4.6-5.5 mg/g), and to a minor degree to citrus-pectin. No differences were found in relation to pH. In vivo: 29 patients completed the scheduled interviews. No significant changes in fibre consumption were observed over time; however, patients consuming a diet...

  1. Synthesis and Characterization of Rare Earth Solid Complexes with Sodium 5-Aminosalicylate

    Institute of Scientific and Technical Information of China (English)

    Zhang Xiuying; Li Shujing; Lei Xuefeng; Ma Junxian

    2005-01-01

    Ten new rare earth solid complexes were synthesized by the reaction of sodium 5-aminosalicyliate with rare earth chloride. The structure character, physical and chemical properties of these complexes were studied by IR, UV, 1H NMR spectra, TG-DTA, fluorescence, elemental analyses, molar conductance and magnetic susceptibility. The ten rare earth complexes exist in dimeric form probably and the coordination number is seven. The antibacterial activity of the ligand and six complexes was also tested against Staphylococcus aureus, Escherichia coli and Bacillus subtilis, and the effect of Yb complex at 20 mg·ml-1 against Staphylococcus aureus is most significant.

  2. Antineoplastic Effects of 5-Aminosalicylates and Potential Cancer Preventive Role in Inflammatory Bowel Disease

    OpenAIRE

    2004-01-01

    Early studies from tertiary referral centers in the United States and Europe showed that patients with long-standing and extensive inflammatory bowel disease (IBD) have an increased risk of colon cancer. It was subsequently appreciated that the degree of risk depended on the population being studied and on both genetic and environmental factors (eg diet, drugs and prior surgical treatment). Indeed, over the past decade or so, the effects of chronically administered medications, including 5-am...

  3. Severe chest pain in a pediatric ulcerative colitis patient after 5-aminosalicylic acid therapy

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    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.

  4. A dynamic model of once-daily 5-aminosalicylic acid predicts clinical efficacy

    Institute of Scientific and Technical Information of China (English)

    Deepak; Parakkal; Eli; D; Ehrenpreis; Matthew; P; Thorpe; Karson; S; Putt; Bruce; Hannon

    2010-01-01

    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 ...

  5. Development of a Web-based concept for patients with ulcerative colitis and 5-aminosalicylic acid treatment

    DEFF Research Database (Denmark)

    Elkjaer, Margarita; Burisch, Johan; Avnstrøm, Søren;

    2009-01-01

    life (QoL). Lack of easy access to inflammatory bowel disease clinics and patient education, their understanding of the importance of early treatment at relapse, poor compliance and self-adherence can be partly solved by a newly developed Web-based concept. AIMS: To describe the development and...... validation of the Web-based 'Constant-Care' concept. METHODS: A Web-based treatment program (www.constant-care.dk) and a Patient Educational Centre for UC patients were developed. The feasibility and acceptance of the concept was validated before (group A) and 6 months after (group B) the start of a......-treatment after the educational training (ET). A significant increase in knowledge from 36 to 69% (group A) and 28 to 75% (group B) was obtained. A majority of the patients were satisfied with the ET. Patients' QoL, anxiety, depression and general well-being showed no difference after the ET. CONCLUSION: Patient...

  6. Identification and Functional Characterization of Arylamine N-Acetyltransferases in Eubacteria: Evidence for Highly Selective Acetylation of 5-Aminosalicylic Acid

    OpenAIRE

    Deloménie, Claudine; Fouix, Sylvaine; Longuemaux, Sandrine; Brahimi, Naïma; Bizet, Chantal; Picard, Bertrand; Denamur, Erick; Dupret, Jean-Marie

    2001-01-01

    Arylamine N-acetyltransferase activity has been described in various bacterial species. Bacterial N-acetyltransferases, including those from bacteria of the gut flora, may be involved in the metabolism of xenobiotics, thereby exerting physiopathological effects. We characterized these enzymes further by steady-state kinetics, time-dependent inhibition, and DNA hybridization in 40 species, mostly from the human intestinal microflora. We report for the first time N-acetyltransferase activity in...

  7. Identification of oxidation products of 5-aminosalicylic acid in faeces and the study of their formation in vitro

    DEFF Research Database (Denmark)

    Jensen, J.; Cornett, Claus; Olsen, C. E.;

    1993-01-01

    products of 5-ASA using H-1-NMR spectroscopy and mass spectrometry. Reactions carried out in vitro between 5-ASA and oxidants suggested to be present in the inflamed bowel verified that the hypochlorite-mediated oxidation of 5-ASA as well as the haemoglobin-catalysed H2O2-dependent oxidation of 5-ASA...

  8. Antimycobacterial, antimicrobial, and biocompatibility properties of para-aminosalicylic acid with zinc layered hydroxide and Zn/Al layered double hydroxide nanocomposites

    OpenAIRE

    Saifullah B; El Zowalaty ME; Arulselvan P; Fakurazi S; Webster TJ; Geilich BM; Hussein MZ

    2014-01-01

    Bullo Saifullah,1 Mohamed E El Zowalaty,2,3 Palanisamy Arulselvan,2 Sharida Fakurazi,2,4 Thomas J Webster,5,6 Benjamin M Geilich,5 Mohd Zobir Hussein1 1Materials Synthesis and Characterization Laboratory, Institute of Advanced Technology (ITMA), Universiti Putra Malaysia, Serdang, Selangor, Malaysia; 2Laboratory of Vaccines and Immunotherapeutics, Institute of Bioscience, Universiti Putra Malaysia, Serdang, Selangor, Malaysia; 3Department of Environmental Health, Faculty of Public Health and ...

  9. Thr202Ala in thyA Is a Marker for the Latin American Mediterranean Lineage of the Mycobacterium tuberculosis Complex Rather than Para-Aminosalicylic Acid Resistance

    KAUST Repository

    Feuerriegel, S.

    2010-08-30

    Single nucleotide polymorphisms (SNPs) involved in the development of resistance represent powerful markers for the rapid detection of first- and second-line resistance in clinical Mycobacterium tuberculosis complex (MTBC) isolates. However, the association between particular mutations and phenotypic resistance is not always clear-cut, and phylogenetic SNPs have been misclassified as resistance markers in the past. In the present study, we investigated the utility of a specific polymorphism in thyA (Thr202Ala) as a marker for resistance to para-aminosalicyclic acid (PAS). Sixty-three PAS-susceptible MTBC strains comprising all major phylogenetic lineages, reference strain H37Rv, and 135 multidrug-resistant (MDR) strains from Germany (comprising 8 PAS-resistant isolates) were investigated for the presence of Thr202Ala. In both strain collections, the Thr202Ala SNP was found exclusively in strains of the Latin American Mediterranean (LAM) lineage irrespective of PAS resistance. Furthermore, PAS MICs (0.5 mg/liter) for selected LAM strains (all containing the SNP) and non-LAM strains (not containing the SNP), as well as the results of growth curve analyses performed in liquid 7H9 medium in the presence of increasing PAS concentrations (0 to 2.0 mg/liter), were identical. In conclusion, our data demonstrate that the Thr202Ala polymorphism in thyA is not a valid marker for PAS resistance but, instead, represents a phylogenetic marker for the LAM lineage of the M. tuberculosis complex. These findings challenge some of the previous understanding of PAS resistance and, as a consequence, warrant further in-depth investigations of the genetic variation in PAS-resistant clinical isolates and spontaneous mutants.

  10. Colon-specific drug delivery systems based on cyclodextrin prodrugs: In vivo evaluation of 5-aminosalicylic acid from its cyclodextrin conjugates

    Institute of Scientific and Technical Information of China (English)

    Mei-Juan Zou; Gang Cheng; Hirokazu Okamoto; Xiu-Hua Hao; Feng An; Fu-De Cui; Kazumi Danjo

    2005-01-01

    AIM: To investigate the release of cyclodextrin-5-amino salicylic acid (CyD-5-ASA) in cecum and colon.METHODS: An anti-inflammatory drug 5-ASA was conjugated onto the hydroxyl groups of α-, β- and γ-cyclodextrins (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 CyD5-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 throughthe 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-5-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.

  11. The effect of probiotic Escherichia coli strain Nissle 1917 lipopolysaccharide on the 5-aminosalicylic acid transepithelial transport across Caco-2 cell monolayers

    Czech Academy of Sciences Publication Activity Database

    Štětinová, V.; Smetanová, L.; Kholová, D.; Květina, J.; Svoboda, Z.; Zídek, Zdeněk; Tlaskalová-Hogenová, Helena

    2013-01-01

    Roč. 32, č. 3 (2013), s. 371-380. ISSN 0231-5882 R&D Projects: GA ČR(CZ) GAP304/11/1252; GA ČR GA305/08/0535 Institutional support: RVO:68378041 ; RVO:61388971 Keywords : probiotic s * lipopolysacharide * drug transport Subject RIV: FR - Pharmacology ; Medidal Chemistry; FR - Pharmacology ; Medidal Chemistry (MBU-M) Impact factor: 0.875, year: 2013

  12. Synthesis of 4-Aminosalicylglycine

    Institute of Scientific and Technical Information of China (English)

    Zheng Bao ZHAO; Jing GUO; Yuan Gui WEI; Tong Da LIANG

    2005-01-01

    To search for a better prodrug of 4-aminosalicylic acid that is expected to deliver stably parent drug to colon against the inflammatory bowel disease, a novel 4-aminosalicylic acid derivative was designed and synthesized from 4-aminosalicylic acid. 4-Aminosalicylglycine was prepared from 4-aminosalicylic acid by protecting amino and hydroxyl groups with benzyloxycarbonyl and acetyl, respectively, then the carboxylic acid was converted to acyl chloride which was treated with glycine. After removing the protection groups, 4-aminosalicylglycine was obtained. All the compounds were characterized by FT-IR, 1H-NMR, 13C-NMR spectra. In vivo experiment on rats suggested that the curative effect of 4-aminosalicylglycine was more effective than that of 4-aminosalicylic acid.

  13. 5-aminosalicylsyre til induktion af remission eller respons ved Crohns sygdom--en gennemgang af et Cochranereview

    DEFF Research Database (Denmark)

    Bjerrum, Jacob Tveiten; Munck, Lars Kristian; Nielsen, Ole Haagen

    2011-01-01

    A systematic review to evaluate the efficacy of 5-aminosalicylates for induction of remission or clinical response in patients with mild to moderately active Crohn's disease is described. The effect of either high (3 to 4.5 g/day) or low dose (1 to 2 g/day) 5-aminosalicylic acid was similar to that...... of placebo. Overall, sulfasalazine was not superior to placebo and was inferior to glucocorticoids for the treatment of mild to moderately active Crohn's disease. Neither published nor unpublished data support any use of 5-aminosalicylates for the treatment of Crohn's disease....

  14. Hyaluronic acid based hydroxamate and conjugates with biologically active amines: In vitro effect on matrix metalloproteinase-2.

    Science.gov (United States)

    Ponedel'kina, Irina Yu; Gaskarova, Aigul R; Khaybrakhmanova, Elvira A; Lukina, Elena S; Odinokov, Victor N

    2016-06-25

    In this study, water soluble hyaluronic acid (HA) based hydroxamate and conjugates with biologically active amines and hydrazides such as p- and o-aminophenols, anthranilic, 4- and 5-aminosalicylic acids, nicotinic, N-benzylnicotinic and isonicotinic hydrazides, p-aminobenzenesulfonamide (Streptocide), p-aminobenzoic acid diethylaminoethyl ester (Procaine), and 4-amino-2,3-dimethyl-1-phenyl-3-pyrazolin-5-one (4-aminoantipyrene) were examined as matrix metalloproteinase-2 inhibitors (MMPIs). In a dose of 0.27-270μM, the most efficient MMPIs were HA conjugates with o-aminophenol=4-aminoantipyrine>4-aminosalicylic acid>5-aminosalicylic acid. Conjugates with Streptocide, Procaine and HA hydroxamate showed 40-50% inhibitory effect at all used concentrations. Conjugates with anthranilic acid and isonicotinic hydrazide (Isoniazid) in a dose of 0.27μM inhibited enzyme activity by ∼70%, but with the concentration increase their inhibitory effect was decreased. PMID:27083788

  15. [Coxitis due to multidrug resistant Mycobacterium tuberculosis in a HIV negative patient].

    Science.gov (United States)

    Palmero, D J; Simboli, N; Alberti, F A; Francos, J L; Güemes Gurtubay, J L; Ochoa, E J; Cardozo, L; Waisman, J L

    2000-01-01

    A case of an HIV negative female patient with coxofemoral arthritis of tuberculous etiology, multidrug-resistant strain, and connective tissue disease associated to glucocorticoid therapy is reported. The patient was treated with cycloserine, ethambutol, p-aminosalicylic acid and ofloxacin, with improvement of the joint lesions. Previous publications on this subject are reviewed. PMID:11050817

  16. Structural and functional characterization of an arylamine N-acetyltransferase from the pathogen Mycobacterium abscessus

    DEFF Research Database (Denmark)

    Cocaign, Angélique; Kubiak, Xavier Jean Philippe; Xu, Ximing;

    2014-01-01

    functional characterization of an arylamine N-acetyltransferase (NAT) from M. abscessus [(MYCAB)NAT1] are reported. This novel prokaryotic NAT displays significant N-acetyltransferase activity towards aromatic substrates, including antibiotics such as isoniazid and p-aminosalicylate. The enzyme is...

  17. Fluorescent carbon dot–molecular salt hydrogels

    OpenAIRE

    Cayuela, Angelina; Kennedy, Stuart R.; Soriano, Laura; Jones, Christopher D.; Valcárcel, M.; Steed, Jonathan W.

    2015-01-01

    The incorporation of functionalised carbon nanodots within a novel low molecular weight salt hydrogel derived from 5-aminosalicylic acid is reported. The carbon dots result in markedly enhanced gelation properties, while inclusion within the hydrophobic gel results in a dramatic fluorescence enhancement for the carbon nanomaterials. The resulting hybrid CD gels exhibit a useful sensor response for heavy metal ions, particularly Pb2+.

  18. IBD medications during pregnancy and lactation

    DEFF Research Database (Denmark)

    Nielsen, Ole Haagen; Maxwell, Cynthia; Hendel, Jakob

    2013-01-01

    contraindicated during pregnancy and breast-feeding, alternatives to ciprofloxacin, natalizumab and sodium phosphate should also be considered for pregnant women. Breast-feeding is also discouraged while on treatment with ciclosporin, metronidazole and ciprofloxacin. However, therapy with 5-aminosalicylic acid...

  19. Treatment of Inflammatory Bowel Disease Associated E. coli with Ciprofloxacin and E. coli Nissle in the Streptomycin-Treated Mouse Intestine

    OpenAIRE

    Petersen, Andreas Munk; Schjørring, Susanne; Gerstrøm, Sarah Choi; Krogfelt, Karen Angeliki

    2011-01-01

    Background E. coli belonging to the phylogenetic group B2 are linked to Inflammatory Bowel Disease (IBD). Studies have shown that antimicrobials have some effect in the treatment of IBD, and it has been demonstrated that E. coli Nissle has prophylactic abilities comparable to 5-aminosalicylic acid (5-ASA) therapy in ulcerative colitis. The objective of this study was to test if ciprofloxacin and/or E. coli Nissle could eradicate IBD associated E. coli in the streptomycin-treated mouse intesti...

  20. Presence of phthalates in gastrointestinal medications: Is there a hidden danger?

    OpenAIRE

    Zane R Gallinger; Nguyen, Geoffrey C.

    2013-01-01

    Pharmaceutical companies that produce gastrointestinal (GI) medications often utilize phthalates for their ability to localize medication release. Commonly prescribed GI medications that may utilize phthalates are 5-Aminosalicylates, proton pump inhibitors, and pancreatic enzymes. Our understanding of the cumulative health effects of phthalates from medications remains unclear, and there is increasing evidence that phthalates are not harmless. Experimental studies in animals have shown that p...

  1. NATURAL AGENTS FOR INFLAMMATORY BOWEL DISEASE

    OpenAIRE

    Darji Vinay Chhanalal; Bariya Aditi Hemrajbhai; Deshpande Shrikalp Shrikant

    2011-01-01

    Inflammatory bowel disease (IBD) is a chronic inflammatory disease of gastrointestinal tract. It comprises the two conditions, Crohn’s disease and ulcerative colitis, characterized by chronic recurrent ulceration of the bowel. Conventional drugs for colitis treatment include aminosalicylate, corticosteroids,antibiotics & immunomodulators. 5- Amino salicylic acid having side effects in 30% of the patients. Systemic corticosteroids producing incidence of complication is 4.3%. Antibiotic therapy...

  2. Low dose balsalazide (1.5 g twice daily) and mesalazine (0.5 g three times daily) maintained remission of ulcerative colitis but high dose balsalazide (3.0 g twice daily) was superior in preventing relapses

    OpenAIRE

    Kruis, W.; Schreiber, S; Theuer, D; Brandes, J; Schutz, E; Howaldt, S; Krakamp, B; Hamling, J; MONNIKES, H.; Koop, I; Stolte, M; Pallant, D; Ewald, U

    2001-01-01

    BACKGROUND—Balsalazide is a new 5-aminosalicylic acid (5-ASA) containing prodrug. Its efficacy in comparison with standard mesalazine therapy and the optimum dose for maintaining remission of ulcerative colitis are still unclear.
AIMS—To compare the relapse preventing effect and safety profile of two doses of balsalazide and a standard dose of Eudragit coated mesalazine.
METHODS—A total of 133 patients with ulcerative colitis in remission were recruited to participate in a double blind, multi...

  3. Olsalazine versus placebo in the treatment of mild to moderate ulcerative colitis: a randomised double blind trial.

    OpenAIRE

    Feurle, G E; Theuer, D; Velasco, S; Barry, B A; Wördehoff, D; Sommer, A; Jantschek, G; Kruis, W.

    1989-01-01

    The effect of olsalazine, an analogue of sulphasalazine, consisting of two molecules 5-aminosalicylic acid linked by an azobond has been investigated for the treatment of ulcerative colitis. In a randomised double blind trial we compared 2 g olsalazine with placebo for four weeks. Of the 105 patients, with mild to moderate ulcerative colitis, entered in the trial 52 received olsalazine, and 53 placebo. Treatment had to be terminated prematurely because of untoward effects of olsalazine (mainl...

  4. Co-existence of hepatitis A and adult Reye's syndrome.

    OpenAIRE

    Duerksen, D R; Jewell, L.D.; Mason, A L; Bain, V. G.

    1997-01-01

    Reye's syndrome is most frequently seen in children but has also been described in adults. This syndrome is usually associated with ingestion of 5-aminosalicylates (ASA) or infection with influenza A, influenza B, or varicella virus. A case of Reye's syndrome in a 47 year old, previously healthy woman precipitated by ingestion of ASA and acute hepatitis A virus infection is described. Reye's syndrome was diagnosed on the basis of her clinical course, and the presence of hepatic microvesicular...

  5. Update in the treatment of paediatric ulcerative colitis.

    Science.gov (United States)

    Greifer, Melanie K; Markowitz, James F

    2006-10-01

    Ulcerative colitis is an important disease in the paediatric population. Ulcerative colitis is one of the chronic inflammatory bowel diseases, and is medically incurable. However, the arsenal of medications has grown as knowledge of the pathogenesis of this disease advances. This review looks at the classical treatments for children with ulcerative colitis, including the 5-aminosalicylates, corticosteroids and imunomodulators, as well as biological therapy and other, newer modalities. PMID:17020417

  6. Immunomodulators and Immunosuppressants for Japanese Patients with Ulcerative Colitis

    OpenAIRE

    Shigeki Bamba; Tomoyuki Tsujikawa; Masaya Sasaki; Yoshihide Fujiyama; Akira Andoh

    2011-01-01

    Ulcerative colitis (UC) is characterized by a long-standing chronic course with remissions and exacerbations. Previously, patients do not respond to 5-aminosalicylic acid compounds and corticosteroids are considered for colectomies, however, in recent years, alternative treatments emerged for steroid-refractory or steroid-dependent UC. In this review article, we focus on immunomodulators (such as azathioprine [AZA] and 6-mercaptopurine [6-MP]) and immunosuppressants (such as cyclosporine A [C...

  7. Soluble mediators and the interaction of drugs in IBD

    DEFF Research Database (Denmark)

    Rask-Madsen, J

    1998-01-01

    , which provides the clinical manifestations of IBD. Other important soluble mediators of inflammation include complement-derived and chemotactic peptides, specific adhesion molecules, neuropeptides and reactive metabolites of oxygen and nitrogen. Current established therapies, such as glucocorticoids and...... 5-aminosalicylic acid (5-ASA), inhibit raised concentrations of these interdependent soluble mediators of inflammation, which may amplify one another or have parallel effects. Future medical options for treatment of IBD aim at removing perpetuating antigens or inhibiting the entry of inflammatory...

  8. Microspheres for drug-delivery to the colon

    OpenAIRE

    Watts, Peter James

    1992-01-01

    The work described in this thesis is concerned with the design and evaluation of microsphere-based systems for drug delivery into the colon. In initial experiments, techniques were devised for the preparation of microspheres from two sustained-release acrylic polymers, Eudragits RL and RS, using emulsification-solvent evaporation techniques. For Eudragit RS microspheres containing the drug 5-aminosalicylic acid, the rate of drug release could be controlled by the type and concentration of...

  9. Advances in treatment of ulcerative colitis with herbs: From bench to bedside

    OpenAIRE

    Wan, Ping; Chen, Hao; Guo, Yuan; Bai, Ai-Ping

    2014-01-01

    Ulcerative colitis (UC), an idiopathic inflammatory disorder in the colon, has become a clinical challenge, owing to the increasing incidence and poor prognosis. The conventional treatments for UC including aminosalicylates, corticosteroids, and immunosuppressants, induce remission in only half of patients. Meanwhile, the treatments often come with serious side effects which can be life-threatening. Herbal medicine, one of the most common traditional Chinese medicine modalities, has been intr...

  10. Treatment of inflammatory bowel disease associated E. coli with ciprofloxacin and E. coli Nissle in the streptomycin-treated mouse intestine

    DEFF Research Database (Denmark)

    Petersen, Andreas Munk; Schjørring, Susanne; Gerstrøm, Sarah Choi;

    2011-01-01

    E. coli belonging to the phylogenetic group B2 are linked to Inflammatory Bowel Disease (IBD). Studies have shown that antimicrobials have some effect in the treatment of IBD, and it has been demonstrated that E. coli Nissle has prophylactic abilities comparable to 5-aminosalicylic acid (5-ASA......) therapy in ulcerative colitis. The objective of this study was to test if ciprofloxacin and/or E. coli Nissle could eradicate IBD associated E. coli in the streptomycin-treated mouse intestine....

  11. Treatment of Inflammatory Bowel Disease Associated E. coli with Ciprofloxacin and E. coli Nissle in the Streptomycin-Treated Mouse Intestine

    OpenAIRE

    Andreas Munk Petersen; Susanne Schjørring; Sarah Choi Gerstrøm; Karen Angeliki Krogfelt

    2011-01-01

    BACKGROUND: E. coli belonging to the phylogenetic group B2 are linked to Inflammatory Bowel Disease (IBD). Studies have shown that antimicrobials have some effect in the treatment of IBD, and it has been demonstrated that E. coli Nissle has prophylactic abilities comparable to 5-aminosalicylic acid (5-ASA) therapy in ulcerative colitis. The objective of this study was to test if ciprofloxacin and/or E. coli Nissle could eradicate IBD associated E. coli in the streptomycin-treated mouse intest...

  12. Relevance of Segmental Colitis with Diverticulosis (SCAD) to Other Forms of Inflammatory Bowel Disease

    OpenAIRE

    Freeman, Hugh J

    2009-01-01

    A well localized inflammatory process involving only the sigmoid colonic segment associated with diverticulosis (SCAD), has become increasingly recognized as a distinct clinical and pathological disorder, usually described in older adults, often with rectal bleeding. Although some resolve spontaneously, most patients appear to respond to treatment only with 5-aminosalicylate. Endoscopic evaluation reveals a nonspecific inflammatory process localized in the sigmoid colon that usually completel...

  13. Synthesis, Characterization and Chelating Properties of Benzimidazole-Salicylic Acid Combined Molecule

    OpenAIRE

    Kamlesh V. Patel; Singh, Arun

    2009-01-01

    Aminomethylation (i.e. Mannich reaction) of benzimidazole was carried out by treating benzimidalzole with formaldehyde and 4-aminosalicylic acid. The resultant compound was designated as 1-(4-carboxy-3-hydroxyphenyl aminomethyl) benzimidazole (BI-SA). The transition metal complexes of Cu2+, Co2+, Ni2+, Mn2+, Zn2+ and Fe3+ of BI-SA have been prepared and characterized by elemental analyses, spectral studies, magnetic moment determination, molar conductivity measurement and microbicidal activity.

  14. Validation of HPLC, DPPH• and nitrosation methods for mesalamine determination in pharmaceutical dosage forms Validação dos métodos de CLAE, DPPH• e nitrosação para determinação de mesalazina em formas farmacêuticas

    OpenAIRE

    Janice Aparecida Rafael; José Roberto Jabor; Rúbia Casagrande; Sandra Regina Georgetti; Maria de Fátima Borin; Maria José Vieira Fonseca

    2007-01-01

    Mesalamine (5-aminosalicylic acid, 5-ASA) is used because of its local effects in the treatment of inflammatory bowel disease. Therefore, the aims of this work were to compare and validate three analytical methods for the quality control of commercial coated tablets containing 5-ASA: high performance liquid chromatography (HPLC), 1,1-diphenyl-2-picrylhydrazyl radicals (DPPH•) and nitrosation. The parameters linearity, precision and accuracy were studied in this work. HPLC with ultraviole...

  15. Management and treatment of distal ulcerative colitis

    Directory of Open Access Journals (Sweden)

    Andrea Calafiore

    2013-12-01

    Full Text Available Ulcerative colitis (UC is a chronic inflammatory condition that is confined to the colonic mucosa. Its main symptoms include diarrhea, rectal bleeding and abdominal pain. Approximately two-thirds of UC patients have disease confined distal to the splenic flexure, which can be treated effectively with topical therapy. This means the active drug can be delivered directly to the site of inflammation, limiting the systemic absorption and potential side effects. Topical treatment with aminosalicylates is the most effective approach in the treatment of these forms, provided that the formulation reaches the upper margin of the disease. Given this, the suppository formulation is the treatment of choice for proctitis and distal sigmoiditis. Thanks to their proximal spread, enemas, foams and gels represent the treatment of choice for proctosigmoiditis and for distal ulcerative colitis. Oral aminosalicylates are less effective than topical therapies in patients with active disease, while the combination of topical and oral treatment is more effective in patients refractory to topical or oral mono-therapy. Topically administered aminosalicylates play an important role in the maintenance of remission, but the long-term adhesion to therapy is poor. For this reason, the oral formulation is the first-line therapy in the maintenance of remission. Refractory patients can be treated with topical steroids or systemic steroids and TNF-alpha inhibitors in severe forms.

  16. Synthesis and characterization of nanoscale magnetic drug-inorganic composites

    Institute of Scientific and Technical Information of China (English)

    SUN Hui; ZHANG Hui; David G. Evans; DUAN Xue

    2005-01-01

    The synthesis by direct coprecipitation and characterization of captopril (Cpl) and 5-aminosalicylic acid (5-ASA) intercalated ZnAl layered double hydroxides coated on MgFe2O4 magnetic core particles are reported. Powder XRD analysis shows the well-defined crystallite structure of the composites. TEM and XPS results reveal that a core-shell structure involving a drug-LDHs layer coated on MgFe2O4 particles is formed through Zn-O-Mg and/or Al-O-Mg linkages. VSM measurements demonstrate that the novel magnetic drug-inorganic composites possess considerable magnetization.

  17. Energy transformation in molecular electronic systems: Comprehensive progress report, 1986--1989

    International Nuclear Information System (INIS)

    Our research focuses on discovering the fundamental issues in proton-transfer and charge-transfer excitations in model systems, with an eye on which molecular systems will serve as the best guide to biological systems. This report addresses an intramolecular proton transfer classification system, proton-transfer potentials, proton-transfer spectroscopy of benzanilides, proton-transfer in aminosalicylates, proton-transfer in lumichrome, development of proton-transfer lasers, and triplet excitation enhancement via proton-transfer tunneling. 6 refs., 2 figs

  18. Spectrophotometric study into complexing of vanadium(3) with salicylic acid derivatives

    International Nuclear Information System (INIS)

    Complexing of vanadium (3) with 5 amino-salicylic acid and amide of salicylhydroxamic acid has been studied. It has been shown that in acidic medium V3+ forms yellow complexes of the composition 1:1 with instability constants 2.2x10-19, 7.8x10-11, and 2.2x10-12, respectively. Complexes of V3+ with derivatives of salicylic acid can be used for determining V(3) content in the presence of V(4)

  19. Evaluation of MGIT 960 System for the Second-Line Drugs Susceptibility Testing of Mycobacterium tuberculosis

    Directory of Open Access Journals (Sweden)

    Hyejin Kim

    2013-01-01

    Full Text Available Many laboratories validate DST of the second-line drugs by BACTEC MGIT 960 system. The objective of this study is to evaluate the critical concentration and perform DST for the 2nd line drugs. We evaluated 193 clinical strains of M. tuberculosis isolated from patients in South Korea. Testing the critical concentration of six second-line drugs was performed by MGIT 960 and compared with L-J proportion method. The critical concentration was determined to establish the most one that gave the difference between drug resistance and susceptibility in MGIT960 system. Good agreement of the following concentrations was found: Concordance was 95% for 0.5 μg/mL of moxifloxacin; 93.6%, 1.0 μg/mL of levofloxacin; 97.5%, 2.5 μg/mL of kanamycin; 90.6%, 2.5 μg/mL of capreomycin; 86.2%, 5.0 μg/mL of ethionamide; and 90.8%, 2.0 μg/mL of ρ-aminosalicylic acid. The critical concentrations of the four drugs, moxifloxacin, levofloxacin, kanamycin, and capreomycin, were concordant and reliable for testing 2nd line drug resistance. Further study of ethionamide and ρ-aminosalicylic acid is required.

  20. Double-blind, placebo-controlled evaluation of 5-ASA suppositories in active distal proctitis and measurement of extent of spread using /sup 99m/Tc-labeled 5-ASA suppositories

    International Nuclear Information System (INIS)

    Patients with active distal proctitis received either 5-aminosalicylic (5-ASA) acid or identical placebo suppositories, 500 mg t.i.d. for 6 weeks. Activity at 3 and 6 wks was assessed using a Disease Activity Index (DAI), derived from four categories: number of daily evacuations more than usual, evacuations containing blood, sigmoidoscopy appearance, and physician's overall assessment. Each category was graded 0-3. There was thus 0-12 points scored ranging from complete remission to severe disease. A minimum score of 3 from two categories was necessary for study entry. Of 27 patients randomized, 14 received active medication and 13 placebo. Of the 14 patients, with initial mean DAI 7.1 +/- 1.8, 11 were in complete remission at 6 wks (78.6%). Whereas, there was no significant change in the placebo group, with initial mean DAI 7.1 +/- 1.8. An additional 6 patients with inflammatory bowel disease and 6 healthy volunteers were given /sup 99m/Tc-labelled 5-aminosalicylic acid suppositories. The extent of spread was limited to the rectum, and the suppositories were retained for 3 hours. There was no absorbed radioactivity. 5-ASA suppositories are safe, well-tolerated, and effective treatment for active distal proctitis

  1. A case of rapid growing colonic NK/T cell lymphoma complicated by Crohn's disease

    Institute of Scientific and Technical Information of China (English)

    Shumei Zheng; Hui Xu; Qin Ouyang; Linyun Xue; Yong Zhang; Dejun Cui

    2013-01-01

    A 37-year-old man developed abdominal pain and bloody diarrhea 11 months before admission.The colonoscopy revealed multifocal ulcers in the colon.Histology showed active chronic inflammation.Although anti-tuberculosis medication was effective,his symptoms repeated 2 months later.The subsequent colonoscopy revealed more extensive irregular ulcers than before,and he was clinically suspected with intestinal malignant lymphoma.He underwent subtotal colectomy and was histologically suggested Crohn's disease,then 5-aminosalicylic and a combination of prednisone and azathioprine were administered in succession postoperatively,but they achieved minimal relief of symptoms for a period of 7 months.The third colonoscopy showed a large irregular ulcer in the ileocolon stomas,and primary colonic NK/T cell lymphoma was diagnosed through histological and immunophenotypic studies.Malignant lymphoma should be taken into consideration when clinically diagnosed Crohn's disease was refractory to medication or when its clinical course became aggressive.

  2. Innovative therapeutics for inflammatory bowel disease

    Institute of Scientific and Technical Information of China (English)

    Jesus K Yamamoto-Furusho

    2007-01-01

    Inflammatory bowel diseases (IBD) are chronic inflammatory conditions of the gastrointestinal tract,which clinically present as one of two disorders, Crohn's disease or ulcerative colitis. Mainstays of drug treatments for IBD include aminosalicylates, corticosteroids and immunosuppressants such as azathioprine, methotrexate and cyclosporin. Advances in basic research of the pathophysiological process in IBD have been applied to generate a variety of new therapeutics targeting at different levels of the inflammatory processes. New therapies are classified as: (1) Anti-TNFα antibodies; (2) Recombinant cytokines; (3) Selective adhesion blockade;(4) Growth factors; (5) Innate immunostimulation; (6) Nucleic acid based therapies; (7) Gene therapy; (8) Autologous bone-marrow transplantation; (9) Helminths and (10) Extracorporeal immunomodulation. All treatments have the potential to provide more effective and safe treatment for IBD.

  3. Clinical and economic outcomes in a population-based European cohort of 948 ulcerative colitis and Crohn's disease patients by Markov analysis

    DEFF Research Database (Denmark)

    Odes, S.; Vardi, H.; Friger, M.;

    2010-01-01

    P>Background Forecasting clinical and economic outcomes in ulcerative colitis (UC) and Crohn's disease (CD) patients is complex, but necessary. Aims To determine: the frequency of treatment-classified clinical states; the probability of transition between states; and the economic outcomes. Methods....../surgical remission (medication-free) and mild disease (on 5-aminosalicylates, antibiotics, topical corticosteroids), comprising 28% and 62% of UC cycles and 24% and 51% of CD cycles respectively. The probability of drug-response in patients receiving systemic corticosteroids/immunomodulators was 0.74 in UC, 0.66 in...... CD. Both diseases had similar likelihood of persistent drug-dependency or drug-refractoriness. Surgery was more probable in CD, 0.20, than UC, 0.08. In terms of economic outcomes, surgery was costlier in UC per cycle, but the outlay over 10 years was greater in CD. Drug-refractory UC and CD cases...

  4. Synthesis, spectral investigation (/sup 1/H, /sup 13/C) of new (N, O and S based) schiff bases and evaluation of their antimicrobial activities

    International Nuclear Information System (INIS)

    Three new series of biologically active amino substituted Schiff bases (1-12) with general formula, R/sub 1/N=CHR/sub 2/ (R/sub 1/ 2-amino-benzthiazole, 4-amino-salicylic acid and 4-aminophenol; R/sub 2/ benzaldehyde, 2-chloro-benzaldehyde, 4-chloro-benzaldehyde, salicylaldehyde and vanillin) were synthesized by the reaction of three different amino substituted compounds and substituted aldehydes in ethanol. The synthesized compounds were characterized by different physico-chemical techniques like, melting point, elemental analysis, multinuclear NMR (/sup 1/H, /sup 13/C). The compounds were subjected for bioassay screening and showed promising antibacterial and antifungal activities using Amoxicillin and Ciprofloxacin as standard drugs. (author)

  5. Mesalamine induced symptom exacerbation of ulcerative colitis: Case report and brief discussion

    Institute of Scientific and Technical Information of China (English)

    Maneesh; Kumar; Gupta; Scott; Pollack; John; J; Hutchings

    2010-01-01

    This paper describes a rare case in which the oral ad-ministration of mesalamine resulted in the exacerbation of ulcerative colitis (UC) in a patient who was previously responsive to mesalamine and whose colitis had been in remission for eight years. Mesalamine and other 5-ami-nosalicylic acid compounds are the mainstay of treatment for UC; however up to 8% of patients are unable to take the medications due to intolerance or hypersensitivity reactions. Common drug reactions are fever, nausea, di-arrhea and abdominal pain; however, exacerbation of UC has rarely been reported. This study highlights the impor-tance of ruling out mesalamine as the causative agent in cases of UC exacerbations.

  6. Mesalazine preparations for the treatment of ulcerative colitis: Are all created equal?

    Institute of Scientific and Technical Information of China (English)

    Bei; Ye; Daniel; R; van; Langenberg

    2015-01-01

    Oral mesalazine(also known as mesalamine) is a 5-aminosalicylic acid compound used in the treatment of mild to moderate ulcerative colitis, with high rates of efficacy in induction and maintenance of remission.The therapeutic effect of mesalazine occurs topically at the site of diseased colonic mucosa. A myriad of oral mesalazine preparations have been formulated with various drug delivery methods to minimize systemic absorption and maximise drug availability at the inflamed colonic epithelium. It remains unclear whether different oral mesalazine formulations are bioequivalent. This review aims to evaluate the differences between mesalazine formulations based on the currently available literature and explore factors which may influence the selection of one agent above another.

  7. Co-infection of long-standing extensively drug-resistant Mycobacterium tuberculosis (XDR-TB and non-tuberculosis mycobacteria: A case report

    Directory of Open Access Journals (Sweden)

    Nafiseh Izadi

    2015-01-01

    Full Text Available We report a 69-years-old Iranian HIV negative male patient, with long-standing pulmonary tuberculosis (eleven years co-infected with non-tuberculosis mycobacteria. Despite of initiation of first line anti-tuberculosis therapy after diagnosis the patient poorly respond because of low compliance with anti-TB treatment. After several incomplete treatments the smear was still positive and thus drug susceptibility tests were performed on isolated organism which revealed that the organisms was resistant not only against isoniazid and rifampin but also against Ofloxacin (OFX, Capreomycin (CAP, p-aminosalicylic acid (PAS, ethionamide (ETH, Kanamycin (KAN, ciprofloxacin (Cip, amikacin (AMK and cycloserine (CYC. Persistence and resistance of infection had led us to do more investigation using molecular methods, which revealed co-infection with Non-tuberculosis mycobacteria (NTM. The patient is still alive with cough and shortness of breath.

  8. A case report of severe ulcerative colitis with mediastinal and subcutaneous emphysema.

    Science.gov (United States)

    Terasaki, Kei; Okuyama, Yusuke; Ueda, Tomohiro; Matsuyama, Kiichi; Urata, Yoji; Yoshida, Norimasa

    2016-01-01

    A 17-year-old boy developed prominent mediastinal and subcutaneous emphysema while receiving treatment with 5-aminosalicylic acid (5-ASA) and oral corticosteroids for severe ulcerative colitis. We ruled out infection and initiated oral administration of tacrolimus, after which both the underlying disease and mediastinal and subcutaneous emphysema improved. However, he continued to experience repeated bouts of ulcerative colitis, so we ultimately opted for surgical intervention. Although mediastinal and subcutaneous emphysema is rare, it is one of the known extra-intestinal complications and can be particularly concerning. In this patient, mediastinal and subcutaneous emphysema might have been caused by the vulnerability of pulmonary alveolar walls to steroid medication and the increase of pulmonary alveolar pressure with abdominal pain and breath holding. Here, we report a case of inflammatory bowel disease with mediastinal and subcutaneous emphysema, along with a review of the literature. PMID:26947047

  9. Advances in treatment of ulcerative colitis with herbs: from bench to bedside.

    Science.gov (United States)

    Wan, Ping; Chen, Hao; Guo, Yuan; Bai, Ai-Ping

    2014-10-21

    Ulcerative colitis (UC), an idiopathic inflammatory disorder in the colon, has become a clinical challenge, owing to the increasing incidence and poor prognosis. The conventional treatments for UC including aminosalicylates, corticosteroids, and immunosuppressants, induce remission in only half of patients. Meanwhile, the treatments often come with serious side effects which can be life-threatening. Herbal medicine, one of the most common traditional Chinese medicine modalities, has been introduced for centuries into clinical treatment of many human diseases such as infections and functional disorders. Recently, the potential effectiveness of herbs has been suggested as the treatment of UC, as shown by a variety of clinical trials and experimental studies. The herbs reported in the literature include aloe vera gel, butyrate, tormentil extracts, wheat grass juice, and curcumin. In the review, bioactivity of the herbs and their involvement in UC treatment are discussed. PMID:25339799

  10. Clinical and economic outcomes in a population-based European cohort of 948 ulcerative colitis and Crohn's disease patients by Markov analysis

    DEFF Research Database (Denmark)

    Odes, S.; Vardi, H.; Friger, M.;

    2010-01-01

    P>Background Forecasting clinical and economic outcomes in ulcerative colitis (UC) and Crohn's disease (CD) patients is complex, but necessary. Aims To determine: the frequency of treatment-classified clinical states; the probability of transition between states; and the economic outcomes. Methods...... CD. Both diseases had similar likelihood of persistent drug-dependency or drug-refractoriness. Surgery was more probable in CD, 0.20, than UC, 0.08. In terms of economic outcomes, surgery was costlier in UC per cycle, but the outlay over 10 years was greater in CD. Drug-refractory UC and CD cases...... engendered high costs in the cohort. Conclusions Most patients on 5-aminosalicylates, corticosteroids and immunomodulators had favourable clinical and economic outcomes over 10 years. Drug-refractory and surgical patients exhibited greater long-term expenses...

  11. Maintaining remission in ulcerative colitis – role of once daily extended-release mesalamine

    Directory of Open Access Journals (Sweden)

    Lilliana Oliveira

    2011-02-01

    Full Text Available Lilliana Oliveira, Russell D CohenThe Department of Medicine, Section of Gastroenterology, University of Chicago Medical Center, Chicago, IL, USAAbstract: The aminosalicylates (5-ASA; also referred to as mesalamine-based agents are considered as first-line in the maintenance of remission of mild to moderate ulcerative colitis (UC. Traditionally these agents have required a large pill burden and multiple daily dosing regimens which may account for the low adherence rates, especially in patients in remission. Extended-release mesalamine is the first once daily mesalamine product approved by the Food and Drug Administration for the maintenance of UC remission. This review will examine the pharmacokinetics, dosing, efficacy, and safety data of extended-release mesalamine, and discuss the potential role of improving medication compliance and decreasing costs in UC maintenance.Keywords: ulcerative colitis, 5-ASA, mesalamine, adherence, compliance, quality of life, costs

  12. Birth outcome in women with ulcerative colitis and Crohn's disease, and pharmacoepidemiological aspects of anti-inflammatory drug therapy

    DEFF Research Database (Denmark)

    Nørgård, Bente Mertz

    2011-01-01

    conception, iii) the risk of adverse birth outcome in women with Crohn's disease according to type of anti-inflammatory drug treatment in pregnancy (sulfasalazine/5-aminosalicylic acid, steroids or azathioprine/6-mercaptopurine), and iv) the impact of disease activity in women with Crohn's disease on adverse......, including patients with ulcerative colitis and Crohn's disease. The third part (and the latest publications) includes birth outcome in women with Crohn's disease; and the methods of cohort establishment in these studies are developed and improved due to the knowledge gathered from conducting the earlier...... increased risk of preterm birth when women give birth 0-6 months after establishment of the diagnosis. It is considered whether the increased risk may be influenced by disease activity around the time of establishing the diagnosis. 2) No increased risk of giving birth to children with low birth weight...

  13. Treatment of Tuberculosis. A Historical Perspective.

    Science.gov (United States)

    Murray, John F; Schraufnagel, Dean E; Hopewell, Philip C

    2015-12-01

    Of all achievements in medicine, the successful treatment of tuberculosis has had one of the greatest impacts on society. Tuberculosis was a leading cause of disease and a mortal enemy of humanity for millennia. The first step in finding a cure was the discovery of the cause of tuberculosis by Robert Koch in 1882. The sanatorium movement that began shortly afterward in Europe, and soon spread to the United States, brought attention to the plight of afflicted persons, and catalyzed public health action. The antituberculosis benefit of streptomycin was announced in 1945, although application was limited by the rapid development of resistance. para-Aminosalicylic acid, also discovered in 1945, when combined with streptomycin was found to greatly reduce the occurrence of drug resistance. In 1952, isoniazid opened the modern era of treatment; it was inexpensive, well tolerated, and safe. In the early 1960s, ethambutol was shown to be effective and better tolerated than para-aminosalicylic acid, which it replaced. In the 1970s, rifampin found its place as a keystone in the therapy of tuberculosis. The use of rifampin enabled the course of treatment to be reduced to nine months. Incorporation of pyrazinamide into the first-line regimen led to a further reduction of treatment duration to six months. Treatment of multiple drug-resistant tuberculosis remains a difficult problem requiring lengthy treatment with toxic drugs. However, shortened regimens show promise, and two new drugs, bedaquiline and delamanid, have demonstrated effectiveness in preliminary studies and are being used for extensively drug-resistant tuberculosis. PMID:26653188

  14. Azo dye removal in a membrane-free up-flow biocatalyzed electrolysis reactor coupled with an aerobic bio-contact oxidation reactor

    Energy Technology Data Exchange (ETDEWEB)

    Cui, Dan; Guo, Yu-Qi; Cheng, Hao-Yi; Liang, Bin; Kong, Fan-Ying [State Key Laboratory of Urban Water Resource and Environment, Harbin Institute of Technology, No. 202 Haihe Road, Harbin 150090 (China); Lee, Hyung-Sool [Department of Civil and Environmental Engineering, University of Waterloo, 200 University Avenue West Waterloo, Ontario, Canada N2L 3G1 (Canada); Wang, Ai-Jie, E-mail: waj0578@hit.edu.cn [State Key Laboratory of Urban Water Resource and Environment, Harbin Institute of Technology, No. 202 Haihe Road, Harbin 150090 (China)

    2012-11-15

    Highlights: Black-Right-Pointing-Pointer A membrane-free up-flow biocatalyzed electrolysis reactor coupled with an aerobic bio-contact oxidation reactor was developed. Black-Right-Pointing-Pointer Alizarin Yellow R as the mode of azo dyes was efficiently converted to p-phenylenediamine (PPD) and 5-aminosalicylic acid (5-ASA). Black-Right-Pointing-Pointer PPD and 5-ASA were further oxidized in a bio-contact oxidation reactor. Black-Right-Pointing-Pointer The mechanism of UBER for azo dye removal was discussed. - Abstract: Azo dyes that consist of a large quantity of dye wastewater are toxic and persistent to biodegradation, while they should be removed before being discharged to water body. In this study, Alizarin Yellow R (AYR) as a model azo dye was decolorized in a combined bio-system of membrane-free, continuous up-flow bio-catalyzed electrolysis reactor (UBER) and subsequent aerobic bio-contact oxidation reactor (ABOR). With the supply of external power source 0.5 V in the UBER, AYR decolorization efficiency increased up to 94.8 {+-} 1.5%. Products formation efficiencies of p-phenylenediamine (PPD) and 5-aminosalicylic acid (5-ASA) were above 90% and 60%, respectively. Electron recovery efficiency based on AYR removal in cathode zone was nearly 100% at HRTs longer than 6 h. Relatively high concentration of AYR accumulated at higher AYR loading rates (>780 g m{sup -3} d{sup -1}) likely inhibited acetate oxidation of anode-respiring bacteria on the anode, which decreased current density in the UBER; optimal AYR loading rate for the UBER was 680 g m{sup -3} d{sup -1} (HRT 2.5 h). The subsequent ABOR further improved effluent quality. Overall the Chroma decreased from 320 times to 80 times in the combined bio-system to meet the textile wastewater discharge standard II in China.

  15. Disease activity and cancer risk in inflammatory bowel disease associated with primary sclerosing cholangitis

    Institute of Scientific and Technical Information of China (English)

    Harry Sokol; Jacques Cosnes; Olivier Chazouilleres; Laurent Beaugerie; Emmanuel Tiret; Raoul Poupon; Philippe Seksik

    2008-01-01

    AIM: To investigate the phenotype of inflammatory bowel disease associated with primary sclerosing cholangitis (PSC-IBD).METHODS: Data from 75 PSC-]BD patients evaluated in our tertiary center between 1963 and 2006 were collected and compared to 150 IBD patients without PSC, matched for sex, birth date, IBD diagnosis date and initial disease location regarding ileal, different colonic segments, and rectum, respectively.RESULTS: While PSC-IBD patients received more 5-aminosalicylates (8.7 years/patient vs 2.9 years/patient, P<0.001), they required less immunosuppressors (24% vs 46% at 10 years; P<0.001) and less intestinal resection (10% vs 44% at 10 years, P<0.001). The 25-year cumulative rate of colectomy was 25.1% in PSC-IBD and 37.3% in controls (P=0.004). The 25-year cumulative rate of colorectal cancer was 23.4% in PSC-IBD vs 0% in controls (P=0.002). PSC was the only independent risk factor for the development of colorectal cancer (OR=10.8; 95%CI, 3.7-31.3). Overall survival rate without liver transplantation was reduced in PSC-IBD patients (67% vs 91% in controls at 25 years, P=0.001).CONCLUSION: This study confirms that patients with PSC-IBD have a particular disease phenotype independent of the initial disease location. Although their disease is less active and they use more 5-aminosalicylates, they present a higher risk of colorectal cancer.

  16. Kinetic characterisation of arylamine N-acetyltransferase from Pseudomonas aeruginosa

    Directory of Open Access Journals (Sweden)

    Sim Edith

    2007-03-01

    Full Text Available Abstract Background Arylamine N-acetyltransferases (NATs are important drug- and carcinogen-metabolising enzymes that catalyse the transfer of an acetyl group from a donor, such as acetyl coenzyme A, to an aromatic or heterocyclic amine, hydrazine, hydrazide or N-hydroxylamine acceptor substrate. NATs are found in eukaryotes and prokaryotes, and they may also have an endogenous function in addition to drug metabolism. For example, NAT from Mycobacterium tuberculosis has been proposed to have a role in cell wall lipid biosynthesis, and is therefore of interest as a potential drug target. To date there have been no studies investigating the kinetic mechanism of a bacterial NAT enzyme. Results We have determined that NAT from Pseudomonas aeruginosa, which has been described as a model for NAT from M. tuberculosis, follows a Ping Pong Bi Bi kinetic mechanism. We also describe substrate inhibition by 5-aminosalicylic acid, in which the substrate binds both to the free form of the enzyme and the acetyl coenzyme A-enzyme complex in non-productive reaction pathways. The true kinetic parameters for the NAT-catalysed acetylation of 5-aminosalicylic acid with acetyl coenzyme A as the co-factor have been established, validating earlier approximations. Conclusion This is the first reported study investigating the kinetic mechanism of a bacterial NAT enzyme. Additionally, the methods used herein can be applied to investigations of the interactions of NAT enzymes with new chemical entities which are NAT ligands. This is likely to be useful in the design of novel potential anti-tubercular agents.

  17. Azo dye removal in a membrane-free up-flow biocatalyzed electrolysis reactor coupled with an aerobic bio-contact oxidation reactor

    International Nuclear Information System (INIS)

    Highlights: ► A membrane-free up-flow biocatalyzed electrolysis reactor coupled with an aerobic bio-contact oxidation reactor was developed. ► Alizarin Yellow R as the mode of azo dyes was efficiently converted to p-phenylenediamine (PPD) and 5-aminosalicylic acid (5-ASA). ► PPD and 5-ASA were further oxidized in a bio-contact oxidation reactor. ► The mechanism of UBER for azo dye removal was discussed. - Abstract: Azo dyes that consist of a large quantity of dye wastewater are toxic and persistent to biodegradation, while they should be removed before being discharged to water body. In this study, Alizarin Yellow R (AYR) as a model azo dye was decolorized in a combined bio-system of membrane-free, continuous up-flow bio-catalyzed electrolysis reactor (UBER) and subsequent aerobic bio-contact oxidation reactor (ABOR). With the supply of external power source 0.5 V in the UBER, AYR decolorization efficiency increased up to 94.8 ± 1.5%. Products formation efficiencies of p-phenylenediamine (PPD) and 5-aminosalicylic acid (5-ASA) were above 90% and 60%, respectively. Electron recovery efficiency based on AYR removal in cathode zone was nearly 100% at HRTs longer than 6 h. Relatively high concentration of AYR accumulated at higher AYR loading rates (>780 g m−3 d−1) likely inhibited acetate oxidation of anode-respiring bacteria on the anode, which decreased current density in the UBER; optimal AYR loading rate for the UBER was 680 g m−3 d−1 (HRT 2.5 h). The subsequent ABOR further improved effluent quality. Overall the Chroma decreased from 320 times to 80 times in the combined bio-system to meet the textile wastewater discharge standard II in China.

  18. Efficacy assessment of paroxetine in the treatment of patients with mild-to-moderate ulcerative colitis accompanied with anxiety/depression%帕罗西汀对轻-中度溃疡性结肠炎伴焦虑/抑郁的疗效评价

    Institute of Scientific and Technical Information of China (English)

    宋军民; 战玉华; 李岩

    2012-01-01

    目的 评价帕罗西汀辅助治疗轻-中度溃疡性结肠炎伴焦虑/抑郁的疗效.方法 将30例轻-中度溃疡性结肠炎(UC)伴焦虑/抑郁患者随机分成2组(每组15例),分别接受5-氨基水杨酸和5-氨基水杨酸+帕罗西汀治疗;所有患者治疗前后均进行临床活动指数(CAI)、内镜指数(EI)和焦虑/抑郁测试,并比较治疗后的改善情况.结果 治疗后5-氨基水杨酸+帕罗西汀组的CAI(腹泻和腹痛)和焦虑/抑郁评分较5-氨基水杨酸组显著下降(P<0.05,P<0.001),而EI和其他表现与5-氨基水杨酸组无显著差异(P>0.05).结论 对于轻中度UC伴焦虑/抑郁的患者,帕罗西汀能改善焦虑/抑郁,通过减轻腹泻和腹痛而促进临床缓解,可作为辅助用药之一,但对组织学表现无改善作用.%Objective To assess the efficacy of paroxetine in the adjuvant treatment of patients with mild-to-moderate ulcerative colitis (UC) accompanied with anxiety/depression. Methods 30 patients diagnosed with mild-to-moderate UC accompanied with anxiety/depression were assigned into two groups (15 ones in each group) randomly, and were treated with 5-aminosalicylic acid and 5-aminosalicylic acid combined with paroxetinc, respectively. Clinical activity index (CAI) , endoscopic index (EI) , and anxiety/depression tests were performed before and after the treatment, and the efficacy of treatment was compared. Results The difference was significant between two groups with respect to CAI (diarrhea and abdominal pain) and anxiety/depression scoring after the treatment ( P 0.05). Conclusion Paroxetine can improve anxiety/ depression, and accelerate the clinical remission through attenuating diarrhea and abdominal pain. Therefore, it might be an adjuvant treatment for patients with mild-to-moderate UC accompanied with anxiety/depression. However, it can not improve the histologic appearance.

  19. Flux et sources des parabènes, du triclosan et du triclocarban en milieux urbains denses : comparaison entre Paris et Beyrouth

    OpenAIRE

    Geara-Matta, Darine

    2012-01-01

    Le triclosan (TCS), le triclocarban (TCC) et les parabènes (esters de l'acide para-hydroxbenzoïque) sont employés en tant qu'antiseptiques et agents conservateurs dans les produits de soins corporels. Leur usage génère des inquiétudes sur leur devenir et leur effet potentiel sur la faune et la flore (Bazin et al., 2010). En effet, ils sont introduits dans le milieu récepteur principalement via les effluents des stations d'épuration et les rejets urbains de temps de pluie (McAvoy et al., 2002;...

  20. Optimización del enriquecimiento de nauplios de Artemia mediante el uso de emulsiones lipídicas formuladas a partir de aceites sintéticos ricos en DHA

    OpenAIRE

    Viciano Delibano, Elena

    2015-01-01

    Los nauplios de Artemia se utilizan como presa viva en criaderos de organimos marinos de todo el mundo debido a su disponibilidad y digestibilidad, pero su valor nutricional no se ajusta a las demandas o necesidades de las larvas de peces, moluscos o crustáceos marinos, ya que carecen de los ácidos grasos esenciales (EFA, Essential Fatty Acids) para estos organismos. Por tanto, es indispensable llevar a cabo un enriquecimiento de los nauplios de Artemia. El enriquecimiento consiste en incubac...

  1. Inflammatory Bowel Disease: An Overview of Immune Mechanisms and Biological Treatments

    Directory of Open Access Journals (Sweden)

    Bruno Rafael Ramos de Mattos

    2015-01-01

    Full Text Available Inflammatory bowel diseases (IBD are characterized by chronic inflammation of the intestinal tract associated with an imbalance of the intestinal microbiota. Crohn’s disease (CD and ulcerative colitis (UC are the most widely known types of IBD and have been the focus of attention due to their increasing incidence. Recent studies have pointed out genes associated with IBD susceptibility that, together with environment factors, may contribute to the outcome of the disease. In ulcerative colitis, there are several therapies available, depending on the stage of the disease. Aminosalicylates, corticosteroids, and cyclosporine are used to treat mild, moderate, and severe disease, respectively. In Crohn’s disease, drug choices are dependent on both location and behavior of the disease. Nowadays, advances in treatments for IBD have included biological therapies, based mainly on monoclonal antibodies or fusion proteins, such as anti-TNF drugs. Notwithstanding the high cost involved, these biological therapies show a high index of remission, enabling a significant reduction in cases of surgery and hospitalization. Furthermore, migration inhibitors and new cytokine blockers are also a promising alternative for treating patients with IBD. In this review, an analysis of literature data on biological treatments for IBD is approached, with the main focus on therapies based on emerging recombinant biomolecules.

  2. Inflammatory Bowel Disease: An Overview of Immune Mechanisms and Biological Treatments

    Science.gov (United States)

    de Mattos, Bruno Rafael Ramos; Garcia, Maellin Pereira Gracindo; Nogueira, Julia Bier; Paiatto, Lisiery Negrini; Albuquerque, Cassia Galdino; Souza, Caique Lopes; Fernandes, Luís Gustavo Romani; Tamashiro, Wirla Maria da Silva Cunha; Simioni, Patricia Ucelli

    2015-01-01

    Inflammatory bowel diseases (IBD) are characterized by chronic inflammation of the intestinal tract associated with an imbalance of the intestinal microbiota. Crohn's disease (CD) and ulcerative colitis (UC) are the most widely known types of IBD and have been the focus of attention due to their increasing incidence. Recent studies have pointed out genes associated with IBD susceptibility that, together with environment factors, may contribute to the outcome of the disease. In ulcerative colitis, there are several therapies available, depending on the stage of the disease. Aminosalicylates, corticosteroids, and cyclosporine are used to treat mild, moderate, and severe disease, respectively. In Crohn's disease, drug choices are dependent on both location and behavior of the disease. Nowadays, advances in treatments for IBD have included biological therapies, based mainly on monoclonal antibodies or fusion proteins, such as anti-TNF drugs. Notwithstanding the high cost involved, these biological therapies show a high index of remission, enabling a significant reduction in cases of surgery and hospitalization. Furthermore, migration inhibitors and new cytokine blockers are also a promising alternative for treating patients with IBD. In this review, an analysis of literature data on biological treatments for IBD is approached, with the main focus on therapies based on emerging recombinant biomolecules. PMID:26339135

  3. Effectiveness of chelation therapy with time after acute uranium intoxication

    International Nuclear Information System (INIS)

    The effect of increasing the time interval between acute uranium exposure and chelation therapy was studied in male Swiss mice. Gallic acid, 4,5-dihydroxy-1,3- benzenedisulfonic acid (Tiron), diethylenetriaminepentaacetic acid (DTPA), and 5-aminosalicylic acid (5-AS) were administered ip at 0, 0.25, 1, 4, and 24 hr after sc injection of 10 mg/kg of uranyl acetate dihydrate. Chelating agents were given at doses equal to one-fourth of their respective LD50 values. Daily elimination of uranium into urine and feces was determined for 4 days after which time the mice were killed, and the concentration of uranium was measured in kidney, spleen, and bone. The excretion of uranium was especially rapid in the first 24 hr. Treatment with Tiron or gallic acid at 0, 0.25, or 1 hr after uranium exposure significantly increased the total excretion of the metal. In kidney and bone, only administration of Tiron at 0, 0.25, or 1 hr after uranium injection, or gallic acid at 1 hr after uranium exposure significantly reduced tissue uranium concentrations. Treatment at later times (4 to 24 hr) did not increase the total excretion of the metal and did not decrease the tissue uranium concentrations 4 days after uranyl acetate administration. The results show that the length of time before initiating chelation therapy for acute uranium intoxication greatly influences the effectiveness of this therapy

  4. Review article: current therapeutic options for radiation proctopathy.

    Science.gov (United States)

    Hong, J J; Park, W; Ehrenpreis, E D

    2001-09-01

    Radiation proctopathy is a common unfortunate complication following radiation therapy of pelvic malignancies. Symptoms of chronic radiation proctopathy include haematochezia, urgency, constipation, tenesmus, diarrhoea and rectal pain. Currently, a wide variety of pharmacological options, endoscopic cautery techniques and surgical procedures have been proposed for the treatment of chronic radiation proctopathy. Although these have been proposed primarily as treatment for rectal bleeding, the control of other symptoms has been noted with some of these agents. Pharmacological options include 5-aminosalicylic acid preparations, coticosteroid enemas, sucralfate (oral, enemas), formalin, short chain fatty acid enemas, oestrogen/progesterone, hyperbaric oxygen, antioxidants, sodium pentosan polysulphate and misoprostol rectal suppositories. Of these, sucralfate and formalin therapy appear to be effective for bleeding control. Misoprostol rectal suppositories and oral sucralfate may be useful in the prevention of acute and chronic symptoms of radiation proctopathy. Endoscopic cautery techniques have included the use of Nd:YAG laser and argon laser for coagulation of bleeding neovascular telangiectasias. Argon plasma coagulation offers a safe non-contact method of delivering haemostasis which has proven to be particularly useful in targeting difficult to reach lesions tangentially. Surgery is generally reserved for severe refractory cases involving ongoing haemorrhage, obstruction, stricture formation, fistulas and perforation. Given that formal randomized placebo-controlled studies are lacking for most treatments, the management of these patients is often challenging and unclear. Hence, there is a need for more research and education on radiation proctopathy. PMID:11552895

  5. Pregnancy related issues in inflammatory bowel disease:Evidence base and patients' perspective

    Institute of Scientific and Technical Information of China (English)

    Christian P Selinger; Rupert WL Leong; Simon Lal

    2012-01-01

    Inflammatory bowel disease (IBD) affects women of childbearing age and can influence fertility,pregnancy and decisions regarding breastfeeding.Women with IBD need to consider the possible course of disease during pregnancy,the benefits and risks associated with medications required for disease management during pregnancy and breastfeeding and the effects of mode of delivery on their disease.When indicated,aminosalicylates and thiopurines can be safely used during pregnancy.Infliximab and Adalimumab are considered probably safe during the first two trimesters.During the third trimester the placenta can be crossed and caution should be applied.Methotrexate is associated with severe teratogenicity due to its folate antagonism and is strictly contraindicated.Women with IBD tend to deliver earlier than healthy women,but can have a vaginal delivery in most cases.Caesarean sections are generally recommended for women with active perianal disease or after ileo-anal pouch surgery.While the impact of disease activity and medication has been addressed in several studies,there are minimal studies evaluating patients' perspective on these issues.Women's attitudes may influence their decision to have children and can positively or negatively influence the chance of conceiving,and their beliefs regarding therapies may impact on the course of their disease during pregnancy and/or breastfeeding.This review article outlines the impact of IBD and its treatment on pregnancy,and examines the available data on patients' views on this subject.

  6. Salicylic acid derivatives as potential anti asthmatic agents using disease responsive drug delivery system for prophylactic therapy of allergic asthma.

    Science.gov (United States)

    Raju, Kalidhindi Rama Satyanarayana; Ambhore, Nilesh S; Mulukutla, Shashank; Gupta, Saurabh; Murthy, Vishakantha; Kumar, M N Kiran; Madhunapantula, Subba Rao V; Kuppuswamy, Gowthamarajan; Elango, Kannan

    2016-02-01

    Asthma is a multi-factorial and complicated lung disorder of the immune system which has expanded to a wider ambit unveiling its etiology to be omnipresent at both ends of the spectrum involving basic pharmacology and in-depth immunology. As asthma occurs through triggered activation of various immune cells due to different stimuli, it poses a great challenge to uncover specific targets for therapeutic interventions. Recent pharmacotherapeutic approaches for asthma have been focused on molecular targeting of transcription factors and their signaling pathways; mainly nucleus factor kappa B (NFκB) and its associated pathways which orchestrate the synthesis of pro-inflammatory cytokines (IL-1β, TNF-α, GM-CSF), chemokines (RANTES, MIP-1a, eotaxin), adhesion molecules (ICAM-1, VCAM-1) and inflammatory enzymes (cyclooxygenase-2 and iNOS). 5-aminosalicylic acid (5-ASA) and sodium salicylate are known to suppress NFκB activation by inhibiting inhibitor of kappa B kinase (IKκB). In order to target the transcription factor, a suitable carrier system for delivering the drug to the intracellular space is essential. 5-ASA and sodium salicylate loaded liposomes incorporated into PEG-4-acrylate and CCRGGC microgels (a polymer formed by crosslinking of trypsin sensitive peptide and PEG-4-acrylate) could probably suit the needs for developing a disease responsive drug delivery system which will serve as a prophylactic therapy for asthmatic patients. PMID:26643666

  7. Gynecomastia caused by ethionamide

    Directory of Open Access Journals (Sweden)

    Parveen K Sharma

    2012-01-01

    Full Text Available A 43 year old male patient, known case of multidrug resistant tuberculosis, was prescribed antitubercular drugs: kanamycin, levofloxacin, ethionamide, terizidone, Para-Aminosalicylate Sodium (PAS, pyrazinamide and pyridoxine. After 4 months of treatment, the patient developed a lump in the right breast which was approximately around 3 × 3 cm in size, tender on palpation, and not fixed to the underlying tissues. Ultrasonography (USG revealed a hypoechoic mass of size 2.5 × 0.92 × 2.6 cm in the right breast region behind the nipple without any infiltration to the deeper structures. Gynecomastia due to ethionamide was suspected and the patient was advised anti-inflammatory drugs for 5 days without any change in drug therapy. The pain subsided; however, the nodule remained. Treatment was continued without any change till the patient stopped using the drugs on his own and without doctor′s consent. Within a week of stopping of treatment the nodule also disappeared.

  8. Microscopic colitis: A review of etiology, treatment and refractory disease.

    Science.gov (United States)

    Park, Tina; Cave, David; Marshall, Christopher

    2015-08-01

    Microscopic colitis is a common cause of chronic, nonbloody diarrhea. Microscopic colitis is more common in women than men and usually affects patients in their sixth and seventh decade. This article reviews the etiology and medical management of microscopic colitis. The etiology of microscopic colitis is unknown, but it is associated with autoimmune disorders, such as celiac disease, polyarthritis, and thyroid disorders. Smoking has been identified as a risk factor of microscopic colitis. Exposure to medications, such as non-steroidal anti-inflammatory drugs, proton pump inhibitors, and selective serotonin reuptake inhibitors, is suspected to play a role in microscopic colitis, although their direct causal relationship has not been proven. Multiple medications, including corticosteroids, anti-diarrheals, cholestyramine, bismuth, 5-aminosalicylates, and immunomodulators, have been used to treat microscopic colitis with variable response rates. Budesonide is effective in inducing and maintaining clinical remission but relapse rate is as high as 82% when budesonide is discontinued. There is limited data on management of steroid-dependent microscopic colitis or refractory microscopic colitis. Immunomodulators seem to have low response rate 0%-56% for patients with refractory microscopic colitis. Response rate 66%-100% was observed for use of anti-tumor necrosis factor (TNF) therapy for refractory microscopic colitis. Anti-TNF and diverting ileostomy may be an option in severe or refractory microscopic colitis. PMID:26269669

  9. Effect of simulated gastrointestinal conditions on drug release from pectin/ethylcellulose as film coating for drug delivery to the colon.

    Science.gov (United States)

    Ahmed, I S

    2005-05-01

    The aim of this work was to investigate the effect of acidic pH representative of gastric fluid on the release of 5-aminosalicylic acid from beads coated with pectin/ethylcellulose as film coating intended for drug delivery to the colon, in media mimicking the lower gastrointestinal (GI) tract and representative of colonic conditions. In this work, the in vitro incubation of the beads in acid medium was found to influence the hydration and the swelling characteristics of pectin after transfer into simulated intestinal fluid and simulated cecal fluid containing pectinolytic enzymes. Moreover, the drug release profiles from the beads in simulated intestinal fluid after incubation for 2 h or 30 min in simulated gastric fluid vs. no acid incubation were found to be very different. The in vitro degradation of pectin in the coat by pectinolytic enzymes in simulated cecal fluid depended on whether the beads were placed in simulated gastric fluid prior to testing in simulated intestinal fluid. The percentage drug release also depended on the ratio of pectin to ethylcellulose in the coat. PMID:16093212

  10. [Case of scattered gastritis associated with ulcerative proctitis].

    Science.gov (United States)

    Ozawa, Toshifumi; Wachi, Eiko; Saitoh, Yasutoshi

    2009-01-01

    A 59-year-old man who had ulcerative proctitis for 18 years visited our hospital because of stomach pain. Proctitis had been in remission stage for five recent years by the mesalazine administration. Esophagogastroduodenoscopy (EGD) showed scattered patchy erosions at the corpus of the stomach. Anti-acid secretory agents was administrated, however, erosive change worsened in multiplicity and in area. Biopsied specimen of gastric mucosa showed specific findings resembling to cryptitis, crypt abcess and focally enhanced gastritis. H. pylori infection was negative by some examinations. Our patient had no history of taking non steroidal anti-inflammatory drugs (NSAIDs) so far. From the findings above, it was considered that gastric lesion was strongly related to the ulcerative proctitis. 5-aminosalicylic acid (750 mg, three times daily) ground to powder was administered with predonisolon (20 mg, once daily). Five month later, all the erosions disappeared completely on EGD and biopsied specimen revealed a reduction of inflammatory cells. The present case has a rare gastric lesion with patchy pattern (not diffuse pattern) which is strongly associated with ulcerative proctitis. PMID:19122423

  11. Killing of intracellular Mycobacterium tuberculosis by receptor-mediated drug delivery

    Energy Technology Data Exchange (ETDEWEB)

    Majumdar, S.; Basu, S.K. (Institute of Microbial Technology, Chandigarh (India))

    1991-01-01

    p-Aminosalicylic acid (PAS) conjugated to maleylated bovine serum albumin (MBSA) was taken up efficiently through high-affinity MBSA-binding sites on macrophages. Binding of the radiolabeled conjugate to cultured mouse peritoneal macrophages at 4 degrees C was competed for by MBSA but not by PAS. At 37 degrees C, the radiolabeled conjugate was rapidly degraded by the macrophages, leading to release of acid-soluble degradation products in the medium. The drug conjugate was nearly 100 times as effective as free PAS in killing the intracellular mycobacteria in mouse peritoneal macrophages infected in culture with Mycobacterium tuberculosis. The killing of intracellular mycobacteria mediated by the drug conjugate was effectively prevented by simultaneous addition of excess MBSA (100 micrograms/ml) or chloroquine (3 microM) to the medium, whereas these agents did not affect the microbicidal action of free PAS. These results suggest that (i) uptake of the PAS-MBSA conjugate was mediated by cell surface receptors on macrophages which recognize MBSA and (ii) lysosomal hydrolysis of the internalized conjugate resulted in intracellular release of a pharmacologically active form of the drug, which led to selective killing of the M. tuberculosis harbored by mouse macrophages infected in culture. This receptor-mediated modality of delivering drugs to macrophages could contribute to greater therapeutic efficacy and minimization of toxic side effects in the management of tuberculosis and other intracellular mycobacterial infections.

  12. New double-walled PH-sensitive hydrogel systems containing nanoparticle drug for colon-specific drug delivery

    International Nuclear Information System (INIS)

    Double-walled (DW) with a Core of mixture of nano or microparticles of carboxymethyl cellulose sodium (CMC) salt and model drug olsalazine [3, 3-azobis (6-hydroxy benzoic acid)] (OSZ) as an azo derivatives of 5-aminosalicylic acid (5-ASA) and an external coat of cross-linked copolymers of (acrylamido methyl) cellulose acetate butyrate (AMCAB) and methacrylic acid (MAA) with various amounts of 1, 6-hexandiol diacrylate (HDD) are considered cross-linking agents (CA). The core with nano composite was prepared by freeze drying method and then used as nuclei for subsequent shell copolymerization. The structure of core was characterized with scanning electron microscopy. The double-walled hydrogels were characterized by differential scanning colorimetry and FT-IR. Studies of drug release were carried out in enzyme-free , simulated gastric and intestinal fluids (SGF and SIF, respectively). The drug-release profiles indicated that the amount of drug released depended ed on the shell layer composition. The releasing was modulated by the amount of cross-linking in shell layer. Bused on the great difference in hydrolysis rates at pH 1 and 7.4, these pH-sensitive hydrogels appear to be good candidates, for colon-specific drug delivery

  13. In vitro test system for evaluating the effectiveness of chelators

    International Nuclear Information System (INIS)

    A procedure has been devised to test in vitro the relative effectiveness of chelating agents for the elimination of radiotoxins from specified, in vivo labeled endogenous ligands. The report describes the elimination of 239Pu from liver homogenates by various chelating agents. The effectivity of a homologous series of polyaminocarboxylic acids (PACA's) was compared to that of certain derivatives containing a straight alkyl group. The effectiveness of these lipophilic PACA's appears to depend on the chain length of the substituent. Lipophilic chelons were more effective in chelating 239Pu than unsubstituted PACA's. Combination of EDTA or DTPA with a number of oligodentate complexing agents were also tested. With EDTA, the removal of Pu was enhanced by p-aminosalicylic acid (PAS), Desferioxamine B (DFOA) and strongly enhanced by 4,5-Dihydroxy-m-benzenedisulfonic acid (Tiron). Only DFOA showed enhanced removal with DTPA. The different behavior of the mixed ligand treatments can be explained by either formation of binary complexes or action on different biological Pu-pools

  14. Promising biological therapies for ulcerative colitis: A review of the literature

    Institute of Scientific and Technical Information of China (English)

    Hirotada; Akiho; Azusa; Yokoyama; Shuichi; Abe; Yuichi; Nakazono; Masatoshi; Murakami; Yoshihiro; Otsuka; Kyoko; Fukawa; Mitsuru; Esaki; Yusuke; Niina; Haruei; Ogino

    2015-01-01

    Ulcerative colitis(UC) is a chronic lifelong condition characterized by alternating flare-ups and remission. There is no single known unifying cause, and the pathogenesis is multifactorial, with genetics, environmental factors, microbiota, and the immune system all playing roles. Current treatment modalities for UC include 5-aminosalicylates, corticosteroids, immunosuppressants(including purine antimetabolites, cyclosporine, and tacrolimus), and surgery. Therapeutic goals for UC are evolving. Medical treatment aims to induce remission and prevent relapse of disease activity. Infliximab, an anti-tumor necrosis factor(TNF)-α monoclonal antibody, is the first biological agent for the treatment of UC. Over the last decade, infliximab and adalimumab(anti-TNF-α agents) have been used for moderate to severe UC, and have been shown to be effective in inducing and maintaining remission. Recent studies have indicated that golimumab(another anti-TNF-α agent), tofacitinib(a Janus kinase inhibitor), and vedolizumab and etrolizumab(integrin antagonists), achieved good clinical remission and response rates in UC. Recently, golimumab and vedolizumab have been approved for UC by the United States Food and Drug Administration. Vedolizumab may be used as a first-line alternative to anti-TNF-α therapy in patients with an inadequate response to corticosteroids and/or immunosuppressants. Here, we provide updated information on various biological agents in the treatment of UC.

  15. 炎症性肠病联合治疗中的药物相互作用

    Institute of Scientific and Technical Information of China (English)

    武丽娜; 张波; 鲁重美

    2015-01-01

    Polypharmacy is an increasing concern in the management of inflammatory bowel disease.This review describes drug interactions in the combination therapy of inflammatory bowel disease,including aminosalicylate ,corticosteroid,azathioprine,methotrexate,cyclosporine,thalidomide,cyclophosphamide and antibiotics,TNF inhibitor.%氨基水杨酸制剂、肾上腺糖皮质激素、硫唑嘌呤、甲氨蝶呤、环孢素、沙利度胺、环磷酰胺、抗肿瘤坏死因子α单克隆抗体等药物在炎症性肠病(Inflammatory bowel dis-ease,IBD)治疗应用较广。目前多种药物联合应用在 IBD 治疗中越来越常见,药物之间的相互作用也日益受到医学界的重视。现介绍 IBD 治疗中常见的药物联用对彼此血药浓度、毒副作用、治疗效果等的影响。

  16. [Impact of formulation and process parameters on the properties of chitosan-based microspheres prepared by external ionic gelation].

    Science.gov (United States)

    Kubánková, Romana; Vysloužil, Jakub; Kejdušová, Martina; Vetchý, David; Dvořáčková, Kateřina

    2014-06-01

    The aim of this experimental study was to optimize a preparation of microspheres from high viscosity chitosan by external ion gelation and to evaluate selected aspects of their preparation. For drug-free microparticles, the concentration of chitosan dispersions was chosen as a formulation variable; the position of instrument for a dispersion extrusion (horizontal vs. vertical) was evaluated as a process variable. On the basis of sphericity and equivalent diameter results, three different concentrations of chitosan dispersions were used for 5-aminosalicylic acid (5-ASA) encapsulation with the extrusion instrument in horizontal position, which was considered as the optimal. In consequent drug-loaded microparticle preparation, the influence of the concentration of chitosan dispersions and composition of hardening solution (10% sodium tripolyphosphate (TPP) vs. 10% TPP containing drug) was evaluated. In prepared 5-ASA microspheres it was found that the equivalent diameter increased with increasing chitosan concentration. In the case of sphericity, significant differences were not found. Samples prepared with the drug in both chitosan dispersion and hardening solution had a higher drug content, a smaller equivalent diameter and they showed a faster in vitro drug release in comparison with the samples prepared with the drug in chitosan dispersion only. PMID:25115666

  17. Stereolithographic (SLA) 3D printing of oral modified-release dosage forms.

    Science.gov (United States)

    Wang, Jie; Goyanes, Alvaro; Gaisford, Simon; Basit, Abdul W

    2016-04-30

    The aim of this work was to evaluate the suitability of stereolithography (SLA) to fabricate drug-loaded tablets with modified-release characteristics. The SLA printer creates solid objects by using a laser beam to photopolymerise monomers. In this work polyethylene glycol diacrylate (PEGDA) was used as a monomer and diphenyl(2,4,6-trimethylbenzoyl)phosphine oxide was used as a photo-initiator. 4-aminosalicylic acid (4-ASA) and paracetamol (acetaminophen) were selected as model drugs. Tablets were successfully printed and formulations with different properties were fabricated by adding polyethylene glycol 300 (PEG 300) to the printing solution. The loading of paracetamol and 4-ASA in the printed tablets was 5.69% and 5.40% respectively. In a realistic dynamic dissolution simulation of the gastrointestinal tract, drug release from the tablets was dependent on the composition of the formulations, but independent of dissolution pH. In conclusion SLA 3DP technology allows the manufacture of drug loaded tablets with specific extended-release profiles. In the future this technology could become a manufacturing technology for the elaboration of oral dosage forms, for industrial production or even for personalised dose. PMID:26976500

  18. Optimal Endpoint of Therapy in IBD: An Update on Factors Determining a Successful Drug Withdrawal

    Directory of Open Access Journals (Sweden)

    Anita Annaházi

    2015-01-01

    Full Text Available Ulcerative colitis (UC and Crohn’s disease (CD are chronic inflammatory disorders, which require long term treatment to achieve remission and to prevent relapses and cancer. While current therapies are effective in most cases, they can have rare but serious side effects and are often associated with high costs. On the other hand, early discontinuation of an effective treatment may lead to a quick relapse and to complications at the restart of therapy. Therefore it is essential to determine the optimal duration of maintenance therapy, but clear guidelines are missing. The most important questions when deciding whether to continue or withdraw therapy in quiescent UC and CD patients are the efficacy of the continuous treatment to maintain remission in the long term, the frequency and severity of side effects, and the chance of relapse after discontinuation of therapy. This review summarizes the current knowledge on these topics with respect to 5-aminosalicylates, thiopurines, methotrexate, and biological therapies and collects information regarding when and in which specific patient groups, in the absence of risk factors, can withdrawal of therapy be considered without a high risk of relapse. Additionally, the particular aspect of colorectal cancer prevention by current therapies will also be discussed.

  19. Current therapy of pediatric Crohn’s disease

    Institute of Scientific and Technical Information of China (English)

    Avishay; Lahad; Batia; Weiss

    2015-01-01

    Inflammatory bowel diseases(IBD), including Crohn’s disease(CD) and ulcerative colitis, are chronic relapsing and remitting diseases of the bowel, with an unknown etiology and appear to involve interaction between genetic susceptibility, environmental factors and the immune system. Although our knowledge and understanding of the pathogenesis and causes of IBD have improved significantly, the incidence in the pediatric population is still rising. In the last decade more drugs and treatment option have become available including 5-aminosalicylate,antibiotics, corticosteroids, immunomodulators and biological agents. Before the use of anti-tumor necrosis factor(TNF)-α became available to patients with IBD, the risk for surgery within five years of diagnosis was very high, however, with anti-TNF-α treatment the risk of surgery has decreased significantly. In the pediatric population a remission in disease can be achieved by exclusive enteral nutrition. Exclusive enteral nutrition also has an important role in the improvement of nutritional status and maintained growth. In this review we summarize the current therapeutic treatments in CD. The progress in the treatment options and the development of new drugs has led to optimized tactics for achieving the primary clinical goals of therapy- induction and maintenance of remission while improving the patient’s growth and overall well-being.

  20. Gastrointestinal Behçet's disease: a review.

    Science.gov (United States)

    Skef, Wasseem; Hamilton, Matthew J; Arayssi, Thurayya

    2015-04-01

    Behçet's disease (BD) is an idiopathic, chronic, relapsing, multi-systemic vasculitis characterized by recurrent oral and genital aphthous ulcers, ocular disease and skin lesions. Prevalence of BD is highest in countries along the ancient silk road from the Mediterranean basin to East Asia. By comparison, the prevalence in North American and Northern European countries is low. Gastrointestinal manifestations of Behçet's disease are of particular importance as they are associated with significant morbidity and mortality. Although ileocecal involvement is most commonly described, BD may involve any segment of the intestinal tract as well as the various organs within the gastrointestinal system. Diagnosis is based on clinical criteria - there are no pathognomonic laboratory tests. Methods for monitoring disease activity on therapy are available but imperfect. Evidence-based treatment strategies are lacking. Different classes of medications have been successfully used for the treatment of intestinal BD which include 5-aminosalicylic acid, corticosteroids, immunomodulators, and anti-tumor necrosis factor alpha monoclonal antibody therapy. Like inflammatory bowel disease, surgery is reserved for those who are resistant to medical therapy. A subset of patients have a poor disease course. Accurate methods to detect these patients and the optimal strategy for their treatment are not known at this time. PMID:25852265

  1. Construction of pH-responsive and up-conversion luminescent NaYF4:Yb3+/Er3+@SiO2@PMAA nanocomposite for colon targeted drug delivery

    Science.gov (United States)

    Tian, Boshi; Liu, Shaohua; Lu, Wei; Jin, Lin; Li, Qingfeng; Shi, Yurong; Li, Chunyang; Wang, Zhenling; Du, Yaping

    2016-01-01

    Colon-targeted drug delivery system has attracted much interest because it can improve therapeutic efficacy and reduce the side effect in practical clinic. Herein, we constructed a multifunctional drug delivery system with colonic targeting and tracking by up-conversion (UC) luminescence based on core-shell structured NaYF4:Yb3+/Er3+@SiO2@PMAA nanocomposite. The resultant materials exhibited bright UC luminescence, pH-responsive property and excellent biocompatibility. The drug release behaviors in different pH environment were investigated using 5-aminosalicylic acid (5-ASA) as a model drug. The 5-ASA molecules release from NaYF4:Yb3+/Er3+@SiO2@PMAA nanocomposite exhibit a significant pH-responsive colon targeted property, i.e., a little amount of drug release in simulated gastric fluid (SGF, pH = 1.2) but a large amount of drug release in simulated colonic fluid (SCF, pH = 7.4) Moreover, the drug release process could be monitored by the change of UC emission intensity. These results implied that the multifunctional nanocomposite is a promising drug carrier for targeted release of 5-ASA in the colon. PMID:26891778

  2. Preparation of Ethylcellulose Coated Gelatin Microspheres as a Multiparticulate Colonic Delivery System for 5-Aminosalicilic Acid

    Directory of Open Access Journals (Sweden)

    Fatemeh Atyabi

    2004-01-01

    Full Text Available In the long-term management of ulcerative colitis patients, repeat dosing maybe required. Since 5-ASAis largely absorbed from the upper intestine, selective delivery of drugs into the colon may be regarded as a better method of drug delivery with fewer side effects and a higher efficacy. The aim of this study was to prepare and evaluate a double coated multiparticulate system for 5-ASA delivery using gelatin and ethylcellulose as the primary and secondarypolymer respectively. Gelatin microspheres containing 5-aminosalicylic acid was produced using the solvent evaporation method. Prepared gelatin microspheres were spherical, freeflowing, non-aggregated and showed no degradation in the acidic medium. Entrapment efficacy of microspheres was about 50%. Results showed that drug release was fast and complete and is affected by the amount of core material entrapped. Gelatin microspheres werethen coated by ethylcellulose using a coacervation phase separation technique. The idea for this approach was to prepare a delayed drug delivery system, in which, ethylcellulose protects particles for the first 6 h transit through the gastrointestinal tract. However, it was shown that this system could provide a suitable drug release pattern for colonic delivery of active agents, as 30% of the drug was released from the ethylcellulose-coated microcapsules within 6 h,while this amount was 90% of the loaded drug for gelatin microspheres under the same condition.

  3. Is there a role for vedolizumab in the treatment of ulcerative colitis and Crohn’s disease?

    Directory of Open Access Journals (Sweden)

    Gilroy L

    2014-05-01

    Full Text Available Leah Gilroy, Patrick B Allen Department of Gastroenterology, Ulster Hospital, Dundonald, Belfast, Northern Ireland Abstract: Inflammatory bowel disease (IBD is an important cause of morbidity and mortality for millions of patients worldwide. Current treatment options include corticosteroids, 5-aminosalicylates, immunosuppressants, and TNFα antagonists. However, these are frequently ineffective in achieving sustained response and remission over time. At present, gastroenterologists lack safe and effective treatments if patients fail anti-TNF therapy. Vedolizumab is a promising new agent for IBD patients refractory to anti-TNF therapy. Vedolizumab is an integrin antagonist which is thought to act by reducing inflammation by selectively inhibiting leukocyte migration in the gut. Emerging evidence from clinical trials suggests a potential role for vedolizumab in both ulcerative colitis (UC and Crohn’s disease (CD, particularly in patients who have previously failed biological therapy. The safety profile of vedolizumab appears reasonable, possibly because it has a “gut-selective” mode of action, with no reported cases of progressive multifocal leukoencephalopathy, a condition which has been linked to another integrin antagonist, natalizumab. This review discusses the available evidence for integrin antagonists and their potential role in the management of IBD. Keywords: vedolizumab, ulcerative colitis, Crohn’s disease, inflammatory bowel disease

  4. Killing of intracellular Mycobacterium tuberculosis by receptor-mediated drug delivery

    International Nuclear Information System (INIS)

    p-Aminosalicylic acid (PAS) conjugated to maleylated bovine serum albumin (MBSA) was taken up efficiently through high-affinity MBSA-binding sites on macrophages. Binding of the radiolabeled conjugate to cultured mouse peritoneal macrophages at 4 degrees C was competed for by MBSA but not by PAS. At 37 degrees C, the radiolabeled conjugate was rapidly degraded by the macrophages, leading to release of acid-soluble degradation products in the medium. The drug conjugate was nearly 100 times as effective as free PAS in killing the intracellular mycobacteria in mouse peritoneal macrophages infected in culture with Mycobacterium tuberculosis. The killing of intracellular mycobacteria mediated by the drug conjugate was effectively prevented by simultaneous addition of excess MBSA (100 micrograms/ml) or chloroquine (3 microM) to the medium, whereas these agents did not affect the microbicidal action of free PAS. These results suggest that (i) uptake of the PAS-MBSA conjugate was mediated by cell surface receptors on macrophages which recognize MBSA and (ii) lysosomal hydrolysis of the internalized conjugate resulted in intracellular release of a pharmacologically active form of the drug, which led to selective killing of the M. tuberculosis harbored by mouse macrophages infected in culture. This receptor-mediated modality of delivering drugs to macrophages could contribute to greater therapeutic efficacy and minimization of toxic side effects in the management of tuberculosis and other intracellular mycobacterial infections

  5. The gut barrier: new acquisitions and therapeutic approaches.

    Science.gov (United States)

    Scaldaferri, Franco; Pizzoferrato, Marco; Gerardi, Viviana; Lopetuso, Loris; Gasbarrini, Antonio

    2012-10-01

    The intestinal barrier serves 2 critical functions for the survival of the individual: first, it allows nutrient absorption and second, it defends the body from dangerous macromolecule penetration. It is a complex multilayer system, consisting of an external "anatomic" barrier and an inner "functional" immunological barrier. The interaction of these 2 barriers enables equilibrated permeability to be maintained. Many factors can alter this balance: gut microflora modifications, mucus layer alterations, and epithelial damage can increase intestinal permeability, allowing the translocation of luminal content to the inner layer of intestinal wall. Several techniques are now available that enable us to study gut permeability: "in vitro" models (Caco-2 and HT29-MTX cells) and "in vivo" not invasive tests (sugar tests and radioisotope scanning tests) are used to estimate permeability and to suggest molecular pathophysiological mechanisms of intestinal permeability in health and diseases. Many medicinal products used in the treatment of gastrointestinal diseases have also found to play an active role in modulate intestinal permeability: corticosteroids, 5-aminosalicylic acid, anti-tumor necrosis factor, probiotics, and mucosal protectors, like gelatin tannate. This review will particularly address the role of the gut barrier in maintaining intestinal permeability (microbiota, mucus, and epithelial cells), the techniques used for estimating intestinal permeability and the therapeutic approaches able to modify it. PMID:22955350

  6. Crohn’s disease and Takayasu’s arteritis: An uncommon association

    Science.gov (United States)

    Taddio, Andrea; Maschio, Massimo; Martelossi, Stefano; Barbi, Egidio; Ventura, Alessandro

    2013-01-01

    Takayasu’s arteritis (TA) and Crohn’s disease (CD) are two rare autoimmune disorders; however some reports describe the presence of both diseases in the same patient. This finding has suggested the possibility that both diseases could share some common etiologic origin. We describe a case of a 13-year-old male affected by CD characterized by fever, diarrhea, weight loss, abdominal pain and elevation of inflammatory markers. Clinical and histological features from colonic specimens were consistent with CD. Treatment with steroids and azathioprine was started, however disease flared every time steroids were tapered. One year later, while still on treatment, he came back to our attention for dyspnea at rest and at night, tiredness and weakness. At physical examination a diastolic heart murmur was found as well as a left carotid artery bruit. A transthoracic echocardiography showed mild aortic valve insufficiency, left ventricular hypertrophy and a dilated ascending aorta with same findings at the aortic arch. A computed tomography scan showed abdominal aorta thickening, dilated thoracic aorta and the presence of a thoracic aortic aneurysm. TA associated with CD was diagnosed and medical treatment with cyclophosphamide, steroids and aminosalicylic acid was started, with good clinical response at 6 mo follow-up. We discuss the presence of possible common causes for the two diseases and the importance of differential diagnosis in those patients characterized for intractable disease. PMID:24124342

  7. Crohn's disease and Takayasu's arteritis: an uncommon association.

    Science.gov (United States)

    Taddio, Andrea; Maschio, Massimo; Martelossi, Stefano; Barbi, Egidio; Ventura, Alessandro

    2013-09-21

    Takayasu's arteritis (TA) and Crohn's disease (CD) are two rare autoimmune disorders; however some reports describe the presence of both diseases in the same patient. This finding has suggested the possibility that both diseases could share some common etiologic origin. We describe a case of a 13-year-old male affected by CD characterized by fever, diarrhea, weight loss, abdominal pain and elevation of inflammatory markers. Clinical and histological features from colonic specimens were consistent with CD. Treatment with steroids and azathioprine was started, however disease flared every time steroids were tapered. One year later, while still on treatment, he came back to our attention for dyspnea at rest and at night, tiredness and weakness. At physical examination a diastolic heart murmur was found as well as a left carotid artery bruit. A transthoracic echocardiography showed mild aortic valve insufficiency, left ventricular hypertrophy and a dilated ascending aorta with same findings at the aortic arch. A computed tomography scan showed abdominal aorta thickening, dilated thoracic aorta and the presence of a thoracic aortic aneurysm. TA associated with CD was diagnosed and medical treatment with cyclophosphamide, steroids and aminosalicylic acid was started, with good clinical response at 6 mo follow-up. We discuss the presence of possible common causes for the two diseases and the importance of differential diagnosis in those patients characterized for intractable disease. PMID:24124342

  8. Crohn’s disease and Takayasu’s arteritis: An uncommon association

    Directory of Open Access Journals (Sweden)

    Alessandro Ventura

    2013-01-01

    Full Text Available Takayasu’s arteritis (TA and Crohn’s disease (CD are two rare autoimmune disorders; however some reports describe the presence of both diseases in the same patient. This finding has suggested the possibility that both diseases could share some common etiologic origin. We describe a case of a 13-year-old male affected by CD characterized by fever, diarrhea, weight loss, abdominal pain and elevation of inflammatory markers. Clinical and histological features from colonic specimens were consistent with CD. Treatment with steroids and azathioprine was started, however disease flared every time steroids were tapered. One year later, while still on treatment, he came back to our attention for dyspnea at rest and at night, tiredness and weakness. At physical examination a diastolic heart murmur was found as well as a left carotid artery bruit. A transthoracic echocardiography showed mild aortic valve insufficiency, left ventricular hypertrophy and a dilated ascending aorta with same findings at the aortic arch. A computed tomography scan showed abdominal aorta thickening, dilated thoracic aorta and the presence of a thoracic aortic aneurysm. TA associated with CD was diagnosed and medical treatment with cyclophosphamide, steroids and aminosalicylic acid was started, with good clinical response at 6 mo follow-up. We discuss the presence of possible common causes for the two diseases and the importance of differential diagnosis in those patients characterized for intractable disease.

  9. A zebrafish model of inflammatory lymphangiogenesis

    Directory of Open Access Journals (Sweden)

    Kazuhide S. Okuda

    2015-10-01

    Full Text Available Inflammatory bowel disease (IBD is a disabling chronic inflammatory disease of the gastrointestinal tract. IBD patients have increased intestinal lymphatic vessel density and recent studies have shown that this may contribute to the resolution of IBD. However, the molecular mechanisms involved in IBD-associated lymphangiogenesis are still unclear. In this study, we established a novel inflammatory lymphangiogenesis model in zebrafish larvae involving colitogenic challenge stimulated by exposure to 2,4,6-trinitrobenzenesulfonic acid (TNBS or dextran sodium sulphate (DSS. Treatment with either TNBS or DSS resulted in vascular endothelial growth factor receptor (Vegfr-dependent lymphangiogenesis in the zebrafish intestine. Reduction of intestinal inflammation by the administration of the IBD therapeutic, 5-aminosalicylic acid, reduced intestinal lymphatic expansion. Zebrafish macrophages express vascular growth factors vegfaa, vegfc and vegfd and chemical ablation of these cells inhibits intestinal lymphatic expansion, suggesting that the recruitment of macrophages to the intestine upon colitogenic challenge is required for intestinal inflammatory lymphangiogenesis. Importantly, this study highlights the potential of zebrafish as an inflammatory lymphangiogenesis model that can be used to investigate the role and mechanism of lymphangiogenesis in inflammatory diseases such as IBD.

  10. Current treatment of ulcerative colitis

    Institute of Scientific and Technical Information of China (English)

    Johannes Meier; Andreas Sturm

    2011-01-01

    Ulcerative colitis (UC) is a chronic disease featuring recurrent inflammation of the colonic mucosa. The goal of medical treatment is to rapidly induce a steroid-free remission while at the same time preventing complications of the disease itself and its treatment. The choice of treatment depends on severity, localization and the course of the disease. For proctitis, topical therapy with 5-aminosalicylic acid (5-ASA) compounds is used. More extensive or severe disease should be treated with oral and local 5-ASA compounds and corticosteroids to induce remission. Patients who do not respond to this treatment require hospitalization. Intravenous steroids or, when refractory, calcineurin inhibitors (cyclosporine, tacrolimus), tumor necrosis factor-α antibodies (infliximab) or immunomodulators (azathioprine, 6-mercaptopurine) are then called for. Indications for emergency surgery include refractory toxic megacolon, perforation, and continuous severe colorectal bleeding. Close collaboration between gastroenterologist and surgeon is mandatory in order not to delay surgical therapy when needed. This article is intended to give a general, practice- orientated overview of the key issues in ulcerative colitis treatment. Recommendations are based on published consensus guidelines derived from national and international guidelines on the treatment of ulcerative colitis.

  11. Classical and recent advances in the treatment of inflammatory bowel diseases

    Directory of Open Access Journals (Sweden)

    H. Sales-Campos

    2015-02-01

    Full Text Available Crohn's disease (CD and ulcerative colitis (UC are intestinal disorders that comprise the inflammatory bowel diseases (IBD. These disorders have a significant effect on the quality of life of affected patients and the increasing number of IBD cases worldwide is a growing concern. Because of the overall burden of IBD and its multifactorial etiology, efforts have been made to improve the medical management of these inflammatory conditions. The classical therapeutic strategies aim to control the exacerbated host immune response with aminosalicylates, antibiotics, corticosteroids, thiopurines, methotrexate and anti-tumor necrosis factor (TNF biological agents. Although successful in the treatment of several CD or UC conditions, these drugs have limited effectiveness, and variable responses may culminate in unpredictable outcomes. The ideal therapy should reduce inflammation without inducing immunosuppression, and remains a challenge to health care personnel. Recently, a number of additional approaches to IBD therapy, such as new target molecules for biological agents and cellular therapy, have shown promising results. A deeper understanding of IBD pathogenesis and the availability of novel therapies are needed to improve therapeutic success. This review describes the overall key features of therapies currently employed in clinical practice as well as novel and future alternative IBD treatment methods.

  12. A pH dependent delivery of mesalazine from polymer coated and drug-loaded SBA-16 systems.

    Science.gov (United States)

    Trendafilova, Ivalina; Szegedi, Ágnes; Yoncheva, Krassimira; Shestakova, Pavletta; Mihály, Judith; Ristić, Alenka; Konstantinov, Spiro; Popova, Margarita

    2016-01-01

    SBA-16 silica was synthesized and modified by post-synthesis method with amino groups. Wet milling in acidic media was applied for loading of poorly soluble drug mesalazine (5-aminosalicylic acid — 5-ASA) in different drug/carrier ratios (1:1; 0.75:1; 0.5:1; 0.25:1). The parent and drug loaded mesoporous silicas were characterized by XRD, TEM,N2 physisorption, thermal analysis, FT-IR and solid state NMR spectroscopy. The drug loaded mesoporous systems were single-coated with Eudragit S or double-coated with Eudragit S and Eudragit RL. The polymer coating significantly modified the rate of mesalazine release fromS BA-16NH2 materials. Applying the double coating method makes possible the sustained delivery of the drug in the intestinal area avoiding the burst release in the gastric fluid. The functionalized, polymer coated mesoporous system could be considered an appropriate oral delivery system for mesalazine. In addition, reduction of mesalazine cytotoxicity on epithelial cells could be achieved by its loading into mesoporous silica particles. PMID:26453768

  13. Pharmaceutical Care in 19 Cases of MDR-TB Patients from the China Global Fund TB Program%19例耐多药结核病患者的药学监护

    Institute of Scientific and Technical Information of China (English)

    魏润新; 李敏

    2014-01-01

    对19例耐多药结核病患者进行药学监护,提高患者的依从性和治疗效果。19例患者有12例出现了不同程度的不良反应;6例使用卷曲霉素的患者中有4例出现低血钾;7例使用对氨基水杨酸的患者中有5例出现腹泻;2例使用环丝氨酸的患者出现了由药物引起的精神症状。药师分别进行了一般药学监护和重点药学监护。%Pharmaceutical care was carried out in 19 cases of multidrug-resistant tuberculosis (MDR-TB) patients to improve treatment effect. In the 19 patients, 12 cases had different degree of ADR; In 6 patients using capreomycin, 4 cases had hypokalemia; In 7 patients using aminosalicylic acid, 5 cases had diarrhea; The 2 patients using cycloserine had psychiatric symptoms caused by drugs. Pharmacists carried out general or intensive pharmaceutical care for these patients. In conclusion, pharmaceutical care can im-prove patient compliance and reduce the incidence of ADR, which should become an important part of MDR-TB treatment.

  14. In Vivo Evaluation of 5-ASA Colon-Specific Tablets Using Experimental-Induced Colitis Rat Animal Model.

    Science.gov (United States)

    Sawarkar, Sujata P; Deshpande, S G; Bajaj, A N; Nikam, V S

    2015-12-01

    Colonic drug delivery is intended not only for local treatment in inflammatory bowel disease (IBD) but also for systemic delivery of therapeutics. Intestinal myeloperoxidase (MPO) determination could be used to estimate the average level of inflammation in colon as well as to determine the efficacy of drugs to be used in the treatment of inflammatory bowel diseases or study the specificity of dosage forms to be used for colonic targeting of anti-inflammatory drugs. Colonic prodrug sulfasalazine (SASP) gets metabolized to give 5-aminosalicylic acid (5-ASA), which is the active portion of SASP. However, when given orally, 5-ASA is absorbed in upper part of gastrointestinal tract (GIT) and not made available in colon. In the present study, colon-targeted delivery of 5-ASA was achieved by formulating tablets with two natural polymers namely guar gum and pectin using compression coating method. Colonic specificity of 5-ASA tablets (prepared using guar gum and pectin as polymers) was evaluated in vitro using simulated fluids mimicking in vivo environment as well as in vivo method using chemically (2,4,6-trinitrobenzenesulfonic acid and acetic acid)-induced colitis rat model. Both colon-specific formulations of 5-ASA (guar gum and pectin) were observed to be more effective in reducing inflammation in chemically induced colitis rat models when compared to colon-specific prodrug sulfasalazine as well as conventional 5-ASA administered orally. PMID:26017284

  15. Cancer in inflammatory bowel disease

    Institute of Scientific and Technical Information of China (English)

    Jianlin Xie; Steven H Itzkowitz

    2008-01-01

    Patients with long-standing inflammatory bowel disease (IBD) have an increased risk of developing colorectal cancer (CRC). Many of the molecular alterations responsible for sporadic colorectal cancer, namely chromosomal instability, microsatellite instability, and hypermethylation, also play a role in colitis-associated colon carcinogenesis. Colon cancer risk in inflammatory bowel disease increases with longer duration of colitis, greater anatomic extent of colitis, the presence of primary sclerosing cholangitis, family history of CRC and degree of inflammation of the bowel. Chemoprevention includes aminosalicylates, ursodeoxycholic acid, and possibly folic acid and statins. To reduce CRC mortality in IBD, colonoscopic surveillance with random biopsies remains the major way to detect early mucosal dysplasia. When dysplasia is confirmed, proctocolectomy is considered for these patients. Patients with small intestinal Crohn's disease are at increased risk of small bowel adenocarcinoma. Ulcerative colitis patients with total proctocolectomy and ileal pouch anal- anastomosis have a rather low risk of dysplasia in the ileal pouch, but the anal transition zone should be monitored periodically. Other extra intestinal cancers, such as hepatobiliary and hematopoietic cancer, have shown variable incidence rates. New endoscopic and molecular screening approaches may further refine our current surveillance guidelines and our understanding of the natural history of dysplasia.

  16. The influence of manganese treatment on the distribution of metal elements in rats and the protection by sodium para-amino salicylic acid.

    Science.gov (United States)

    Yuan, Zong-Xiang; Chen, Hai-Bin; Li, Shao-Jun; Huang, Xiao-Wei; Mo, Yu-Huan; Luo, Yi-Ni; He, Sheng-Nan; Deng, Xiang-Fa; Lu, Guo-Dong; Jiang, Yue-Ming

    2016-07-01

    Manganese (Mn) overexposure induced neurological damages, which could be potentially protected by sodium para-aminosalicylic acid (PAS-Na). In this study, we systematically detected the changes of divalent metal elements in most of the organs and analyzed the distribution of the metals in Mn-exposed rats and the protection by PAS-Na. Sprague Dawley (SD) rats received intraperitoneal injections of 15mg/kg MnCl2·4H2O (5d/week for 3 weeks), followed by subcutaneous (back) injections of PAS-Na (100 and 200mg/kg, everyday for 5 weeks). The concentrations of Mn and other metal elements [Iron (Fe), Copper (Cu), Zinc (Zn), Magnesium (Mg), Calcium (Ca)] in major organs (liver, spleen, kidney, thighbone and iliac bone, cerebral cortex, hippocampus and testes) and blood by Inductively Coupled Plasma-Atomic Emission Spectrometry (ICP-AES). The results showed that Mn overexposure significantly increased Mn in most organs, Fe and Zn in liver, Fe and Mg in blood; however decreased Fe, Cu, Zn, Mg and Ca in cortex, Cu and Zn in kidney, Cu and Mg in iliac bone, and Zn in blood. In contrast, PAS-Na treatment restored most changes particularly in cortex. In conclusion, excessive Mn exposure disturbed the balance of other metal elements but PAS-Na post-treatments could restore these alterations. PMID:27259357

  17. Olsalazine is contraindicated during pelvic radiation therapy: results of a double-blind, randomized clinical trial

    International Nuclear Information System (INIS)

    Purpose: A randomized clinical trial from Great Britain suggested a possible beneficial effect of acetylsalicylate in the prevention of radiation-induced bowel toxicity. Olsalazine is an orally administered drug designed to deliver 5-aminosalicylate to the large bowel with minimal systemic absorption. A randomized clinical trial was undertaken to assess the effectiveness of olsalazine in preventing acute diarrhea in patients receiving pelvic radiation therapy. Methods and Materials: Patients receiving pelvic radiation therapy were randomized, in double-blind fashion, to olsalazine 250 mg, two capsules twice daily, or an identical appearing placebo, two capsules twice daily. Patients were then evaluated weekly during radiation therapy for the primary study endpoint, diarrhea, as well as rectal bleeding, abdominal cramping, and tenesmus. Results: The study was closed early, after entry of 58 evaluable patients, when a preliminary analysis showed excessive diarrhea in patients randomized to olsalazine. The incidence and severity of diarrhea were worse in patients randomized to olsalazine (p 0.0036). Sixty percent of the patients randomized to olsalazine experienced Grade 3 or 4 diarrhea compared to only 14% randomized to placebo. There was also a trend toward higher incidence and greater severity of abdominal cramping in patients who were randomized to olsalazine (p = 0.084). Conclusion: Administration of olsalazine during pelvic radiation therapy resulted in an increased incidence and severity of diarrhea. Olsalazine is contraindicated in patients receiving pelvic radiation therapy

  18. Diverticular disease: changing epidemiology and management.

    Science.gov (United States)

    Razik, Roshan; Nguyen, Geoffrey C

    2015-05-01

    Diverticulosis is the most common pathological finding in routine colonoscopy. Diverticular disease comprises both diverticulitis and diverticular hemorrhage. This review examines the pathophysiological basis for disease including the importance of the elastin/collagen profile in diverticula formation. It summarizes the latest epidemiological findings with an emphasis on age- and sex-related differences. Risk factors including obesity, medications, hereditary factors, and diet are critically reviewed with the most up-to-date evidence. A detailed appraisal of therapeutic options is provided with special emphasis on 5-aminosalicylate, probiotics, mesalamine, percutaneous abscess drainage, and image-guided embolization. The role of antibiotics and surgery is discussed and compared with guideline recommendations. A more conservative approach, averting admission and even antibiotics, is explored. Finally, a careful review of the data surrounding the utility of colonoscopy in diagnosis and management is provided given the increasing number of reports citing the low incidence of colorectal neoplasia after an episode of diverticulitis. Throughout the review we focus on the older patient with diverticular disease. PMID:25893309

  19. Determination of mesalazine, a low bioavailability olsalazine metabolite in human plasma by UHPLC-MS/MS: Application to a pharmacokinetic study.

    Science.gov (United States)

    Banda, Jagadeesh; Lakshmanan, Ramalingam; Katepalli, Ramesh Babu; Reddy Venati, Uday Kumar; Koppula, Ramesh; Shiva Prasad, V V S

    2016-01-01

    Olsalazine sodium, salicylate derivative (prodrug) is effectively bioconverted to mesalazine (5-aminosalicylic acid; 5-ASA), which has an anti-inflammatory activity in ulcerative colitis. In this article, a novel highly sensitive and selective method was developed and validated to determine mesalazine in human plasma using a derivatization technique to enhance the signal intensity by using ultra- high performance liquid chromatography coupled to tandem mass spectrometry (UHPLC-MS/MS) with an electrospray ionization interface. The sample preparation consisted of a derivatization with propionyl anhydride followed by liquid liquid extraction (LLE) to remove the interference and minimize the matrix effect of human plasma. The multiple reaction monitoring (MRM) mode of the negative ion was performed and the transitions of m/z 208.1→107.0 and m/z 211.1→110.1 were used to measure the derivative of mesalazine and mesalazine-d3. The chromatographic separation was achieved using kinetex XB-C18 (100×4.6mm 2.6μ) analytical column with 0.1% formic acid in water and acetonitrile as mobile phase with a gradient elution. Nominal retention times of mesalazine and IS were 3.08 and 3.07min, respectively. Absolute recovery was found to be between 82-95% for analyte and about 78% for IS. The standard curves was linear (r(2)>0.995) in the concentration range 0.10 to 12.0ng/mL with lower limit of quantification (LLOQ) in human plasma was 0.10ng/mL. The average intra-day/inter-day precision values (%CV) were in the range from 0.6-2.9 % and 1.3-3.8 %, respectively, while the average accuracy value was 103.8-107.2%. This method has been successfully applied to the human pharmacokinetics of olsalazine sodium 250mg capsules following single oral administration. PMID:26606108

  20. Treatment of inflammatory bowel disease associated E. coli with ciprofloxacin and E. coli Nissle in the streptomycin-treated mouse intestine.

    Directory of Open Access Journals (Sweden)

    Andreas Munk Petersen

    Full Text Available BACKGROUND: E. coli belonging to the phylogenetic group B2 are linked to Inflammatory Bowel Disease (IBD. Studies have shown that antimicrobials have some effect in the treatment of IBD, and it has been demonstrated that E. coli Nissle has prophylactic abilities comparable to 5-aminosalicylic acid (5-ASA therapy in ulcerative colitis. The objective of this study was to test if ciprofloxacin and/or E. coli Nissle could eradicate IBD associated E. coli in the streptomycin-treated mouse intestine. RESULTS: After successful colonization with the IBD associated E. coli strains in mice the introduction of E. coli Nissle did not result in eradication of either IBD associated strains or an E. coli from a healthy control, instead, co-colonization at high levels were obtained. Treatment of mice, precolonized with IBD associated E. coli, with ciprofloxacin for three days alone apparently resulted in effective eradication of tested E. coli. However, treatment of precolonized mice with a combination of ciprofloxacin for 3 days followed by E. coli Nissle surprisingly allowed one IBD associated E. coli to re-colonize the mouse intestine, but at a level 3 logs under E. coli Nissle. A prolonged treatment with ciprofloxacin for 7 days did not change this outcome. CONCLUSIONS: In the mouse model E. coli Nissle can not be used alone to eradicate IBD associated E. coli; rather, 3 days of ciprofloxacin are apparently efficient in eradicating these strains, but surprisingly, after ciprofloxacin treatment (3 or 7 days, the introduction of E. coli Nissle may support re-colonization with IBD associated E. coli.

  1. Cytokine and anti-cytokine therapies for inflammatory bowel disease.

    Science.gov (United States)

    Ogata, Haruhiko; Hibi, Toshifumi

    2003-01-01

    Although the pathogenesis of inflammatory bowel disease (IBD) remains elusive, it appears that there is chronic activation of the immune and inflammatory cascade in genetically susceptible individuals. Current disease management guidelines have therefore focused on the use of anti-inflammatory agents, aminosalicylates and corticosteroids. These conventional therapies continue to be a first choice in the management of IBD. Immunomodulators, such as azathioprine, 6-mercaptopurine, methotrexate or cyclosporin, are demonstrating increasing importance against steroid-resistant and steroid-dependent patients. However, some patients are still refractory to these therapies. Recent advances in the understanding of the pathophysiological conditions of IBD have provided new immune system modulators as therapeutic tools. Other immunosuppressive agents including FK506 and thalidomide have expanded the choice of medical therapies available for certain subgroups of patients. Furthermore, biological therapies have begun to assume a prominent role. Studies with chimeric monoclonal anti-TNF-alpha antibody treatment have been reported with dramatic successes. However, observations in larger numbers of treated patients are needed to explicate fully the safety of or risks posed by this agent such as developing lymphoma, or other malignancies. Another anti-inflammatory cytokine-therapy includes anti anti-IL-6R, anti-IL-12 or toxin-conjugated anti IL-7R, recombinant cytokines (IL-10 or IL-11). Given the diversity of proinflammatory products under its control, NF-kappaB may be viewed as a master switch in lymphocytes and macrophages, regulating inflammation and immunity. Although some of them still need more confirmatory studies, those immune therapies will provide new insights into cell-based and gene-based treatment against IBD in near future. PMID:12769750

  2. Biologics in the management of ulcerative colitis – comparative safety and efficacy of TNF-α antagonists

    Directory of Open Access Journals (Sweden)

    Fausel R

    2015-01-01

    Full Text Available Rebecca Fausel,1 Anita Afzali1,2 1Division of Gastroenterology, Department of Medicine, University of Washington, Seattle, WA, USA; 2Inflammatory Bowel Disease Program, UW Medicine – Harborview Medical Center, Seattle, WA, USA Abstract: Ulcerative colitis can cause debilitating symptoms and complications such as colonic strictures, colonic dysplasia, colorectal cancer, and toxic megacolon or perforation. Goals of treatment in ulcerative colitis include resolution of gastrointestinal symptoms, healing of colonic mucosa, and prevention of disease complications. Our treatment armamentarium has expanded dramatically over the past 10 years, and we now have multiple biologic agents approved for the treatment of moderate-severe disease, in addition to conventional therapies such as 5-aminosalicylates, thiopurines, and corticosteroids. In this review, we will provide a detailed discussion of the three tumor necrosis factor-alpha (TNF-α inhibitors currently approved for treatment of ulcerative colitis: infliximab, adalimumab, and golimumab. All three agents are effective for inducing and maintaining clinical response and remission in patients with ulcerative colitis, and they have comparable safety profiles. There are no head-to-head trials comparing their efficacy, and the choice of agent is most often based on insurance coverage, route of administration, and patient preference. Combination therapy with an immunomodulator is proven to be more effective than anti-TNF monotherapy, and patients who lose response to an anti-TNF agent should undergo dose intensification in order to regain clinical response. Despite therapeutic optimization, a significant percentage of patients will not achieve clinical remission with anti-TNF agents, and so newer therapies are on the horizon. Keywords: ulcerative colitis, inflammatory bowel disease, infliximab, adalimumab, golimumab

  3. Postoperative Crohn's disease recurrence: A practical approach

    Institute of Scientific and Technical Information of China (English)

    Pilar Nos; Eugeni Domènech

    2008-01-01

    Crohn's disease is a chronic inflammatory condition that may involve any segment of the gastrointestinal tract. Although several drugs have proven efficacy in inducing and maintaining disease in remission, resectional surgery remains as a cornerstone in the management of the disease, mainly for the treatment of its stenosing and penetrating complications. However, the occurrence of new mucosal (endoscopic) lesions in the neoterminal ileum early after surgery is almost constant, it is followed in the mid-term by clinical symptoms and, in a proportion of patients, repeated intestinal resections are required. Pathogenesis of postoperative recurrence (POR) is not fully understood, but luminal factors (commensal microbes, dietary antigens) seem to play an important role, and environmental and genetic factors may also have a relevant influence. Hany studies tried to identify clinical predictors for POR with heterogeneous results, and only smoking has repeatedly been associated with a higher risk of POR. Ileocolonoscopy remains as the gold standard for the assessment of appearance and severity of POR, although the real usefulness of the available endoscopic score needs to be revisited and alternative techniques are emerging. Several drugs have been evaluated to prevent POR with limited success. Smoking cessation seems to be one of the more beneficial therapeutic measures. Aminosalicylates have only proved to be of marginal benefit, and they are only used in lowrisk patients. Nitroimidazolic antibiotics, althoug efficient, are associated with a high rate of intolerano and might induce irreversible side effects when used for a long-term. Thiopurines are not widely used after ileocecal resection, maybe because some concerns igiving immunomodulators in asymptomatic patient still remain. In the era of biological agents and geneti testing, a well-established preventive strategy for POR I still lacking, and larger studies to identify good clinica serological, and genetic

  4. Mycobacterial Interspersed Repetitive Unit Can Predict Drug Resistance of Mycobacterium tuberculosis in China

    Science.gov (United States)

    Cheng, Xian-feng; Jiang, Chao; Zhang, Min; Xia, Dan; Chu, Li-li; Wen, Yu-feng; Zhu, Ming; Jiang, Yue-gen

    2016-01-01

    Background: Recently, Mycobacterial Interspersed Repetitive Unit (MIRU) was supposed to be associated with drug resistance in Mycobacterium tuberculosis (M. tuberculosis), but whether the association exists actually in local strains in China was still unknown. This research was conducted to explore that association and the predictability of MIRU to drug resistance of Tuberculosis (TB). Methods: The clinical isolates were collected and the susceptibility test were conducted with Lowenstein–Jensen (LJ) medium for five anti-TB drug. Based on PCR of MIRU-VNTR (Variable Number of Tandem Repeat) genotyping, we tested the number of the repeat unite of MIRU. Then, we used logistic regression to evaluate the association between 15 MIRU and drug resistance. In addition, we explored the most suitable MIRU locus of identified MIRU loci for drug resistance by multivariate logistic regression. Results: Of the 102 strains, one isolate was resistant to rifampicin and one isolate was resistant to streptomycin. Among these fifteen MIRU, there was a association between MIRU loci polymorphism and anti-tuberculosis drug resistance, ETRB (P = 0.03, OR = 0.19, 95% CI 0.05–0.81) and ETRC (P = 0.01, OR = 0.14, 95% CI 0.03–0.64) were negatively related to isoniazid resistance; MIRU20 (P = 0.05, OR = 2.87, 95% CI 1.01–8.12) was positively associated with ethambutol resistance; and QUB11a (P = 0.02, OR = 0.79, 95% CI 0.65–0.96) was a negative association factor of p-aminosalicylic acid resistance. Conclusion: Our research showed that MIRU loci may predict drug resistance of tuberculosis in China. However, the mechanism still needs further exploration. PMID:27047485

  5. Design and preparation of matrine surface-imprinted material and studies on its molecule recognition selectivity.

    Science.gov (United States)

    Lei, Qingjuan; Gao, Baojiao; Zhang, Dandan

    2016-01-01

    A matrine molecule surface-imprinted material was designed and prepared using an effective surface-imprinting technique developed by our group, and its molecular recognition performance and mechanism were investigated in depth. Monomer glycidyl methacrylate (GMA) was first graft-polymerized on the surfaces of micron-sized silica gel particles in surface-initiated graft polymerization manner, obtaining the grafted particles PGMA/SiO(2) with high grafting degree. Subsequently, the ring-opening reaction of the epoxy groups of the grafted macromolecules PGMA with 5-aminosalicylic acid (5-ASA) was carried out, resulting in the functional grafted particle SA-PGMA/SiO(2), on whose surfaces salicylic acid as functional group was chemically bonded. By right of the mutual strong secondary bond forces, electrostatic interaction and hydrogen bonding, SA-PGMA/SiO(2) particles produced strong adsorption for matrine. Finally, with this strong adsorption, matrine molecule surface imprinting was carried out on the surfaces of SA-PGMA/SiO(2) particles with ethylene glycol diglycidyl ether as cross-linking agent, resulting in the matrine molecule surface-imprinted material MIP-SAP/SiO(2). The binding characteristic of MIP-SAP/SiO(2) toward matrine was investigated in depth with both batch and column methods and using oxymatrine and cytisine as two contrast alkaloids. The experimental results show that MIP-SAP/SiO(2) has special recognition selectivity and excellent binding affinity for matrine. Relative to oxymatrine and cytisine, the selectivity coefficients of MIP-SAP/SiO(2) for matrine are 5.66 and 11.17, respectively. PMID:26426206

  6. Rectal administration of d-alpha tocopherol for active ulcerative colitis: A preliminary report

    Institute of Scientific and Technical Information of China (English)

    Seyed Amir Mirbagheri; Behtash Ghazi Nezami; Solmaz Assa; Mannan Hajimahmoodi

    2008-01-01

    AIM: To investigate the anti-oxidant and anti-neutrophil recruitment effects of rectal d-alpha (d-α) tocopherol administration on mild and moderately active ulcerative colitis (UC).METHODS: Fifteen patients with mild and moderately active ulcerative colitis were enrolled in an open-label study of d-α tocopherol enema (8000 U/d) for 12 wk. All patients were receiving concomitant therapy with 5-aminosalicylic acid derivatives (5-ASA) and/or immunomodulator medications. Endoscopic evaluation was performed at baseline and after 4th and 12th weeks. Disease activity was measured with the Mayo disease activity index (DAI) and remission was defined as DAI of≤2 with no blood in stool. Clinical response was defined as a DAI reduction of≥2.RESULTS: At the end of 12th week, the average DAI score significantly decreased compared to the beginning of the study (2.3±0.37 vs 8±0.48, P < 0.0001). One patient was withdrawn after 3 wk for being unavailable to follow-up. On the 4th week of therapy, 12 patients showed clinical response, 3 of whom (21.4%) achieving remission. After 12 wk, all 14 patients responded clinically to the therapy and remission was induced in 9 of them (64%). No patient reported adverse events or was hospitalized due to worsened disease activity.CONCLUSION: This preliminary report suggests that rectal d-α tocopherol may represent a novel therapy for mild and moderately active UC. The observed results might be due to the anti-inflammatory and anti-oxidative properties of vitamin E.

  7. Whole-Genome Sequencing Analysis of Serially Isolated Multi-Drug and Extensively Drug Resistant Mycobacterium tuberculosis from Thai Patients.

    Science.gov (United States)

    Faksri, Kiatichai; Tan, Jun Hao; Disratthakit, Areeya; Xia, Eryu; Prammananan, Therdsak; Suriyaphol, Prapat; Khor, Chiea Chuen; Teo, Yik-Ying; Ong, Rick Twee-Hee; Chaiprasert, Angkana

    2016-01-01

    Multi-drug and extensively drug-resistant tuberculosis (MDR and XDR-TB) are problems that threaten public health worldwide. Only some genetic markers associated with drug-resistant TB are known. Whole-genome sequencing (WGS) is a promising tool for distinguishing between re-infection and persistent infection in isolates taken at different times from a single patient, but has not yet been applied in MDR and XDR-TB. We aim to detect genetic markers associated with drug resistance and distinguish between reinfection and persistent infection from MDR and XDR-TB patients based on WGS analysis. Samples of Mycobacterium tuberculosis (n = 7), serially isolated from 2 MDR cases and 1 XDR-TB case, were retrieved from Siriraj Hospital, Bangkok. The WGS analysis used an Illumina Miseq sequencer. In cases of persistent infection, MDR-TB isolates differed at an average of 2 SNPs across the span of 2-9 months whereas in the case of reinfection, isolates differed at 61 SNPs across 2 years. Known genetic markers associated with resistance were detected from strains susceptible to streptomycin (2/7 isolates), p-aminosalicylic acid (3/7 isolates) and fluoroquinolone drugs. Among fluoroquinolone drugs, ofloxacin had the highest phenotype-genotype concordance (6/7 isolates), whereas gatifloxcain had the lowest (3/7 isolates). A putative candidate SNP in Rv2477c associated with kanamycin and amikacin resistance was suggested for further validation. WGS provided comprehensive results regarding molecular epidemiology, distinguishing between persistent infection and reinfection in M/XDR-TB and potentially can be used for detection of novel mutations associated with drug resistance. PMID:27518818

  8. Clinical, endoscopical and morphological efficacy of mesalazine in patients with irritable bowel syndrome

    Directory of Open Access Journals (Sweden)

    Dorofeyev AE

    2011-06-01

    Full Text Available Andrey E Dorofeyev1, Elena A Kiriyan2, Inna V Vasilenko1, Olga A Rassokhina1, Andrey F Elin11National Medical University, Donetsk, Ukraine; 2Gastroenterological Center of Poltava Hospital Clinic, Poltava, UkraineObjectives: The aim of this study was to analyze the clinical efficacy and cytomorphologic changes of colon mucosa following the treatment of patients suffering from irritable bowel syndrome (IBS with mesalazine (5-aminosalicylic acid [5-ASA].Methods: In this controlled, randomized, blind clinical trial, a total of 360 patients with varying subtypes of IBS were randomly treated with 500 mg of mesalazine qid or by standard therapy without mesalazine for a period of 28 days. Pre- and post-treatment pain intensity, pain duration, meteorism, stool abnormalities and endoscopic parameters were monitored, and biopsies or brush biopsies were examined histologically.Results: Treatment of IBS patients with mesalazine significantly reduced intensity and duration of pain in all subtypes of IBS, except for duration of pain in the subtype “undifferentiated”, where the difference was not significant. In addition, in patients with diarrhea type and undifferentiated type of IBS, mesalazine also significantly reduced the abnormal stool pattern. In comparison to the control group, administration of mesalazine reduced the incidence of endoscopic and cytomorphologic changes of the bowel mucosa, including changes in colon mucus, mucus production, cytologic or histologic parameters, epithelial cell degeneration, appearance of leukocytes and macrophages and cell infiltrations.Conclusion: Mesalazine was effective in reducing several symptoms characteristic of IBS. It significantly reduced pain intensity and duration and improved cytohistologic parameters of the bowel mucosa.Keywords: 5-amino salicylic acid, 5-ASA, abdominal pain, irritable bowel syndrome, IBS, meteorism, stool abnormalities

  9. The immunologic effects of mesalamine in treated HIV-infected individuals with incomplete CD4+ T cell recovery: a randomized crossover trial.

    Directory of Open Access Journals (Sweden)

    Ma Somsouk

    Full Text Available The anti-inflammatory agent, mesalamine (5-aminosalicylic acid has been shown to decrease mucosal inflammation in ulcerative colitis. The effect of mesalamine in HIV-infected individuals, who exhibit abnormal mucosal immune activation and microbial translocation (MT, has not been established in a placebo-controlled trial. We randomized 33 HIV-infected subjects with CD4 counts <350 cells/mm3 and plasma HIV RNA levels <40 copies/ml on antiretroviral therapy (ART to add mesalamine vs. placebo to their existing regimen for 12 weeks followed by a 12 week crossover to the other arm. Compared to placebo-treated subjects, mesalamine-treated subjects did not experience any significant change in the percent CD38+HLA-DR+ peripheral blood CD4+ and CD8+ T cells at week 12 (P = 0.38 and P = 0.63, respectively, or in the CD4+ T cell count at week 12 (P = 0.83. The percent CD38+HLA-DR+ CD4+ and CD8+ T cells also did not change significantly in rectal tissue (P = 0.86, P = 0.84, respectively. During the period of mesalamine administration, plasma sCD14, IL-6, D-dimer, and kynurenine to tryptophan ratio were not changed significantly at week 12 and were similarly unchanged at week 24. This study suggests that, at least under the conditions studied, the persistent immune activation associated with HIV infection is not impacted by the anti-inflammatory effects of mesalamine.ClinicalTrials.gov NCT01090102.

  10. Quantitative determination of sulfisoxazole and its three N-acetylated metabolites using HPLC-MS/MS, and the saturable pharmacokinetics of sulfisoxazole in mice.

    Science.gov (United States)

    Oh, Kyungsoo; Baek, Moon-Chang; Kang, Wonku

    2016-09-10

    Sulfisoxazole (SFX) is still used in combination with trimethoprim in cattle despite adverse drug reactions (e.g., urolithiasis). Recently, SFX is known to be a promising repositioned drug candidate for pulmonary hypertension and cancer. We developed a simultaneous determination method of SFX and its N-acetylated metabolites (N(1)-acetyl SFX, N1AS; N(4)-acetyl SFX, N4AS; diacetyl SFX, DAS) using HPLC-MS/MS for the first time, and examined the pharmacokinetics of SFX in mice. N1AS and DAS were converted rapidly to SFX and N4AS, respectively, in mouse plasma. The time courses of plasma SFX and N4AS concentrations were well-characterised following the oral administration of SFX to mice. The absorption, metabolism, and/or excretion of SFX given at >700mg/kg may be saturable, and in contrast to humans and rats, the extent of systemic exposure of mice to N4AS was much greater than that of SFX. Interestingly, the acetyl groups at both N1- and N4-positions were degraded during the ionisation required to generate precursor ions. In additional experiments the carboxyl group of N-acetyl-5-aminosalicylic acid (NA5AS) was lost instead of the acetyl group during the ionisation, and acetaminophen (AAP) appeared. As the acetyl and carboxyl groups of some substances can be degraded during ionisation in the mass spectrometer, caution is appropriate when it is sought to simultaneously quantify similar structures containing these moieties; chromatographic separation is essential. PMID:27454084

  11. Boswellia serrata Preserves Intestinal Epithelial Barrier from Oxidative and Inflammatory Damage.

    Directory of Open Access Journals (Sweden)

    Daniela Catanzaro

    Full Text Available Aminosalicylates, corticosteroids and immunosuppressants are currently the therapeutic choices in inflammatory bowel diseases (IBD, however, with limited remission and often serious side effects. Meanwhile complementary and alternative medicine (CAM use is increasing, particularly herbal medicine. Boswellia serrata is a traditional Ayurvedic remedy with anti-inflammatory properties, of interest for its usefulness in IBDs. The mechanism of this pharmacological potential of Boswellia serrata was investigated in colonic epithelial cell monolayers exposed to H2O2 or INF-γ+TNF-α, chosen as in vitro experimental model of intestinal inflammation. The barrier function was evaluated by the transepithelial electrical resistance (TEER and paracellular permeability assay, and by the tight junction proteins (zonula occludens-1, ZO-1 and occludin immunofluorescence. The expression of phosphorylated NF-κB and reactive oxygen species (ROS generation were determined by immunoblot and cytofluorimetric assay, respectively. Boswellia serrata oleo-gum extract (BSE and its pure derivative acetyl-11-keto-β-boswellic acid (AKBA, were tested at 0.1-10 μg/ml and 0.027 μg/ml, respectively. BSE and AKBA safety was demonstrated by no alteration of intestinal cell viability and barrier function and integrity biomarkers. H2O2 or INF-γ+TNF-α treatment of Caco-2 cell monolayers significantly reduced TEER, increased paracellular permeability and caused the disassembly of tight junction proteins occludin and ZO-1. BSE and AKBA pretreatment significantly prevented functional and morphological alterations and also the NF-κB phosphorylation induced by the inflammatory stimuli. At the same concentrations BSE and AKBA counteracted the increase of ROS caused by H2O2 exposure. Data showed the positive correlation of the antioxidant activity with the mechanism involved in the physiologic maintenance of the integrity and function of the intestinal epithelium. This study

  12. Drogas antituberculose: interações medicamentosas, efeitos adversos e utilização em situações especiais - parte 2: fármacos de segunda linha Antituberculosis drugs: drug interactions, adverse effects, and use in special situations - part 2: second line drugs

    Directory of Open Access Journals (Sweden)

    Marcos Abdo Arbex

    2010-10-01

    Full Text Available Os objetivos principais do tratamento da tuberculose são curar o paciente e minimizar a possibilidade de transmissão do bacilo para indivíduos saudáveis. Reações adversas ou interações das drogas antituberculose entre si e com outros fármacos podem causar modificação ou descontinuação da terapêutica. Descrevemos os mecanismos gerais de ação, absorção, metabolização e excreção dos medicamentos utilizados no tratamento da tuberculose multidroga resistente (aminoglicosídeos, fluoroquinolonas, cicloserina/terizidona, etionamida, capreomicina e ácido para-aminossalicílico. Descrevemos as reações adversas e as interações (com medicamentos, alimentos e antiácidos assim como a abordagem mais adequada para situações especiais, como gravidez, amamentação, insuficiência hepática e renal.The main objectives of tuberculosis therapy are to cure the patients and to minimize the possibility of transmission of the bacillus to healthy subjects. Adverse effects of antituberculosis drugs or drug interactions (among antituberculosis drugs or between antituberculosis drugs and other drugs can make it necessary to modify or discontinue treatment. We describe the general mechanism of action, absorption, metabolization, and excretion of the drugs used to treat multidrug resistant tuberculosis (aminoglycosides, fluoroquinolones, cycloserine/terizidone, ethionamide, capreomycin, and para-aminosalicylic acid. We describe adverse drug reactions and interactions (with other drugs, food, and antacids, as well as the most appropriate approach to special situations, such as pregnancy, breastfeeding, liver failure, and kidney failure.

  13. Interaction of 4-aminosalieylic Acid and Surfactants in Aqueous Solutions Using UV-Vis Spectra and Steady-state Fluorescence Spectroscopy

    Institute of Scientific and Technical Information of China (English)

    XU Dongying; REN Jiaoyan; LIAO Zhengfu; WANG Hui; ZHAO Mouming; LI Guangji

    2011-01-01

    The interactions of 4-aminosalicylic acid (4-ASA) and surfactants in aqueous solutions were investigated by using UV-Vis spectra and steady-state fluorescence spectroscopy.The results showed that the strongest peak at UV-vis spectra of 4-ASA aqueous solution in the presence of cationic surfactant and cetyltrimethyl ammonium bromide (CTAB) appeared at 206 nm and took.a red shift from 206 nm to 221 nm with the increase of 4-ASA concentrations from 0.8× 10-5 to 4.4× 10-4 mol/L.Similarly,the strongest peak at UV-vis spectra of 4-ASA aqueous solution in the presence of nonionic surfactant and polyvinylpyrrolidone (PVP)appeared at 206 nm and took a red shift from 206 nm to 219 nm with the increase of 4-ASA concentrations from 0.8× 10-5 to 4.4x 10-4 mol/L.However,the similar phenomena did not appeared in the presence of anion surfactant,sodium dodecyl sulfate (SDS),the UV-vis spectra of 4-ASA aqueous solution remained the same peak position and the peak value increased with the 4-ASA concentration increase.The results could be attributed to the electrostatic attraction between 4-ASA and CTAB or PVP,as well as the electrostatic repulsion between 4-ASA and SDS.Furthermore,the value of critical micelle concentration (CMC) of surfactants in the presence of 4-ASA was determined with Fluorescence method.The first and second CMC of CTAB was 1.2×10-4 M and 2.4x10-4 M,respectively.The first and second CMC of PVP was 1.2×10 4 M and 2.8x 10 4 M.SDS realized the multiple micellizations to form multiple CMC.

  14. The prevalence and clinical characteristics of anemia in Korean patients with inflammatory bowel disease

    Science.gov (United States)

    Lee, Dae Sung; Bang, Ki Bae; Kim, Ji Yeon; Jung, Yoon Suk; Park, Jung Ho; Kim, Hong Joo; Cho, Yong Kyun; Sohn, Chong Il; Jeon, Woo Kyu; Kim, Byung Ik; Choi, Kyu Young

    2016-01-01

    Background/Aims Quality of life is closely related to anemia in patients with inflammatory bowel disease (IBD). Several studies have reported on anemia in patients with IBD in Western countries. This study investigated the prevalence and clinical characteristics of anemia in Korean patients with IBD. Methods We reviewed the medical records of 92 patients with ulcerative colitis (UC) and 76 patients with Crohn's disease (CD) who were followed regularly at a single tertiary medical center in Korea between January 2003 and December 2012. Hemoglobin (Hb) thresholds used to define anemia were <13.0 g/dL in men and <12.0 g/dL in women according to the World Health Organization criteria. We chose the lowest Hb level in each year as a representative value because Hb levels changed at each examination and anemia was associated with disease deterioration. The relationship between clinical variables and lowest Hb level was assessed. Results The prevalence of anemia was 36.3% in patients with UC and 41.6% in patients with CD. Anemia in patients with CD was associated with hospital admission, 5-aminosalicylate (5-ASA) and infliximab treatment in men. Anemia in patients with UC was associated with hospital admission, oral steroid use, thiopurine and infliximab treatment in men. Conclusions The prevalence of anemia in Korean patients with IBD was comparable to that of patients in Western countries. Anemia was associated with male patients with CD who were admitted to the hospital and received medications including 5-ASA and infliximab, and men with UC who were admitted to the hospital and received medications including oral steroids, thiopurine and infliximab. PMID:26884734

  15. Therapeutic efficacy of the Qing Dai in patients with intractable ulcerative colitis

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    Hideo Suzuki

    2013-01-01

    Full Text Available Ulcerative colitis (UC is a chronic inflammatory bowel disease that may become intractable when treated with conventional medications such as aminosalicylates, corticosteroids, and azathioprine. The herbal medicine Qing Dai has traditionally been used in Chinese medicine to treat UC patients, but there is a lack of published data on the efficacy of Qing Dai in UC treatment. We report several cases of patients with intractable UC who take Qing Dai in a retrospective observational study. Furthermore, we explore the mechanisms of action of Qing Dai. Nine patients with active UC who received conventional medications but wished to receive Qing Dai as an alternative medication were included in our analysis. The UC severity level was determined based on the clinical activity index (CAI. Additionally, 5 of the 9 patients were endoscopically evaluated according to the Matts grading system. Each patient received 2 g/d of Qing Dai orally and continued taking other medications for UC as prescribed. Electron spin resonance was applied to explore the mechanisms of action of Qing Dai. After 4 mo of treatment with Qing Dai, the CAI score decreased from 8.3 ± 2.4 to 2.4 ± 3.4 (mean ± SD; P < 0.001. Similarly, the endoscopic Matts grade decreased from 3.4 ± 0.5 to 2.2 ± 0.8 (P = 0.02. Six of 7 patients who were on prednisolone upon enrollment in the study were able to discontinue this corticosteroid. Electron spin resonance revealed that Qing Dai possesses strong hydroxyl radical scavenging activity. Qing Dai showed significant clinical and endoscopic efficacy in patients who failed to respond to conventional medications. Scavenging of hydroxyl radicals appears to be a potential mechanism through which Qing Dai acts, but the significance of the scavenging ability of Qing Dai with respect to the anti-inflammatory effect in UC patients warrants further investigation.

  16. The heart in inflammatory bowel disease

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    Tsianos E.V.

    2007-03-01

    Full Text Available SUMMARY Cardiovascular involvement in inflammatory bowel disease (IBD has been occasionally reported, mainly in the form of case reports. Endocardium derangement in IBD involves endocarditis and subendocardial abscess. Endocarditis may occur as a result of septicemia or due to the prolonged use of total parental nutrition (TPN catheters or/and immunosuppression. The cause of endocarditis may be bacterial or fungal and require surgery in several cases. Prophylaxis for endocarditis in selected IBD patients is discussed. Myocarditis or perimyocarditis in IBD is reported as an autoimmune phenomenon during bowel disease excacerbations or as a side-effect of 5-aminosalicylic acid (5-ASA formulations. Ulcerative colitis (UC patients seem to be at a higher risk for this complication compared to Crohn�s disease (CD patients. Myocardial infarctions, selenium deficiency during TPN, the role of prolonged steroid use and the association with giant cell myocarditis are topics which need further analysis. Pericardium involvement seems to be the most frequent type of cardiovascular complication in IBD caused by drugs (5-ASA, azathioprine, cyclosporine, pericardio-colonic fistulas or unknown causes (idiopathic and it may occasionally be the disease presenting symptom. Coronary artery status and other factors for cardiovascular risk, such as smoking, hyperlipidemia and exercise are also discussed. Electrocardiogram and ultrasonographic changes are not so uncommon and cardiogenic sudden death in IBD is reviewed. Intracavitary coagulation abnormalities, amyloidosis, heart failure and aortitis syndrome are topics included and discussed in this review. A list of tables contributes to a more systemic overview of this current knowledge. Key Words: heart, inflammatory bowel disease, ulcerative colitis, Crohn�s diseas

  17. How expensive is inflammatory bowel disease? A critical analysis

    Institute of Scientific and Technical Information of China (English)

    Selwvn Odes

    2008-01-01

    Economic analysis of chronic diseases is required for proper allocation of resources and understanding costeffectiveness studies of new therapies.Studies on health care cost of ulcerative colitis (UC) and Crohn's disease (CD) are reviewed here.These studies were carried out in various countries with disparate health care systems.In the United States,data were of ten modeled or retrieved from large insurance schemes.Surgery and in-patient hospitalization accounted for over half the outlay on UC and CD.Fistulous disease in CD and parenteral nutrition were very costly.In Canada,overall charges were lower than in the United States,but there too,surgical costs were relatively high.In European studies,economic data were abstracted directly from patients' files.One pan-European study examined the outlay on UC and CD in a community-based prospective inception cohort followed for 10 years.Overall costs in Europe were lower than in the United States.Surgery,hospitalization,year of follow-up,disease phenotype in CD and ASCA-positivity impacted significantly on costs.In all studies,the cost data were right skewed,aminosalicylates were expensive drugs,and biological agents the most expensive; moreover indirect costs were not calculated.Infliximab raised costs considerably in CD,but there were no long-term followup studies,so that the cost-benefit of biological agents remains unknown.In conclusion,costs of managing UC and CD vary by country,surgery,genotype and several other factors.The most important question for further research is whether the biological therapies are cost-effective in the long-term.

  18. Melt-Extruded Eudragit® FS-Based Granules for Colonic Drug Delivery.

    Science.gov (United States)

    Zhang, Feng

    2016-02-01

    The purpose of this study is to characterize the properties of Eudragit® FS-based granules prepared using melt extrusion process for colonic drug delivery. 5-Aminosalicylic acid (5-ASA), theophylline, and diclofenac sodium were used as the model compounds. Drug and polymer blends were melt-extruded into thin rods using a single screw extruder. Drugs were found to be dispersed as crystalline particles in the granules. A hammer mill was used to reduce the extrudate into 16-40 mesh granules, which were mixed with lactose and filled into hard gelatin capsules. Three-stage dissolution testing performed using USP paddle method was used to simulate drug release in gastrointestinal tract. In this study, melt extrusion has been demonstrated to be a suitable process to prepare granules for colonic delivery of 5-amino salicylic acid. At 30% drug loading, less than 25% 5-ASA was released from melt-extruded granules of 20-30 mesh in the first two stages (0.1 N hydrochloric acid solution and phosphate buffer pH 6.8) of the dissolution testing. All 5-ASA was released within 4 h when dissolution medium was switched to phosphate buffer pH 7.4. Drug loading, granule size, and microenvironment pH induced by the solubilized drug were identified as the key factors controlling drug release. Granules prepared with melt extrusion demonstrated lower porosity, smaller pore size, and higher physical strength than those prepared with conventional compression process. Eudragit® FS was found to be stable even when processed at 200°C. PMID:26162974

  19. Altered colonic mucosal Polyunsaturated Fatty Acid (PUFA derived lipid mediators in ulcerative colitis: new insight into relationship with disease activity and pathophysiology.

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    Mojgan Masoodi

    Full Text Available OBJECTIVES: Ulcerative colitis (UC is a relapsing inflammatory disorder of unconfirmed aetiology, variable severity and clinical course, characterised by progressive histological inflammation and with elevation of eicosanoids which have a known pathophysiological role in inflammation. Therapeutic interventions targetting eicosanoids (5-aminosalicylates (ASA are effective first line and adjunctive treatments in mild-moderate UC for achieving and sustaining clinical remission. However, the variable clinical response to 5-ASA and frequent deterioration in response to cyclo-oxygenase (COX inhibitors, has prompted an in depth simultaneous evaluation of multiple lipid mediators (including eicosanoids within the inflammatory milieu in UC. We hypothesised that severity of inflammation is associated with alteration of lipid mediators, in relapsing UC. DESIGN: Study was case-control design. Mucosal lipid mediators were determined by LC-MS/MS lipidomics analysis on mucosal biopsies taken from patients attending outpatients with relapsing UC. Univariate and multivariate statistical analyses were used to investigate the association of mucosal lipid mediators, with the disease state and severity graded histologically. RESULTS: Levels of PGE2, PGD2, TXB2, 5-HETE, 11-HETE, 12-HETE and 15-HETE are significantly elevated in inflamed mucosa and correlate with severity of inflammation, determined using validated histological scoring systems. CONCLUSIONS: Our approach of capturing inflammatory mediator signature at different stages of UC by combining comprehensive lipidomics analysis and computational modelling could be used to classify and predict mild-moderate inflammation; however, predictive index is diminished in severe inflammation. This new technical approach could be developed to tailor drug treatments to patients with active UC, based on the mucosal lipid mediator profile.

  20. Multiplex Assay of Second-Line Anti-Tuberculosis Drugs in Dried Blood Spots Using Ultra-Performance Liquid Chromatography-Tandem Mass Spectrometry.

    Science.gov (United States)

    Lee, Kyunghoon; Jun, Sun Hee; Han, Minje; Song, Sang Hoon; Park, Jong Sun; Lee, Jae Ho; Park, Kyoung Un; Song, Junghan

    2016-09-01

    As dried blood spots (DBSs) have various advantages over conventional venous blood sampling, some assays for detection of one or two anti-tuberculosis (TB) drugs in DBSs have been developed. However, there are no assays currently available for the simultaneous measurement of three or more anti-TB drugs in DBSs. In this study, we developed and evaluated a multiplex method for detecting nine anti-TB drugs including streptomycin, kanamycin, clarithromycin, cycloserine, moxifloxacin, levofloxacin, para-aminosalicylic acid, prothionamide, and linezolid in DBSs by using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Seventy-nine patient samples of DBS were analyzed on the UPLC-MS/MS system. All drug concentrations were determined within 4 min, and assay performance was evaluated. All drugs were clearly separated without ion suppression. Within-run and between-run precisions were 1.7-13.0% and 5.7-17.0%, respectively, at concentrations representing low and high levels for the nine drugs. Lower limits of detection and quantification were 0.06-0.6 and 0.5-5.0 μg/mL, respectively. Linearity was acceptable at five level concentrations for each drug. Correlations between drug concentrations in plasma and DBSs by using Passing-Bablock regression and Pearson's rho (ρ 0.798-0.989) were acceptable. In conclusion, we developed a multiplex assay to measure nine second-line anti-TB drugs in DBSs successfully. This assay provided convenient and rapid drug quantification and could have applications in drug monitoring during treatment. PMID:27374716

  1. Pharmacological- and non-pharmacological therapeutic approaches in inflammatory bowel disease in adults.

    Science.gov (United States)

    Leitner, Gerda C; Vogelsang, Harald

    2016-02-01

    Inflammatory bowel diseases (IBDs) are a group of chronic inflammatory conditions mainly of the colon and small intestine. Crohn's disease (CD) and ulcerative colitis (UC) are the most frequent types of IBD. IBD is a complex disease which arises as a result of the interaction of environmental, genetic and immunological factors. It is increasingly thought that alterations of immunological reactions of the patients to their own enterable bacteria (microfilm) may contribute to inflammation. It is characterized by mucosal and sub mucosal inflammation, perpetuated by infiltration of activated leukocytes. CD may affect the whole gastrointestinal tract while UC only attacks the large intestine. The therapeutic goal is to achieve a steroid-free long lasting remission in both entities. UC has the possibility to be cured by a total colectomy, while CD never can be cured by any operation. A lifelong intake of drugs is mostly necessary and essential. Medical treatment of IBD has to be individualized to each patient and usually starts with anti-inflammatory drugs. The choice what kind of drugs and what route administered (oral, rectal, intravenous) depends on factors including the type, the localization, and severity of the patient's disease. IBD may require immune-suppression to control symptoms such as prednisolone, thiopurines, calcineurin or sometimes folic acid inhibitors or biologics like TNF-α inhibitors or anti-integrin antibodies. For both types of disease (CD, UC) the same drugs are available but they differ in their preference in efficacy between CD and UC as 5-aminosalicylic acid for UC or budesonide for ileocecal CD. As therapeutic alternative the main mediators of the disease, namely the activated pro-inflammatory cytokine producing leukocytes can be selectively removed via two apheresis systems (Adacolumn and Cellsorba) in steroid-refractory or dependent cases. Extracorporeal photopheresis results in an increase of regulatory B cells, regulatory CD8(+) T cells

  2. Randomized clinical trial: pharmacokinetics and safety of multimatrix mesalamine for treatment of pediatric ulcerative colitis

    Directory of Open Access Journals (Sweden)

    Cuffari C

    2016-02-01

    Full Text Available Carmen Cuffari,1 David Pierce,2 Bartosz Korczowski,3 Krzysztof Fyderek,4 Heather Van Heusen,5 Stuart Hossack,6 Hong Wan,5 Alena YZ Edwards,7 Patrick Martin5 1Department of Pediatrics, Division of Pediatric Gastroenterology and Nutrition, The Johns Hopkins University School of Medicine, Baltimore, MD, USA; 2Shire, Basingstoke, UK; 3Medical College, University of Rzeszów, Rzeszów, Poland; 4University Children’s Hospital of Cracow, Cracow, Poland; 5Shire, Wayne, PA, USA; 6Covance Clinical Research Unit Limited, Leeds, UK; 7ICON Early Phase Services, Marlow, Buckinghamshire, UK Background: Limited data are available on mesalamine (5-aminosalicylic acid; 5-ASA use in pediatric ulcerative colitis (UC.Aim: To evaluate pharmacokinetic and safety profiles of 5-ASA and metabolite acetyl-5-ASA (Ac-5-ASA after once-daily, oral administration of multimatrix mesalamine to children and adolescents with UC.Methods: Participants (5–17 years of age; 18–82 kg, stratified by weight with UC received multimatrix mesalamine 30, 60, or 100 mg/kg/day once daily (to 4,800 mg/day for 7 days. Blood samples were collected pre-dose on days 5 and 6. On days 7 and 8, blood and urine samples were collected and safety was evaluated. 5-ASA and Ac-5-ASA plasma and urine concentrations were analyzed by non-compartmental methods and used to develop a population pharmacokinetic model.Results: Fifty-two subjects (21 [30 mg/kg]; 22 [60 mg/kg]; 9 [100 mg/kg] were randomized. On day 7, systemic exposures of 5-ASA and Ac-5-ASA exhibited a dose-proportional increase between 30 and 60 mg/kg/day cohorts. For 30, 60, and 100 mg/kg/day doses, mean percentages of 5-ASA absorbed were 29.4%, 27.0%, and 22.1%, respectively. Simulated steady-state exposures and variabilities for 5-ASA and Ac-5-ASA (coefficient of variation approximately 50% and 40%–45%, respectively were similar to those observed previously in adults at comparable doses. Treatment-emergent adverse events were

  3. 耐多药肺结核病治疗方案中使用莫西沙星的临床效果%Clinical effect of applying moxifloxacin in treatment scheme for multi-drug resistant tuberculosis

    Institute of Scientific and Technical Information of China (English)

    吴颖

    2015-01-01

    Objective To compare and analyze clinical effects of applying moxifloxacin and levofloxacin in the treatment scheme for multi-drug resistant tuberculosis. Methods A total of 48 patients with multi-drug resistant tuberculosis were divided into two groups, as moxifloxacin group with 24 cases and levofloxacin group with 24 cases. Both groups received basic antituberculous scheme by isoniazid aminosalicylate tablets, ethambutol, pyrazinamide, and protionamide. The levofloxacin group was treated by additional levofloxacin tablets, and the moxifloxacin group received additional moxifloxacintablets. Curative effects and adverse reactions were observed after 12 months of treatment. Results The total effective rate after treatment of the moxifloxacin group was 91.7%, which was higher than 75.0%of the levofloxacin group, and the difference had statistical significance (P0.05). Conclusion Moxifloxacin has remarkably better effect than levofloxacin in the treatment scheme for multi-drug resistant tuberculosis.%目的:对比分析耐多药肺结核病治疗方案中使用莫西沙星和左氧氟沙星的临床效果。方法48例耐多药肺结核病患者分为两组,即莫西沙星组24例和左氧氟沙星组24例,两组患者均以对氨基水杨酸异烟肼片、乙胺丁醇、吡嗪酰胺和丙硫异烟胺为基础抗结核方案,左氧氟沙星组联合应用左氧氟沙星片,莫西沙星组联合应用莫西沙星片,治疗12个月观察疗效和不良反应。结果治疗后莫西沙星组总有效率为91.7%,高于左氧氟沙星组的75.0%,差异有统计学意义(P0.05)。结论在耐多药肺结核病治疗方案中莫西沙星的疗效明显优于左氧氟沙星。

  4. Thiopurine treatment in inflammatory bowel disease: clinical pharmacology and implication of pharmacogenetically guided dosing.

    Science.gov (United States)

    Teml, Alexander; Schaeffeler, Elke; Herrlinger, Klaus R; Klotz, Ulrich; Schwab, Matthias

    2007-01-01

    This review summarises clinical pharmacological aspects of thiopurines in the treatment of chronic inflammatory bowel disease (IBD). Current knowledge of pharmacogenetically guided dosing is discussed for individualisation of thiopurine therapy, particularly to avoid severe adverse effects. Both azathioprine and mercaptopurine are pro-drugs that undergo extensive metabolism. The catabolic enzyme thiopurine S-methyltransferase (TPMT) is polymorphically expressed, and currently 23 genetic variants have been described. On the basis of an excellent phenotype-genotype correlation for TPMT, genotyping has become a safe and reliable tool for determination of a patient's individual phenotype. Thiopurine-related adverse drug reactions are frequent, ranging from 5% up to 40%, in both a dose-dependent and -independent manner. IBD patients with low TPMT activity are at high risk of developing severe haematotoxicity if pharmacogenetically guided dosing is not performed. Based on several cost-benefit analyses, assessment of TPMT activity is recommended prior to thiopurine therapy in patients with IBD. The underlying mechanisms of azathioprine/mercaptopurine-related hepatotoxicity, pancreatitis and azathioprine intolerance are still unknown. Although the therapeutic response appears to be related to 6-thioguanine nucleotide (6-TGN) concentrations above a threshold of 230-260 pmol per 8 x 10(8) red blood cells, at present therapeutic drug monitoring of 6-TGN can be recommended only to estimate patients' compliance.Drug-drug interactions between azathioprine/mercaptopurine and aminosalicylates, diuretics, NSAIDs, warfarin and infliximab are discussed. The concomitant use of allopurinol without dosage adjustment of azathioprine/mercaptopurine leads to clinically relevant severe haematotoxicity due to elevated thiopurine levels. Several studies indicate that thiopurine therapy in IBD during pregnancy is safe. Thus, azathioprine/mercaptopurine should not be withdrawn in strictly

  5. Characterization and pharmacological modulation of intestinal inflammation induced by ionizing radiation; Caracterisation et modulation pharmacologique de l'inflammation intestinale induite par les rayonnements ionisants

    Energy Technology Data Exchange (ETDEWEB)

    Gremy, O

    2006-12-15

    treatment with a PPARg synthetic ligand, the so-called 5-aminosalicylic acid (5-ASA), protects against the development of the acute mucosal colon inflammation. This pharmacological drug restrains radio-induced expression of pro inflammatory molecular actors such as TNFa, MCP-1 and iNOS, it also limits the repression of nuclear receptors involved in inflammation control such as PPARg, and reduces the radio-induced accumulation of macrophages. These results could give some leads to find therapeutic drug to limit radio-induced early mucosal and consequently, to improve patients' comfort during and after the radiotherapy schedule. (author)

  6. Over-expression, purification, and characterization of recombinant human arylamine N-acetyltransferase 1.

    Science.gov (United States)

    Wang, Haiqing; Vath, Gregory M; Kawamura, Akane; Bates, Caleb A; Sim, Edith; Hanna, Patrick E; Wagner, Carston R

    2005-02-01

    Human arylamine N-acetyltransferase 1 (NAT1) has been overexpressed in E. coli as a mutant dihydrofolic acid reductase (DHFR) fusion protein with a thrombin sensitive linker. An initial DEAE anion-exchange chromatography resulted in partial purification of the fusion protein. The fusion protein was cleaved with thrombin, and human rNAT1 was purified with a second DEAE column. A total of 8 mg of human rNAT1 from 2 1 of cell culture was purified to homogeneity with this methodology. Arylamine substrate specificities were determined for human rNATI and hamster rNAT2. With both NATs, the second order rate constants (k(cat)/ Kmb) for p-aminobenzoic acid (PABA) and 2-aminofluorene (2-AF) were several thousand-fold higher than those for procainamide (PA), consistent with the expected substrate specificities of the enzymes. However, p-aminosalicylic acid (PAS), previously reported to be a human NAT1 and hamster NAT2 selective substrate, exhibits 20-fold higher specificity for hamster rNAT2 (k(cat)/Kmb 3410 microM(-1) s(-1)) than for human rNAT1 (k(cat)/Kmb 169.4 microM(-1) s(-1)). p-aminobenzoyl-glutamic acid (pABglu) was acetylated 10-fold more efficiently by human rNAT1 than by hamster rNAT2. Inhibition studies of human rNAT1 and hamster rNAT2 revealed that folic acid and methotrexate (MTX) are competitive inhibitors of both the unacetylated and acetylated forms of the enzymes, with K(I) values in 50 - 300 micro range. Dihydrofolic acid (DHF) was a much poorer inhibitor of human rNAT1 than of hamster rNAT2. The combined results demonstrate that human rNAT1 and hamster rNAT2 have similar but distinct kinetic properties with certain substrates, and suggest that folic acid, at least in the non-polyglutamate form, may not have an effect on human NAT1 activity in vivo. PMID:16003948

  7. [Clinical and evolutive profile of Crohn's disease in Hospital Rebagliati (Lima-Peru)].

    Science.gov (United States)

    Bendaño, Teófilo; Frisancho, Oscar

    2010-01-01

    Crohn's Disease (CD) is uncommon in Peru, in that respect, we don't know its clinical and developmental profile. This is a descriptive, retrospective, transversal and observational patients diagnosed with CD in the last 20 years in the Department of Gastroenterology, Hospital Nacional Edgardo Rebagliati Martins'. For the small size of the population, we used a census record. The diagnosis was made using the criteria of Lennard-Jones. We present seventeen cases, most female (11 / 6). The average age was 39.9 years (60% over 40 years). Only one patient had family history (second degree of consanguinity). Sixteen were latins and one white. Clinical manifestations were abdominal pain (88.2%), diarrhea (76.5%), weight loss (76, 5%), bleeding (58.8%) and fever (58.8%). Laboratory findings showed: anemia (76.5%), thrombocytosis (58.8%), hypoalbuminemia (52.9%), leukocytosis (23.5%), nitrogen retention (11.7%), leukopenia (5.9%), and elevated acute phase reactants ( c-reactive protein or erythrocyte sedimentation rate) 76.5%. Extraintestinal manifestations were cutaneous (29.4%), articular diseases (17.6%) and hepatobiliary (11.7%). Five patients (29.4%) received treatment of tuberculosis without success (before diagnosis). Nine patients (52.9%) had acute complications requiring emergency care. The phenotypic pattern type (Montreal's classification) was: non-stricturing non-penetrating 35.3%, stricturing 35.3% and penetrating 29.4%. Inflammation of the ileon was found in 70.5% (47% ileocolonic and ileal 23.5%), nine (53%) had perianal lesions. The activity at diagnosis was mild moderate disease in 8 (47.0%), moderate severe disease in 7 (41.2%) and severe ulminant 2 (11.8%). The macroscopic lesions were predominant stenosis 13 (76.5%), followed by ulcers in 12 (70.6%), erosive erythematous inflammation 11 (64.7%) and thickening of folds in 10 (58.8 %), seven (41%) had fistulas. As initial treatment were used aminosalicylates (13 patients) and systemic corticosteroids in 6

  8. Characterization and pharmacological modulation of intestinal inflammation induced by ionizing radiation

    International Nuclear Information System (INIS)

    treatment with a PPARg synthetic ligand, the so-called 5-aminosalicylic acid (5-ASA), protects against the development of the acute mucosal colon inflammation. This pharmacological drug restrains radio-induced expression of pro inflammatory molecular actors such as TNFa, MCP-1 and iNOS, it also limits the repression of nuclear receptors involved in inflammation control such as PPARg, and reduces the radio-induced accumulation of macrophages. These results could give some leads to find therapeutic drug to limit radio-induced early mucosal and consequently, to improve patients' comfort during and after the radiotherapy schedule. (author)

  9. Effect of MMX® mesalamine coadministration on the pharmacokinetics of amoxicillin, ciprofloxacin XR, metronidazole, and sulfamethoxazole: results from four randomized clinical trials

    Directory of Open Access Journals (Sweden)

    Pierce D

    2014-05-01

    Full Text Available David Pierce,1 Mary Corcoran,2 Patrick Martin,2 Karen Barrett,1 Susi Inglis,1 Peter Preston,2 Thomas N Thompson,3 Sandra K Willsie3 1Shire, Basingstoke, UK; 2Shire, Wayne, PA, USA; 3PRA International, Lenexa, KS, USA Background: MMX® mesalamine is a once daily oral 5-aminosalicylic acid formulation, effective in induction and maintenance of ulcerative colitis remission. Patients on long-term mesalamine maintenance may occasionally require concomitant antibiotic treatment for unrelated infections. Aim: To evaluate the potential for pharmacokinetic interactions between MMX mesalamine and amoxicillin, ciprofloxacin extended release (XR, metronidazole, or sulfamethoxazole in four open-label, randomized, placebo-controlled, two-period crossover studies. Methods: In all four studies, healthy adults received placebo once daily or MMX mesalamine 4.8 g once daily on days 1–4 in one of two treatment sequences. In studies 1 and 2, subjects also received a single dose of amoxicillin 500 mg (N=62 or ciprofloxacin XR 500 mg (N=30 on day 4. In studies 3 and 4, subjects received metronidazole 750 mg twice daily on days 1–3 and once on day 4 (N=30; or sulfamethoxazole 800 mg/trimethoprim 160 mg twice daily on days 1–3 and once on day 4 (N=44. Results: MMX mesalamine had no significant effects on systemic exposure to amoxicillin, ciprofloxacin, or metronidazole; the 90% confidence intervals (CIs around the geometric mean ratios (antibiotic + MMX mesalamine: antibiotic + placebo for maximum plasma concentration (Cmax and area under the plasma concentration–time curve (AUC fell within the predefined equivalence range (0.80–1.25. Sulfamethoxazole exposure increased by a statistically significant amount when coadministered with MMX mesalamine; however, increased exposure (by 12% in Cmax at steady state; by 15% in AUC at steady state was not considered clinically significant, as the 90% CIs for each point estimate fell entirely within the predefined

  10. Current approaches to management of ulcerative colitis%溃疡性结肠炎治疗的现代观点

    Institute of Scientific and Technical Information of China (English)

    田玲玲; 刘丽娜

    2016-01-01

    溃疡性结肠炎(ulcerative colitis,UC)目前尚无有效的根治手段,但多数患者可通过药物治疗使病情得到有效控制.目前,氨基水杨酸类制剂仍是UC治疗的中流砥柱;糖皮质激素抗炎作用强,诱导缓解速度快,但考虑到其不良反应及激素依赖或抵抗等问题,临床应用要严格掌握其适应症及使用方法;生物制剂对UC患者,尤其是难治性UC患者显示出较大的潜力.近年来,UC治疗的新型药物及传统药物的新剂型相继面世,治疗方案亦是不断推陈出新,尤其是与以往传统"升阶梯"治疗方案截然相反的"降阶梯"方案的提出,更是为UC的治疗提供了新思路.本文旨在对UC治疗的新进展进行系统总结.%Ulcerative colitis (UC) still lacks the cure, but most patients can be well managed with drug therapy.Aminosalicylates remain the mainstay treatment for UC patients.Glucocorticoids have remarkable anti-inflammatory effects and can induce remission rapidly.However, many cases may develop dependency or resistance, and adverse events during long-term use may also occur.As a result, glucocorticoids should be prescribed strictly according to the indication and application methods.Biologicals have great potentials for UC patients, especially for refractory UC patients.Nowadays, more and more new drugs and new formulations of traditional drugs, as well as novel regimens are introduced.The top-down therapy, which is utterly contradictory to the conventional step-up strategy, revolutionizes UC treatment.This paper aims to provide a comprehensive, evidencebased summary of current therapies for UC.

  11. Comparative tolerability of treatments for inflammatory bowel disease.

    Science.gov (United States)

    Stein, R B; Hanauer, S B

    2000-11-01

    Despite limited understanding of therapeutic aetiopathogenesis of ulcerative colitis and Crohn's disease, there is a strong evidence base for the efficacy of pharmacological and biological therapies. It is equally important to recognise toxicity of the medical armamentarium for inflammatory bowel disease (IBD). Sulfasalazine consists of sulfapyridine linked to 5-aminosalicylic acid (5-ASA) via an azo bond. Common adverse effects related to sulfapyridine 'intolerance' include headache, nausea, anorexia, and malaise. Other allergic or toxic adverse effects include fever, rash, haemolytic anaemia, hepatitis, pancreatitis, paradoxical worsening of colitis, and reversible sperm abnormalities. The newer 5-ASA agents were developed to deliver the active ingredient of sulfasalazine while minimising adverse effects. Adverse effects are infrequent but may include nausea, dyspepsia and headache. Olsalazine may cause a secretory diarrhoea. Uncommon hypersensitivity reactions, including worsening of colitis, pancreatitis, pericarditis and nephritis, have also been reported. Corticosteroids are commonly prescribed for treatment of moderate to severe IBD. Despite short term efficacy, corticosteroids have numerous adverse effects that preclude their long term use. Adverse effects include acne, fluid retention, fat redistribution, hypertension, hyperglycaemia, psycho-neurological disturbances, cataracts, adrenal suppression, growth failure in children, and osteonecrosis. Newer corticosteroid preparations offer potential for targeted therapy and less corticosteroid-related adverse effects. Azathioprine and mercaptopurine are associated with pancreatitis in 3 to 15% of patients that resolves upon drug cessation. Bone marrow suppression is dose related and may be delayed. The adverse effects of methotrexate include nausea, leucopenia and, rarely, hypersensitivity pneumonia or hepatic fibrosis. Common adverse effects of cyclosporin include nephrotoxicity, hypertension, headache

  12. Targeted Delivery of LXR Agonist Using a Site-Specific Antibody-Drug Conjugate.

    Science.gov (United States)

    Lim, Reyna K V; Yu, Shan; Cheng, Bo; Li, Sijia; Kim, Nam-Jung; Cao, Yu; Chi, Victor; Kim, Ji Young; Chatterjee, Arnab K; Schultz, Peter G; Tremblay, Matthew S; Kazane, Stephanie A

    2015-11-18

    Liver X receptor (LXR) agonists have been explored as potential treatments for atherosclerosis and other diseases based on their ability to induce reverse cholesterol transport and suppress inflammation. However, this therapeutic potential has been hindered by on-target adverse effects in the liver mediated by excessive lipogenesis. Herein, we report a novel site-specific antibody-drug conjugate (ADC) that selectively delivers a LXR agonist to monocytes/macrophages while sparing hepatocytes. The unnatural amino acid para-acetylphenylalanine (pAcF) was site-specifically incorporated into anti-CD11a IgG, which binds the α-chain component of the lymphocyte function-associated antigen 1 (LFA-1) expressed on nearly all monocytes and macrophages. An aminooxy-modified LXR agonist was conjugated to anti-CD11a IgG through a stable, cathepsin B cleavable oxime linkage to afford a chemically defined ADC. The anti-CD11a IgG-LXR agonist ADC induced LXR activation specifically in human THP-1 monocyte/macrophage cells in vitro (EC50-27 nM), but had no significant effect in hepatocytes, indicating that payload delivery is CD11a-mediated. Moreover, the ADC exhibited higher-fold activation compared to a conventional synthetic LXR agonist T0901317 (Tularik) (3-fold). This novel ADC represents a fundamentally different strategy that uses tissue targeting to overcome the limitations of LXR agonists for potential use in treating atherosclerosis. PMID:25945727

  13. Hepatic and intestinal blood flow following thermal injury

    International Nuclear Information System (INIS)

    Because cardiac output decreases after burn injuries, investigators have assumed, based upon dye clearance techniques, that hepatic and intestinal blood flow are also decreased following these injuries. Blood flow to the liver, stomach, small intestine, and kidney was determined by the uptake of 201thallium and 125I-labeled fatty acid (para-125I-phenyl-3-methyl pentanoic acid) in a 20% body surface area scald injury that also included plasma volume replacement resuscitation. Uptake of these radioisotopes was determined 15 minutes, 18 hours, and 72 hours after injury. The uptake of the 201thallium and 125I-labeled fatty acid by the gastrointestinal tissues was not statistically different at any of the time periods after comparison of the injured and control (sham-treated) animals. 201Thallium uptake by the kidney was significantly diminished 15 minutes after the burn injury (P less than 0.01). Based on these blood flow measurement techniques, the data suggest that the 20% body surface area scald injury did not alter blood flow to the liver or gastrointestinal tract within the initial 72 hours after the burn injury even though a decrease in renal blood flow was easily detected. These results suggest that the dysfunction of the gastrointestinal system or hepatic system observed after an acute burn injury is not simply the result of hypovolemic shock, which reduces both renal and mesenteric blood flow. These gastrointestinal and hepatic alterations may be related to a factor or factors other than intestinal ischemia

  14. The impact of biologics on health-related quality of life in patients with inflammatory bowel disease

    Directory of Open Access Journals (Sweden)

    Lauran Vogelaar

    2009-09-01

    Full Text Available Lauran Vogelaar1, Adriaan van’t Spijker2, C Janneke van der Woude11Department of Gastroenterology and Hepatology, 2Department of Psychology and Psychotherapy, Erasmus Medical Centre, RotterdamBackground: Inflammatory bowel disease (IBD is characterized by a chronic relapsing inflammation of the gastrointestinal tract. Adult IBD patients suffer from a disabling disease which greatly affects health-related quality of life (HRQoL. A worse HRQoL in these patients may result in a defensive and ineffective use of medical attention and thus higher medical costs. Because of its chronic nature, IBD may also cause psychological problems in many patients which may also influence HRQoL and care-seeking behavior. An important factor reducing HRQoL is disease activity. Induction of remission and long-term remission are important goals for improving HRQoL. Furthermore, remission is associated with a decreased need for hospitalization and surgery and increased employment, which in turn improve HRQoL. Treatment strategies available for many years are corticosteroids, 5-aminosalicylates and immunnosuppressants, but these treatments did not show significant long-term improvement on HRQoL. The biologics, which induce rapid and sustained remission, may improve HRQoL.Objective: To review and evaluate the current literature on the effect of biologics on HRQoL of IBD patients.Methods: We performed a MEDLINE search and reviewed the effect of different biologics on HRQoL. The following subjects and synonyms of these terms were used: inflammatory bowel disease, Crohn’s disease, ulcerative colitis, quality of life, health-related quality of life, fatigue, different anti-TNF medication, and biologicals/biologics (MESH. Studies included were limited to English-language, adult population, full-text, randomized, double-blind, placebo-controlled in which HRQoL was measured.Results: Out of 202 identified articles, 8 randomized controlled trials (RCT met the inclusion

  15. Adalimumab in prevention of postoperative recurrence of Crohn's disease in high-risk patients

    Institute of Scientific and Technical Information of China (English)

    Mariam Aguas; Guillermo Bastida; Elena Cerrillo; Belén Beltrán; Marisa Iborra; Cristina Sánchez-Montes; Fernando Mu(n)oz

    2012-01-01

    AIM:To evaluate the effectiveness of adalimumab in preventing recurrence after intestinal resection for Crohn's disease in high-risk patients.METHODS:A multicenter,prospective,observational study was conducted from June 2009 until June 2010.We consecutively included high-risk Crohn's disease patients who had undergone an ileal/ileocolonic resection.High-risk patients were defined as two or more criteria:smokers,penetrating pattern,one or more previous surgical resections or prior extensive resection.Subcutaneous adalimumab was administered 2 wk (±5 d) after surgery at a dose of 40 mg eow,with an initial induction dose of 160/80 mg at weeks 0 and 2.Demographic data,previous and concomitant treatments (antibiotics,5-aminosalicylates,corticosteroids,immunomodulators or biologic therapies),smoking status at the time of diagnosis and after the index operation and number of previous resections (type and reason for surgery) were all recorded.Biological status was assessed with C-reactive protein,erythrocyte sedimentation rate and fecal calprotectin.One year (± 3 mo) after surgery,an ileocolonoscopy and/or magnetic resonance enterography was performed.Endoscopic recurrence was defined as Rutgeerts score ≥ i2.Morphological recurrence was based on magnetic resonance (MR) score ≥ MR1.RESULTS:Twenty-nine patients (55.2% males,48.3% smokers at diagnosis and 13.8% after the index operation),mean age 42.3 years and mean duration of the disease 13.8 years were included in the study.A mean of 1.76 (range:1-4) resections previous to adalimumab administration and in 37.9% was considered extensive resection.51.7% had previously received infliximab.Immunomodulators were given concomitantly to 17.2% of patients.Four of the 29 (13.7%) developed clinical recurrence,6/29 (20.7%) endoscopic recurrence and 7/19 (36.8%) morphological recurrence after 1-year.All patients with clinical recurrence showed endoscopic and morphological recurrence.A high degree of concordance

  16. Interventional effect of electroacupuncture combined with medicine on monoamine neurotransmitters in hypothalamus of rats with ulcerative colitis

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    BACKGROUND: Ulcerative colitis (UC) is conventionally treated with sulfasalazine and other aminosalicylic acids. The symptoms of UC can be rapidly controlled, but high recurrence, severe adverse reactions and other shortages exist commonly. Whether electroacupuncture combined with medicine can make up these shortages remains unclear.OBJECTIVE: This study was to observe the regulatory effect of electroacupuncture combined with medicine on monoamine neurotransmitter in hypothalamus of rats with ulcerative colitis, and to analyze the pathogenesis of UC and the action pathway of electroacupuncture combined with medicine.DESIGN: A randomized controlled observation.SETTING: Shanghai Institute of Acupuncture and Meridian.MATERIALS: Thirty involved male SD rats of clean grade, weighing (200 ±20) g, were provided by the Experimental Animal Center, Shanghai University of Traditional Chinese Medicine. Sulfasalazine was produced in the Shanghai Sanwei Pharmaceutical Co., Ltd [certification No. (1995)002083].METHODS: This study was carried out in the State Laboratory (grade 3) for Acupuncture and Immunology,Shanghai Institute of Acupuncture and Meridian. The involved 30 rats were randomized into 5 groups:normal group, model group, electroacupuncture group, medicine group and electroacupuncture combined with medicine group, with 6 rats in each group. Rats in the latter 4 groups were prepared into models of UC.In the electroacupuncture group, Zusanli(shuang) point was selected. Electro-acupuncture apparatus (G6805 Ⅱ type) was connected to the point and used to stimulate it with continuous wave, frequency of 2 Hz, electrical intensity 4 mA, 20 minutes a day, for 14 days successively. In the medicine group, rats were intragastrically administrated with sulfasalazine, twice a day, 3 mL once, for 14 days successively. In the electroacupuncture combined with medicine group, rats were treated with electroacupuncture and medicine simultaneously as described in the previous two groups

  17. Validation of HPLC, DPPH• and nitrosation methods for mesalamine determination in pharmaceutical dosage forms Validação dos métodos de CLAE, DPPH• e nitrosação para determinação de mesalazina em formas farmacêuticas

    Directory of Open Access Journals (Sweden)

    Janice Aparecida Rafael

    2007-03-01

    Full Text Available Mesalamine (5-aminosalicylic acid, 5-ASA is used because of its local effects in the treatment of inflammatory bowel disease. Therefore, the aims of this work were to compare and validate three analytical methods for the quality control of commercial coated tablets containing 5-ASA: high performance liquid chromatography (HPLC, 1,1-diphenyl-2-picrylhydrazyl radicals (DPPH• and nitrosation. The parameters linearity, precision and accuracy were studied in this work. HPLC with ultraviolet detection at 254 nm was carried out with a C18 column and a mobile phase constituted of 30 mmol/L monobasic phosphate buffer (pH 7.0 and methanol (70:30; v/v, with 25% tetrabutylammonium hydrogen sulphate. The DPPH• method was performed at 517 nm and using 100 mmol/L acetate buffer, pH 5.5, ethanol and 250 µmol/L ethanolic solution of DPPH•. The nitrosation method was accomplished by using a platinum electrode and standard 0.1 mol/L sodium nitrite as titrant solution. Repeatability (intra-day and intermediate precision (inter-day, expressed as RSD, were lower than 3%. The experimental recoveries were between 72.5 and 99.9%. Statistical analysis by one-way ANOVA, followed by the multiple comparison test of Bonferroni showed no significant difference among the three methods. All proposed methods can be used for the reliable quantitation of 5-ASA in pharmaceutical dosage forms.Mesalazina (ácido 5-aminosalicílico, 5-ASA é utilizado devido seu efeito local no tratamento de doença inflamatória intestinal. Assim, o objetivo deste trabalho foi comparar e validar três métodos analíticos para o controle de qualidade de comprimidos comerciais revestidos contendo 5-ASA: cromatografia líquida de alta eficiência (CLAE, radical 1,1-difenil-2-picril-hidrazil (DPPH• e nitrosação. Os parâmetros linearidade, precisão e exatidão foram estudados neste trabalho. CLAE com detecção ultravioleta em 254 nm foi realizada utilizando coluna C18 e a eluição em fase m

  18. Inflammatory bowel disease. Current concepts of pathogenesis and implications for therapy.

    Science.gov (United States)

    Fiocchi, C

    2002-09-01

    . Cytokines, chemokines and other soluble factors dominate immunological studies aimed at understanding how different anti-inflammatory and pro-inflammatory mediators are improperly regulated and how immune imbalance can be restored. The extent to which T-cells live or die is also a key determinant of chronicity. In addition to classical immune cells, epithelial, endothelial, mesenchymal and nerve cells are slowly gaining more importance in IBD pathogenesis, as they contribute to the ultimate fate of tissue damage. Medical and surgical therapies are vastly better now that they were only a couple of decades ago, but they are still far from satisfactory. Steroid and aminosalicylates are still the most common drugs after 60 years of use, and it is time to renovate our therapeutic approach to a more effective one. The value of biologicals has been highlighted by the recent success of anti-TNF therapy. Timing of therapy must also change. The concept of the step-by-step approach is slowly fading away, and the idea of an ''all-out'' approach with multiple concomitant drugs early in the disease is gaining credibility. New reports on early aggressive therapies, and the demonstration that early and late experimental IBD are caused by different mechanisms are changing the way we think about managing IBD. Both ulcerative colitis and Crohn's disease will continue to challenge the medical establishment for year to come, but the possibility that IBD can be conquered is more realistic now that never before. PMID:16491045

  19. 浙江省耐多药结核病例中二线耐药状况分析%Analysis on second-line drug resistance situation of multiple drug resistant tuberculosis in Zhejiang, China

    Institute of Scientific and Technical Information of China (English)

    陈松华; 王晓萌; 柳正卫; 何海波; 陈彬; 黄玉

    2011-01-01

    ), ofloxacin (OFLX) and para-Aminosalicylate (PAS). The extensive drug resistance (XDR) rate of MDR cases was 3. 85%. Conclusion Tuberculosis drug resistance to second-line drugs was in a serious situation in Zhejiang. We should enhance the implementation quality of Directly Observed Treatment Short-course (DOTS), strengthen the detection capability of MDR and XDR, as well as improve the medical treatment comprehensive system for drug resistance TB.

  20. Propionyl-L-carnitine hydrochloride for treatment of mild to moderate colonic inflammatory bowel diseases

    Institute of Scientific and Technical Information of China (English)

    Giuseppe Merra; Giovanni Gasbarrini; Lucrezia Laterza; Marco Pizzoferrato; Andrea Poscia; Franco Scaldaferri; Vincenzo Arena

    2012-01-01

    AIM:To assess clinical and endoscopic response to propionyl-L-carnitine hydrochloride (PLC) in colonic inflammatory bowel disease.METHODS:Patients suffering from mild to moderate ulcerative colitis (UC) or Crohn's disease (CD) colitis,with disease activity index (DAI) between 3 and 10 and under stable therapy with oral aminosalicylates,mercaptopurine or azathioprine,for at least 8 wk prior to baseline assessments,were considered suitable for enrollment.Fourteen patients were enrolled to assume PLC 2 g/d (two active tablets twice daily) orally.Clinical-endoscopic and histological activity were assessed by DAI and histological index (HI),respectively,following a colonoscopy performed immediately before and after 4 wk treatment.Clinical response was defined as a lowering of at least 3 points in DAI and clinical remission as a DAI score ≤ 2.Histological response was defined as an improvement of HI of at least 1 point.We used median values for the analysis.Differences pre-and post-treatment were analyzed by Wilcoxon signed rank test.RESULTS:All patients enrolled completed the study.One patient,despite medical advice,took deflazacort 5 d before follow-up colonoscopy examination.No side effects were reported by patients during the trial.After treatment,71% (SE 12%) of patients achieved clinical response,while 64% (SE 13%) obtained remission.Separating UC from CD patients,we observed a clinical response in 60% (SE 16%) and 100%,respectively.Furthermore 60% (SE 16%) of UC patients and 75% (SE 25%) of CD patients were in clinical remission after therapy.The median DAI was 7 [interquartile range (IQR):4-8] before treatment and decreased to 2 (IQR:1-3) (P < 0.01) after treatment.Only patients with UC showed a significant reduction of DAI,from a median 6.5 (IQR:4-9) before treatment to 2(IQR:1-3) after treatment (P < 0.01).Conversely,in CD patients,although displaying a clear reduction of DAI from 7 (IQR:5.5-7.5) before therapy to 1.5 (IQR:0

  1. Protective effect of Radix Acanthopanacis Senticosi capsule on colon of rat depression model

    Institute of Scientific and Technical Information of China (English)

    Gao-Hua Wang; Hai-Yan Dong; Wei-Guo Dong; Xiao-Ping Wang; He-Sheng Luo; Jie-Ping Yu

    2005-01-01

    AIM: To investigate the abnormity of rat colon caused by depression and the ameliorative effects of Radix Acanthopanacis Senticosi (RAS) capsule on colon and their mechanisms in rat depression model.METHODS: Chronic stress-induced model of depression of Wistar rats was produced. The experimental animals were randomly divided into model control, 5-aminosalicylic acid (5-ASA) therapy group and three RAS capsule therapy groups. These five groups were intracolonically treated daily (8:00 a.m.) for 2 wk with normal saline, 5-ASA(100 mg/ kg) and RAS capsule at the doses of 300, 600and 900 mg/kg, respectively. A normal control group of rats was also included in the study. Colonic activities of nitric oxide (NO) and superoxide dismutase (SOD), levels of malondialdehyde (MDA) and indudble nitric oxide synthase (iNOS) were determined by ultraviolet spectrophotometry.The expression of cyclooxygenase-2 (COX-2) in colonic tissue was detected by immunohistochemistry.RESULTS: Enhanced colon inflammatory response and oxidative stress were observed in the chronic stressinduced rat depression model, which manifested as the significant increase of MDA, iNOS and NO levels, as well as the expressions of COX-2 in the colon tissue, but the colonic SOD activity was significantly decreased compared with the normal control (MDA: 10.34±2.77 vs 2.55±0.70;iNOS: 1.11±0.44 vs0.25±0.16; COX2:53.26±8.16 vs4.87±1.65; NO: 11.28±5.66 vs 4.76±1.55; SOD: 53.39±11.15vs 84.45±22.31; P<0.01). However, these parameters were significantly ameliorated in rats treated locally with RAS capsule at the doses of 300, 600 and 900 mg/kg(iNOS: 0.65±0.31, 0.58±0.22 and 0.64±0.33; NO: 5.99±2.73,6.87±1.96 and 6.50±1.58; MDA: 2.92±0.75, 3.19±1.08and 3.26±1.24; SOD: 70.81±12.36, 73.30±15.30 and69.09±11.03, respectively). The expressions of COX-2 in the colon were significantly ameliorated (28.83±9.48 and27.04±9.56, respectively) when RAS capsule was administered at the doses of 600 and 900 mg

  2. Urinary pesticide metabolites in school students from northern Thailand.

    Science.gov (United States)

    Panuwet, Parinya; Prapamontol, Tippawan; Chantara, Somporn; Barr, Dana B

    2009-05-01

    We evaluated exposure to pesticides among secondary school students aged 12-13 years old in Chiang Mai Province, Thailand. Pesticide-specific urinary metabolites were used as biomarkers of exposure for a variety of pesticides, including organophosphorus insecticides, synthetic pyrethroid insecticides and selected herbicides. We employed a simple solid-phase extraction with analysis using isotope dilution high-performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS). A total of 207 urine samples from Thai students were analyzed for 18 specific pesticide metabolites. We found 14 metabolites in the urine samples tested; seven of them were detected with a frequency > or=17%. The most frequently detected metabolites were 2-[(dimethoxyphosphorothioyl) sulfanyl] succinic acid (malathion dicarboxylic acid), para-nitrophenol (PNP), 3,5,6-trichloro-2-pyridinol (TPCY; metabolite of chlorpyrifos), 2,4-dichlorophenoxyacetic acid (2,4-D), cis- and trans-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane-1-carboxylic acids (c-DCCA and t-DCCA; metabolite of permethrin) and 3-phenoxybenzoic acid (3-PBA; metabolite of pyrethroids). The students were classified into 4 groups according to their parental occupations: farmers (N=60), merchants and traders (N=39), government and company employees (N=52), and laborers (N=56). Children of farmers had significantly higher urinary concentrations of pyrethroid insecticide metabolites than did other children (pmetabolite concentrations. Males had significantly higher values of PNP (Mann-Whitney test, p=0.009); however, no other sex-related differences were observed. Because parental occupation and agricultural activities seemed to have little influence on pesticide levels, dietary sources were the likely contributors to the metabolite levels observed. PMID:18760967

  3. Artificial Metalloenzymes through Chemical Modification of Engineered Host Proteins

    KAUST Repository

    Zernickel, Anna

    2014-10-01

    With a few exceptions, all organisms are restricted to the 20 canonical amino acids for ribosomal protein biosynthesis. Addition of new amino acids to the genetic code can introduce novel functionalities to proteins, broadening the diversity of biochemical as well as chemical reactions and providing new tools to study protein structure, reactivity, dynamics and protein-protein-interactions. The site directed in vivo incorporation developed by P. G. SCHULTZ and coworkers, using an archeal orthogonal tRNA/aaRS (aminoacyl-tRNA synthase) pair, allows site-specifically insertion of a synthetic unnatural amino acid (UAA) by reprogramming the amber TAG stop codon. A variety of over 80 different UAAs can be introduced by this technique. However by now a very limited number can form kinetically stable bonds to late transition metals. This thesis aims to develop new catalytically active unnatural amino acids or strategies for a posttranslational modification of site-specific amino acids in order to achieve highly enantioselective metallorganic enzyme hybrids (MOEH). As a requirement a stable protein host has to be established, surviving the conditions for incorporation, posttranslational modification and the final catalytic reactions. mTFP* a fluorescent protein was genetically modified by excluding any exposed Cys, His and Met forming a variant mTFP*, which fulfills the required specifications. Posttranslational chemical modification of mTFP* allow the introduction of single site metal chelating moieties. For modification on exposed cysteines different maleiimid containing ligand structures were synthesized. In order to perform copper catalyzed click reactions, suitable unnatural amino acids (para-azido-(L)-phenylalanine, para-ethynyl-(L)-phenylalanine) were synthesized and a non-cytotoxic protocol was established. The triazole ring formed during this reaction may contribute as a moderate σ-donor/π-acceptor ligand to the metal binding site. Since the cell limits the

  4. Flavonoids and phenolic acids from pearl millet (Pennisetum glaucum based foods and their functional implications

    Directory of Open Access Journals (Sweden)

    Vanisha S Nambiar

    2012-07-01

    Full Text Available Background: Pearl millet (Pennisetum glaucum, considered a poor man’s cereal, may be a repository of dietary antioxidants, especially flavonoids and phenolic acids, which provide bioactive mechanisms to reduce free radical induced oxidative stress and probably play a role in the prevention of ageing and various diseases associated with oxidative stress, such as cancer, cardiovascular, and neurodegenerative diseases.Objective: The present study focused on the identification of individual flavonoids and phenolic acids from seven commercial varieties of pearl millet and five samples of pearl millet-based traditional recipes of Banaskantha, Gujarat, India.Methods: Total phenols were determined by the Folin-Ciocalteu method, and individual polyphenol separation included the isolation and identification of (a flavonoids, (b phenolic acids, and (c glycoflavones involving interaction with diagnostic reagents and paper chromatographic separation of compounds and their UV-visible spectroscopic studies including hypsochromic and bathchromic shifts with reagents such as AlCl3, AlCl3/HCl, NaOMe, NaOAc,and NaOAc/H3PO3. Five traditional recipes consumed in the pearl millet producing belt of Banaskantha, Gujarat, India, were standardized in the laboratory and analyzed for phenol and individual flavonoids. Results: Total phenols in raw samples ranged from 268.5 - 420mg/100g of DW and 247.5 -Functional Foods in Health and Disease 2012, 2(7:251-264335mg/100g of DW in cooked recipes. The commonly identified flavonoids were tricin, acacetin, 3, 4 Di-OMe luteolin, and 4-OMe tricin. Five phenolic acids were identified: namely vanilic acid, syringic acid, melilotic acid, para-hydroxyl benzoic acid, and salicylic acid.Conclusion: The presence of flavonoids, such as tricin, acacetin, 3, 4 Di-OMe luteolin, and 4-OMe tricin, indicate the chemopreventive efficacy of pearl millet. They may be inversely related to mortality from coronary heart disease and to the incidence

  5. Guías para el manejo de la tuberculosis resistente: OMS 2011 WHO guidelines for the management of drug-resistant tuberculosis: 2011 update

    Directory of Open Access Journals (Sweden)

    Juan Carlos Rodríguez D

    2012-06-01

    multidrug-resistant tuberculosis (MDR-TB. However, most of them are based on expert opinion, without good evidence. The new guidelines are the following: I. Rapid sensitivity testing of isoniazid and rifampicin or of rifampicin alone is recommended over conventional testing or no testing at the time of diagnosis of tuberculosis, subject to available resources. II. The use of sputum smear microscopy and culture rather than sputum smear microscopy alone is recommended for the monitoring of patients with MDR-TB during treatment. III. In the treatment of patients with MDR-TB the following rules are given: 1 a fluoroquinolone should be used; 2 a later-generation fluoroquinolone rather than an earlier-generation fluoroquinolone should be used; 3 ethionamide (or prothionamide should be used; 4 four second-line anti-TB drugs likely to be effective (including a parenteral agent from among the second-line injectables kanamycin, amika-cin or capreomycin, as well as pyrazinamide, should be included in the intensive phase of treatment; 5 regimens should include at least pyrazinamide, a fluoroquinolone, a parenteral agent (kanamycin, amikacin or capreomycin, ethionamide (or prothionamide, and either cycloserine or p-aminosalicylic acid (PAS if cycloserine cannot be used; 6 an intensive phase of 8 months' duration is recommended. 7 a total treatment duration of 20 months is recommended in patients without any previous MDR-TB treatment. IV.- Anti-retroviral treatment is recommended for all patients with HIV and drug-resistant TB requiring second-line anti-TB drugs, irrespective of CD4 cell count, as early as possible (within the first 8 weeks following initiation of anti-TB treatment. V.-Patients with MDR-TB should be treated using mainly ambulatory care rather than models of care based principally on hospitalization.

  6. Role of Mutations in Dihydrofolate Reductase DfrA (Rv2763c) and Thymidylate Synthase ThyA (Rv2764c) in Mycobacterium tuberculosis Drug Resistance

    KAUST Repository

    Koser, C. U.

    2010-09-17

    We would like to comment on a number of recent reports in this journal (6, 8, 12, 18) concerning Mycobacterium tuberculosis dihydrofolate reductase (DHFR), encoded by dfrA (Rv2763c). Around 36% of phenotypically para-aminosalicylic acid (PAS)-resistant M. tuberculosis strains harbor mutations in thyA (Rv2764c), which encodes a thymidylate synthase (20). In their effort to elucidate the remaining unknown resistance mechanism(s), Mathys et al. extended their sequence analysis to a number of additional genes, including dfrA (12). It was unclear whether the three dfrA mutations they identified in the PAS-resistant strains P-693 and P-3158 could contribute to PAS resistance on their own. Nonetheless, these findings are notable for two reasons. First, isoniazid (INH) has been shown to inhibit M. tuberculosis DHFR in vitro (1). Whether the same holds true for ethionamide, which shares a number of common resistance mechanisms with INH, was not tested (J. Blanchard, personal communication). In any case, the clinical relevance of DHFR-mediated INH resistance remains enigmatic. To date, only Ho et al. have addressed this question, but they did not identify any dfrA mutations in a screen of 127 INH-resistant clinical isolates (8). Consequently, Mathys et al. remain the first to describe mutations in this target (12). However, given that isolates with mutated DHFR are members of a cluster with baseline INH resistance, the importance of these mutations with respect to INH resistance remains unclear. Irrespective of their relevance in INH resistance, these dfrA mutations are noteworthy for a second reason. Contrary to previous wisdom, Forgacs et al. recently showed that M. tuberculosis is sensitive to the drug combination trimethoprim-sulfamethoxazole (TMP-SMX) (6, 18). DHFR is competitively inhibited by TMP, and consequently, mutations therein lead to resistance in a variety of organisms (9, 16, 19). The crystal structures of the wild-type M. tuberculosis DHFR in complex with

  7. Analysis of drug resistance on culture positive tuberculosis patients in Qingdao Chest Hospital from 2010 to 2012%青岛市胸科医院2010~2012年痰标本阳性肺结核患者耐药情况分析

    Institute of Scientific and Technical Information of China (English)

    周伟杰; 窦泽燕

    2014-01-01

    Objective To find out the situation of drug-resistant tuberculosis patients in Qingdao Chest Hospital,to draft scientific prevention and control strategy.Methods Using the World-Health Organization (WHO) mycobacterium tuberculosis drug resistance monitoring scheme to test drug susceptibility of mycobacterium tuberculosis,using the absolute concentration method to determine the resistance of 1 950 cases of culture positive pulmonary tuberculosis patients in the hospital.Results In 1 950 cases of culture positive pulmonary tuberculosis patients,1 120 cases were all sensitive,830 cases were resistant(42.5%).There were 425 cases of primary drug resistance,405 cases of acquired drug resistance.In the three years,the drug resistant rate was respectively:isoniazid 47.3%,rifampicin 24.0%,streptomycin 41.4%,ethambutol 24.2%,paraaminosalicylicacid 4.5%,amikacin 0.7%, prothionamide 5.6%,levofloxacin 9.4%,isoniazid aminosalicylate 0.7%;Among 425 primary drug-resistant cases, there were 253 cases of drug-resistant tuberculosis(59.5%),101 cases of polydrug-resistant tuberculosis(23.7%),71 cases of multidrug-resistant tuberculosis(16.4%).Conclusion The data obtained strongly suggests that the present situation of resistant tuberculosis in the hospital is still very serious.It is imperative to strengthen the management of tuberculosis prevention and control,and expand the testing points of Mycobacterium tuberculosis drug resistance,and supervise pulmonary tuberculosis under full-course management of the tuberculosis.%目的:了解青岛市胸科医院住院肺结核患者结核分枝杆菌耐药情况,制定科学的防治对策。方法采用世界卫生组织制定的结核分枝杆菌耐药监测方案进行结核分枝杆菌耐药监测,使用绝对浓度法对住院的1950例痰标本人型结核分枝杆菌的肺结核患者耐药性进行测定。结果1950例痰标本阳性肺结核患者中,全敏感1120例,耐药830例(42.5%)。其中原发耐药425

  8. Optimization of Detection System for Polyphenol and Its Compositions and Contents in Different Parts of Pomegranate Fruit%石榴果实酚类物质测定体系优化与不同部位组分及含量测定

    Institute of Scientific and Technical Information of China (English)

    韩玲玲; 苑兆和; 冯立娟; 杨尚尚; 朱峰

    2012-01-01

    A high performance liquid chromatographic method was developed for the analysis of polyphenol compositions and contents in different parts of ' Taishanhong' pomegranate fruit including peel, seed and juice. The chromatographic separation was performed on a Kromasil (250 mm×4. 6 mm, 5μm). The mobile phase was acetonitrile and 1% acetate acid solution for gradient elution. The column temperature was 30℃; the flow rate was 1. 1 ml/min and the wave length was 280 nm. The results indicated that thirteen phenolic compounds were identified in pomegranate peel and seed, including gallic acid, chlorogenic acid, para-hydroxybenzoic acid, epicatechin, caffeic acid, catechin, vanillin, ferulic acid, benzoic acid, phloridzin, quercetin, cinnamic acid and phloretin. Twelve phenolic compounds were identified in pomegranate juice, and epicatechin was not detected. The content of polyphenols was the highest in pomegranate peel, followed by pomegranate juice and pomegranate seed. The major acidic phenolic compound and flavonoid compound in pomegranate peel were parahydroxybenzoic acid (0.828 mg/g) and epicatechin (0.915 mg/g) respectively, while those in pomegranate juice were parahydroxybenzoic acid (0. 12 mg/g) and catechin (0. 149 mg/g) respectively, and those in pomegranate seed were caffeic acid (0.026 mg/g) and phloridzin (0.075 mg/g) respectively.%以“泰山红”石榴为试材,利用高效液相色谱仪(HPLC)测定成熟期石榴果实中果皮、籽粒和果汁中酚类物质的组分及含量.色谱条件:色谱柱为Kromasil色谱柱(250mm×4.6 mm,5μm),以乙腈-1%乙酸水溶液为流动相进行梯度洗脱.流速为1.1 ml/min,柱温30℃,检测波长280 nm.结果表明:在石榴皮和石榴籽中检测到13种酚类成分,包括没食子酸、绿原酸、对羟基苯甲酸、表儿茶素、咖啡酸、儿茶素、香草醛、阿魏酸、苯甲酸、根皮苷、槲皮素、肉桂酸、根皮素;在石榴汁中检测到上述12种酚类物质,未检测到表

  9. Effect of carvacrol on the oxidative stability of palm oil during frying

    Directory of Open Access Journals (Sweden)

    İnanç, T.

    2014-12-01

    Full Text Available Fats and oils deteriorate physically and chemically at frying temperatures due to several reasons. The objective of this study was to assess the effect of carvacrol on the oxidative stability of palm oil during a repeated frying process. Potatoes were serially fried in carvacrol-added palm oil, BHT-added palm oil and a control oil (without any antioxidants. After each tenth frying cycle, several chemical analyses were carried out on collected samples to evaluate deterioration in the oils. The free fatty acid, para-anisidine, iodine, and total polar component values of the fresh oil were 0.080, 2.85, 57.1 and 7.5, respectively. These values changed to 0.165, 11.80, 46.7, 11.0, respectively for the control oil; 0.151, 11.28, 49.2 and 10.5 for BHT-added oil; 0.140, 7.19, 51.7, 10.0 for carvacrol-added oil after 40 frying cycles. The results revealed that the use of carvacrol could significantly improve the oxidative stability of palm oil when compared to the control samples. This effect was also comparable to BHT. Using carvacrol in frying oil slowed down the rate of the formation of conjugated dienes and trienes compared to the oil with BHT and the control. The frying process significantly changed the viscosity of the oil samples.Las grasas y aceites se deterioran física y químicamente a las temperaturas de fritura debido a diferentes razones. El objetivo de este estudio fue evaluar el efecto del carvacrol en la estabilidad oxidativa del aceite de palma durante el proceso de fritura repetida. Se sometió a fritura repetida patatas en el aceite de palma con carvacrol agregado, en aceite de palma con BHT agregado y en aceite control (sin antioxidante. Después de cada décimo ciclo de fritura, se realizaron diferentes análisis sobre las muestras recogidas para evaluar el deterioro de los aceites. Ácidos grasos libre, para-anisidina, índice de yodo y componentes polares totales del aceite fresco fueron: 0,080, 2,85, 57,1 y 7,5, respectivamente

  10. Development of probes for bioanalytic applications of the surface-enhanced Raman scattering; Entwicklung neuer Sonden fuer bioanalytische Anwendungen der oberflaechenverstaerkten Raman-Streuung

    Energy Technology Data Exchange (ETDEWEB)

    Matschulat, Andrea Isabel

    2011-07-01

    Surface-enhanced Raman scattering (SERS) has been established as a versatile tool for probing and labeling in analytical applications, based on the vibrational spectra of samples as well as label molecules in the proximity of noble metal nanostructures. The aim of this work was the construction of novel SERS hybrid probes. The hybrid probes consisted of Au and Ag nanoparticles and reporter molecules, as well as a targeting unit. The concept for the SERS hybrid probe design was followed by experiments comprising characterization techniques such as UV/Vis-spectroscopy (UV/Vis), Transmission electron microscopy (TEM) and Dynamic Light Scattering (DLS), respectively. SERS experiments were performed for studying and optimizing the plasmonic properties of nanoparticles with respect to their enhancement capabilities. The SERS-probes had to meet following requirements: biocompatibility, stability in physiological media, and enhancement of Raman-signals from Raman reporter molecules enabling the identification of different probes even in a complex biological environment. Au and Ag nanoaggregates were found to be the most appropriate SERS substrates for the hybrid probe design. The utilization of Raman reporters enabled the identification of different SERS probes in multiplexing experiments. In particular, the multiplexing capability of ten various reporter molecules para-aminobenzenethiol, 2-naphthalenethiol, crystal violet, rhodamine (B) isothiocyanate, fluorescein isothiocyanate, 5,5'dithiobis(2-nitrobenzoic acid), para-mercaptobenzoic acid, acridine orange, safranine O und nile blue was studied using NIR-SERS excitation. As demonstrated by the results the reporters could be identified through their specific Raman signature even in the case of high structural similarity. Chemical separation analysis of the reporter signatures was performed in a trivariate approach, enabling the discrimination through an automated calculation of specific band ratios. The trivariate