WorldWideScience

Sample records for aminosalicylic acid-para

  1. 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

    1. A new metabolite of the drug 5-aminosalicylic acid (5-ASA) has been found in urine from pigs and in plasma of humans. The metabolite has been isolated from pig urine using an XAD-2 column and purified using preparative h.p.l.c. 2. The metabolite has been identified as N-formyl-5-ASA (5...

  2. The role of aminosalicylates in the treatment of ulcerative colitis

    NARCIS (Netherlands)

    van Assche, Gert; Baert, Filip; de Reuck, Marc; de Vos, Martine; de Wit, Olivier; Hoang, Pierre; Louis, Edouard; Mana, Fazia; Pelckmans, Paul; Rutgeerts, Paul; van Gossum, Andre; D'Haens, Geert

    2002-01-01

    Aminosalicylates (5-ASA, sulfasalazine and mesalazine) play a central role in the treatment of ulcerative colitis (UC). For acute treatment of mild to moderate flares and in maintenance treatment, their efficacy has been established. Since ulcerative colitis is limited to the distal colon in two

  3. Effect of 5-aminosalicylic acid on myocardial capillary permeability following ischaemia and reperfusion

    DEFF Research Database (Denmark)

    Hansen, P R; Svendsen, Jesper Hastrup; Høst, N B

    1992-01-01

    The aim was to evaluate the effect of 5-aminosalicylic acid on myocardial capillary permeability for small hydrophilic molecules after ischaemia and reperfusion.......The aim was to evaluate the effect of 5-aminosalicylic acid on myocardial capillary permeability for small hydrophilic molecules after ischaemia and reperfusion....

  4. 5-Aminosalicylate intolerance causing exacerbation in pediatric ulcerative colitis.

    Science.gov (United States)

    Shimizu, Hirotaka; Arai, Katsuhiro; Tang, Julian; Hosoi, Kenji; Funayama, Rie

    2017-05-01

    5-Aminosalicylate (5-ASA) is widely used as the first-line drug for ulcerative colitis (UC). 5-ASA is mostly a safe and effective drug, but it can bring about exacerbation due to 5-ASA intolerance. 5-ASA intolerance can be confusing and it can mislead physicians into considering unnecessary treatment escalation, including corticosteroid (CS), biologics, or even surgery. In spite of the clinical importance of 5-ASA intolerance, there have been few studies on its incidence, clinical features, and diagnosis. In order to evaluate the incidence, characteristic symptoms, disease course, and laboratory data of children with 5-ASA intolerance, we retrospectively reviewed the medical records of 80 children with UC. Eleven of 80 children (13.8%) with UC were diagnosed with 5-ASA intolerance. The median time between the initiation of 5-ASA and the onset of 5-ASA intolerance was 10 days (range, 4-20 days) in patients not receiving CS. Drug-induced lymphocyte stimulation test (DLST) was performed in 10 patients, and was positive in eight. C-reactive protein (CRP) increased significantly when exacerbation of colitis symptoms occurred. The incidence of 5-ASA intolerance was relatively high. Besides the challenge test, elevation of CRP and positive DLST appeared to support the diagnosis of 5-ASA intolerance. © 2017 Japan Pediatric Society.

  5. 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...

  6. 5-Aminosalicylates reduce the risk of colorectal neoplasia in patients with ulcerative colitis: an updated meta-analysis.

    Directory of Open Access Journals (Sweden)

    Li-Na Zhao

    Full Text Available BACKGROUND: Although the chemopreventive effect of 5-aminosalicylates on patients with ulcerative colitis has been extensively studied, the results remain controversial. This updated review included more recent studies and evaluated the effectiveness of 5-aminosalicylates use on colorectal neoplasia prevention in patients with ulcerative colitis. METHODS: Up to July 2013, we searched Medline, Embase, Web of Science, Cochrane CENTRAL, and SinoMed of China for all relevant observational studies (case-control and cohort about the effect of 5-aminosalicylates on the risk of colorectal neoplasia among patients with ulcerative colitis. The Newcastle-Ottawa Scale was used to assess the quality of studies. Adjusted odds ratios (ORs were extracted from each study. A random-effects model was used to generate pooled ORs and 95% confidence intervals (95%CI. Publication bias and heterogeneity were assessed. RESULTS: Seventeen studies containing 1,508 cases of colorectal neoplasia and a total of 20,193 subjects published from 1994 to 2012 were analyzed. 5-aminosalicylates use was associated with a reduced risk of colorectal neoplasia in patients with ulcerative colitis (OR 0.63; 95%CI 0.48-0.84. Pooled OR of a higher average daily dose of 5-aminosalicylates (sulfasalazine ≥ 2.0 g/d, mesalamine ≥ 1.2 g/d was 0.51 [0.35-0.75]. Pooled OR of 5-aminosalicylates use in patients with extensive ulcerative colitis was 1.00 [0.53-1.89]. CONCLUSION: Our pooled results indicated that 5-aminosalicylates use was associated with a reduced risk of colorectal neoplasia in patients with ulcerative colitis, especially in the cases with a higher average daily dose of 5-aminosalicylates use. However, the chemopreventive benefit of 5-aminosalicylates use in patients with extensive ulcerative colitis was limited.

  7. Application of 5-Aminosalicylic Acid Preparations in the Treatment of Inflammatory Bowel Diseases

    Directory of Open Access Journals (Sweden)

    Yu.M. Stepanov

    2016-09-01

    Full Text Available The article is devoted to the comparative characterization of different derivatives of 5-aminosalicylic acid. Researches of the past decades have changed the presentation of the potential use of aminosalicylates in the therapy of various inflammatory bowel diseases. In connection with unknown etiology of Crohn’s disease and ulcerative colitis, there is no causal treatment of these diseases. The essence of treatment is reduced to inhibition of inflammatory activity during exacerbations and a course of preventive treatment. Numerous studies over the past 20 years have shown that the basis of basic treatment for nonspecific chronic inflammatory bowel diseases is 5-aminosalicylic acid drugs, or salicylates. When choosing the dosage form, you should take into account the differences between mesalazine preparations depending on the type of the coat. It is shown that in terms of pharmacokinetics, the most effective mesalazine dosage forms for the treatment of ulcerative colitis and Crohn’s disease with lesions of the colon are enteric coated tablets that provides a pH-dependent gradual release of 5-aminosalicylic acid throughout the entire colon. 5-aminosalicylic acid drugs available today on the pharmaceutical market are able to control the course of ulcerative colitis and Crohn’s disease with lesions of the colon in the majority of patients. The use of 5-aminosalicylic acid preparations is not limited to the treatment of ulcerative colitis and Crohn’s disease. The drug is widely used in other diseases of the bowel, such as diverticular disease of the colon, colitis banal, radiation damages of the colon, as well as to treat common diseases, such as irritable bowel syndrome. The study, which was conducted in the department bowel disease of the State Institution «Institute of Gastroenterology» for 2 years, showed a positive effect of 20-day treatment with Mesacol in uncomplicated diverticular disease. The use of Mesacol at a dose of 1,600 mg

  8. A practical perspective on ulcerative colitis: patients' needs from aminosalicylate therapies.

    Science.gov (United States)

    Loftus, Edward V

    2006-12-01

    A large, Internet-based survey of a random sample of members of the Crohn's and Colitis Foundation of America was undertaken to gain knowledge and understanding of patients' experiences with ulcerative colitis and first-line therapies. From 49,410 invitations to participate, 1,595 usable responses were received from patients with ulcerative colitis. Patients were prescribed a range of aminosalicylates for their ulcerative colitis. Treatments with the highest proportion of satisfied patients were associated with highest remission rates. Forty-three percent of patients considered their disease to be in remission; however, 74% reported disease relapse during the previous 12 months. Over 60% of patients reported that they were noncompliant with prescribed aminosalicylate dosing schedules, with reasons attributed to frequency of dosing, the number of pills, and the inconvenience of the medication. Many respondents reported that they had made significant lifestyle changes because of their ulcerative colitis, including spending more time at home (46%) and participating in fewer social activities (37%). When asked to describe their ideal treatment, patients considered high efficacy (97%), lack of side effects (74%), nonparenteral dosing (46%), nonrectal dosing (36%), low cost (23%), fewer pills (23%), and less frequent dosing (23%) as "very important." This study demonstrates that continuous symptomatic remission is central to patient satisfaction and that patients find currently available aminosalicylates to be inconvenient. Patients' ideal therapy would be an effective, oral formulation with fewer tablets, less frequent dosing, and minimal side effects. Development of such a therapy would, therefore, potentially improve both patient compliance and overall treatment success.

  9. 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

    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...... extrudates were film coated with ethyl cellulose in a typical lab system coater equipped with one Wurster partition. Dissolution testing was performed first in a conventional paddle dissolution apparatus and second, in a flow through geometry equipped with a UV imaging system. Selected film coated extrudates...... dissolution testing. The release from defect extrudates was visualized by the absorbance maps and the release was highest from the compromised part of the extrudates. UV imaging has proven to be a useful technique to visualize the release of 5-aminosalicylic acid from single film coated extrudates and it has...

  10. Severe side effects with the application of Mesalazine (5-aminosalicylic acid) during radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Freund, U.; Siems, H.; Wannenmacher, M.; Schoelmerich, J.; Kluge, F.; Schaefer, H.E.

    1987-10-01

    In a prospective randomized placebo controlled double blind study, the prophylactic effect of Mesalazine (5-aminosalicylic acid, 5-ASA) as suppositories (3x250 mg/day) on radiation induced proctitis during radiotherapy for prostatic carcinoma was studied. The study ended when 16 patients had been included (5-ASA: Eight, placebo: Eight) because of severe side effects in the 5-ASA group. 75% of patients treated with 5-ASA reported symptoms of a severe proctitis while only one patient in the placebo group had similar complaints. The application of Mesalazine as suppositories is not useful in preventing radiation induced proctitis during radiotherapy of prostate carcinoma.

  11. Severe side effects with the application of Mesalazine (5-aminosalicylic acid) during radiotherapy

    International Nuclear Information System (INIS)

    Freund, U.; Siems, H.; Wannenmacher, M.; Schoelmerich, J.; Kluge, F.; Schaefer, H.E.

    1987-01-01

    In a prospective randomized placebo controlled double blind study, the prophylactic effect of Mesalazine (5-aminosalicylic acid, 5-ASA) as suppositories (3x250 mg/day) on radiation induced proctitis during radiotherapy for prostatic carcinoma was studied. The study ended when 16 patients had been included (5-ASA: Eight, placebo: Eight) because of severe side effects in the 5-ASA group. 75% of patients treated with 5-ASA reported symptoms of a severe proctitis while only one patient in the placebo group had similar complaints. The application of Mesalazine as suppositories is not useful in preventing radiation induced proctitis during radiotherapy of prostate carcinoma. (orig.) [de

  12. Release of 5-aminosalicylate from an MMX mesalamine tablet during transit through a simulated gastrointestinal tract system

    NARCIS (Netherlands)

    Tenjarla, S.; Romasanta, V.; Zeijdner, E.; Villa, R.; Moro, L.

    2007-01-01

    5-Aminosalicylate (5-ASA; mesalamine) is the current first-line treatment for mild to moderate ulcerative colitis, a chronic inflammatory condition that most commonly affects the distal part of the colon. MMX™ mesalamine (Lialda™ [US]; Mezavant™ XL [UK and Ireland]; Mezavant™ [elsewhere]; Shire

  13. Effect of ascorbate and 5-aminosalicylic acid on light-induced 8-hydroxydeoxyguanosine formation in V79 Chinese hamster cells

    DEFF Research Database (Denmark)

    Fischer-Nielsen, A; Loft, S; Jensen, K G

    1993-01-01

    Recently we showed that ascorbate and 5-aminosalicylic acid (5-ASA) prevented 8-hydroxydeoxyguanosine (8-OHdG) formation in calf thymus DNA exposed to UV-visible light. However, the ultimate defense against oxidative DNA damage depends on an intracellular/intranuclear effect of the compounds...

  14. Clinical Features and HLA Association of 5-Aminosalicylate (5-ASA)-induced Nephrotoxicity in Inflammatory Bowel Disease

    NARCIS (Netherlands)

    Heap, G.A.; So, K.; Weedon, M.; Edney, N.; Bewshea, C.; Singh, A.; Annese, V.; Beckly, J.; Buurman, D.; Chaudhary, R.; Cole, A.T.; Cooper, S.C.; Creed, T.; Cummings, F.; de Boer, N.K.; D'Inca, R.; D'Souza, R.; Daneshmend, T.K.; Delaney, M.; Dhar, A.; Direkze, N.; Dunckley, P.; Gaya, D.R.; Gearry, R.; Gore, S.; Halfvarson, J.; Hart, A.; Hawkey, C.J.; Hoentjen, F.; Iqbal, T.; Irving, P.; Lal, S.; Lawrence, I.; Lees, C.W.; Lockett, M.; Mann, S.; Mansfield, J.; Mowat, C.; Mulgrew, C.J.; Muller, F.; Murray, C.; Oram, R.; Orchard, T.; Parkes, M.; Phillips, R.; Pollok, R.; Radford-Smith, G.; Sebastian, S.; Sen, S.; Shirazi, T.; Silverberg, M.; Solomon, L.; Sturniolo, G.C.; Thomas, M.; Tremelling, M.; Tsianos, E.V.; Watts, D.; Weaver, S.; Weersma, R.K.; Wesley, E.; Holden, A.; Ahmad, T.

    2016-01-01

    BACKGROUND AND AIMS: Nephrotoxicity is a rare idiosyncratic reaction to 5-aminosalicylate (5-ASA) therapies. The aims of this study were to describe the clinical features of this complication and identify clinically useful genetic markers so that these drugs can be avoided or so that monitoring can

  15. A novel preparation method for 5-aminosalicylic acid loaded Eudragit S100 nanoparticles.

    Science.gov (United States)

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

    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 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.

  16. 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.

  17. 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.

  18. Release of 5-Aminosalicylic Acid (5-ASA) from Mesalamine Formulations at Various pH Levels.

    Science.gov (United States)

    Abinusawa, Adeyinka; Tenjarla, Srini

    2015-05-01

    Oral formulations of 5-aminosalicylic acid (5-ASA) for treatment of ulcerative colitis have been developed to minimize absorption prior to the drug reaching the colon. In this study, we investigate the release of 5-ASA from available oral mesalamine formulations in physiologically relevant pH conditions. Release of 5-ASA from 6 mesalamine formulations (APRISO®, Salix Pharmaceuticals, Inc., USA; ASACOL® MR, Procter & Gamble Pharmaceuticals UK Ltd.; ASACOL® HD, Procter & Gamble Pharmaceuticals, USA; MEZAVANT XL®, Shire US Inc.; PENTASA®, Ferring Pharmaceuticals, Ltd., UK; SALOFALK®, Dr. Falk Pharma UK Ltd.) was evaluated using United States Pharmacopeia apparatus I and II at pH values of 1.0 (2 h), 6.0 (1 h), and 6.8 (8 h). Dissolution profiles were determined for each formulation, respectively. Of the tested formulations, only the PENTASA formulation demonstrated release of 5-ASA at pH 1.0 (48%), with 56% cumulative release after exposure to pH 6.0 and 92% 5-ASA release after 6-8 h at pH 6.8. No other mesalamine formulation showed >1% drug release at pH 1.0. The APRISO formulation revealed 36% 5-ASA release at pH 6.0, with 100% release after 3 h at pH 6.8. The SALOFALK formulation revealed 11% 5-ASA release at pH 6.0, with 100% release after 1 h at pH 6.8. No 5-ASA was released by the ASACOL MR, ASACOL HD, and MEZAVANT XL formulations at pH 6.0. At pH 6.8, the ASACOL MR and ASACOL HD formulations exhibited complete release of 5-ASA after 4 and 2 h, respectively, and the MEZAVANT XL formulation demonstrated complete 5-ASA release over 6-7 h. 5-Aminosalicylic acid release profiles were variable among various commercially available formulations. Shire Development LLC.

  19. 5-aminosalicylic acid agents for prevention of recurrent diverticulitis: A systematic review and meta-analysis.

    Science.gov (United States)

    Urushidani, Seigo; Kuriyama, Akira; Matsumura, Masami

    2018-01-01

    Prevalence of colonic diverticulosis is increasing worldwide with age, and up to 25% of patients who have colonic diverticulosis might experience diverticulitis. However, a definitive approach of preventing recurrent diverticulitis remains unknown. 5-aminosalicylic acid (5-ASA) agents are anti-inflammatory agents and have been used to prevent recurrent diverticulitis, and there have been some randomized clinical trials (RCTs). However, the efficacy results for secondary prevention in uncomplicated diverticulitis differed across studies. Our aim was to clarify the efficacy and safety of 5-ASA agents in the prevention of recurrent diverticulitis. We searched MEDLINE, EMBASE, Web of Science, and the Cochrane library with no language restrictions. Two reviewers independently assessed and selected RCTs. The data were pooled using a random effect model and were presented in the pooled risk ratio (RR) and 95% confidence interval (CI). Cochrane's Q and I-squared statistics were used to assess heterogeneity. The protocol was registered at PROSPERO. Seven articles with eight RCTs from 329 potentially relevant articles were included. 5-ASA agents were not superior to controls in preventing recurrent diverticulitis (RR 0.86, 95% CI 0.63 to 1.17, I 2  = 60%) and the incidence of adverse events was not different between 5-ASA agents and controls (RR 0.97, 95% CI 0.84 to 1.11, I 2  = 45%). However, some included studies were few in number of participants and substantial risk of bias. 5-aminosalicylic acid agents were not associated with prevention of recurrent diverticulitis. © 2017 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

  20. Resveratrol modulates cytokine-induced Jak/STAT activation more efficiently than 5-aminosalicylic acid: an in vitro approach.

    Directory of Open Access Journals (Sweden)

    Diana Serra

    Full Text Available Many advances have been recently made focused on the valuable help of dietary polyphenols in chronic inflammatory diseases. On the other hand, current treatment options for intestinal bowel disease patients are unsatisfying and, for this reason, it is estimated that many patients use dietary supplements to achieve extra benefits.The aim of this work was to analyze under a mechanistic perspective the anti-inflammatory potential of resveratrol, a natural polyphenolic compound, and to compare it with a pharmaceutical agent, 5-aminosalicylic acid, using the intestinal HT-29 cell line, as a cellular model.In the present study, HT-29 colon epithelial cells were pre-treated with 25 µM resveratrol and/or 500 µM 5-aminosalicylic acid and then exposed to a combination of cytokines (IL-1α, TNF-α, IFN-γ for a certain period of time. Our data showed that resveratrol, used in a concentration 20 times lower than 5-aminosalicylic acid, was able to significantly reduce NO and PGE2 production, iNOS and COX-2 expression and reactive oxidant species formation induced by the cytokine challenge. However, as already verified with 5-aminosalicylic acid, in spite of not exhibiting any effect on IkB-α degradation, resveratrol down-regulated JAK-STAT pathway, decreasing the levels of activated STAT1 in the nucleus. Additionally, resveratrol decreased the cytokine-stimulated activation of SAPK/JNK pathway but did not counteract the cytokine-triggered negative feedback mechanism of STAT1, through p38 MAPK.Taken together, our results show that resveratrol may be considered a future nutraceutical approach, promoting remission periods, limiting the inflammatory process and preventing colorectal cancer, which is common in these patients.

  1. Antioxidant effect of vitamin E and 5-aminosalicylic acid on acrylamide induced kidney injury in rats

    Directory of Open Access Journals (Sweden)

    Nisreen A. Rajeh

    2017-02-01

    Full Text Available exposure of acrylamide and to study the protective effect of 5-Aminosalicylic acid (5-ASA and Vitamin E (vit-Eon Acrylamide (ACR induced renal toxicity. Methods: This study was conducted at King Fahad Medical Research Centre, King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia, between August and November 2015. A total of 49 adult Wistar rats (250 ± 20g aged 60 days were kept in a controlled environment and used in the present study. The rats were divided into 7 groups (control, ACR alone, ACR+5-ASA, ACR+vit-E, ACR+ASA+vit-E, vit-E alone, and ASA alone. After 5 days of ACR oral gavage treatment, the rats were observed for 24 hours then killed. Histopathology for the kidney and lactate dehydrogenase assay were carried out. Results: Acrylamide produced significant pathological changes in the kidney with acute tubular necrosis in the distal tubules that could be reversed by concomitant injection of rat with 5-ASA. Together with vitamin E, 5-ASA, showed maximum renal protection. No statistically significant difference was observed in either body weights or lactate dehydrogenase activity of ACR treated rats. Conclusion: Acrylamide exposure leads to adverse clinical pathologies of renal tubules, which were reversed by a concomitant treatment with 5-ASA and vitamin-E

  2. Antioxidant effect of vitamin E and 5-aminosalicylic acid on acrylamide induced kidney injury in rats

    Science.gov (United States)

    Rajeh, Nisreen A.; Al-Dhaheri, Najlaa M.

    2017-01-01

    Objectives: To explore renal toxicity caused by sub-acute exposure of acrylamide and to study the protective effect of 5-Aminosalicylic acid (5-ASA) and Vitamin E (vit-E)on Acrylamide (ACR) induced renal toxicity. Methods: This study was conducted at King Fahad Medical Research Centre, King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia, between August and November 2015. A total of 49 adult Wistar rats (250 ± 20g) aged 60 days were kept in a controlled environment and used in the present study. The rats were divided into 7 groups (control, ACR alone, ACR+5-ASA, ACR+vit-E, ACR+ASA+vit-E, vit-E alone, and ASA alone). After 5 days of ACR oral gavage treatment, the rats were observed for 24 hours then killed. Histopathology for the kidney and lactate dehydrogenase assay were carried out. Results: Acrylamide produced significant pathological changes in the kidney with acute tubular necrosis in the distal tubules that could be reversed by concomitant injection of rat with 5-ASA. Together with vitamin E, 5-ASA, showed maximum renal protection. No statistically significant difference was observed in either body weights or lactate dehydrogenase activity of ACR treated rats. Conclusion: Acrylamide exposure leads to adverse clinical pathologies of renal tubules, which were reversed by a concomitant treatment with 5-ASA and vitamin-E PMID:28133684

  3. Expanding applications: the potential usage of 5-aminosalicylic acid in diverticular disease.

    Science.gov (United States)

    Tursi, Antonio; Joseph, Raymond E; Streck, Paul

    2011-11-01

    Diverticular disease is a common bowel condition, the pathogenesis of which is incompletely understood. Acute exacerbations of diverticular disease usually require dietary changes, antibiotic therapy, and may necessitate urgent surgery. Approximately 25-33% of patients experience symptomatic and acute inflammatory disease recurrence, suggesting that current long-term management is inadequate. Because inflammatory complications of diverticular disease, including diverticulitis, are similarities to inflammatory bowel diseases, evidence suggests that patients may respond to anti-inflammatory therapies used in these conditions. Here, we explore the rationale and evidence for use of inflammatory bowel disease treatment, namely 5-aminosalicylic acid (5-ASA; mesalamine), in diverticular disease, and review clinical data on the efficacy of mesalamine either alone or in combination with other agents for the treatment of diverticular disease. PubMed and conference abstracts were searched for clinical studies examining the use of mesalamine in treating diverticular disease. Studies were evaluated for treatment efficacy in symptom reduction, recurrence prevention, or improving quality of life. The results of our search suggest that single-agent mesalamine can reduce diverticular disease symptoms and improve quality of life more effectively than antibiotic treatment alone. Mesalamine in combination with antibiotics can also reduce symptoms and improve quality of life with greater efficacy than either treatment alone. Combining mesalamine and probiotics treatments may reduce recurrent attacks of diverticular disease. Further randomized, well-controlled studies are required for validation; however, it seems that mesalamine is an important agent in future diverticular disease management.

  4. 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

    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......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...... dose of 5-ASA into mercapturic acids of 5-ASA, when 1 g of 5-ASA was ingested. In spite of the low detection limits, none of the mercapturic acid conjugates was detected in the urine from persons treated with 5-ASA....

  5. Medical Management of Ulcerative Colitis with a Specific Focus on 5-Aminosalicylates

    Directory of Open Access Journals (Sweden)

    Hugh James Freeman

    2012-01-01

    Full Text Available Medical management of ulcerative colitis has continued to evolve over more than half of a century. Perhaps, the important advance was the development of sulfasalazine, a drug initially used for the treatment of inflammatory joint disease and only later in the treatment of inflammatory bowel disease. Sulfasalazine was a combination designer drug consisting of sulfapyridine, a sulfa-containing antibacterial agent, and 5-amino-salicylate (5-ASA, an anti-inflammatory agent. Its value appeared to be its ability to target a therapeutic concentration of the 5-ASA component of the medication primarily in the colon, largely avoiding proximal small intestinal absorption. With increasing experience, however, it also became evident that many patients treated with sulfasalazine developed intolerance to the drug and, in some rare instances, serious drug-induced hypersensitivity reactions, largely to the sulfapyridine portion. As a result, a number of alternative forms of delivery of 5-ASA were developed consisting of either a similar sulfasalazine-like prodrug formulation requiring luminal destruction of an azo-bond releasing the 5-ASA or a pH-dependent 5-ASA packaging system that permitted release in the distal intestine, particularly in the colon. As a result, 5-ASA—containing medications continue to provide a valuable management tool for remission induction in mildly to moderately active distal or extensive ulcerative colitis, an additional option for more severely symptomatic disease and value for maintenance therapy with limited potential side effects, even with long-term use.

  6. Medical management of ulcerative colitis with a specific focus on 5-aminosalicylates.

    Science.gov (United States)

    Freeman, Hugh James

    2012-01-01

    Medical management of ulcerative colitis has continued to evolve over more than half of a century. Perhaps, the important advance was the development of sulfasalazine, a drug initially used for the treatment of inflammatory joint disease and only later in the treatment of inflammatory bowel disease. Sulfasalazine was a combination designer drug consisting of sulfapyridine, a sulfa-containing antibacterial agent, and 5-amino-salicylate (5-ASA), an anti-inflammatory agent. Its value appeared to be its ability to target a therapeutic concentration of the 5-ASA component of the medication primarily in the colon, largely avoiding proximal small intestinal absorption. With increasing experience, however, it also became evident that many patients treated with sulfasalazine developed intolerance to the drug and, in some rare instances, serious drug-induced hypersensitivity reactions, largely to the sulfapyridine portion. As a result, a number of alternative forms of delivery of 5-ASA were developed consisting of either a similar sulfasalazine-like prodrug formulation requiring luminal destruction of an azo-bond releasing the 5-ASA or a pH-dependent 5-ASA packaging system that permitted release in the distal intestine, particularly in the colon. As a result, 5-ASA-containing medications continue to provide a valuable management tool for remission induction in mildly to moderately active distal or extensive ulcerative colitis, an additional option for more severely symptomatic disease and value for maintenance therapy with limited potential side effects, even with long-term use.

  7. 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

    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....... In the 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...

  8. 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

    resulted in the formation of a single oxidation product of 5-ASA. This product was similar to, but not identical to any of the products identified in faeces from patients receiving 5-ASA. Oxygen radical-mediated oxidation of 5-ASA gave several products, different from the products isolated. Finally......The formation of three oxidant-derived products of 5-aminosalicylic acid (5-ASA) in vivo was demonstrated in patients with active ulcerative colitis as well as is healthy subjects. The products were isolated from faeces by preparative HPLC and their chemical structures were found to be oxidation...... 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...

  9. 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.

  10. Safety of 5-Aminosalicylic Acid Derivatives in Patients with Sensitivity to Acetylsalicylic Acid and Nonsteroidal Anti-inflammatory Drugs.

    Science.gov (United States)

    Poh, Jennifer; Knowles, Sandra

    2014-01-01

    One of the cornerstones of the management of inflammatory bowel disease is the use of 5-aminosalicylic acid (5-ASA) compounds for treatment of flares and as maintenance therapy during remission. There are concerns about using 5-ASA in patients with a history of hypersensitivity to acetylsalicylic acid (ASA). To assess the literature with respect to the safety of 5-ASA compounds in patients with documented sensitivity to ASA or nonsteroidal anti-inflammatory drugs (NSAIDs). A literature search was conducted in the MEDLINE and Embase databases, using various search terms, including "aminosalicylic acids", "non-steroidal anti-inflammatory agents," "hypersensitivity", and "allergy". The search was limited to articles (of any study design) published in English. Abstracts, full articles, and reference lists from retrieved articles were assessed to identify further relevant literature. Of 485 citations identified in the initial search, 4 case reports were relevant to the study objective and were analyzed in detail. Three of the case reports described the successful use of 5-ASA compounds in patients with prior sensitivity to ASA or an NSAID. The fourth report described a reaction to 5-ASA in a patient who had previously tolerated ASA. All of the reports were limited by lack of investigation into the validity of the reported sensitivity to ASA or 5-ASA. There is a dearth of evidence demonstrating cross-reactivity between ASA or NSAID and 5-ASA. This lack of information may relate to the mechanism of action of 5-ASA. This agent controls inflammation by inhibiting prostaglandin E2 and leukotrienes. In contrast, ASA-induced or NSAID-induced reactions are due to inhibition of the cycloxygenase-1 enzyme and subsequent release of histamine and synthesis of leukotrienes. Further reports describing the safety of 5-ASA use in patients with sensitivity to ASA or NSAIDs are needed before safety in this situation can be definitively determined. In patients with sensitivity to ASA or

  11. 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.

  12. Synthesis and evaluation of mutual azo prodrug of 5-aminosalicylic acid linked to 2-phenylbenzoxazole-2-yl-5-acetic acid in ulcerative colitis

    Directory of Open Access Journals (Sweden)

    Jilani JA

    2013-07-01

    Full Text Available Jamal A Jilani,1 Maha Shomaf,2 Karem H Alzoubi3 1Department of Medicinal Chemistry and Pharmacognosy, Jordan University of Science and Technology, Irbid, Jordan; 2Department of Pathology, Jordan University, Amman, Jordan; 3Department of Clinical Pharmacy, Jordan University of Science and Technology, Irbid, Jordan Abstract: In this study, the syntheses of 4-aminophenylbenzoxazol-2-yl-5-acetic acid, (an analogue of a known nonsteroidal anti-inflammatory drug [NSAID] and 5-[4-(benzoxazol-2-yl-5-acetic acidphenylazo]-2-hydroxybenzoic acid (a novel mutual azo prodrug of 5-aminosalicylic acid [5-ASA] are reported. The structures of the synthesized compounds were confirmed using infrared (IR, hydrogen-1 nuclear magnetic resonance (1H NMR, and mass spectrometry (MS spectroscopy. Incubation of the azo compound with rat cecal contents demonstrated the susceptibility of the prepared azo prodrug to bacterial azoreductase enzyme. The azo compound and the 4-aminophenylbenzoxazol-2-yl-5-acetic acid were evaluated for inflammatory bowel diseases, in trinitrobenzenesulfonic acid (TNB-induced colitis in rats. The synthesized diazo compound and the 4-aminophenylbenzoxazol-2-yl-5-acetic acid were found to be as effective as 5-aminosalicylic acid for ulcerative colitis. The results of this work suggest that the 4-aminophenylbenzoxazol-2-yl-5-acetic acid may represent a new lead for treatment of ulcerative colitis. Keywords: benzoxazole acetic acid, azo prodrug, colon drug delivery

  13. The Importance of Wireless Capsule Endoscopy for Research into the Intestin al Absorption Window of 5-Aminosalicylic Acid in Experimental Pigs.

    Science.gov (United States)

    Kvetina, Jaroslav; Tacheci, Ilja; Nobilis, Milan; Kopacova, Marcela; Kunes, Martin; Bures, Jan

    2017-01-01

    Absorption windows in particular segments of the small intestine can contribute to the development of orally administered drug formulations and can limit the bioavailability of released compounds. The aim of this study was to evaluate use of wireless capsule enteroscopy regarding the disintegration kinetic process of tablets in the small intestine and its comparison with the levels of the model drug (5- aminosalicylic acid; 5-ASA), and its majority metabolite (N-acetyl-5-aminosalicylic acid; N-acetyl-5-ASA) in blood plasma. Tablets were endoscopically introduced into the duodenum and their disintegration was monitored using wireless capsule enteroscopy in anaesthetised pigs. In parallel, blood plasma time profiles of the model drug (5-ASA) released from tablets and its metabolite (N-acetyl-5-ASA) were detected. The disintegration of tablets was evident in the proximal jejunum (until the 90-minute mark) and culminated at the 3rd hour. The maximum plasmatic concentration of 5-ASA was reached at the 3rd hour and in the case of its metabolite (N-acetyl-5-ASA) at the 4th hour. The study demonstrated the advantage of combination of wireless capsule enteroscopy and bioanalytical determination of pharmacokinetic parameters in an animal experiment to localise the disintegration site of solid dosage form and following kinetics of intestinal absorption of the released active agent. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  14. Sodium Para-aminosalicylic Acid Protected Primary Cultured Basal Ganglia Neurons of Rat from Manganese-Induced Oxidative Impairment and Changes of Amino Acid Neurotransmitters.

    Science.gov (United States)

    Li, Shao-Jun; Li, Yong; Chen, Jing-Wen; Yuan, Zong-Xiang; Mo, Yu-Huan; Lu, Guo-Dong; Jiang, Yue-Ming; Ou, Chao-Yan; Wang, Fang; Huang, Xiao-Wei; Luo, Yi-Ni; Ou, Shi-Yan; Huang, Yan-Ni

    2016-04-01

    Manganese (Mn), an essential trace metal for protein synthesis and particularly neurotransmitter metabolism, preferentially accumulates in basal ganglia. However, excessive Mn accumulation may cause neurotoxicity referred to as manganism. Sodium para-aminosalicylic acid (PAS-Na) has been used to treat manganism with unclear molecular mechanisms. Thus, we aim to explore whether PAS-Na can inhibit Mn-induced neuronal injury in basal ganglia in vitro. We exposed basal ganglia neurons with 50 μM manganese chloride (MnCl2) for 24 h and then replaced with 50, 150, and 450 μM PAS-Na treatment for another 24 h. MnCl2 significantly decreased cell viability but increased leakage rate of lactate dehydrogenase and DNA damage (as shown by increasing percentage of DNA tail and Olive tail moment). Mechanically, Mn reduced glutathione peroxidase and catalase activity and interrupted amino acid neurotransmitter balance. However, PAS-Na treatment reversed the aforementioned Mn-induced toxic effects. Taken together, these results showed that PAS-Na could protect basal ganglia neurons from Mn-induced neurotoxicity.

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

    Directory of Open Access Journals (Sweden)

    Alireza Garjani

    2004-06-01

    Full Text Available 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 hour prior to induction of colitis with sulfasalazin (300 mg/kg, azo compounds I, II, III and polyethylene glycol conjugates of azo compounds II and III in doses which had the same amount of 5-ASA as sulfasalazin contains. The colonic damage was examined 24 hours later and characterized by gross microscopic injury and colonic edema. Among prodrugs only azo compound III (215 mg/kg produced a significant (p<0.01 protective effect against colonic injury comparable with sulfasalazin. Doubling the dose (430 mg/kg showed more anti-colitis effects. Polyethylene glycol conjugate of azo compounds II and III also showed reduction in the extent of the cell death and tissue disorganization similar to sulfasalazin. While neither sulfasalazin, nor azo compound II and its PEG polymer produced anti-edema effects, both azo compound III and its PEG polymer decreased colon edema significantly (p<0.05. Histological examinations also indicated a marked reduction in tissue injury and inhibition in neutrophil infiltration in rats treated with azo compound III and PEG conjugates of azo compounds II and III. Results of this investigation provide experimental evidence supporting new cytoprotective, anti-inflammatory and anti-edema properties of the azo derivatives of 5-ASA and their PEGylated prodrugs.

  16. Electro-Fenton oxidation of para-aminosalicylic acid: degradation kinetics and mineralization pathway using Pt/carbon-felt and BDD/carbon-felt cells.

    Science.gov (United States)

    Oturan, Nihal; Aravindakumar, Charuvila T; Olvera-Vargas, Hugo; Sunil Paul, Mathew M; Oturan, Mehmet A

    2017-05-31

    Degradation of a widely used antibiotic, the para-aminosalicylic acid (PAS), and mineralization of its aqueous solution was investigated by electro-Fenton process using Pt/carbon-felt and boron-doped diamond (BDD)/carbon-felt cells with applied currents in the range of 50-1000 mA. This process produces the highly oxidizing species, the hydroxyl radical ( • OH), which is mainly responsible for the oxidative degradation of PAS. An absolute rate constant of 4.17 × 10 9  M -1  s -1 for the oxidation of PAS by ● OH was determined from the competition kinetics method. Degradation rate of PAS increased with current reaching an optimal value of 500 mA with complete disappearance of 0.1 mM PAS at 7 min using Pt/carbon-felt cell. The optimum degradation rate was reached at 300 mA for BDD/carbon-felt. The latter cell was found more efficient in total organic carbon (TOC) removal where a complete mineralization was achieved within 240 min. A multi-step mineralization process was observed with the formation of a number of aromatic intermediates, short-chain carboxylic acids, and inorganic ions. Eight aromatic intermediate products were identified using both LC-Q-ToF-MS and GC-MS techniques. These products were the result of hydroxylation of PAS followed by multiple additions of hydroxyl radicals to form polyhydroxylated derivatives. HPLC and GC/MS analyses demonstrated that extended oxidation of these intermediate products conducted to the formation of various short-chain carboxylic acids. Prolonged electrolysis resulted in a complete mineralization of PAS with the evolution of inorganic ions such as NO 3 - and NH 4 + . Based on the identified intermediates, carboxylic acids and inorganic ions, a plausible mineralization pathway is also deduced. The remarkably high degree of mineralization (100%) achieved by the present EF process highlights the potential application of this technique to the complete removal of salicylic acid-based pharmaceuticals from

  17. 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)

    Yang, Yifei; Mu, Shaolin

    2013-01-01

    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

  18. Comparison of anti-inflammatory activities of an anthocyanin-rich fraction from Portuguese blueberries (Vaccinium corymbosum L. and 5-aminosalicylic acid in a TNBS-induced colitis rat model.

    Directory of Open Access Journals (Sweden)

    Sónia R Pereira

    Full Text Available Despite the actual therapeutic approaches for inflammatory bowel disease (IBD, efficient and secure alternative options remain a research focus. In this context, anthocyanins seem promising natural anti-inflammatory agents, but their action mechanisms and efficacy as compared with established drugs still require more clarification. The main aim of this study was to compare the anti-inflammatory action of a chemically characterized anthocyanin-rich fraction (ARF, obtained from Portuguese blueberries (Vaccinium corymbosum L., with that of 5-aminosalicylic acid (5-ASA, a first-line drug in IBD, in a 2,4,6-trinitrobenzenesulfonic acid (TNBS-induced colitis rat model. Such fraction showed a high content and great molecular diversity of anthocyanins, with malvidin-3-galactoside and petunidin-3-arabinoside in the highest concentrations. After daily administration by intragastric infusion for 8 days, ARF, at a molar anthocyanin concentration about 30 times lower than 5-ASA, showed a higher effectiveness in counteracting the intestinal inflammation, as assessed by i body weight variation and colon damage score, ii reduction in leukocyte infiltration, iii increase in antioxidant defenses and iv by downregulation of inducible nitric oxide synthase (iNOS and cyclooxygenase-2 (COX-2 in colon tissue homogenates. The strong inhibition of COX-2 expression seems to be a crucial anti-inflammatory mechanism common to both ARF and 5-ASA, but the additional higher abilities of anthocyanins to downregulate iNOS and to decrease leukocytes infiltration and to increase antioxidant defenses in colon may account for the much higher anti-inflammatory action of anthocyanins. These data may contribute to the development of a promising natural approach in IBD management.

  19. 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].

  20. Sodium P-Aminosalicylic Acid Improved Manganese-Induced Learning and Memory Dysfunction via Restoring the Ultrastructural Alterations and γ-Aminobutyric Acid Metabolism Imbalance in the Basal Ganglia.

    Science.gov (United States)

    Ou, Chao-Yan; Luo, Yi-Ni; He, Sheng-Nan; Deng, Xiang-Fa; Luo, Hai-Lan; Yuan, Zong-Xiang; Meng, Hao-Yang; Mo, Yu-Huan; Li, Shao-Jun; Jiang, Yue-Ming

    2017-03-01

    Excessive intake of manganese (Mn) may cause neurotoxicity. Sodium para-aminosalicylic acid (PAS-Na) has been used successfully in the treatment of Mn-induced neurotoxicity. The γ-aminobutyric acid (GABA) is related with learning and memory abilities. However, the mechanism of PAS-Na on improving Mn-induced behavioral deficits is unclear. The current study was aimed to investigate the effects of PAS-Na on Mn-induced behavioral deficits and the involvement of ultrastructural alterations and γ-aminobutyric acid (GABA) metabolism in the basal ganglia of rats. Sprague-Dawley rats received daily intraperitoneally injections of 15 mg/kg MnCl 2 .4H 2 O, 5d/week for 4 weeks, followed by a daily back subcutaneously (sc.) dose of PAS-Na (100 and 200 mg/kg), 5 days/week for another 3 or 6 weeks. Mn exposure for 4 weeks and then ceased Mn exposure for 3 or 6 weeks impaired spatial learning and memory abilities, and these effects were long-lasting. Moreover, Mn exposure caused ultrastructural alterations in the basal ganglia expressed as swollen neuronal with increasing the electron density in the protrusions structure and fuzzed the interval of neuropil, together with swollen, focal hyperplasia, and hypertrophy of astrocytes. Additionally, the results also indicated that Mn exposure increased Glu/GABA values as by feedback loops controlling GAT-1, GABA A mRNA and GABA A protein expression through decreasing GABA transporter 1(GAT-1) and GABA A receptor (GABA A ) mRNA expression, and increasing GABA A protein expression in the basal ganglia. But Mn exposure had no effects on GAT-1 protein expression. PAS-Na treatment for 3 or 6 weeks effectively restored the above-mentioned adverse effects induced by Mn. In conclusion, these findings suggest the involvement of GABA metabolism and ultrastructural alterations of basal ganglia in PAS-Na's protective effects on the spatial learning and memory abilities.

  1. Controlled Release of 5-Aminosalicylic Acid (5-ASA from New Biodegradable Polyurethanes

    Directory of Open Access Journals (Sweden)

    El-Refaie Kenawy

    2010-03-01

    Full Text Available Segmented polyurethanes containing azo aromatic groups in the main chain were synthesized by reaction of 3,3'-azobis(6-hydroxybenzoic acid (ABHB, 5-[4-(hydroxyphenylazo] salicylic acid (HPAS, and 5-[1-hydroxynaphthylazo] salicylic acid (HNAS with hexamethylenediisocyanate (HDI. All synthesized monomers and polymers were characterized by elemental analysis, FTIR, 1H-NMR spectra, TGA and DSC analysis. All the synthesized azo polymers showed good thermal stability and the onset decomposition temperature of all these polymers was found to be above 195 ºC under nitrogen atmosphere.The release of 5-ASA under physiological conditions (pH = 7.8 and pH = 1.5 was investigated at body temperature (37 ºC. The release rate of 5-ASA increased with increasing pH (i.e., 7.8 > 1.5.

  2. 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

    of 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...... education and training through a Web-based program (www.constant-care.dk) seems to be a feasible concept for increasing patients' ability to self-initiate treatment and increase the level of disease-specific knowledge. Relevant adjustment of the concept was implemented. The final outcome of the 'Constant......BACKGROUND: Ulcerative colitis (UC) is a lifelong disease with increasing incidence. UC requires frequent outpatient clinic visits and continuous medical treatment. Web-based self-management in other chronic diseases influences disease course, and increases self-adherence, compliance and quality...

  3. Synthesis of New Fluorine Substituted Heterocyclic Nitrogen Systems Derived from p-Aminosalicylic Acid as Antimycobacterial Agents

    Directory of Open Access Journals (Sweden)

    Mohammed Saleh I. T. Makki

    2013-01-01

    Full Text Available Some new fluorine substituted heterocyclic nitrogen systems 2–17 have been synthesized from ring closure reactions of substituted p-amino salicylic acids (PAS. The Schiffs base of PAS was cyclized with chloroacetyl chloride and mercaptoacetic acid to give azetidinone 2, thiazolidinone 3, and spiro-fluoroindolothiazoline-dione 10. However, PAS when reacted directly with 4-fluorobenzoyl chloride and 5-oxazolinone yielded derivatives 4, 5, and 7. Aminomethylation of PAS using formaldehyde and piperidine or piperazine formed N-alkyl and N,N′-dialkyl derivatives (11 and 12 respectively upon fluorinated benzoylation gave compounds 13 and 14. Similarly, treatment of PAS with thiosemicarbazide 15 and subsequent cyclization with diethyl oxalate yielded the fluorinated heterocycle 17. The structures of the fluorinated heterocyclic systems have been established on the basis of elemental analysis, 1H NMR, 13C NMR, and MS spectral data. Some of the targets exhibited a high inhibition towards Mycobacterium strain with favorable log P values.

  4. 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.

  5. 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 : probiotics * lipopolysacharide * drug transport Subject RIV: FR - Pharmacology ; Medidal Chemistry; FR - Pharmacology ; Medidal Chemistry (MBU-M) Impact factor: 0.875, year: 2013

  6. short communication synthesis, characterization and radical ...

    African Journals Online (AJOL)

    Preferred Customer

    ABSTRACT. 5-Aminosalicylic acid is an anti-inflammatory drug used in the treatment of inflammatory bowel diseases including ulcerative colitis and Crohn's disease. Due to its rapid and extensive absorption in the upper gastro-intestinal tract, substantial amount of 5-aminosalicylic acid is already lost before reaching the site ...

  7. 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....

  8. Untitled

    Indian Academy of Sciences (India)

    aminOSalicylic acid (PAS) has attracted wide interest, directed towards its synthesis by different methods,' estimation, pharmacology, preparation of derivatives and the study of compounds analogous to it. With a view to obtain drugs more potent ...

  9. IBD medications during pregnancy and lactation

    DEFF Research Database (Denmark)

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

    2013-01-01

    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 preparations...

  10. 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. Copyright © 2016 Elsevier Ltd. All rights reserved.

  11. Electrochemical and Spectroscopic Characterization of Aluminium(III)-para-methyl-meso-tetraphenylporphyrin Complexes Containing Substituted Salicylates as Axial Ligands

    OpenAIRE

    Gauri D. Bajju; Deepmala; Sunil Kumar Anand; Sujata Kundan; Narinder Singh

    2013-01-01

    A series of aluminium(III)-p-methyl-meso-tetraphenylporphyrin (p-CH3TPP-Al(III)) containing axially coordinated salicylate anion [p-CH3TPP-Al-X)], where X = salicylate (SA), 4-chlorosalicylate (4-CSA), 5-chlorosalicylate (5-CSA), 5-flourosalicylate (5-FSA), 4-aminosalicylate (4-ASA), 5-aminosalicylate (5-ASA), 5-nitrosalicylate (5-NSA), and 5-sulfosalicylate (5-SSA), have been synthesized and characterized by various spectroscopic techniques including ultraviolet-visible (UV-vis), infrared (I...

  12. New Spectrophotometric Methods for the Determination of p ...

    African Journals Online (AJOL)

    Purpose: To develop a new spectrophotometric method with improved sensitivity and at higher wavelength for the determination of p-aminosalicylic acid in tablets. Methods: Two simple and sensitive spectrophotometric methods (methods A and B) were developed using p-dimethylaminobenzaldehyde (DAB), and ...

  13. High mucosal healing rates in 5-ASA-treated ulcerative colitis patients: results of a meta-analysis of clinical trials

    NARCIS (Netherlands)

    Romkens, T.E.H.; Kampschreur, M.T.; Drenth, J.P.H.; Oijen, M.G.H. van; de Jong, D.J.

    2012-01-01

    BACKGROUND: Recently, mucosal healing (MH) is regarded as an important treatment goal in ulcerative colitis (UC). 5-Aminosalicylates (5-ASA) are the standard treatment in mild-to-moderate UC, but the effect on MH is less known. The aim of this study was to systematically review the medical

  14. 5-ASA - colorectal cancer - cell death : an intriguing threesome

    NARCIS (Netherlands)

    Koelink, Pim Johan

    2010-01-01

    Colorectal cancer (CRC) is a complicated disease in which both genetic pre-desposition and environmental factors are important. Patients with inflammatory bowel disease (IBD) have an increased risk of developing CRC, and it is believed that treatment of IBD patients with 5-Aminosalicylic acid

  15. Nanoformulations and Clinical Trial Candidates as Probably ...

    African Journals Online (AJOL)

    Hearing loss, tinnitus, eosinophilia, transient proteinuria, and nitrogen retention. Para-aminosalicylic acid. 10-12 g. Dihydropteroate synthase. Inhibits folate biosynthesis. GIT disturbance, High fever Hypersensitivity, and hematological abnormalities. Cycloserine. 15-20 mg/kg. (≤ 1 g). D-alanine racemase and ligase.

  16. Simultaneous assessments of exocrine pancreatic function by cholesteryl-[14C]octanoate breath test and measurement of plasma p-aminobenzoic acid

    NARCIS (Netherlands)

    Bruno, M. J.; Hoek, F. J.; Delzenne, B.; van Leeuwen, D. J.; Schteingart, C. D.; Hofmann, A. F.; Tytgat, G. N.

    1995-01-01

    Two noninvasive tests for assessing pancreatic exocrine function, the cholesteryl-[14C]octanoate breath test and the HPLCN-benzoyl-tyrosyl-p-aminobenzoic acid/p-aminosalicylic acid (NBT-PABA/PAS) test, were simultaneously performed in nine patients with pancreatic exocrine insufficiency due to

  17. mwnts composite film modified glassy carbon electrode

    African Journals Online (AJOL)

    Preferred Customer

    ABSTRACT: A poly p-aminosalicylic acid (Poly(p-ASA)) and multiwall carbon nanotubes. (MWCNTs) composite modified glassy carbon (GC) electrode was constructed by casting the MWNTs on the GC electrode surface followed by electropolymerization of the p-ASA on the MWCNTs/GCE. The electrochemical behaviours ...

  18. Electrochemical and Spectroscopic Characterization of Aluminium(III-para-methyl-meso-tetraphenylporphyrin Complexes Containing Substituted Salicylates as Axial Ligands

    Directory of Open Access Journals (Sweden)

    Gauri D. Bajju

    2013-01-01

    Full Text Available A series of aluminium(III-p-methyl-meso-tetraphenylporphyrin (p-CH3TPP-Al(III containing axially coordinated salicylate anion [p-CH3TPP-Al-X], where X = salicylate (SA, 4-chlorosalicylate (4-CSA, 5-chlorosalicylate (5-CSA, 5-flourosalicylate (5-FSA, 4-aminosalicylate (4-ASA, 5-aminosalicylate (5-ASA, 5-nitrosalicylate (5-NSA, and 5-sulfosalicylate (5-SSA, have been synthesized and characterized by various spectroscopic techniques including ultraviolet-visible (UV-vis, infrared (IR spectroscopy, proton nuclear magnetic resonance (1H NMR spectroscopy, 13C NMR, and elemental analysis. A detailed study of electrochemistry of all the synthesized compounds has been done to compare their oxidation and reduction mechanisms and to explain the effect of axial coordination on their redox properties.

  19. Drug-induced eosinophilic pneumonia in a patient with Crohn's disease: diagnosis and treatment using fraction of exhaled nitric oxide

    Directory of Open Access Journals (Sweden)

    Jina Yeo

    2017-10-01

    Full Text Available Oral 5-aminosalicylic acid agents (mesalazine and sulfasalazine and azathioprine are the mainstays of treatment for inflammatory bowel disease. Reports of pulmonary toxicity induced by oral 5-aminosalicylic acid agents or azathioprine in patients with inflammatory bowel disease are very rare; to date, only 38 cases have been reported worldwide. We, herein, report a case involving a 26-year-old man who was diagnosed with eosinophilic pneumonia after using mesalazine and azathioprine for the treatment of Crohn's disease and recovered after treatment. We also found that the fraction of exhaled nitric oxide level was elevated in this patient. After treatment, the fraction of exhaled nitric oxide level decreased and the symptoms improved. The present case shows that fraction of exhaled nitric oxide is related to the disease activity and treatment effectiveness of druginduced eosinophilic pneumonia.

  20. Innovative therapeutics for inflammatory bowel disease

    OpenAIRE

    Yamamoto-Furusho, Jesus K

    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 le...

  1. Investigation of neighbour group effects in releasing of 5-aminosicylic acid from acrylic polymeric prodrugs

    OpenAIRE

    Babzadeh, Mirzaagha; Naserian, Sona

    2011-01-01

    Acrylic-type polymeric systems having degradable ester bonds linked to 5-ASA were synthesized and evaluated az materials for drug delivery. prodrugs. 5-aminosalicylic acid (5-ASA) was linked to 2-hydroxypropyl methacrylate by carbonyldiimidazole (CDI) to obtain metachryloyloxy propyl 5-amino salicylate. The resulting acrylic derivative of 5-ASA was copolymerized with 2-hydroxyethyl methacrylat, methyl metacrylat and 2-ethylh hexyl acrylate (in 1:3 mole ratio) by free radical polymerization me...

  2. Will novel oral formulations change the management of inflammatory bowel disease?

    DEFF Research Database (Denmark)

    Nielsen, Ole Haagen; Seidelin, Jakob Benedict; Ainsworth, Mark Andrew

    2016-01-01

    INTRODUCTION: The traditional management of inflammatory bowel disease (IBD) with sulphasalazine/5-aminosalicylic acid, glucocorticoids and immunomodulators (i.e., thiopurines and methotrexate) was nearly two decades ago extended with intravenously or subcutaneously administered biologics (i...... the current approaches with promising new oral drugs with distinct modes of action, including: the Janus kinase inhibitors (i.e., tofacitinib, filgotinib and peficitinib); the immunomodulatory drug (laquinimod); a small α4 antagonist (AJM300); agonists for sphingosine-phosphate receptors (i.e., ozanimod, APD...

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

    Directory of Open Access Journals (Sweden)

    Kamlesh V. Patel

    2009-01-01

    Full Text Available 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.

  4. 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....

  5. 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.

  6. Effect of methylcellulose on the formation and drug release behavior of silk fibroin hydrogel.

    Science.gov (United States)

    Park, Cho Hee; Jeong, Lim; Cho, Donghwan; Kwon, Oh Hyeong; Park, Won Ho

    2013-10-15

    In this study, methylcellulose (MC) was used to control the gelation time of silk fibroin (SF) aqueous solution. The gelation time was measured using a Vibro Viscometer at 50 °C. Fourier transform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM), and a texture meter were used to investigate the effect of MC on the hydrogelation of SF solution. SF/MC hydrogels could be formed by the addition of MC, although their gelation time was increased with MC content. To examine the conformational change of SF/MC hydrogels, time-resolved FT-IR spectra were obtained at constant temperature using a custom-made IR chamber. From FT-IR spectra focused on the amide I peak position, the transition of SF molecules in SF/MC solution from a random coil to a β-sheet structure was inhibited in the presence of MC molecules. In addition, the drug release of SF/MC hydrogels loaded with 5-aminosalicylic acid was studied in 2-dimensional (2-D) and 3-dimensional (3-D) conditions in vitro. The drug release behavior of SF or SF/MC hydrogels was measured using UV-Vis spectroscopy. The release rate of 5-aminosalicylic acid in SF/MC hydrogel was lower than that of SF hydrogel, which may be closely associated with the hydrophilic interaction between MC and 5-aminosalicylic acid. This approach to controlling the sol-gel transition and the drug release of SF hydrogels by the addition of MC will be useful in the design and tailoring of novel materials for biomedical applications. Copyright © 2013 Elsevier Ltd. All rights reserved.

  7. Management of diverticulosis: what's new?

    Science.gov (United States)

    Elisei, Walter; Brandimarte, Giovanni; Tursi, Antonio

    2017-10-01

    The incidence of diverticulosis and diverticular disease (DD) of the colon, including acute diverticulitis, is increasing worldwide, and becoming a significant burden on national health systems in terms of direct and indirect costs. Thus, significant efforts are now being focused to identify the correct therapeutic approach to treat symptomatic patients and to prevent diverticulitis. Fiber, non-absorbable antibiotics, 5-aminosalicylic acid and probioticsare currently being investigated in this way. Unfortunately, current evidences on the effectiveness of some medical treatment in preventing acute diverticulitis recurrence are still lacking. The effectiveness and the future perspectives of these treatments are discussed herein.

  8. Preventing recurrent acute diverticulitis with pharmacological therapies

    Science.gov (United States)

    2013-01-01

    Acute diverticulitis of the colon represents a significant burden for national health systems, in terms of direct and indirect costs. Past guidelines claimed that recurrent episodes (two or more) of diverticulitis need surgery, but revised guidelines recommend an individualized approach to patients after an attack of acute diverticulitis. For these reasons, conservative treatment has become the preferred choice after an episode of diverticulitis. Thus, significant efforts are now being focused to identify the correct therapeutic approach to prevent diverticulitis relapses. Nonabsorbable antibiotics, 5-aminosalicylic acid and probiotics are currently being investigated in this way. The effectiveness and the future perspectives of these treatments are discussed herein. PMID:24179670

  9. Limited risks of major congenital anomalies in children of mothers with IBD and effects of medications.

    Science.gov (United States)

    Ban, Lu; Tata, Laila Jal; Fiaschi, Linda; Card, Timothy

    2014-01-01

    Concerns persist about the risk of major congenital anomalies in children of women with inflammatory bowel disease (IBD), and whether medication use affects risk. We assessed these risks, and variations in use of medications by women with IBD before, during, and after pregnancy. We accessed data on children born to women 15-45 y old from 1990 through 2010, using a mother-child linked dataset from an electronic database of primary care records containing medical diagnoses, events, and drug prescriptions from across the United Kingdom. We identified pregnant women with IBD, and all prescriptions for 5-aminosalicylates azathioprine/6-mercaptopurine, and corticosteroids were extracted from their primary care records. We calculated risks of major congenital anomaly in children of mothers with and without IBD, and in children exposed or not exposed to 5-aminosalicylates, azathioprine/6-mercaptopurine, or corticosteroids during their first trimester of fetal development. Logistic regression with a generalized estimating equation was used to provide risk estimates adjusted for confounders. We calculated proportions of women taking medications before, during, and after pregnancy and assessed whether cessation was associated with subsequent disease flares. Risks of a major congenital anomaly in 1703 children of mothers with IBD and 384,811 children of mothers without IBD were 2.7% and 2.8%, respectively. This corresponded to an adjusted odds ratio of 0.98 (95% confidence interval [CI], 0.73-1.31). In children of women with IBD, the adjusted odds ratios of a major congenital anomaly associated with drug use were 0.82 (95% CI, 0.42-1.61) for 5-aminosalicylates 0.48 (95% CI, 0.15-1.50) for corticosteroids, and 1.27 (95% CI, 0.48-3.39) for azathioprine/6-mercaptopurine. No increases in heart, limb, or genital anomalies were found in children of women with IBD; 31.2% of women discontinued 5-aminosalicylates and 24.6% discontinued azathioprine/6-mercaptopurine in early pregnancy

  10. Preventing recurrent acute diverticulitis with pharmacological therapies.

    Science.gov (United States)

    Tursi, Antonio

    2013-11-01

    Acute diverticulitis of the colon represents a significant burden for national health systems, in terms of direct and indirect costs. Past guidelines claimed that recurrent episodes (two or more) of diverticulitis need surgery, but revised guidelines recommend an individualized approach to patients after an attack of acute diverticulitis. For these reasons, conservative treatment has become the preferred choice after an episode of diverticulitis. Thus, significant efforts are now being focused to identify the correct therapeutic approach to prevent diverticulitis relapses. Nonabsorbable antibiotics, 5-aminosalicylic acid and probiotics are currently being investigated in this way. The effectiveness and the future perspectives of these treatments are discussed herein.

  11. Natural disease course of Crohn's disease during the first 5 years after diagnosis in a European population-based inception cohort

    DEFF Research Database (Denmark)

    Burisch, Johan; Kiudelis, Gediminas; Kupcinskas, Limas

    2018-01-01

    OBJECTIVE: The Epi-IBD cohort is a prospective population-based inception cohort of unselected patients with inflammatory bowel disease from 29 European centres covering a background population of almost 10 million people. The aim of this study was to assess the 5-year outcome and disease course...... to either stricturing and/or penetrating disease. These rates did not differ between patients from Western and Eastern Europe. However, significant geographic differences were noted regarding treatment: more patients in Western Europe received biological therapy (33%) and immunomodulators (66%) than did...... those in Eastern Europe (14% and 54%, respectively, PEuropean patients received 5-aminosalicylates (90% vs 56%, P

  12. Radiation-induced formation of 8-hydroxy-2'-deoxyguanosine and its prevention by scavengers

    DEFF Research Database (Denmark)

    Fischer-Nielsen, A; Jeding, I B; Loft, S

    1994-01-01

    measured 8-OHdG formation in calf thymus DNA exposed to ionizing radiation under conditions generating either hydroxyl radicals (OH.), superoxide anions (O2-) or both. Additionally, we investigated the relationship between the scavenger effect of the drug 5-aminosalicylic acid (5-ASA) and increasing OH...... and 100 Gy radiation, i.e. within a wide range of OH. exposure, which is useful information considering clinical applications where the exact amount of ROS formed is unknown. Both 5-ASA and ascorbate at low concentrations (

  13. Downstream Processability of Crystal Habit-Modified Active Pharmaceutical Ingredient

    DEFF Research Database (Denmark)

    Pudasaini, Nawin; Upadhyay, Pratik Pankaj; Parker, Christian Richard

    2017-01-01

    Efficient downstream processing of active pharmaceutical ingredients (APIs) can depend strongly on their particulate properties, such as size and shape distributions. Especially in drug products with high API content, needle-like crystal habit of an API may show compromised flowability...... and tabletability, creating significant processability difficulties on a production scale. However, such a habit can be adapted to the needs of downstream processing. To this end, we modified the needle-like crystal habit of the model API 5-aminosalicylic acid (5-ASA). This study reports processability assessment...

  14. 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)

    Williams, C.N.; Haber, G.; Aquino, J.A.

    1987-01-01

    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

  15. 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

    Energy Technology Data Exchange (ETDEWEB)

    Williams, C.N.; Haber, G.; Aquino, J.A.

    1987-12-01

    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.

  16. Systematic review of medical therapy to prevent recurrent diverticulitis.

    Science.gov (United States)

    Unlü, Cagdas; Daniels, Lidewine; Vrouenraets, Bart C; Boermeester, Marja A

    2012-09-01

    One of today's controversies remains the prevention of recurrent diverticulitis. Current guidelines advise a conservative approach, based on studies showing low recurrence rates and a high operative morbidity and mortality. Conservative measures in prevention recurrence are dietary advises and medical therapies, including probiotics and 5-aminosalicylic acid. The aim of this systematic review is to assess whether medical or dietary therapies can prevent recurrent diverticulitis after a primary episode of acute diverticulitis. METHOD AND SEARCH STRATEGY: We searched different databases for papers published between January 1966 and January 2011. Clinical studies were eligible for inclusion if they assessed the prevention of recurrent diverticulitis with a medical or dietary therapy. Exclusion criteria were studies without a control group. Three randomized controlled trials (RCT), all with a Jadad quality score of 2 out of 5, were included in this systematic review. Mesalazine results in significantly less disease recurrence and fewer symptoms after an acute episode. The use of probiotics decreases symptoms but does not reduce recurrence. No difference in effect is seen when Balsalazide is added to probiotics compared to probiotics only. No relevant studies on dietary therapy/advices or antibiotics for prevention of recurrent diverticulitis were found. The evidence that supports medical therapy to prevent recurrent diverticulitis is of poor quality. Treatment with 5-aminosalicylic acid seems promising. Based on current data, no recommendation of any non-operative relapse prevention therapy for diverticular disease can be made.

  17. Inflammatory Bowel Disease.

    Science.gov (United States)

    Wehkamp, Jan; Götz, Martin; Herrlinger, Klaus; Steurer, Wolfgang; Stange, Eduard F

    2016-02-05

    Inflammatory bowel diseases are common in Europe, with prevalences as high as 1 in 198 persons (ulcerative colitis) and 1 in 310 persons (Crohn's disease). This review is based on pertinent articles retrieved by a search in PubMed and in German and European guidelines and Cochrane reviews of controlled trials. Typically, the main clinical features of inflammatory bowel diseases are diarrhea, abdominal pain, and, in the case of ulcerative colitis, peranal bleeding. These diseases are due to a complex immunological disturbance with both genetic and environmental causes. A defective mucosal barrier against commensal bowel flora plays a major role in their pathogenesis. The diagnosis is based on laboratory testing, ultrasonography, imaging studies, and, above all, gastrointestinal endoscopy. Most patients with Crohn's disease respond to budesonide or systemic steroids; aminosalicylates are less effective. Refractory exacerbations may be treated with antibodies against tumor necrosis factor (TNF) or, more recently, antibodies against integrin, a protein of the cell membrane. In ulcerative colitis, aminosalicylates are given first; if necessary, steroids or antibodies against TNF-α or integrin are added. Maintenance therapy to prevent further relapses often involves immunosuppression with thiopurines and/or antibodies. Once all conservative treatment options have been exhausted, surgery may be necessary. The treatment of chronic inflammatory bowel diseases requires individually designed therapeutic strategies and the close interdisciplinary collaboration of internists and surgeons.

  18. 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.

  19. Genome-wide analysis of multi- and extensively drug-resistant Mycobacterium tuberculosis

    KAUST Repository

    Coll, Francesc

    2018-01-16

    To characterize the genetic determinants of resistance to antituberculosis drugs, we performed a genome-wide association study (GWAS) of 6,465 Mycobacterium tuberculosis clinical isolates from more than 30 countries. A GWAS approach within a mixed-regression framework was followed by a phylogenetics-based test for independent mutations. In addition to mutations in established and recently described resistance-associated genes, novel mutations were discovered for resistance to cycloserine, ethionamide and para-aminosalicylic acid. The capacity to detect mutations associated with resistance to ethionamide, pyrazinamide, capreomycin, cycloserine and para-aminosalicylic acid was enhanced by inclusion of insertions and deletions. Odds ratios for mutations within candidate genes were found to reflect levels of resistance. New epistatic relationships between candidate drug-resistance-associated genes were identified. Findings also suggest the involvement of efflux pumps (drrA and Rv2688c) in the emergence of resistance. This study will inform the design of new diagnostic tests and expedite the investigation of resistance and compensatory epistatic mechanisms.

  20. Studies on biphenyl disulphonic acid doped polyanilines: Synthesis ...

    Indian Academy of Sciences (India)

    zed protonic acids, such as camphorsulfonic acid, dodecyl- benzene sulfonic acid, para-toluene sulfonic acid, benzene sulfonic acid, sulfanilic acid, sulfamic acid, octyl-benzene sulfonic acid, sulfosalicylic acid or methane sulfonic acid as dopants (Epstein et al 1987; Li et al 1987; Dhawan and Trivedi 1991, 1992; Kobayashi ...

  1. Septic knee arthritis in Crohn’s disease biological therapy-free patient. Case report

    Science.gov (United States)

    Pop, C; Calagiu, D; Jantea, P; Nemes, R

    2015-01-01

    A 52-year-old woman with Crohn’s disease presented with septic arthrtis of the knee. This condition coincided with a symptomatic flare of her Crohn’s disease due to an ileal inflammatory stenosis, manifested as a phlegmonous mass palpable in the right lower quadrant and a small bowel obstruction. Results of synovial fluid cultures showed the presence of Gram-negative bacillus, Klebsiella pneumoniae and the CT scan images were highly suggestive of abdominal abscess within Crohn’s disease. The patient’s condition improved after following an antibiotic treatment and after the initiation of Anti-TNF-alpha agent Adalimumab, with no further exacerbation. Septic arthritis in Crohn’s disease should be considered to have a communicating source of sepsis consisting of an abdominal abscess or fistula. Abbreviations: Anti-TNF-alpha agent = anti tumor necrosis factor alpha agent, 5-ASA = 5-aminosalicylic acid PMID:26664477

  2. Septic knee arthritis in Crohn's disease biological therapy-free patient. Case report.

    Science.gov (United States)

    Pop, C; Calagiu, D; Jantea, P; Nemes, R

    2015-01-01

    A 52-year-old woman with Crohn's disease presented with septic arthrtis of the knee. This condition coincided with a symptomatic flare of her Crohn's disease due to an ileal inflammatory stenosis, manifested as a phlegmonous mass palpable in the right lower quadrant and a small bowel obstruction. Results of synovial fluid cultures showed the presence of Gram-negative bacillus, Klebsiella pneumoniae and the CT scan images were highly suggestive of abdominal abscess within Crohn's disease. The patient's condition improved after following an antibiotic treatment and after the initiation of Anti-TNF-alpha agent Adalimumab, with no further exacerbation. Septic arthritis in Crohn's disease should be considered to have a communicating source of sepsis consisting of an abdominal abscess or fistula. Anti-TNF-alpha agent = anti tumor necrosis factor alpha agent, 5-ASA = 5-aminosalicylic acid.

  3. 5-ASA Suppositories in Hemorrhoidal Disease

    Directory of Open Access Journals (Sweden)

    P Gionchetti

    1992-01-01

    Full Text Available Forty patients with active hemorrhoidal disease were entered into this double-blind trial, 20 of whom were randomized to treatment with 5-aminosalicylic acid (5-ASA (500 mg suppositories. Clinical and sigmoidoscopic assessment was carried out before the start of the trial and after two weeks of treatment. At the end of the study, 5-ASA suppositories showed results superior to those of placebo for all parameters evaluated (P<0.01. There were no adverse events reported related to the use of suppositories. 5-ASA suppositories are a valid therapeutic approach for hemorrhoidal disease as it reduces the intensity of all symptoms and significantly decreases congestion of the hemorrhoidal plexus.

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

    Directory of Open Access Journals (Sweden)

    Hugh J Freeman

    2009-01-01

    Full Text Available 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 completely resolves with histologically normal colonic mucosa. Recurrent symptoms with evidence of recurrent segmental colitis may occur, but most have an entirely benign clinical course. Further definition of the underlying molecular signalling that occurs in this apparently distinctive disorder may be critically important to understand the elements of a colonic inflammatory process that can completely and spontaneously resolve.

  5. [Inflammatory bowel diseases: conservative therapy].

    Science.gov (United States)

    Bansky, G

    1991-07-01

    Recent advances in the medical treatment of the inflammatory bowel diseases are reviewed with emphasizes on controlled clinical trials. The newly developed mesalazine contains the active moiety of sulfasalazine, the 5-aminosalicylic acid. In ulcerative colitis mesalazine appears to be as efficacious as the time-honored sulfasalazine; it has however less adverse effects. Corticosteroids remain the most effective drugs in severe attacks of all forms of inflammatory bowel diseases. The immunosuppressive agents 6-mercoptopurine and azathioprine are useful second-line drugs in otherwise refractory Crohn's disease. The place of cyclosporin is at present uncertain. Metronidazole is the only efficient antibiotics in the treatment of Crohn's disease. The relative merits of various diets are discussed.

  6. The Prevalence in Canada of Drug-Resistant Tubercle Bacilli in Newly Discovered Untreated Patients with Tuberculosis

    Science.gov (United States)

    Armstrong, A. Riley

    1966-01-01

    During the period February 1963 to September 1964, the incidence of strains of tubercle bacilli excreted by newly diagnosed, previously untreated patients with tuberculosis in Canada that were resistant to the major antituberculosis drugs, viz. streptomycin, para-aminosalicylic acid and isoniazid, was 4.8%. Resistance to a single drug (3.8%) was observed more commonly than was resistance to two drugs (0.9%) or to all three drugs (0.3%), and the drug most frequently involved in this regard was streptomycin (1.8%). Data for the province of Ontario were almost the same as those for Canada. These data are compared with results of surveys in other countries and it is concluded that while drug-resistant tubercle bacilli do not constitute a major problem in Canada at present, awareness of this potential hazard should be maintained. PMID:20328514

  7. Predicting, treating and preventing postoperative recurrence of Crohn's disease: the state of the field.

    Science.gov (United States)

    Borowiec, Anna M; Fedorak, Richard N

    2011-03-01

    The majority of patients diagnosed with Crohn's disease eventually require surgical intervention. Unfortunately, postsurgical remission tends to be short lived; a significant number of patients experience clinical relapse and many require additional operations. The pathogenesis of this postoperative recurrence is poorly understood and, currently, there are no reliable tools to predict when and in whom the disease will recur. Furthermore, the postoperative prophylaxis profiles of available Crohn's disease therapeutic agents such as 5-aminosalicylates, immunomodulators, steroids and probiotics have been disappointing. Recently, the combination of antibiotics and azathioprine in selected high-risk patients has demonstrated some potential for benefit. The goal of the present article is to provide a coherent summary of previous and new research to guide clinicians in managing the challenging and complex problem of postoperative Crohn's disease recurrence.

  8. Predicting, Treating and Preventing Postoperative Recurrence of Crohn’s Disease: The State of the Field

    Directory of Open Access Journals (Sweden)

    Anna M Borowiec

    2011-01-01

    Full Text Available The majority of patients diagnosed with Crohn’s disease eventually require surgical intervention. Unfortunately, postsurgical remission tends to be short lived; a significant number of patients experience clinical relapse and many require additional operations. The pathogenesis of this postoperative recurrence is poorly understood and, currently, there are no reliable tools to predict when and in whom the disease will recur. Furthermore, the postoperative prophylaxis profiles of available Crohn’s disease therapeutic agents such as 5-aminosalicylates, immunomodulators, steroids and probiotics have been disappointing. Recently, the combination of antibiotics and azathioprine in selected high-risk patients has demonstrated some potential for benefit. The goal of the present article is to provide a coherent summary of previous and new research to guide clinicians in managing the challenging and complex problem of postoperative Crohn’s disease recurrence.

  9. 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)

    Khosa, M.K.; Nisar, M.; Jamal, M.A.; Yousaf, M.; Chatha, S.A.S.; Zia, K.M.

    2011-01-01

    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)

  10. Diverticular disease: Epidemiology and management

    Science.gov (United States)

    Weizman, Adam V; Nguyen, Geoffrey C

    2011-01-01

    Diverticular disease of the colon is among the most prevalent conditions in western society and is among the leading reasons for outpatient visits and causes of hospitalization. While previously considered to be a disease primarily affecting the elderly, there is increasing incidence among individuals younger than 40 years of age. Diverticular disease most frequently presents as uncomplicated diverticulitis, and the cornerstone of management is antibiotic therapy and bowel rest. Segmental colitis associated with diverticula shares common histopathological features with inflammatory bowel disease and may benefit from treatment with 5-aminosalicylates. Surgical management may be required for patients with recurrent diverticulitis or one of its complications including peridiverticular abscess, perforation, fistulizing disease, and strictures and/or obstruction. PMID:21876861

  11. Recent advances in the treatment of colonic diverticular disease and prevention of acute diverticulitis

    Science.gov (United States)

    Elisei, Walter; Tursi, Antonio

    2016-01-01

    The incidence of diverticulosis and diverticular disease of the colon is increasing worldwide. Although the majority of patients remains asymptomatic long-life, the prevalence of diverticular disease of the colon, including acute diverticulitis, is substantial and is becoming a significant burden on National Health Systems in terms of direct and indirect costs. Focus is now being drawn on identifying the correct therapeutic approach by testing various treatments. Fiber, non-absorbable antibiotics and probiotics seem to be effective in treating symptomatic and uncomplicated patients, and 5-aminosalicylic acid might help prevent acute diverticulitis. Unfortunately, robust evidence on the effectiveness of a medical strategy to prevent acute diverticulitis recurrence is still lacking. We herein provide a concise review on the effectiveness and future perspectives of these treatments. PMID:26752946

  12. Diverticular Disease: Epidemiology and Management

    Directory of Open Access Journals (Sweden)

    Adam V Weizman

    2011-01-01

    Full Text Available Diverticular disease of the colon is among the most prevalent conditions in western society and is among the leading reasons for outpatient visits and causes of hospitalization. While previously considered to be a disease primarily affecting the elderly, there is increasing incidence among individuals younger than 40 years of age. Diverticular disease most frequently presents as uncomplicated diverticulitis, and the cornerstone of management is antibiotic therapy and bowel rest. Segmental colitis associated with diverticula shares common histopathological features with inflammatory bowel disease and may benefit from treatment with 5-aminosalicylates. Surgical management may be required for patients with recurrent diverticulitis or one of its complications including peridiverticular abscess, perforation, fistulizing disease, and strictures and/or obstruction.

  13. Colorectal neoplasia in patients with primary sclerosing cholangitis undergoing liver transplantation

    DEFF Research Database (Denmark)

    Jørgensen, Kristin Kaasen; Lindström, Lina; Cvancarova, Milada

    2012-01-01

    OBJECTIVE: Several studies have implicated primary sclerosing cholangitis (PSC) as an additional risk factor for colorectal neoplasia in inflammatory bowel disease (IBD). Some reports have indicated that the risk is even higher in PSC-IBD patients after liver transplantation (Ltx), but this issue...... is controversial. We aimed to compare the risk of colorectal neoplasia in PSC-IBD patients before and after Ltx and to identify risk factors for colorectal neoplasia post-transplant. MATERIAL AND METHODS: In a multicenter study within the Nordic Liver Transplant Group, we assessed the risk of colorectal neoplasia......-one (25%) PSC-IBD patients developed colorectal neoplasia. The cumulative risk of colorectal neoplasia was higher after than before Ltx (HR: 1.9, 95% CI: 1.3-2.9, p = 0.002). A multivariate analysis demonstrated aminosalicylates and ursodeoxycholic acid as significantly associated with an increased risk...

  14. Differential response of flat and polypoid colitis-associated colorectal neoplasias to chemopreventive agents and heterocyclic amines

    Science.gov (United States)

    Chang, Wen-Chi L.; Zenser, Terry V.; Cooper, Harry S.; Clapper, Margie L.

    2013-01-01

    Individuals with ulcerative colitis face an increased risk of developing colorectal cancer and would benefit from early chemopreventive intervention. Results from preclinical studies in the mouse model of dextran sulfate sodium-induced colitis demonstrate that flat and polypoid colitis-associated dysplasias arise via distinct genetic pathways, impacted by the allelic status of p53. Furthermore, flat and polypoid dysplasias vary in their response to induction by the heterocyclic amine 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) and inhibition by 5-aminosalicylic acid, a common therapy for the maintenance of colitis patients. These data suggest that use of combination therapy is essential for the optimal inhibition of colitis-associated colorectal cancer. PMID:23415736

  15. Paramagnetic Gd IIIFe III heterobimetallic complexes of DTPA-bis-salicylamide

    Science.gov (United States)

    Aime, S.; Botta, M.; Fasano, M.; Terreno, E.

    1993-08-01

    The reaction between DTPA (diethylenetriaminepenta-acetic acid)-anhydride and p-aminosalicylic acid (PAS) affords a novel ligand, [DTPA(PAS) 2], able to form stable heterobimetallic complexes with Gd 3+ and Fe 3+ ions. The lanthanide ion occupies an internal coordination cage formed by three nitrogen atoms, two carboxylate and two carboxoamido groups of the ligand, whereas the outer salicylic moieties form stable chelate rings with Fe III ions. The stoichiometry of the resulting heterobimetallic complexes, established by measurements of water proton relaxation enhancement, is [(H 2O)-Gd-DTPA(PAS) 2] 2-Fe(H 2O) 2 or [(H 2O)-Gd-DTPA(PAS) 2] 3-Fe depending on the pH of the aqueous solution. The individual contributions to the observed relaxation enhancement from Gd 3+ and Fe 3+ paramagnetic ions have been clearly distinguished and analysed.

  16. Phytochemicals and their potential usefulness in inflammatory bowel disease.

    Science.gov (United States)

    Somani, Sahil J; Modi, Ketan P; Majumdar, Anuradha S; Sadarani, Bhakti N

    2015-03-01

    Inflammatory bowel disease (IBD) is a chronic inflammatory condition of the gastrointestinal tract with unclear etiology, namely ulcerative colitis and Crohn's disease. Various drug therapies including aminosalicylates and immunomodulators have been approved for use; they have shown to produce diverse side effects. To overcome these limitations of the current therapeutics for IBD, extensive research is underway to identify drugs that are effective and free of undesirable side effects. Recently, various naturally occurring phytochemicals that cover a wide range of chemical entities such as polyphenols, terpeniods, flavonoids, and alkaloids have received attention as alternative candidates for IBD therapy. These phytochemicals act by modulating the immune response, various transcription factors, or reduce cytokine secretion. This review summarizes the findings of recent studies on phytochemicals as therapeutic agents in the management of IBD. Copyright © 2015 John Wiley & Sons, Ltd.

  17. The effects of repeated parenteral administration of chelating agents on the distribution and excretion of uranium

    International Nuclear Information System (INIS)

    Domingo, J.L.; Ortega, A.; Llobet, J.M.; Paternain, J.L.; Corbella, J.

    1989-01-01

    The effects of repeated ip administration of gallic acid, 4,5-dihydroxy-1,3-benzenedisulfonic acid (Tiron), diethylenetriaminepentaacetic acid (DTPA), and 5-aminosalicylic acid (5-AS) on the distribution and excretion of uranium were assessed in male Swiss mice. Only Tiron significantly increased the amount of uranium excreted into urine and feces. A significant decrease in the concentration of uranium in liver, spleen and bone was observed after administration of Tiron, whereas injection of gallic acid or DTPA resulted in a significant decrease in the concentration of the metal in the liver. The results show that Tiron was consistently the most effective chelator of those tested in the treatment of uranium poisoning after repeated daily administration of the metal

  18. 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

  19. 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...... Newly diagnosed UC and CD patients, allocated into seven clinical states by medical and surgical treatments recorded in serial 3-month cycles, underwent Markov analysis. Results Over 10 years, 630 UC and 318 CD patients had 22,823 and 11 871 cycles. The most frequent clinical outcomes were medical....../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...

  20. [Classical medications in the treatment of inflammatory bowel diseases].

    Science.gov (United States)

    Duvnjak, Marko; Bilić, Ante; Barsić, Neven; Tomasić, Vedran; Stojsavljević, Sanja

    2013-04-01

    The treatment of inflammatory bowel diseases is complex and requires individual approach to every single patient. Traditionally, the approach is based on introduction of so called "classical" medication into the treatment regimen, from ones less potent and with fewer side effects to the ones more toxic but also therapeutically more effective. Aminosalicylates were the first choice of treatment for a long time. However, the role of aminosalicylates is becoming more and more diminished, although they are still the drug of choice in the treatment of mild to moderate ulcerative colitis. Corticosteroids are the therapy of choice in treatment of active IBD for achieving remission in moderate to severe disease. Azathioprine and 6- mercaptopurine belong to a group of thiopurines with an immunomodulatory effect which, in Crohn's disease as well as in ulcerative colitis, primarily have a role in a steroid dependant or steroid refractory type of disease and in maintenance of remission. Lately, early introduction of these medications is proposed to enhance the number of patients that remain in remission. Methotrexate is used for the therapy of active and relapsing Crohn's disease and represents an alternative in patients who do not tolerate or do not respond to azathioprine or 6-mercaptopurine therapy. Cyclosporine is used in treating steroid refractory ulcerative colitis and in some patients can postpone the need for colectomy. Antibiotics do not have a proven effect on the course of inflammatory bowel diseases and their primary role is to treat septic complications. Classic medications today represent a standard in the management of inflammatory bowel diseases, and the combination of the previously mentioned drugs often has a more potent effect on the course of the disease than any medication on its own and their combination is still an object of investigations and clinical studies.

  1. 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.

  2. Critical evaluation of colon submucosal microdialysis in awake, mobile rats.

    Directory of Open Access Journals (Sweden)

    Norbert Cibicek

    Full Text Available Sensors able to record large bowel physiology and biochemistry in situ in awake rodents are lacking. Microdialysis is a mini-invasive technique that may be utilized to continuously deliver or recover low-molecular substances from various tissues. In this experiment we evaluated the feasibility of in vivo microdialysis to monitor extracellular fluid chemistry in the descending colon submucosa of conscious, freely moving rodents. Following surgical implantation of a microdialysis probe, male Wistar rats were housed in metabolic cages where they were analgized and clinically followed for four days with free access to standard diet and water. To assess local microcirculation and probe function, glucose, lactate, glucose-to-lactate ratio and urea clearance were determined in the dialysates from the three postoperative days with focus on the final 24-h period. In an attempt to mitigate the expected tissue inflammatory response, one group of animals had the catheters perfused with 5-aminosalicylic acid-enriched medium with final concentration 1 μmol/L. For verification of probe position and the assessment of the surrounding foreign body reaction, standard histological and immunohistochemical methods were employed. Microdialysis of rat gut is associated with considerable technical challenges that may lead to the loss of probe function and high drop-out rate. In this setting, limited data did not allow to draw any firm conclusion regarding local anti-inflammatory effectiveness of 5-aminosalicylic acid perfusion. Although intestinal microdialysis may be suitable for larger anesthetized animals, low reproducibility of the presented method compromises its routine experimental use in awake and freely moving small-sized rodents.

  3. Inflammatory Bowel Disease and the Risk of Autoimmune Diseases.

    Science.gov (United States)

    Wilson, J Claire; Furlano, Raoul I; Jick, Susan S; Meier, Christoph R

    2016-02-01

    An increased risk of autoimmune disease has been reported in patients with inflammatory bowel disease [IBD]. Using data from the Clinical Practice Research Datalink [CPRD], this study set out to further examine this relationship. Patients with a first-time IBD diagnosis were randomly matched to an equal-sized IBD-free comparison group. Incidence rates for new-onset autoimmune diseases were estimated. A nested case-control analysis comprising IBD patients was conducted, using conditional logistic regression to assess whether IBD severity, duration, or treatment influences the risk of developing autoimmune diseases. During follow-up, 1069 IBD and 585 IBD-free patients developed an incident autoimmune disease. An increased incidence of autoimmune disease was observed in IBD patients (incidence rate [IR] 9.65, 95% confidence interval [CI] 9.09-10.24) compared with the non-IBD comparison group [IR 5.22, 95% CI 4.82-5.66]. In IBD patients, increased disease severity was associated with an increased risk of autoimmune disease development (odds ratio [OR] 1.62, 95% CI 1.28-2.05). Current antibiotic use was also associated with an increased risk [adjusted OR 1.72, 95% CI 1.07-2.78]. A reduced risk of incident autoimmune diseases was observed for current long-term users of aminosalicylates [adjusted OR 0.72, 95% CI 0.57-0.91]. Individuals with IBD had an increased risk of developing an autoimmune disease. Increased disease severity and current antibiotic use were associated with an increased relative risk of developing additional autoimmune diseases in IBD patients. Long-term current aminosalicylate use was associated with a reduced risk. Copyright © 2015 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  4. Discontinuation of Infliximab in Patients With Ulcerative Colitis Is Associated With Increased Risk of Relapse: A Multinational Retrospective Cohort Study.

    Science.gov (United States)

    Fiorino, Gionata; Cortes, Pablo Navarro; Ellul, Pierre; Felice, Carla; Karatzas, Pantelis; Silva, Marco; Lakatos, Peter L; Bossa, Fabrizio; Ungar, Bella; Sebastian, Shaji; Furfaro, Federica; Karmiris, Konstantinos; Katsanos, Konstantinos H; Muscat, Martina; Christodoulou, Dimitrios K; Maconi, Giovanni; Kopylov, Uri; Magro, Fernando; Mantzaris, Gerassimos J; Armuzzi, Alessandro; Boscà-Watts, Marta Maia; Ben-Horin, Shomron; Bonovas, Stefanos; Danese, Silvio

    2016-10-01

    Infliximab is a safe and effective therapy for ulcerative colitis (UC). We conducted a multicenter retrospective cohort study that included 7 European countries and Israel to examine whether infliximab discontinuation can be considered for patients who achieve sustained remission. We performed a retrospective cohort study, collecting medical records from 13 tertiary care referral inflammatory bowel disease centers of all patients with UC treated with infliximab (n = 193). We compared the disease course of patients with at least 12 months of clinical remission who discontinued infliximab (n = 111) with that of patients who continued scheduled treatment (controls, n = 82). We examined the incidence rates of relapse, hospitalization and colectomy, the comparative effectiveness of different therapeutic strategies after discontinuation, and assessed the rates of response, remission, and adverse effects after infliximab re-initiation. Statistical analyses used time-to-event methods. In the entire cohort, 67 patients (34.7%) relapsed during the follow-up period. The incidence rate of relapse was significantly higher after discontinuation (23.3 per 100 person-years) compared with the control group (7.2 per 100 person-years) in univariable analysis (log-rank P infliximab discontinuation (incidence of relapse: 15.0 per 100 person-years for thiopurines, 27.4 per 100 person-years for thiopurines plus aminosalicylates, and 31.2 per 100 person-years for aminosalicylates alone; log-rank P = .032). Response was regained in 77.1% of patients and remission in 51.4% of patients who re-initiated infliximab. However, 17.1% had infusion reactions and 17.1% reported other adverse events. In a multinational retrospective cohort study of patients with UC in sustained clinical remission, we associated discontinuation of infliximab with an increased risk of relapse. Treatment re-initiation is effective and safe. Copyright © 2016 AGA Institute. Published by Elsevier Inc. All rights

  5. Maintenance treatment with azathioprine in ulcerative colitis: outcome and predictive factors after drug withdrawal.

    Science.gov (United States)

    Cassinotti, Andrea; Actis, Giovanni C; Duca, Piergiorgio; Massari, Alessandro; Colombo, Elisabetta; Gai, Elisa; Annese, Vito; D'Albasio, Giuseppe; Manes, Gianpiero; Travis, Simon; Porro, Gabriele Bianchi; Ardizzone, Sandro

    2009-11-01

    Whether the duration of maintenance treatment with azathioprine (AZA) affects the outcome of ulcerative colitis (UC) is unclear. We investigated clinical outcomes and any predictive factors after withdrawal of AZA in UC. In this multicenter observational retrospective study, 127 Italian UC patients, who were in steroid-free remission at the time of withdrawal of AZA, were followed-up for a median of 55 months or until relapse. The frequency of clinical relapse or colectomy after AZA withdrawal was analyzed according to demographic, clinical, and endoscopic variables. After drug withdrawal, a third of the patients relapsed within 12 months, half within 2 years and two-thirds within 5 years. After multivariable analysis, predictors of relapse after drug withdrawal were lack of sustained remission during AZA maintenance (hazard ratio, HR 2.350, confidence interval, CI 95% 1.434-3.852; P=0.001), extensive colitis (HR 1.793, CI 95% 1.064-3.023, P=0.028 vs. left-sided colitis; HR 2.024, CI 95% 1.103-3.717, P=0.023 vs. distal colitis), and treatment duration, with short treatments (3-6 months) more disadvantaged than >48-month treatments (HR 2.783, CI 95% 1.267-6.114, P=0.008). Concomitant aminosalicylates were the only predictors of sustained remission during AZA therapy (P=0.009). The overall colectomy rate was 10%. Predictors of colectomy were drug-related toxicity as the cause of AZA withdrawal (P=0.041), no post-AZA drug therapy (P=0.031), and treatment duration (P<0.0005). Discontinuation of AZA while UC is in remission is associated with a high relapse rate. Disease extent, lack of sustained remission during AZA, and discontinuation due to toxicity could stratify relapse risk. Concomitant aminosalicylates were advantageous. Prospective randomized controlled trials are needed to confirm whether treatment duration is inversely associated with outcome.

  6. What strategies do ulcerative colitis patients employ to facilitate adherence?

    Directory of Open Access Journals (Sweden)

    Kawakami A

    2017-01-01

    Full Text Available Aki Kawakami,1,2 Makoto Tanaka,3 Makoto Naganuma,4 Shin Maeda,5 Reiko Kunisaki,1 Noriko Yamamoto-Mitani2 1Inflammatory Bowel Disease Center, Yokohama City University Medical Center, Minami-ku, Yokohama, Japan; 2Department of Gerontological Home Care and Long-term Care Nursing, Graduate School of Medicine, University of Tokyo, Bunkyo-ku, Tokyo, Japan; 3Ramathibodi School of Nursing, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Ratchathewi, Bangkok, Thailand; 4Division of Gastroenterology and Hepatology, Keio University, Shinjuku-ku, Tokyo, Japan; 5Department of Gastroenterology, Yokohama City University Graduate School of Medicine, Kanazawa-ku, Yokohama, Japan Background: Overall, 30%–45% of patients with ulcerative colitis (UC are non-adherent and have difficulties taking their medications; this non-adherence increases the risk of clinical relapse 1.4- to 5.5-fold. This study aimed to clarify the strategies patients employ to facilitate adherence and determine whether the strategies had an impact on good adherence.Methods: This was a cross-sectional survey using a self-administered questionnaire and review of medical records. Patients diagnosed as having UC and attending one of the outpatient clinics of four urban hospitals from June 2009 to December 2012 were enrolled. A questionnaire was developed to identify the strategies patients employ to facilitate adherence and then administered to patients with UC. Adherence to 5-aminosalicylic acid was calculated, and univariate and multiple logistic regression analyses were performed to determine the strategies that were associated with good adherence.Results: The final analyses included 671 participants (mean age 40.2 years; 54.3% males. The valid response rate was 96.9%; 186 (27.7% participants were classified as non-adherent, the mean adherence rate being 86.1% (standard deviation [SD] 17.9. Seven strategies that patients employ to facilitate adherence were identified, the

  7. Treatment and outcomes: medical and surgical treatment for intestinal Behçet's disease

    Directory of Open Access Journals (Sweden)

    Tadakazu Hisamatsu

    2017-07-01

    Full Text Available Behçet's disease (BD is a chronic relapsing disease involving multiple organ systems. BD is characterized clinically by oral and genital aphthae, cutaneous lesions, and ophthalmological, neurological, and/or gastrointestinal manifestations. It is widely recognized that the presence of intestinal lesions may be a poor prognostic factor in intestinal BD, increasing the risk of surgery and decreasing the quality of life. Despite this, the management of intestinal BD has not been standardized. Empirical therapies including 5-aminosalicylic acid and corticosteroids have been used anecdotally to treat intestinal BD, but recent studies have provided evidence for the efficacy of anti-tumor necrosis factor α monoclonal antibodies. The development of agents targeting tumor necrosis factor α continues, it seems likely that they will change the therapeutic strategy and clinical outcomes of intestinal BD and inflammatory bowel disease. Monitoring disease activity such as endoscopic evaluation will become more important to obtain better outcomes. Here, we review current and future perspectives in the treatment and outcomes of intestinal BD.

  8. The Promoter of Rv0560c Is Induced by Salicylate and Structurally-Related Compounds in Mycobacterium tuberculosis

    Science.gov (United States)

    Schuessler, Dorothée L.; Parish, Tanya

    2012-01-01

    Mycobacterium tuberculosis, the causative agent of tuberculosis (TB), is a major global health threat. During infection, bacteria are believed to encounter adverse conditions such as iron depletion. Mycobacteria synthesize iron-sequestering mycobactins, which are essential for survival in the host, via the intermediate salicylate. Salicylate is a ubiquitous compound which is known to induce a mild antibiotic resistance phenotype. In M. tuberculosis salicylate highly induces the expression of Rv0560c, a putative methyltransferase. We identified and characterized the promoter and regulatory elements of Rv0560c. PRv0560c activity was highly inducible by salicylate in a dose-dependent manner. The induction kinetics of PRv0560c were slow, taking several days to reach maximal activity, which was sustained over several weeks. Promoter activity could also be induced by compounds structurally related to salicylate, such as aspirin or para-aminosalicylic acid, but not by benzoate, indicating that induction is specific to a structural motif. The −10 and −35 promoter elements were identified and residues involved in regulation of promoter activity were identified in close proximity to an inverted repeat spanning the −35 promoter element. We conclude that Rv0560c expression is controlled by a yet unknown repressor via a highly-inducible promoter. PMID:22485172

  9. Direct Ring Fission of Salicylate by a Salicylate 1,2-Dioxygenase Activity from Pseudaminobacter salicylatoxidans

    Science.gov (United States)

    Hintner, Jan-Peter; Lechner, Christa; Riegert, Ulrich; Kuhm, Andrea Elisabeth; Storm, Thomas; Reemtsma, Thorsten; Stolz, Andreas

    2001-01-01

    In cell extracts of Pseudaminobacter salicylatoxidans strain BN12, an enzymatic activity was detected which converted salicylate in an oxygen-dependent but NAD(P)H-independent reaction to a product with an absorbance maximum at 283 nm. This metabolite was isolated, purified, and identified by mass spectrometry and 1H and 13C nuclear magnetic resonance spectroscopy as 2-oxohepta-3,5-dienedioic acid. This metabolite could be formed only by direct ring fission of salicylate by a 1,2-dioxygenase reaction. Cell extracts from P. salicylatoxidans also oxidized 5-aminosalicylate, 3-, 4-, and 5-chlorosalicylate, 3-, 4-, and 5-methylsalicylate, 3- and 5-hydroxysalicylate (gentisate), and 1-hydroxy-2-naphthoate. The dioxygenase was purified and shown to consist of four identical subunits with a molecular weight of about 45,000. The purified enzyme showed higher catalytic constants with gentisate or 1-hydroxy-2-naphthoate than with salicylate. It was therefore concluded that P. salicylatoxidans synthesized a gentisate 1,2-dioxygenase with an extraordinary substrate range, which also allowed the oxidation of salicylate. PMID:11698383

  10. Budesonide multi-matrix system formulation for treating ulcerative colitis.

    Science.gov (United States)

    Prantera, Cosimo; Scribano, Maria Lia

    2014-04-01

    Budesonide is a corticosteroid characterized by high topical activity and low systemic effect associated with fewer glucocorticoid-related adverse events than conventional steroids. Differently from Crohn's disease, no evidence suggests that oral budesonide is effective for the induction of remission of ulcerative colitis (UC). Budesonide multi-matrix (MMX) system is a new oral preparation that, by employing a MMX, provides the release of the drug throughout the entire colon. Its efficacy in inducing UC remission, at a dose of 9 mg, is based on some recent trials. However, in two studies the absolute differences between budesonide MMX and placebo were much lower than the rate of success reported in previous trials with mesalazines. In addition, the therapeutic advantage of budesonide MMX 9 mg over 5-aminosalicylic acid (5-ASA) showed by one study, and the advantage of budesonide MMX over budesonide reported in the other study, was only 5.8 and 4.8%, respectively. The evidence supporting the use of budesonide MMX at a dose of 6 mg for maintenance is weak. Therefore, the effective dosage should be 9 mg also in maintenance, but not for > 4 - 6 months, because a prolonged treatment has showed to increase the rate of side effects.

  11. Safety of treatments for inflammatory bowel disease: Clinical practice guidelines of the Italian Group for the Study of Inflammatory Bowel Disease (IG-IBD).

    Science.gov (United States)

    Biancone, Livia; Annese, Vito; Ardizzone, Sandro; Armuzzi, Alessandro; Calabrese, Emma; Caprioli, Flavio; Castiglione, Fabiana; Comberlato, Michele; Cottone, Mario; Danese, Silvio; Daperno, Marco; D'Incà, Renata; Frieri, Giuseppe; Fries, Walter; Gionchetti, Paolo; Kohn, Anna; Latella, Giovanni; Milla, Monica; Orlando, Ambrogio; Papi, Claudio; Petruzziello, Carmelina; Riegler, Gabriele; Rizzello, Fernando; Saibeni, Simone; Scribano, Maria Lia; Vecchi, Maurizio; Vernia, Piero; Meucci, Gianmichele

    2017-04-01

    Inflammatory bowel diseases are chronic conditions of unknown etiology, showing a growing incidence and prevalence in several countries, including Italy. Although the etiology of Crohn's disease and ulcerative colitis is unknown, due to the current knowledge regarding their pathogenesis, effective treatment strategies have been developed. Several guidelines are available regarding the efficacy and safety of available drug treatments for inflammatory bowel diseases. Nevertheless, national guidelines provide additional information adapted to local feasibility, costs and legal issues related to the use of the same drugs. These observations prompted the Italian Group for the Study of Inflammatory Bowel Disease (IG-IBD) to establish Italian guidelines on the safety of currently available treatments for Crohn's disease and ulcerative colitis. These guidelines discuss the use of aminosalicylates, systemic and low bioavailability corticosteroids, antibiotics (metronidazole, ciprofloxacin, rifaximin), thiopurines, methotrexate, cyclosporine A, TNFα antagonists, vedolizumab, and combination therapies. These guidelines are based on current knowledge derived from evidence-based medicine coupled with clinical experience of a national working group. Copyright © 2017 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

  12. CO2 Preactivation in Photoinduced Reduction via Surface Functionalization of TiO2 Nanoparticles.

    Science.gov (United States)

    Finkelstein-Shapiro, Daniel; Petrosko, Sarah Hurst; Dimitrijevic, Nada M; Gosztola, David; Gray, Kimberly A; Rajh, Tijana; Tarakeshwar, Pilarisetty; Mujica, Vladimiro

    2013-02-07

    Salicylate and salicylic acid derivatives act as electron donors via charge-transfer complexes when adsorbed on semiconducting surfaces. When photoexcited, charge is injected into the conduction band directly from their highest occupied molecular orbital (HOMO) without needing mediation by the lowest unoccupied molecular orbital (LUMO). In this study, we successfully induce the chemical participation of carbon dioxide in a charge transfer state using 3-aminosalicylic acid (3ASA). We determine the geometry of CO2 using a combination of ultraviolet-visible spectroscopy (UV-vis), surface enhanced Raman scattering (SERS), (13)C NMR, and electron paramagnetic resonance (EPR). We find CO2 binds on Ti sites in a carbonate form and discern via EPR a surface Ti-centered radical in the vicinity of CO2, suggesting successful charge transfer from the sensitizer to the neighboring site of CO2. This study opens the possibility of analyzing the structural and electronic properties of the anchoring sites for CO2 on semiconducting surfaces and proposes a set of tools and experiments to do so.

  13. A Multicenter, Randomized Study to Evaluate the Efficacy and Safety of Mesalamine Suppositories 1 g at Bedtime and 500 mg Twice Daily in Patients with Active Mild-to-Moderate Ulcerative Proctitis

    Science.gov (United States)

    2010-01-01

    Abstract Background Ulcerative proctitis (UP) is a prevalent condition associated with increased morbidity and mortality. Topical mesalamine (5-aminosalicylic acid [5-ASA]) inhibits inflammatory processes in UP. Methods We evaluated effects of mesalamine 1-g suppository administered QHS compared with 500-mg suppository administered BID on UP activity (e.g., disease extension/mucosal appearance), remission, onset of response, safety and compliance in 97 patients with UP. A 6-week, randomized, multicenter, parallel-group, noninferiority study was conducted (and published) with Disease Activity Index (DAI) at week 6 as the primary efficacy variable and individual components of DAI at week 6 (i.e., stool frequency, rectal bleeding, mucosal appearance, global assessment) as secondary variables. Unreported outcomes were remission (DAI 70%) after 6 weeks in both groups. Mesalamine was well tolerated. Compliance was >96%. Conclusions Mesalamine 500-mg BID and 1-g QHS suppositories are safe and effective for patients with UP. Most patients reported significant improvement within 3 weeks and UP remission and reduced disease extension after 6 weeks of treatment. Validity of QHS administration was confirmed. PMID:20676771

  14. Balsalazide is more effective and better tolerated than mesalamine in the treatment of acute ulcerative colitis. The Abacus Investigator Group.

    Science.gov (United States)

    Green, J R; Lobo, A J; Holdsworth, C D; Leicester, R J; Gibson, J A; Kerr, G D; Hodgson, H J; Parkins, K J; Taylor, M D

    1998-01-01

    Aminosalicylates are widely used in the treatment of ulcerative colitis (UC). Balsalazide is a novel mesalamine prodrug, activated by colonic bacteria. The aim of this study was to compare the efficacy and safety of balsalazide with that of a pH-dependent formulation of mesalamine in active UC. A randomized, double-blind study was performed comparing balasalazide, 6.75 g daily, with mesalamine, 2.4 g daily, administered for 4, 8, or 12 weeks to 101 (99 evaluable) patients with symptomatic, sigmoidoscopically verified UC. More patients treated with balsalazide achieved symptomatic remission after 2 (64% [balsalazide] vs. 43% [mesalamine]), 4 (70% vs. 51%), 8 (78% vs. 45%), and 12 weeks (88% vs. 57%) and complete remission (none/mild symptoms, sigmoidoscopy grade 0/1, no rectal steroid use within 4 days) after 4 (38% vs. 12%), 8 (54% vs. 22%), and 12 weeks (62% vs. 37%). Patients taking balsalazide experienced more asymptomatic days (4 weeks, 24% vs. 14%) and achieved the first asymptomatic day more rapidly (median, 10 vs. 25 days). Fewer patients in the balsalazide group reported adverse events (48% vs. 71%); four serious adverse events occurred in the mesalamine group. Balsalazide is more effective and better tolerated than mesalamine as treatment for acute UC.

  15. 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.

  16. Prevalence of colorectal cancer in patients with ulcerative colitis: A retrospective, monocenter study in China

    Directory of Open Access Journals (Sweden)

    Qin Zhang

    2015-01-01

    Full Text Available Background: Ulcerative colitis-associated colorectal cancer (UC-CRC is a serious complication of UC. Data on the clinical characteristics of patients in China are scarce. Aims: We aimed to study the incidence, characteristics, treatment, and prognosis of CRC patients with a history of UC. Materials and Methods: We identified patients with UC and followed them until the first occurrence of cancer, death, or emigration in a single study center in China. Results: A total of 4 UC-associated CRC patients were identified among the 642 cases recorded from January 2000 to December 2012. The overall risk of cancer was 0.64%. The overall median duration of UC was 15.5 years (range 6-21 years in patients with UC-associated CRC. Of these patients, 75% (3/4 were at an advanced stage when they were diagnosed. Longer disease duration and extensive colitis were identified as risk factors for developing CRC, and 5-aminosalicylic acid and steroid therapies were not identified as protective factors against UC-associated CRC. Conclusions: Patients with UC are at an increased risk for CRC. However, the prevalence of CRC in China remains lower than that in the West.

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

    International Nuclear Information System (INIS)

    Majumdar, S.; Basu, S.K.

    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

  18. Turner Syndrome with Ulcerative Colitis

    Science.gov (United States)

    Hyodo, Hiromi; Tomita, Yuichiro; Hirai, Kohta; Hirakawa, Hitoshi; Ueno, Shigeru; Ishiguro, Hiroyuki

    2009-01-01

    Turner syndrome is a chromosomal disease frequently associated with autoimmune disorders including diabetes mellitus, thyroid disease and inflammatory bowel disease (IBD). Although the etiology of IBD has not been fully elucidated, genetic analysis has recently revealed several susceptibility genes. Recently, cases with Turner syndrome associated with IBD have been reported. We report here a 13-yr-old girl with Turner syndrome associated with ulcerative colitis. The patient was undergoing growth hormone treatment and presented with abdominal discomfort and bloody diarrhea. Her karyotype pattern was 46,X,i(Xq). Barium enema revealed punctate collections of barium suggesting microulcerations in the descending and sigmoid colon with loss of haustra. Flexible sigmoidoscopy showed that the mucosa was erythematous and friable upon touch and that the wall had frank hemorrhage and inflammatory polyp formation from the anal verge through the splenic flexure. Histologically, mucosal and submucosal inflammation was prominent, suggesting cryptitis and crypt abscess formation. Based on these findings, she was diagnosed as having ulcerative colitis, and 5-aminosalicylic acid, prednisolone and dietary therapy were initiated. Our observations in this patient suggest that X chromosome abnormality may influence the development of IBD and that screening for gastrointestinal disease in patients with Turner syndrome may help lengthen life expectancy in these patients. PMID:23926368

  19. Dual role of Helicobacter and Campylobacter species in IBD: a systematic review and meta-analysis.

    Science.gov (United States)

    Castaño-Rodríguez, Natalia; Kaakoush, Nadeem O; Lee, Way Seah; Mitchell, Hazel M

    2017-02-01

    To conduct a comprehensive global systematic review and meta-analysis on the association between Helicobacter pylori infection and IBD. As bacterial antigen cross-reactivity has been postulated to be involved in this association, published data on enterohepatic Helicobacter spp (EHS) and Campylobacter spp and IBD was also analysed. Electronic databases were searched up to July 2015 for all case-control studies on H. pylori infection/EHS/Campylobacter spp and IBD. Pooled ORs (P-OR) and 95% CIs were obtained using the random effects model. Heterogeneity, sensitivity and stratified analyses were performed. Analyses comprising patients with Crohn's disease (CD), UC and IBD unclassified (IBDU), showed a consistent negative association between gastric H. pylori infection and IBD (P-OR: 0.43, p value Campylobacter spp, in particular C. concisus (P-OR: 3.76, p value=0.006) and C. showae (P-OR: 2.39, p value=0.027), increase IBD risk. H. pylori infection is negatively associated with IBD regardless of ethnicity, age, H. pylori detection methods and previous use of aminosalicylates and corticosteroids. Antibiotics influenced the magnitude of this association. Closely related bacteria including EHS and Campylobacter spp increase the risk of IBD. These results infer that H. pylori might exert an immunomodulatory effect in IBD. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  20. Patients with Crohn's disease on anti-tumor necrosis factor therapy are at significant risk of inadequate response to the 23-valent pneumococcal polysaccharide vaccine.

    Science.gov (United States)

    Lee, Chang Kyun; Kim, Hyun-Soo; Ye, Byong Duk; Lee, Kang-Moon; Kim, You Sun; Rhee, Sang Youl; Kim, Hyo-Jong; Yang, Suk-Kyun; Moon, Won; Koo, Ja-Seol; Lee, Suck-Ho; Seo, Geom Seog; Park, Soo Jung; Choi, Chang Hwan; Jung, Sung-Ae; Hong, Sung Noh; Im, Jong Pil; Kim, Eun Soo

    2014-05-01

    The effect of immunosuppressants on the efficacy of a variety of vaccines is a controversial issue in patients with inflammatory bowel disease (IBD). In this study we determined whether specific immunosuppressants impair the serological response to the standard 23-valent pneumococcal polysaccharide vaccine (PPSV23) in a large cohort of patients with Crohn's disease (CD). This was a multi-center, prospective observational study of adult patients with CD at 15 academic teaching hospitals in Korea. The study population received one intramuscular injection of PPSV23. Anti-pneumococcal IgG antibody titers were measured by immunoassay prior to and 4weeks after vaccination. All vaccination-related adverse events and the effect of the vaccine on disease activity were also evaluated. The overall serological response rate was 67.5% (133/197). The serological response rate was significantly lower in patients on anti-tumor necrosis factor (anti-TNF) therapy (50.0% on anti-TNF alone; 58.0% on anti-TNF combined with an immunomodulator, IM) than patients on 5-aminosalicylate (78.4%; all P-values vs. 5-aminosalicylaterisk of an inadequate response to PPSV23. The pneumococcal vaccination strategy should be optimized for patients with CD on anti-TNF therapy. © 2013 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.

  1. Ulcerative proctitis: an update on the pharmacotherapy and management.

    Science.gov (United States)

    Gecse, Krisztina B; Lakatos, Peter L

    2014-08-01

    Ulcerative colitis (UC) presents as proctitis in approximately a quarter of the patients. It may progress into left-sided or extensive colitis in up to 50% of cases upon long-term follow-up. Currently available data on ulcerative proctitis are summarized and critically reviewed. Extensive literature search (MEDLINE) was performed to identify relevant articles up to March 2014. The short-term goal of the treatment in UC is to induce remission, whereas long-term goals are to maintain remission and prevent disease progression. Topically administered 5-aminosalicylates (5-ASA) and corticosteroids are effective in the treatment of proctitis, although they seem to be underused in everyday practice. Locally administered 5-ASA preparations are more effective than oral compounds. The combination of topical and oral 5-ASA and steroids should be considered for escalation of treatment. Refractory patients should be re-evaluated to exclude for compliance failures, infections or proximal disease extent. True refractory or steroid-dependent patients may require immunomodulators or biological therapy. Alternative medicine can be used complementarily, while experimental approaches are reserved for patients failing conventional medication. Proctocolectomy may be the last resort of treatment. Upon long-term, 5-ASA maintenance treatment is indicated in all UC cases to prevent relapse and disease progression.

  2. Current trends and challenges in the postoperative medical management of Crohn's disease: A systematic review.

    Science.gov (United States)

    Schlussel, Andrew T; Cherng, Nicole B; Alavi, Karim

    2017-11-01

    Crohn's disease is an aggressive chronic inflammatory disorder, and despite medical advances no cure exists. There is a great risk of requiring an operative intervention, with evidence of recurrence developing in up to 80-90% of cases. Therefore, we sought to systematically review the current status in the postoperative medical management of Crohn's disease. A systematic literature review of medications administered following respective therapy for Crohn's disease was performed from 1979 through 2016. Twenty-six prospective articles provided directed guidelines for recommendations and these were graded based on the level of evidence. The postoperative management of Crohn's disease faces multiple challenges. Current indicated medications in this setting include: antibiotics, aminosalicylates, immunomodulators, and biologics. Each drug has inherent risks and benefits, and the optimal regimen is still unknown. Initiating therapy in a prophylactic fashion compared to endoscopic findings, or escalating therapy versus treating with the most potent drug first is debated. Although a definitive consensus on postoperative treatment is necessary, aggressive and early endoluminal surveillance is paramount in the treatment of these complicated patients. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Mycobacteria: laboratory methods for testing drug sensitivity and resistance

    Science.gov (United States)

    Canetti, G.; Froman, S.; Grosset, J.; Hauduroy, P.; Langerová, Miloslava; Mahler, H. T.; Meissner, Gertrud; Mitchison, D. A.; Šula, L.

    1963-01-01

    In its seventh report, published in 1960, the WHO Expert Committee on Tuberculosis “noted the need for international standards for the definition and determination of drug resistance which will permit comparisons to be made from one area to another, and recommended that the World Health Organization take appropriate steps to establish such standards”.10 Acting on this recommendation, WHO took the first step towards standardization by convening in Geneva, in December 1961, an informal international meeting of specialists in the bacteriology of tuberculosis. At this meeting an attempt was made to formulate prerequisites for reliable sensitivity tests and to specify the technical procedures for them. The first part of the present paper is a joint contribution by the participants in the meeting, summarizing the general conclusions reached and recommendations made with regard to tests of sensitivity to the three main antituberculosis drugs—isoniazid, streptomycin and p-aminosalicylic acid. The other three parts describe, in turn, three different tests for determining drug sensitivity—the absolute-concentration method, the resistance-ratio method and the proportion method—that are generally considered to give reasonably accurate results. PMID:14102034

  4. Advances in techniques of testing mycobacterial drug sensitivity, and the use of sensitivity tests in tuberculosis control programmes

    Science.gov (United States)

    Canetti, G.; Fox, Wallace; Khomenko, A.; Mahler, H. T.; Menon, N. K.; Mitchison, D. A.; Rist, N.; Šmelev, N. A.

    1969-01-01

    In a paper arising out of an informal international consultation of specialists in the bacteriology of tuberculosis held in 1961, an attempt was made to formulate criteria, and specify technical procedures, for reliable tests of sensitivity (the absolute-concentration method, the resistance-ratio method and the proportion method) to the 3 main antituberculosis drugs (isoniazid, streptomycin and p-aminosalicylic acid). Seven years later, a further consultation was held to review the latest developments in the field and to suggest how sensitivity tests might be put to practical use in tuberculosis control programmes. The participants reached agreement on how to define drug sensitivity and resistance, and stressed the importance of using a discrimination approach to the calibration of sensitivity tests. Their views are contained in the present paper, which also includes descriptions of the sensitivity tests used by the Medical Research Council of Great Britain for first- and second-line drugs (minimal inhibitory concentration and resistance-ratio methods), the two main variants of the proportion method developed by the Institut Pasteur, Paris, and a method for calibrating sensitivity tests. PMID:5309084

  5. De novo inflammatory bowel disease after pediatric kidney or liver transplant.

    Science.gov (United States)

    Fernandes, Melissa A; Braun, Hillary J; Evason, Kim; Rhee, Sue; Perito, Emily R

    2017-02-01

    A subset of children who receive a liver and/or kidney transplant develop de novo inflammatory bowel disease-like chronic intestinal inflammation, not explained by infection or medications, following transplant. We have conducted a single-center, retrospective case series describing the unique clinical and histologic features of this IBD-like chronic intestinal inflammation following solid organ transplant. At our center, nine of 327 kidney or liver recipients developed de novo IBD following transplant (six liver, two kidney, one liver-kidney). Most children presented with prolonged hematochezia and diarrhea and were treated with aminosalicylates. At time of diagnosis, five were not currently using mycophenolate mofetil for transplant immunosuppression. Histologic and endoscopic findings at IBD diagnosis included inflammation, ulcerations, granulomas, and chronic colitis. Since diagnosis, no patients have required surgical intervention, or escalation to biologic therapy, nor developed stricturing or perianal disease. In this case series, de novo post-transplant IBD developed in 4% of pediatric liver and/or kidney recipients; however, it often does not fit the classic patterns of Crohn's disease or ulcerative colitis. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  6. Novel NaCS-CS-PPS microcapsules as a potential enzyme-triggered release carrier for highly-loading 5-ASA.

    Science.gov (United States)

    Wu, Qing-Xi; Yao, Shan-Jing

    2013-09-01

    In order to develop novel spherical micro-drug-carriers, an orifice-polymerization method was used to prepare spherical microcapsules which were composed of chemically crosslinked chitosan (CS) with sodium cellulose sulfate (NaCS) and sodium polyphosphate (PPS). 5-Aminosalicylic acid (5-ASA) was chosen as a model drug. The microcapsules prepared had an average diameter of 1.90 mm with loading efficiency of 60.77% and encapsulation efficiency of 90.03%. SEM results showed that the microcapsules had a double-walled capsule structure with an outer wall thickness of approximately 4.40 μm and inner wall (shell) thickness of approximately 187.14 μm. SEM transection images of the microcapsules showed that 5-ASA entrapped in the microcapsule was in a crystal form. The results of in vitro swelling/erosion and release analysis showed that the drug was preferentially and completely released in simulated colonic fluid (SCF, pH 6.4) under the mechanism of Anomalous transport. All these results indicate that the microcapsules could be a good candidate as an enzyme-triggered controlled release drug carrier. Copyright © 2013 Elsevier B.V. All rights reserved.

  7. Pas de Deux: Active Ulcerative Colitis in an HIV-Positive Patient

    Directory of Open Access Journals (Sweden)

    David C Pearson

    1996-01-01

    Full Text Available A 40-year-old male who was found to be human immunodeficiency virus-positive when he presented with bloody diarrhea in 1986 is described. Clinical, laboratory, endoscopic and histological findings were all compatible with ulcerative colitis, and stool cultures were repeatedly negative for pathogens. Colitis was initially mild and controlled with intermittent oral aminosalicylic acid products. Since 1993 he has had more significant symptoms requiring prednisone up to 40 mg/day. Repeat colonoscopy disclosed pancolitis and biopsies did not show evidence of cytomegalovirus infection. He has not had an acquired immune deficiency syndrome-defining illness. CD4 cells fell below normal as his colitis worsened. This case raises questions about immune regulation in ulcerative colitis because the patient has active disease in addition to a reduced number of T helper cells. It also presents a difficult management problem because the patient has a limited life expectancy and is reluctant to accept colectomy, and further immunosuppressive therapy may be dangerous.

  8. A horizontal plug-flow baffled bioelectrocatalyzed reactor for the reductive decolorization of Alizarin Yellow R.

    Science.gov (United States)

    Sun, Qian; Li, Zhiling; Wang, Youzhao; Cui, Dan; Liang, Bin; Thangavel, Sangeetha; Chung, Jong Shik; Wang, Aijie

    2015-11-01

    An application-oriented membrane-free, continuous plug-flow baffled bioelectrocatalyzed reactor (PFB-BER), was designed and testified for the decolorization of Alizarin Yellow R. Decolorization efficiency (DE) with an external power source of 0.5 V was higher than without electrolysis, i.e. 93.4% versus 73.6% (HRT of 24 h). Product formation efficiencies of p-phenylenediamine and 5-aminosalicylic acid were above 95% and 50%, respectively. When HRT decreased to 8 h and 4 h, DE reduced to 69.9% and 44.9%, respectively. An additional electrode assembly improved DE to 96.4% (HRT of 8 h) and 80% (HRT of 4 h), while energy consumption (HRT of 4 h) was lower than that of HRT of 12 h with single electrode assembly under comparable DE. The PFB-BER with higher removal capacity, lower internal resistance and energy consumption provides a new solution to treat the high loading azo dye-containing wastewaters. Copyright © 2015. Published by Elsevier Ltd.

  9. 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.

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

    International Nuclear Information System (INIS)

    Mahkam, M.; Ranaei Siadat, S. O.

    2006-01-01

    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

  11. Unanticipated Mycobacterium tuberculosis complex culture inhibition by immune modulators, immune suppressants, a growth enhancer, and vitamins A and D: clinical implications.

    Science.gov (United States)

    Greenstein, Robert J; Su, Liya; Shahidi, Azra; Brown, William D; Clifford, Anya; Brown, Sheldon T

    2014-09-01

    The development of novel antibiotics to treat multidrug-resistant (MDR) tuberculosis is time-consuming and expensive. Multiple immune modulators, immune suppressants, anti-inflammatories, and growth enhancers, and vitamins A and D, inhibit Mycobacterium avium subspecies paratuberculosis (MAP) in culture. We studied the culture inhibition of Mycobacterium tuberculosis complex by these agents. Biosafety level two M. tuberculosis complex (ATCC 19015 and ATCC 25177) was studied in radiometric Bactec or MGIT culture. Agents evaluated included clofazimine, methotrexate, 6-mercaptopurine, cyclosporine A, rapamycin, tacrolimus, monensin, and vitamins A and D. All the agents mentioned above caused dose-dependent inhibition of the M. tuberculosis complex. There was no inhibition by the anti-inflammatory 5-aminosalicylic acid, which causes bacteriostatic inhibition of MAP. We conclude that, at a minimum, studies with virulent M. tuberculosis are indicated with the agents mentioned above, as well as with the thioamide 5-propothiouricil, which has previously been shown to inhibit the M. tuberculosis complex in culture. Our data additionally emphasize the importance of vitamins A and D in treating mycobacterial diseases. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

  12. Preoperative hypoalbuminemia is associated with an increased risk for intra-abdominal septic complications after primary anastomosis for Crohn's disease.

    Science.gov (United States)

    Liu, Xuanhui; Wu, Xianrui; Zhou, Chi; Hu, Tuo; Ke, Jia; Chen, Yufeng; He, Xiaosheng; Zheng, Xiaobin; He, Xiaowen; Hu, Jiancong; Zhi, Min; Gao, Xiang; Hu, Pinjin; Wu, Xiaojian; Lan, Ping

    2017-11-01

    The aim of this study was to evaluate the impact of preoperative hypoalbuminemia on the development of intra-abdominal septic complications (IASCs) after primary anastomosis for patients with Crohn's disease (CD). All CD patients undergoing bowel resection with a primary anastomosis during the study period from 2007 to 2015 were enrolled. The association of preoperative hypoalbuminemia (preoperative albumin level. Preoperative hypoalbuminemia occurred in 13 (11.7%) patients. The duration from diagnosis to surgery was longer for patients with preoperative hypoalbuminemia than those without ( p = 0.012). Patients with preoperative hypoalbuminemia were more likely to have a history of preoperative use of 5-aminosalicylic acid ( p = 0.013) and have an intraoperative finding of small bowel obstruction ( p = 0.015). Of all patients, 24 (19.4%) developed postoperative IASCs. Univariate analysis showed that patients with preoperative hypoalbuminemia had an increased risk for IASCs ( p = 0.012). Multivariate analysis confirmed the association between preoperative hypoalbuminemia and IASCs (odds ratio 4.67, 95% confidence interval: 1.28-17.04, p = 0.02). Similar findings were also obtained when preoperative albumin level was analysed as a continuous variable ( p = 0.019). Preoperative hypoalbuminemia is a significant predictor for the development of postoperative IASCs in CD patients after bowel resection with a primary anastomosis. Favorable preoperative nutrition status might lessen the risk for IASCs.

  13. Physician Perspectives on Unresolved Issues in the Management of Ulcerative Colitis: The UC Horizons Project.

    Science.gov (United States)

    Gisbert, Javier P; Barreiro-de Acosta, Manuel; Esteve, María; García-Sánchez, Valle; Gomollón, Fernando; Guardiola, Jordi; Hinojosa, Joaquin; Martín Arranz, Maria-Dolores; Minguez, Miguel; Taxonera, Carlos; Vera, Isabel

    2016-03-01

    There is still uncertainty about what constitutes the best therapeutic practice in ulcerative colitis (UC). The purpose of the "UC Horizons Project" was to raise a series of questions regarding the management of UC to provide responses based on the best scientific evidence available. The 11 members of the scientific committee prepared draft answers to the 10 questions from available evidence after a literature search. A total of 48 Spanish gastroenterology specialists nationwide participated in the project. The national meeting discussed the 10 issues in working groups and reached consensus regarding the recommendations by anonymous, interactive vote following the Delphi methodology. Final answers were developed, based on evidence and clinical experience of the participants. All the recommendations achieved a high level of agreement in the plenary vote, although the quality of the evidence was markedly heterogeneous. The lowest percentage of agreement corresponded to the questions with the weakest level of evidence, highlighting the necessity of conducting further studies in these areas. The recommendations focused on (1) aminosalicylates therapy (regarding dose and appropriateness of coadministration with thiopurines), (2) corticosteroid therapy (regarding dose and route of administration), (3) thiopurine treatment (regarding indications and possibility of withdrawal), (4) anti-tumor necrosis factor therapy (regarding appropriateness of combination with thiopurines, intensification, or discontinuation of treatment), and (5) colorectal cancer (regarding risk and time trends). The UC Horizons Project raised a series of eminently practical questions about the management of UC and provided responses based on the best scientific evidence available.

  14. Recurrent Hepatocellular Carcinoma in Patient with Crohn’s Disease: Incidental or Expected Outcome of Azathioprine?

    Directory of Open Access Journals (Sweden)

    Youssef Botros

    2015-01-01

    Full Text Available Hepatocellular carcinoma (HCC usually occurs in patients with underlying risk factors such as liver cirrhosis and chronic hepatitis B. Although patients with Crohn’s disease (CD are at an increased risk to develop malignancies such as colon cancer, the incidence of HCC in this population is extremely rare. We report a case of 62-year-old male with long history of CD treated with azathioprine (AZA and aminosalicylic acid (ASA who was incidentally diagnosed with HCC, for which left hepatectomy was done. Four years later during routine follow-up, patient had another hepatic lesion and underwent resection of the mass. The mechanism of occurrence of HCC in patient with CD is still controversial and may include immune mediated changes and medication related complications. AZA was reported in all case reports of CD that developed HCC. Through this report we hope to explore the complex pathophysiological mechanisms contributing to the development of HCC in the Crohn’s disease patient population.

  15. Effect of charcoal-drug ratio on antidotal efficacy of oral activated charcoal in man.

    Science.gov (United States)

    Olkkola, K T

    1985-01-01

    The effect of charcoal-drug ratio on the antidotal efficacy of oral activated charcoal was studied in six healthy volunteers in a randomized cross-over study and compared with the adsorption capacity of activated charcoal in vitro. Aminosalicylic acid (PAS) 1 g and 5 g were ingested on an empty stomach in 30 ml of water. Immediately afterwards the subjects ingested 50 g of activated charcoal in 300 ml of water or 300 ml of water only. PAS 10 g 20 g were only given with 50 g of activated charcoal administered immediately afterwards. The plasma concentrations and the cumulative excretion of PAS into urine were measured for 48 h. Increasing the dose of PAS from 1 g to 20 g reduced the antidotal efficacy of activated charcoal: at a charcoal-drug ratio of 50:1 under 5% of the dose was absorbed but at a ratio of 2.5:1 about 37%. These data correlated well to the saturation of adsorption capacity of charcoal in vitro. To minimize the possibility of saturation of the adsorption capacity of charcoal in acute intoxications where the amount and type of drug taken is usually unknown, large doses (50-100 g) of activated charcoal should be used. PMID:4027120

  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. Copyright © 2016 Elsevier GmbH. All rights reserved.

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

    International Nuclear Information System (INIS)

    Martenson, James A.; Hyland, Glenn; Moertel, Charles G.; Mailliard, James A.; O'Fallon, Judith R.; Collins, Roger T.; Morton, Roscoe F.; Tewfik, Hamed H.; Moore, Randy L.; Frank, Albert R.; Urias, Rodolfo E.; Deming, Richard L.

    1996-01-01

    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. Development and Improvement of Simple Colonic Mucosal Ulcer during Treatment of Severe Ulcerative Colitis with Tacrolimus

    Directory of Open Access Journals (Sweden)

    Ayumi Ito

    2017-03-01

    Full Text Available Diarrhea, melena, and lower abdominal pain developed in a male in his 20s and colonoscopy showed pancolitis-type severe ulcerative colitis (UC. Treatment was initiated with 4,000 mg of 5-aminosalicylic acid and 60 mg/day of prednisolone, but the symptoms and inflammatory reaction worsened with prednisolone dose reduction. Tacrolimus was added to the treatment, which subsequently induced remission. Serial colonoscopies during the treatment showed improvement in ulcer and mucosal edema throughout the entire large intestine, but a new solitary round ulcer appeared at the end of the ileum. Since no signs of Behçet’s disease were noted, it was considered as a simple ulcer, a complication of UC. Tacrolimus treatment was continued based on continued improvement in clinical features and colonic mucosa, excluding the end of the ileum. Colonoscopy at 6 months after initiation of tacrolimus showed healing of the large intestinal mucosa, although mild congestion was still noted. The solitary round ulcer at the end of the ileum improved to a small erosion. We report the improvement of a simple ulcer that developed during tacrolimus treatment.

  19. Anti-inflammatory effects of Dioscorea alata L. anthocyanins in a TNBS-induced colitis model.

    Science.gov (United States)

    Chen, Tao; Hu, Shihui; Zhang, Haiwen; Guan, Qingfeng; Yang, Yuhui; Wang, Xuemei

    2017-02-22

    The purple yam, Dioscorea alata L., is an important source of starch, vitamins and polyphenols. Five different pigments from the purple tubers of this plant were separated by high-performance liquid chromatography-mass spectrometry, and the anthocyanin fraction (DACN) was collected. The anti-inflammatory effects of DACNs were investigated at different concentrations and compared with the standard colitis treatment, 5-aminosalicylic acid, in a trinitrobenzenesulfonic acid (TNBS)-induced colitis mouse model. Macro- and microscopic parameters including body weight change, disease activity index (DAI) and intestinal histology were used for the determination of the anti-inflammatory effects of DACNs. The gene expression levels of tight junction-related proteins in the intestine, myeloperoxidase activity, inducible nitric oxide synthase activity in colonic tissues and pro-inflammatory cytokine production in serum were also measured to elucidate the mechanism of DACN action. Eighty micrograms of DACNs per kilogram of body weight produced potent anti-inflammatory effects in the mouse model of inflammatory bowel disease (IBD), as shown by the DAI (2.78 ± 0.38 vs. 0.44 ± 0.51). Therefore, DACNs may be applied as a potential food supplement in IBD therapy.

  20. Immunotherapy of Crohn's disease

    Directory of Open Access Journals (Sweden)

    C. van Montfrans

    1998-01-01

    Full Text Available Although the initiating events of Crohn's disease are unknown, models of experimental colitis have provided new insights in the immunologically mediated pathways of mucosal inflammation. In Crohn's disease activated mucosal T lymphocytes produce proinflammatory cytokines within the mucosal compartment. With this understanding, there has been a shift in past years from the use of unspecific anti-inflammatory agents (corticosteroids, aminosalicylates to the use of immunomodulatory drugs (azathioprine, methotrexate. Moreover, novel strategies have been designed for specific targets in Crohn's disease, in particular T lymphocytes and cytokines. In an open label study treatment of steroid-refractory Crohn's disease with anti- CD4+ antibodies was well tolerated and showed clinical benefit. However, a sustained depletion of the CD4+ cells precluded further clinical trials. In controlled clinical studies, anti-tumour necrosis factor (TNF-α antibodies induced com plete remissions and few side effects were observed. One study suggested efficacy in active Crohn's disease of recombinant interleukin-10. Long term treatment studies will have to answer questions about the indications for use, benefit and toxicity. Altogether, these results hold promise for future management of Crohn's disease, where disease-modifying interventions and strategies that effectively maintain disease remission will play a key role.

  1. Ulcerative colitis-associated colorectal cancer

    Science.gov (United States)

    Yashiro, Masakazu

    2014-01-01

    The association between ulcerative colitis (UC) and colorectal cancer (CRC) has been acknowledged. One of the most serious and life threatening consequences of UC is the development of CRC (UC-CRC). UC-CRC patients are younger, more frequently have multiple cancerous lesions, and histologically show mucinous or signet ring cell carcinomas. The risk of CRC begins to increase 8 or 10 years after the diagnosis of UC. Risk factors for CRC with UC patients include young age at diagnosis, longer duration, greater anatomical extent of colonic involvement, the degree of inflammation, family history of CRC, and presence of primary sclerosing cholangitis. CRC on the ground of UC develop from non-dysplastic mucosa to indefinite dysplasia, low-grade dysplasia, high-grade dysplasia and finally to invasive adenocarcinoma. Colonoscopy surveillance programs are recommended to reduce the risk of CRC and mortality in UC. Genetic alterations might play a role in the development of UC-CRC. 5-aminosalicylates might represent a favorable therapeutic option for chemoprevention of CRC. PMID:25469007

  2. Peroxisome Proliferator-Activated Receptors Family Is Involved in the Response to Treatment and Mild Clinical Course in Patients with Ulcerative Colitis

    Directory of Open Access Journals (Sweden)

    J. K. Yamamoto-Furusho

    2014-01-01

    Full Text Available Background. PPARs play an important role in the regulation of intestinal inflammation. Methods. We included a total of 46 UC patients and 31 controls. The gene expression of PPARs was measured by RT-PCR and protein expression by immunohistochemistry. Results. PPARα gene expression was significantly decreased in patients with active UC compared with remission UC group (P=0.001 and controls (P=0.001. We found that low gene expression of PPARα in mucosa confers a higher risk of UC activity (P≤0.0001, OR = 22.6. We observed an increase of PPARα expression in patients with UC who were treated with 5-aminosalicylates compared with those who received any other combined therapy (P=0.03, OR = 0.08. PPARγ gene expression was decreased in the active UC group compared with UC in remission (P=0.001 and control group (P=0.001. An increased expression of PPARγ gene was associated with mild clinical course of the disease (P≤0.001, OR = 0.05. No gene expression of PPARβ/δ was found in the colonic mucosa from UC patients and controls. Conclusion. Our results suggest that patients with high gene expression of PPARs have a better response to medical treatment and a mild clinical course of the disease.

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

    Science.gov (United States)

    Nørgård, Bente Mertz

    2011-12-01

    during pregnancy our data suggest. No significantly increased overall relative risk of congenital abnormalities and no significantly increased risks of selected congenital abnormalities. After exposure to 5-aminosalicylic acid during pregnancy our data suggest. No significantly increased relative risk of low birth weight, intrauterine growth retardation or congenital abnormalities (evaluated overall). A significantly increased relative risk of preterm birth and stillbirth in ulcerative colitis women, compared to women with no prescription of reimbursed medicine in pregnancy - and also after comparing with women with chronic inflammatory bowel disease not taking 5-aminosalicylic acid during pregnancy. It is not clear whether these associations are causal or influenced by confounding by disease activity in particular. After maternal exposure to azathioprine/6-mercaptopurine during pregnancy our data suggest. An increased relative risk of preterm birth, congenital abnormalities, and perinatal mortality - also after using controls with similar underlying diseases. It is difficult to rule out an influence of uncontrolled confounding. These were the first published data from a controlled observational study on exposed women with chronic inflammatory bowel disease. After preconceptional paternal use of azathioprine/6-mercaptopurine our data suggest An increased risk of congenital abnormalities, although not significantly increased. The birth outcomes in women with Crohn's disease are examined in nationwide sub-cohorts classified according to type of anti-inflammatory drug exposure during pregnancy, and based on data from the Danish National Hospital Discharge Registry, the nationwide Danish Prescription Database and the Danish Medical Birth Registry. Furthermore, birth outcomes are examined in Crohn's disease women with disease activity during pregnancy, based on data from review of hospital records, the Danish National Hospital Discharge Registry and the Danish Medical Birth

  4. Use of mesalazine slow release suppositories 1 g three times per week to maintain remission of ulcerative proctitis: a randomised double blind placebo controlled multicentre study

    Science.gov (United States)

    Marteau, P; Crand, J; Foucault, M; Rambaud, J

    1998-01-01

    Background—Daily administration of rectal formulations of mesalazine is effective in preventing relapse of ulcerative proctitis. Maintenance of remission with lower doses would be an advantage. 
Aim—The efficacy of mesalazine suppositories (Pentasa) 1 g three times a week v placebo to maintain remission in patients with cryptogenetic proctitis was studied. 
Methods—Ninety five patients with cryptogenetic proctitis were randomised within two weeks of remission to receive for one year or until relapse three suppositories per week of either Pentasa (n=48) or placebo (n=47). In the case of a relapse, the patients received one suppository/day. 
Results—It was found that 25 of 48 subjects v 18 of 47 remained in remission in the mesalazine and placebo groups respectively. The relapse rate was lower in the mesalazine group for the following time intervals: 0-90 days (19% v 38%, p=0.035), 0-180 days (29% v 54%, p=0.017), 0-270 days (38% v 60%, p=0.031), and 0-365 days (48% v 62%, p=0.18). Treatment of relapse with one suppository/day induced remission in 11 of 18 and 2 of 26 patients in the mesalazine and placebo groups respectively (p=0.001). Overall, 61% v 28% patients remained in the protocol and were in remission at one year (p=0.001). Tolerance was good. 
Conclusion—Mesalazine suppositories 1 g three times a week are effective for preventing relapses of cryptogenetic proctitis. Increasing the dose to 1 g/day is effective in a high proportion of subjects who relapsed. 

 Keywords: inflammatory bowel disease; mesalazine; 5-aminosalicylic acid; topical treatments; proctitis PMID:9536943

  5. Dissolution of Commercially Available Mesalamine Formulations at Various pH Levels.

    Science.gov (United States)

    Tenjarla, Srini

    2015-06-01

    Mesalamine (5-aminosalicylic acid; 5-ASA) is recommended first-line therapy for mild-to-moderate ulcerative colitis. Many mesalamine formulations employ a pH-dependent release mechanism designed to maximize drug release in the colon. This study compared the in vitro release of 5-ASA from six commercially available mesalamine formulations at pH levels similar to those typically encountered in the human gastrointestinal tract. The release of 5-ASA from six mesalamine formulations [Mesalazin-Kohlpharma (Kohlpharma, Germany), Mesalazin-Eurim (Eurimpharm, Germany), Mesalazina-Faes (Faes Farma, Spain), Mesalazine EC (Actavis B.V., Netherlands), Mesalazine EC 500 PCH (Pharmachemie B.V., Netherlands); multimatrix mesalamine (Shire US Inc., USA)] was monitored separately at three different pH levels [1.0 (2 h), 6.4 (1 h), and 7.2 (8 h)] using United States Pharmacopeia dissolution apparatus II. The dissolution percentage was calculated as a mean of 12 units for each formulation. At pH 1.0 and 6.4, pH 7.2, complete release of 5-ASA occurred within 1 h for Mesalazine EC and Mesalazine EC 500 PCH, and within 2 h for Mesalazin-Kohlpharma, Mesalazin-Eurim, and Mesalazina-Faes; complete release of 5-ASA from multimatrix mesalamine occurred within 7 h. Little variability in rate of 5-ASA dissolution was observed between tablets of each formulation. At pH 7.2, 5-ASA release profiles were variable among the commercially available mesalamine formulations that were tested.

  6. Maintenance of remission of ulcerative colitis: a comparison between balsalazide 3 g daily and mesalazine 1.2 g daily over 12 months. ABACUS Investigator group.

    Science.gov (United States)

    Green, J R; Gibson, J A; Kerr, G D; Swarbrick, E T; Lobo, A J; Holdsworth, C D; Crowe, J P; Schofield, K J; Taylor, M D

    1998-12-01

    Despite widespread use of aminosalicylates as maintenance treatment for ulcerative colitis (UC), patients still report troublesome symptoms, often nocturnally. To compare the efficacy and safety of balsalazide (Colazide) with mesalazine (Asacol) in maintaining UC remission. A randomized, double-blind comparison of balsalazide 3 g daily (1.04 g 5-ASA) and mesalazine 1.2 g daily for 12 months, in 99 (95 evaluable) patients in UC remission. Balsalazide patients experienced more asymptomatic nights (90% vs. 77%, P=0.0011) and days (58% vs. 50%, N.S.) during the first 3 months. Balsalazide patients experienced more symptom-free nights per week (6.4+/-1.7 vs. 4.7+/-2.8; P=0.0006) and fewer nights per week with blood on their stools or on the toilet paper, mucus with their stools or with sleep disturbance resulting from symptoms or lavatory visits (each P < 0.05). Fewer balsalazide patients relapsed within 3 months (10% vs. 28%; P=0.0354). Remission at 12 months was 58%, in both groups. Similar proportions of patients reported adverse events (61% balsalazide vs. 65% mesalazine). There were five serious adverse events (two balsalazide, three mesalazine) and four withdrawals due to unacceptable adverse events (three balsalazide, one mesalazine), of which one in each group was also a serious adverse event. Balsalazide 3 g/day and mesalazine 1.2 g/ day effectively maintain UC remission and are equally well tolerated over 12 months. At this dose balsalazide prevents more relapses during the first 3 months of treatment and controls nocturnal symptoms more effectively.

  7. First Report in China on the Identification and Drug Sensitivity of Mycobacterium elephantis Isolated from the Milk of a Cow with Mastitis.

    Science.gov (United States)

    Ji, Ling Yun; Xu, Dong Lei; Yin, Shu Peng; Liu, Hai Can; Li, Gui Lian; Jiang, Yi; Wei, Jian Hao; Zeng, Hao; Lou, Yong Liang; Lyu, Jian Xin; Wan, Kang Lin

    2017-07-01

    In this study, milk from a cow with mastitis was analyzed to determine the presence of mycobacterial infection. Milk quality and security problems pertaining to the safe consumption of dairy products were also discussed in this study. Milk was preprocessed with 4% NaOH. Then, mycobacteria were isolated from the milk sample on L-J medium. The isolate was identified using multiple loci Polymerase Chain Reaction (PCR) and multi-locus sequence analysis with 16S rRNA, sodA, hsp65, and ITS genes. The drug sensitivity of the isolate to 27 antibiotics was tested through alamar blue assay. Smooth, moist, pale yellow colonies appeared on the L-J medium within a week after inoculation. Based on the results of multiple loci PCR analysis, the isolate was preliminarily identified as non-tuberculous mycobacteria. The 16S rRNA, SodA, hsp65, and ITS gene sequences of the isolate exhibited 99%, 99%, 99%, and 100% similarities, respectively, with those of the published reference strains of Mycobacterium elephantis (M. elephantis). The drug sensitivity results showed that the strain is resistant to isoniazid, p-aminosalicylic acid, and trimesulf but is sensitive to ofloxacin, rifampicin, amikacin, capreomycin, moxifloxacin, kanamycin, levofloxacin, cycloserine, ethambutol, streptomycin, tobramycin, rifabutin, ciprofloxacin, linezolid, cefoxitin, clarithromycin, and minocycline. To the best of our knowledge, this study is initially to report the isolation of M. elephantis from the milk of a cow with mastitis in China. Copyright © 2017 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.

  8. Quantitation of underivatized branched-chain amino acids in sport nutritional supplements by capillary electrophoresis with direct or indirect UV absorbance detection.

    Directory of Open Access Journals (Sweden)

    Jun Qiu

    Full Text Available The branched-chain amino acids (BCAAs including leucine (Leu, isoleucine (Ile and valine (Val play a pivotal role in the human body. Herein, we developed capillary electrophoresis (CE coupled with conventional UV detector to quantify underivatized BCAAs in two kinds of sport nutritional supplements. For direct UV detection at 195 nm, the BCAAs (Leu, two enantiomers of Ile and Val were separated in a background electrolyte (BGE consisting of 40.0 mmol/L sodium tetraborate, and 40.0 mmol/L β-cyclodextrin (β-CD at pH 10.2. In addition, the indirect UV detection at 264 nm was achieved in a BGE of 2.0 mmol/L Na2HPO4, 10.0 mmol/L p-aminosalicylic acid (PAS as UV absorbing probe, and 40.0 mmol/L β-CD at pH 12.2. The β-CD significantly benefited the isomeric separation of Leu, L- and D-Ile. The optimal conditions allowed the LODs (limit of detections of direct and indirect UV absorption detection to be tens μmol/L level, which was comparable to the reported CE inline derivatization method. The RSDs (relative standard deviations of migration time and peak area were less than 0.91% and 3.66% (n = 6. Finally, CE with indirect UV detection method was applied for the quantitation of BCAAs in two commercial sport nutritional supplements, and good recovery and precision were obtained. Such simple CE method without tedious derivatization process is feasible of quality control and efficacy evaluation of the supplemental proteins.

  9. 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

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

    Science.gov (United States)

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

    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. 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. 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.

  11. A Randomized, Double-blind, Placebo-controlled, Parallel-group, Pilot Study of Cannabidiol-rich Botanical Extract in the Symptomatic Treatment of Ulcerative Colitis.

    Science.gov (United States)

    Irving, Peter M; Iqbal, Tariq; Nwokolo, Chuka; Subramanian, Sreedhar; Bloom, Stuart; Prasad, Neeraj; Hart, Ailsa; Murray, Charles; Lindsay, James O; Taylor, Adam; Barron, Rachel; Wright, Stephen

    2018-03-19

    Cannabidiol (CBD) exhibits anti-inflammatory properties that could improve disease activity in inflammatory bowel disease. This proof-of-concept study assessed efficacy, safety and tolerability of CBD-rich botanical extract in ulcerative colitis (UC) patients. Patients aged 18 years or older, with left-sided or extensive UC, Mayo scores of 4-10 (endoscopy scores ≥1), and on stable 5-aminosalicylic acid dosing, were randomized to 10-weeks' CBD-rich botanical extract or placebo capsules. The primary endpoint was the percentage of patients in remission after treatment. Statistical testing was 2-sided, using a 10% significance level. Patients were less tolerant of CBD-rich botanical extract compared with placebo, taking on average one-third fewer capsules, and having more compliance-related protocol deviations (principally insufficient exposure), prompting identification of a per protocol (PP) analysis set. The primary endpoint was negative; end of treatment remission rates were similar for CBD-rich botanical extract (28%) and placebo (26%). However, PP analysis of total and partial Mayo scores favoured CBD-rich botanical extract (P = 0.068 and P = 0.038, respectively). Additionally, PP analyses of the more subjective physician's global assessment of illness severity, subject global impression of change, and patient-reported quality-of-life outcomes were improved for patients taking CBD-rich botanical extract (P = 0.069, P = 0.003, and P = 0.065, respectively). Adverse events (AEs) were predominantly mild/moderate with many in the CBD-rich botanical extract group potentially attributable to the ∆9-tetrahydrocannabinol content. A greater proportion of gastrointestinal-related AEs, indicative of UC worsening, was seen on placebo. Although the primary endpoint was not reached, several signals suggest CBD-rich botanical extract may be beneficial for symptomatic treatment of UC.

  12. Pouchitis – What’s new in etiology and management

    Directory of Open Access Journals (Sweden)

    R John Nicholls

    1995-01-01

    Full Text Available Pouchitis requires a clear clinicopathological definition. There are many conflicting data concerning etiology. It is linked to an initial diagnosis of ulcerative colitis by clinical association and occurrence of extra-alimentary manifestations, histologically and by macrophage types and inflammatory mediators. Evidence for a bacteriological cause comes from response to metronidazole, increased counts of intramucosal bacteria in pouchitis and the possible association of hypochlorhydria. Most studies have, however, shown no specific bacterial pathogen or luminal bacterial count differences in pouches with or without pouchitis. Abnormal fecal bile salt concentrations have been reported. Stasis and evacuation efficiency of the pouch are not associated with pouchitis in most studies. Reduced mucosal bloodflow may be associated perhaps leading to increased permeability to toxins causing activation of interleukin-1, platelet-activating factor (PAF and tumour necrosis factor (TNF. PAF may be increased in pouchitis. Pouchitis may respond to allopurinol. Volatile short chain fatty acids (VSFA may be reduced in ileal reservoirs compared with straight ileoanal segments and in pouchitis. The response of pouchitis to administered VSFA is, however, variable. Glutamine administration may help. There is evidence that intraepithelial T lymphocytes are reduced. Crypt cell turnover is higher in colitic than in polypotic pouches. Mucosal morphological changes of villous atrophy and inflammation occur early after relapsing polychondritis and may predict future susceptibility to pouchitis. Early mucosal biopsy appears to have prognostic value. Metronidazole and antibiotics (amoxicillin/potassium clavulanate, ciprofloxacin may be effective although in a controlled trial of the former there was little advantage over placebo. The results of treatment using VSFA, glutamine, allopurinol sucralfate and anti-inflammatory agents, including aminosalicylic acid (5-ASA and

  13. Randomised clinical trial: a herbal preparation of myrrh, chamomile and coffee charcoal compared with mesalazine in maintaining remission in ulcerative colitis--a double-blind, double-dummy study.

    Science.gov (United States)

    Langhorst, J; Varnhagen, I; Schneider, S B; Albrecht, U; Rueffer, A; Stange, R; Michalsen, A; Dobos, G J

    2013-09-01

    The herbal treatment with myrrh, dry extract of chamomile flowers and coffee charcoal has anti-inflammatory and antidiarrhoeal potential and might benefit patients with UC. Aminosalicylates are used as standard treatment for maintaining remission in ulcerative colitis (UC). To compare the efficacy of the two treatments in maintaining remission in patients with ulcerative colitis. We performed a randomised, double-blind, double-dummy study over a 12-month period in patients with UC. Primary endpoint was non-inferiority of the herbal preparation as defined by mean Clinical Colitis Activity Index (CAI-Rachmilewitz). Secondary endpoints were relapse rates, safety profile, relapse-free times, endoscopic activity and faecal biomarkers. A total of 96 patients (51 female) with inactive UC were included. Mean CAI demonstrated no significant difference between the two treatment groups in the intention-to-treat (P = 0.121) or per-protocol (P = 0.251) analysis. Relapse rates in total were 22/49 patients (45%) in the mesalazine treatment group and 25/47 patients (53%) in the herbal treatment group (P = 0.540). Safety profile and tolerability were good and no significant differences were shown in relapse-free time, endoscopy and faecal biomarkers. The herbal preparation of myrrh, chamomile extract and coffee charcoal is well tolerated and shows a good safety profile. We found first evidence for a potential efficacy non-inferior to the gold standard therapy mesalazine, which merits further study of its clinical usefulness in maintenance therapy of patients with ulcerative colitis. EudraCT-Number 2007-007928-18. © 2013 John Wiley & Sons Ltd.

  14. Communication Between Physicians and Patients with Ulcerative Colitis: Reflections and Insights from a Qualitative Study of In-Office Patient-Physician Visits.

    Science.gov (United States)

    Rubin, David T; Dubinsky, Marla C; Martino, Steve; Hewett, Kathleen A; Panés, Julian

    2017-04-01

    We analyzed in-office communication between patients with ulcerative colitis (UC) and their gastroenterologists. Participating gastroenterologists (United States N = 15; Europe N = 8) identified eligible patients with scheduled clinic visits. Patients (United States N = 40; Europe N = 28; ≥18 yr old; physician-defined moderately-to-severely active ulcerative colitis for approximately ≥1 yr; ≥1 flare in preceding year; prior or current therapy with 5-aminosalicylates and/or corticosteroids) consented to have their visit recorded. Follow-up interviews were conducted separately with gastroenterologists and patients. Transcripts were analyzed using sociolinguistic methods to explore quality of life (QoL) impacts, treatment goals, and attitudes to therapies. In the European and U.S. research, the trend was for patients not to discuss ulcerative colitis QoL impacts during their visits. In the U.S. research, complete patient-physician alignment on QoL impacts (patient and physician stating the same impacts) was seen in 40% of cases. Variation in treatment goals was seen between gastroenterologists and patients: 3% of U.S. patients described absence of inflammation as a treatment goal versus 25% of gastroenterologists. This goal was not always conveyed to the patient during visits. Consistent with guidelines, physicians generally framed biologic therapy as suitable for patients refractory to conventional therapies. However, although putative efficacy offered by biologic therapy is generally aligned with patients' stated treatment goals, many considered biologic therapy as more appropriate for more severe disease than theirs. Alignment between patients and physicians on ulcerative colitis QoL impact, treatment goals, and requirement of advanced therapies is poor. New tools are needed to cover this gap.

  15. Thromboembolism as an important complication of inflammatory bowel disease.

    Science.gov (United States)

    Bollen, Lize; Vande Casteele, Niels; Ballet, Vera; van Assche, Gert; Ferrante, Marc; Vermeire, Séverine; Gils, Ann

    2016-01-01

    Patients with inflammatory bowel disease (IBD) have a higher risk of developing thromboembolic events (TE) compared with the healthy population. This study aimed to describe a cohort of IBD patients with a history of TE focusing on recurrence of TE, disease activity and IBD medication at the time of TE and surgery before TE. In a retrospective monocentric cohort study, we included IBD patients in whom an arterial and/or venous TE occurred. Eighty-four IBD patients with a history of TE (63% Crohn's disease, 44% men) and a mean age of 45±15 years were included; 25/84 patients (30%) were identified to have recurrent TE. Seventy out of 84 (83%) developed a venous TE, with a deep vein thrombosis as the major manifestation (28/70, 40%), followed by a pulmonary embolism (16/70, 23%). At the time of TE, 60/84 (71%) patients were diagnosed with active disease. In all, 23% patients were on 5-aminosalicylic acids, 36% on steroids, 18% on azathioprine, 5% on methotrexate, 12% on biologicals and 23% were not receiving specific IBD treatment. Moreover, within a 6-month period preceding the TE, 28/84 (33%) patients underwent surgery, of whom 17% received thromboprophylaxis at hospital discharge. We confirm the association between disease activity and the occurrence of TE. A substantial number of patients had additional risk factors such as recurrence of TE. In all, 36% received steroids at the time of TE and 33% underwent recent surgery, of whom only a minority received thromboprophylaxis at hospital discharge. Further efforts are required to increase thromboprophylaxis in at-risk patients.

  16. Facile preparation and characterization of new green emitting carbon dots for sensitive and selective off/on detection of Fe3+ion and ascorbic acid in water and urine samples and intracellular imaging in living cells.

    Science.gov (United States)

    Shamsipur, Mojtaba; Molaei, Karam; Molaabasi, Fatemeh; Alipour, Mohsen; Alizadeh, Naader; Hosseinkhani, Saman; Hosseini, Morteza

    2018-06-01

    Carbon dots (CDs) have gained great attention as multifunctional materials because of their interesting properties and general applicability. However, there are some reports for the preparation of highly luminescent green-emitting CDs (G-CDs), although these reports seem not to be extensible. Herein, new G-CDs (quantum yield: 27.2%) were synthesized from a facile hydrothermal treatment of p-aminosalicylic acid and ethylene glycol dimethacrylate as both carbon and nitrogen source and cross-linking agent, respectively. The chemical composition and optical properties of the as-prepared G-CDs were successfully investigated using transmission electron microscopy, atomic force microscopy, dynamic light scattering, X-ray diffraction, energy dispersive X-ray spectroscopy, Fourier transform infrared spectroscopy and fluorescence and UV-vis spectroscopies. Interestingly, the fluorescence intensity of G-CDs was selectivity quenched by Fe 3+ in the range of 0.05-10.0 µmol L- 1 , with a detection limit of 13.7 nmol L- 1 . Meanwhile, ascorbic acid found to reduce Fe 3+ to Fe 2+ , thereby causing restoration of the fluorescence of G-CDs. The detection limit for ascorbic acid detection was estimated as 82.0 nmol L- 1 over a linear range from 0.2 to 11.0 µmol L- 1 . Furthermore, the designed sensing platform was successfully utilized to the detection of Fe 3+ and ascorbic acid in water and urine samples and to intracellular imaging without surface modification. Copyright © 2018 Elsevier B.V. All rights reserved.

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

    Science.gov (United States)

    Pierce, David; Corcoran, Mary; Martin, Patrick; Barrett, Karen; Inglis, Susi; Preston, Peter; Thompson, Thomas N; Willsie, Sandra K

    2014-01-01

    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 equivalence range. Adverse events in all studies were generally mild. Conclusion MMX mesalamine may be coadministered with amoxicillin, ciprofloxacin, metronidazole, or sulfamethoxazole, without affecting pharmacokinetics or safety of

  18. Real-time PCR using mycobacteriophage DNA for rapid phenotypic drug susceptibility results for Mycobacterium tuberculosis.

    Science.gov (United States)

    Pholwat, Suporn; Ehdaie, Beeta; Foongladda, Suporn; Kelly, Kimberly; Houpt, Eric

    2012-03-01

    Managing drug-resistant Mycobacterium tuberculosis requires drug susceptibility testing, yet conventional drug susceptibility testing is slow, and molecular testing does not yield results for all antituberculous drugs. We addressed these challenges by utilizing real-time PCR of mycobacteriophage D29 DNA to evaluate the drug resistance of clinical M. tuberculosis isolates. Mycobacteriophages infect and replicate in viable bacterial cells faster than bacterial cells replicate and have been used for detection and drug resistance testing for M. tuberculosis either by using reporter cells or phages with engineered reporter constructs. Our primary protocol involved culturing M. tuberculosis isolates for 48 h with and without drugs at critical concentrations, followed by incubation with 10(3) PFU/ml of D29 mycobacteriophage for 24 h and then real-time PCR. Many drugs could be incubated instantly with M. tuberculosis and phage for 24 h alone. The change in phage DNA real-time PCR cycle threshold (C(T)) between control M. tuberculosis and M. tuberculosis treated with drugs was calculated and correlated with conventional agar proportion drug susceptibility results. Specifically, 9 susceptible clinical isolates, 22 multidrug-resistant (MDR), and 1 extensively drug-resistant (XDR) M. tuberculosis strains were used and C(T) control-C(T) drug cutoffs of between +0.3 and -6.0 yielded 422/429 (98%) accurate results for isoniazid, rifampin, streptomycin, ethambutol, amikacin, kanamycin, capreomycin, ofloxacin, moxifloxacin, ethionamide, para-aminosalicylic acid, cycloserine, and linezolid. Moreover, the ΔC(T) values correlated with isolate MIC for most agents. This D29 quantitative PCR assay offers a rapid, accurate, 1- to 3-day phenotypic drug susceptibility test for first- and second-line drugs and may suggest an approximate MIC.

  19. 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.

  20. Purinergic Ligands as Potential Therapeutic Tools for the Treatment of Inflammation-Related Intestinal Diseases

    Directory of Open Access Journals (Sweden)

    Diego Dal Ben

    2018-03-01

    Full Text Available Inflammation-related intestinal diseases are a set of various conditions presenting an overactive enteric immune system. A continuous overproduction of pro-inflammatory cytokines and a decreased production of anti-inflammatory modulators are generally observed, while morpho-functional alterations of the enteric nervous system lead to intestinal secretory and motor dysfunctions. The factors at the basis of these conditions are still to be totally identified and current therapeutic strategies are aimed only at achieving and maintaining remission states, by using therapeutic tools like aminosalicylates, corticosteroids, immunomodulators, biological drugs (i.e., monoclonal antibodies, and eventually surgery. Recent reports described a key role of purinergic mediators (i.e., adenosine and its nucleotides ATP and ADP in the regulation of the activity of immune cells and enteric nervous system, showing also that alterations of the purinergic signaling are linked to pathological conditions of the intestinal tract. These data prompted to a series of investigations to test the therapeutic potential for inflammation-related intestinal conditions of compounds able to restore or modulate an altered purinergic signaling within the gut. This review provides an overview on these investigations, describing the results of preclinical and/or clinical evaluation of compounds able to stimulate or inhibit specific P2 (i.e., P2X7 or P1 (i.e., A2A or A3 receptor signaling and to modify the adenosine levels through the modulation of enzymes activity (i.e., Adenosine Deaminase or nucleoside transporters. Recent developments in the field are also reported and the most promising purine-based therapeutic strategies for the treatment of inflammation-related gastrointestinal disorders are schematically summarized.

  1. Inflammatory Bowel Disease and Risk of Adverse Pregnancy Outcomes

    Science.gov (United States)

    Boyd, Heather A.; Basit, Saima; Harpsøe, Maria C.; Wohlfahrt, Jan; Jess, Tine

    2015-01-01

    Background and Objectives Existing data on pregnancy complications in inflammatory bowel disease (IBD) are inconsistent. To address these inconsistencies, we investigated potential associations between IBD, IBD-related medication use during pregnancy, and pregnancy loss, pre-eclampsia, preterm delivery, Apgar score, and congenital abnormalities. Methods We conducted a cohort study in >85,000 Danish National Birth Cohort women who were pregnant in the period 1996-2002 and had information on IBD, IBD-related medication use (systemic or local corticosteroids, 5-aminosalicylates), pregnancy outcomes and potential confounders. We evaluated associations between IBD and adverse pregnancy/birth outcomes using Cox regression and log-linear binomial regression. Results IBD was strongly and significantly associated with severe pre-eclampsia, preterm premature rupture of membranes and medically indicated preterm delivery in women using systemic corticosteroids during pregnancy (hazard ratios [HRs] >7). IBD was also associated with premature preterm rupture of membranes in women using local corticosteroid medications (HR 3.30, 95% confidence interval [CI] 1.33-8.20) and with medically indicated preterm delivery (HR 1.91, 95% CI 0.99-3.68) in non-medicated women. Furthermore, IBD was associated with low 5-minute Apgar score in term infants (risk ratio [RR] 2.19, 95% CI 1.03-4.66). Finally, Crohn’s disease (but not ulcerative colitis) was associated with major congenital abnormalities in the offspring (RR 1.85, 95% CI 1.06-3.21). No child with a congenital abnormality born to a woman with IBD was exposed to systemic corticosteroids in utero. Conclusion Women with IBD are at increased risk of severe pre-eclampsia, medically indicated preterm delivery, preterm premature rupture of membranes, and delivering infants with low Apgar score and major congenital malformations. These associations are only partly explained by severe disease as reflected by systemic corticosteroid use

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

    Directory of Open Access Journals (Sweden)

    Mojgan Masoodi

    Full Text Available 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.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.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.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.

  3. Regulation of antimycin biosynthesis by the orphan ECF RNA polymerase sigma factor σAntA

    Directory of Open Access Journals (Sweden)

    Ryan F. Seipke

    2014-02-01

    Full Text Available Antimycins are an extended family of depsipeptides that are made by filamentous actinomycete bacteria and were first isolated more than 60 years ago. Recently, antimycins have attracted renewed interest because of their activities against the anti-apoptotic machineries inside human cells which could make them promising anti-cancer compounds. The biosynthetic pathway for antimycins was recently characterised but very little is known about the organisation and regulation of the antimycin (ant gene cluster. Here we report that the ant gene cluster in Streptomyces albus is organized into four transcriptional units; the antBA, antCDE, antGF and antHIJKLMNO operons. Unusually for secondary metabolite clusters, the antG and antH promoters are regulated by an extracytoplasmic function (ECF RNA polymerase sigma factor named σAntA which represents a new sub-family of ECF σ factors that is only found in antimycin producing strains. We show that σAntA controls production of the unusual precursor 3-aminosalicylate which is absolutely required for the production of antimycins. σAntA is highly conserved in antimycin producing strains and the −10 and −35 elements at the σAntA regulated antG and antH promoters are also highly conserved suggesting a common mechanism of regulation. We also demonstrate that altering the C-terminal Ala-Ala residues found in all σAntA proteins to Asp-Asp increases expression of the antFG and antGHIJKLMNO operons and we speculate that this Ala-Ala motif may be a signal for the protease ClpXP.

  4. Low temperature fused deposition modeling (FDM) 3D printing of thermolabile drugs.

    Science.gov (United States)

    Kollamaram, Gayathri; Croker, Denise M; Walker, Gavin M; Goyanes, Alvaro; Basit, Abdul W; Gaisford, Simon

    2018-04-26

    Fused deposition modelling (FDM) is the most commonly investigated 3D printing technology for the manufacture of personalized medicines, however, high temperatures associated with the process limit its wider application. The objective of this study was to print low-melting and thermolabile drugs by reducing the FDM printing temperature. Two immediate release polymers, Kollidon VA64 and Kollidon 12PF were investigated as potential candidates for low-temperature FDM printing. Ramipril was used as the model low melting temperature drug (109°C); to the authors' knowledge this is the lowest melting point drug investigated to date by FDM printing. Filaments loaded with 3% drug were obtained by hot melt extrusion at 70°C and ramipril printlets with a dose equivalent of 8.9 mg were printed at 90°C. HPLC analysis confirmed that the drug was stable with no signs of degradation and dissolution studies revealed that drug release from the printlets reached 100% within 20 to 30 mins. Variable temperature Raman and solid state nuclear magnetic resonance (SSNMR) spectroscopy techniques were used to evaluate drug stability over the processing temperature range. These data indicated that ramipril did not undergo degradation below its melting point (which is above the processing temperature range: 70-90 °C) but it was transformed into the impurity diketopiperazine upon exposure to temperatures higher than its melting point. The use of the excipients Kollidon VA64 and Kollidon 12PF in FDM was further validated by printing with the drug 4-aminosalicylic acid (4-ASA), which in previous work was reported to undergo degradation in FDM printing, but here it was found to be stable. This work demonstrates that the selection and use of new excipients can overcome one of the major disadvantages in FDM printing, drug degradation due thermal heating, making this technology suitable for drugs with lower melting temperatures. Copyright © 2018. Published by Elsevier B.V.

  5. Health-related quality of life in patients with inflammatory bowel disease: a single-center experience

    Science.gov (United States)

    Kalafateli, Maria; Triantos, Christos; Theocharis, Georgios; Giannakopoulou, Dimitra; Koutroumpakis, Efstratios; Chronis, Aristidis; Sapountzis, Apostolos; Margaritis, Vasileios; Thomopoulos, Konstantinos; Nikolopoulou, Vasiliki

    2013-01-01

    Background Inflammatory bowel disease (IBD) has a negative impact on health-related quality of life (HRQoL). The aim of the study was to assess HRQoL of IBD patients in South-Western Greece. Methods 89 IBD patients [38 (42.7%) Crohn's disease (CD), 51 (57.3%) ulcerative colitis (UC)] were included. HRQoL was assessed using IBD questionnaire (IBDQ), which tests four health domains: bowel symptoms (BS), systemic symptoms (SS), emotional function (EF) and social function (SF). Total score (TS) ranges from 32 to 224. Disease activity was measured using Crohn's Disease Activity Index (CDAI) (CD), and Truelove and Witts classification (UC). The impact of epidemiological and disease-specific characteristics on IBDQ was studied. Results No statistically significant difference was found in all IBDQ scores between UC and CD patients. No correlation was found regarding age, sex, smoking, anemia, disease duration and use of corticosteroids, 5-aminosalicylates or immunosuppressives with HRQoL. The factors found to have a major negative impact on all IBDQ scores was disease severity both in CD and UC, and education on bowel symptoms in CD. On multivariate analysis, only high disease activity had significant effects on total and dimensional scores of IBDQ in UC (TS, P=0.005; BS, P<0.001; SS, P=0.004; EF, P=0.05; SF, P=0.001), whereas in CD, only CDAI (TS, P=0.001; BS, P=0.004; SS, P=0.001; EF, P=0.003; SF, P=0.003) and education (TS, P=0.047; BS, P=0.004; SS, P=0.03) had significant effects. Conclusions IBD patients in remission experience better HRQoL than patients with active disease. Induction of remission should become the mainstay of care regarding improvement in HRQoL. PMID:24714279

  6. Concomitant herpes simplex virus colitis and hepatitis in a man with ulcerative colitis: Case report and review of the literature.

    Science.gov (United States)

    Phadke, Varun K; Friedman-Moraco, Rachel J; Quigley, Brian C; Farris, Alton B; Norvell, J P

    2016-10-01

    Herpesvirus infections often complicate the clinical course of patients with inflammatory bowel disease; however, invasive disease due to herpes simplex virus is distinctly uncommon. We present a case of herpes simplex virus colitis and hepatitis, review all the previously published cases of herpes simplex virus colitis, and discuss common clinical features and outcomes. We also discuss the epidemiology, clinical manifestations, diagnosis, and management of herpes simplex virus infections, focusing specifically on patients with inflammatory bowel disease. A 43-year-old man with ulcerative colitis, previously controlled with an oral 5-aminosalicylic agent, developed symptoms of a colitis flare that did not respond to treatment with systemic corticosteroid therapy. One week later he developed orolabial ulcers and progressive hepatic dysfunction, with markedly elevated transaminases and coagulopathy. He underwent emergent total colectomy when imaging suggested bowel micro-perforation. Pathology from both the colon and liver was consistent with herpes simplex virus infection, and a viral culture of his orolabial lesions and a serum polymerase chain reaction assay also identified herpes simplex virus. He was treated with systemic antiviral therapy and made a complete recovery. Disseminated herpes simplex virus infection with concomitant involvement of the colon and liver has been reported only 3 times in the published literature, and to our knowledge this is the first such case in a patient with inflammatory bowel disease. The risk of invasive herpes simplex virus infections increases with some, but not all immunomodulatory therapies. Optimal management of herpes simplex virus in patients with inflammatory bowel disease includes targeted prophylactic therapy for patients with evidence of latent infection, and timely initiation of antiviral therapy for those patients suspected to have invasive disease.

  7. Quantitation of underivatized branched-chain amino acids in sport nutritional supplements by capillary electrophoresis with direct or indirect UV absorbance detection.

    Science.gov (United States)

    Qiu, Jun; Wang, Jinhao; Xu, Zhongqi; Liu, Huiqing; Ren, Jie

    2017-01-01

    The branched-chain amino acids (BCAAs) including leucine (Leu), isoleucine (Ile) and valine (Val) play a pivotal role in the human body. Herein, we developed capillary electrophoresis (CE) coupled with conventional UV detector to quantify underivatized BCAAs in two kinds of sport nutritional supplements. For direct UV detection at 195 nm, the BCAAs (Leu, two enantiomers of Ile and Val) were separated in a background electrolyte (BGE) consisting of 40.0 mmol/L sodium tetraborate, and 40.0 mmol/L β-cyclodextrin (β-CD) at pH 10.2. In addition, the indirect UV detection at 264 nm was achieved in a BGE of 2.0 mmol/L Na2HPO4, 10.0 mmol/L p-aminosalicylic acid (PAS) as UV absorbing probe, and 40.0 mmol/L β-CD at pH 12.2. The β-CD significantly benefited the isomeric separation of Leu, L- and D-Ile. The optimal conditions allowed the LODs (limit of detections) of direct and indirect UV absorption detection to be tens μmol/L level, which was comparable to the reported CE inline derivatization method. The RSDs (relative standard deviations) of migration time and peak area were less than 0.91% and 3.66% (n = 6). Finally, CE with indirect UV detection method was applied for the quantitation of BCAAs in two commercial sport nutritional supplements, and good recovery and precision were obtained. Such simple CE method without tedious derivatization process is feasible of quality control and efficacy evaluation of the supplemental proteins.

  8. Strategies in maintenance for patients receiving long-term therapy (SIMPLE): a study of MMX mesalamine for the long-term maintenance of quiescent ulcerative colitis.

    Science.gov (United States)

    Kane, Sunanda; Katz, Seymour; Jamal, M Mazen; Safdi, Michael; Dolin, Ben; Solomon, Dory; Palmen, Mary; Barrett, Karen

    2012-06-01

    This was a phase IV, multicenter, open-label, 12-14-month study to assess clinical recurrence in patients with ulcerative colitis (UC) who received maintenance treatment with MMX Multi Matrix System (MMX) mesalamine. A secondary outcome was the relationship between long-term efficacy and adherence. Patients with quiescent UC (no rectal bleeding; 0-1 bowel movements more than normal per day) were enrolled directly into a 12-month maintenance phase of the study during which they received MMX mesalamine 2.4 g/day given once daily (QD). Patients with active, mild-to-moderate UC at screening were enrolled into a 2-month acute phase; those who achieved quiescence could continue into the maintenance phase. The primary endpoint was clinical recurrence at Month 6. Of the 290 patients enrolled, 208 entered the maintenance phase; 152 directly and 56 via the acute phase. Following 6 and 12 months of treatment, 76.5% and 64.4% of evaluable patients, respectively, were recurrence-free. The majority of evaluable patients at Month 6 (81.6%) and Month 12 (79.4%) in the maintenance phase were ≥ 80% adherent to MMX mesalamine. At Month 6, clinical recurrence was observed in 20.6% of patients who were ≥ 80% adherent and 36.1% of patients with post-hoc chi-square analysis]); 31.2% and 52.5% at Month 12 (P = 0.01 [post-hoc chi-square analysis]). MMX mesalamine 2.4 g/day QD is effective for maintaining quiescence in patients with UC. Furthermore, adherence to prescribed treatment yielded lower rates of clinical recurrence. Continued education regarding the importance of long-term 5-aminosalicylic acid therapy is warranted. Copyright © 2011 Crohn's & Colitis Foundation of America, Inc.

  9. Systematic review with meta-analysis: the efficacy of probiotics in inflammatory bowel disease.

    Science.gov (United States)

    Derwa, Y; Gracie, D J; Hamlin, P J; Ford, A C

    2017-08-01

    Ulcerative colitis (UC) and Crohn's disease (CD) are inflammatory bowel diseases (IBD). Evidence implicates disturbances of the gastrointestinal microbiota in their pathogenesis. To perform a systematic review and meta-analysis to examine the efficacy of probiotics in IBD. MEDLINE, EMBASE, and the Cochrane Controlled Trials Register were searched (until November 2016). Eligible randomised controlled trials (RCTs) recruited adults with UC or CD, and compared probiotics with 5-aminosalicylates (5-ASAs) or placebo. Dichotomous symptom data were pooled to obtain a relative risk (RR) of failure to achieve remission in active IBD, or RR of relapse of disease activity in quiescent IBD, with 95% confidence intervals (CIs). The search identified 12 253 citations. Twenty-two RCTs were eligible. There was no benefit of probiotics over placebo in inducing remission in active UC (RR of failure to achieve remission=0.86; 95% CI=0.68-1.08). However, when only trials of VSL#3 were considered there appeared to be a benefit (RR=0.74; 95% CI=0.63-0.87). Probiotics appeared equivalent to 5-ASAs in preventing UC relapse (RR=1.02; 95% CI=0.85-1.23). There was no benefit of probiotics in inducing remission of active CD, in preventing relapse of quiescent CD, or in preventing relapse of CD after surgically induced remission. VSL#3 may be effective in inducing remission in active UC. Probiotics may be as effective as 5-ASAs in preventing relapse of quiescent UC. The efficacy of probiotics in CD remains uncertain, and more evidence from RCTs is required before their utility is known. © 2017 John Wiley & Sons Ltd.

  10. Natural disease course of Crohn's disease during the first 5 years after diagnosis in a European population-based inception cohort: an Epi-IBD study.

    Science.gov (United States)

    Burisch, Johan; Kiudelis, Gediminas; Kupcinskas, Limas; Kievit, Hendrika Adriana Linda; Andersen, Karina Winther; Andersen, Vibeke; Salupere, Riina; Pedersen, Natalia; Kjeldsen, Jens; D'Incà, Renata; Valpiani, Daniela; Schwartz, Doron; Odes, Selwyn; Olsen, Jóngerð; Nielsen, Kári Rubek; Vegh, Zsuzsanna; Lakatos, Peter Laszlo; Toca, Alina; Turcan, Svetlana; Katsanos, Konstantinos H; Christodoulou, Dimitrios K; Fumery, Mathurin; Gower-Rousseau, Corinne; Zammit, Stefania Chetcuti; Ellul, Pierre; Eriksson, Carl; Halfvarson, Jonas; Magro, Fernando Jose; Duricova, Dana; Bortlik, Martin; Fernandez, Alberto; Hernández, Vicent; Myers, Sally; Sebastian, Shaji; Oksanen, Pia; Collin, Pekka; Goldis, Adrian; Misra, Ravi; Arebi, Naila; Kaimakliotis, Ioannis P; Nikuina, Inna; Belousova, Elena; Brinar, Marko; Cukovic-Cavka, Silvija; Langholz, Ebbe; Munkholm, Pia

    2018-01-23

    The Epi-IBD cohort is a prospective population-based inception cohort of unselected patients with inflammatory bowel disease from 29 European centres covering a background population of almost 10 million people. The aim of this study was to assess the 5-year outcome and disease course of patients with Crohn's disease (CD). Patients were followed up prospectively from the time of diagnosis, including collection of their clinical data, demographics, disease activity, medical therapy, surgery, cancers and deaths. Associations between outcomes and multiple covariates were analysed by Cox regression analysis. In total, 488 patients were included in the study. During follow-up, 107 (22%) patients received surgery, while 176 (36%) patients were hospitalised because of CD. A total of 49 (14%) patients diagnosed with non-stricturing, non-penetrating disease progressed to either stricturing and/or penetrating disease. These rates did not differ between patients from Western and Eastern Europe. However, significant geographic differences were noted regarding treatment: more patients in Western Europe received biological therapy (33%) and immunomodulators (66%) than did those in Eastern Europe (14% and 54%, respectively, P<0.01), while more Eastern European patients received 5-aminosalicylates (90% vs 56%, P<0.05). Treatment with immunomodulators reduced the risk of surgery (HR: 0.4, 95% CI 0.2 to 0.6) and hospitalisation (HR: 0.3, 95% CI 0.2 to 0.5). Despite patients being treated early and frequently with immunomodulators and biological therapy in Western Europe, 5-year outcomes including surgery and phenotype progression in this cohort were comparable across Western and Eastern Europe. Differences in treatment strategies between Western and Eastern European centres did not affect the disease course. Treatment with immunomodulators reduced the risk of surgery and hospitalisation. © Article author(s) (or their employer(s) unless otherwise stated in the text of the

  11. Infliximab for the Treatment of Crohn'S Disease: Review and Indications for Clinical Use in Canada

    Directory of Open Access Journals (Sweden)

    Remo Panaccione

    2001-01-01

    Full Text Available Crohn's disease is a chronic inflammatory disorder of the gastrointestinal tract. It may affect any portion of the gastrointestinal tract from the mouth to the anus. Symptoms typically include cramping abdominal pain, diarrhea (which may be bloody and nausea. As the severity of the illness worsens, patients may experience constant abdominal pain, vomiting, weight loss and fever. From the perspective of the patient, disease symptoms significantly impair quality of life, and interfere with their work environment and activities of daily living. Unfortunately, there is no cure for Crohn's disease. Patients experience a chronic, relapsing course characterized by recurrent flares of their disease. Conventional medical treatment of Crohn's disease includes the use of non-specific anti-inflammatory drugs (5-aminosalicylic acid agents, prednisone, budesonide, immunosuppressives (6-mercaptopurine, azathioprine, methotrexate and antibiotics. A variable onset of action, incomplete response rates and a significant risk of adverse effects characterize current therapies. Although surgery is frequently used to treat complications or medically refractory disease, postoperative recurrence is a common problem. Infliximab, a murine chimeric monoclonal antibody directed toward tumour necrosis factor-alpha, is a highly effective treatment of active Crohn's disease. In randomized, placebo-controlled clinical trials, 33% of patients treated with infliximab 5 mg/kg achieved remission (Crohn's Disease Activity Index score less than 150, compared with only 4% of those receiving placebo (P<0.001. Additionally, infliximab is the only drug therapy shown to be effective for the treatment of fistulizing Crohn's disease. In studies done to date, infliximab appears to be well tolerated and has a favourable side effect profile.

  12. Prevalence and Risk Factors for Therapy Escalation in Ulcerative Colitis in the Swiss IBD Cohort Study

    Science.gov (United States)

    Safroneeva, Ekaterina; Vavricka, Stephan R.; Fournier, Nicolas; Straumann, Alex; Rogler, Gerhard

    2015-01-01

    Background: Physicians traditionally treat ulcerative colitis (UC) using a step-up approach. Given the paucity of data, we aimed to assess the cumulative probability of UC-related need for step-up therapy and to identify escalation-associated risk factors. Methods: Patients with UC enrolled into the Swiss IBD Cohort Study were analyzed. The following steps from the bottom to the top of the therapeutic pyramid were examined: (1) 5-aminosalicylic acid and/or rectal corticosteroids, (2) systemic corticosteroids, (3) immunomodulators (IM) (azathioprine, 6-mercaptopurine, methotrexate), (4) TNF antagonists, (5) calcineurin inhibitors, and (6) colectomy. Results: Data on 996 patients with UC with a median disease duration of 9 years were examined. The point estimates of cumulative use of different treatments at years 1, 5, 10, and 20 after UC diagnosis were 91%, 96%, 96%, and 97%, respectively, for 5-ASA and/or rectal corticosteroids, 63%, 69%, 72%, and 79%, respectively, for systemic corticosteroids, 43%, 57%, 59%, and 64%, respectively, for IM, 15%, 28%, and 35% (up to year 10 only), respectively, for TNF antagonists, 5%, 9%, 11%, and 12%, respectively, for calcineurin inhibitors, 1%, 5%, 9%, and 18%, respectively, for colectomy. The presence of extraintestinal manifestations and extended disease location (at least left-sided colitis) were identified as risk factors for step-up in therapy with systemic corticosteroids, IM, TNF antagonists, calcineurin inhibitors, and surgery. Cigarette smoking at diagnosis was protective against surgery. Conclusions: The presence of extraintestinal manifestations, left-sided colitis, and extensive colitis/pancolitis at the time of diagnosis were associated with use of systemic corticosteroids, IM, TNF antagonists, calcineurin inhibitors, and colectomy during the disease course. PMID:25806845

  13. The chemotherapy of osteo-articular tuberculosis with recommendations for treatment of children.

    Science.gov (United States)

    Donald, P R

    2011-06-01

    To review literature regarding osteo-articular tuberculosis (OATB) and make recommendations made for the chemotherapy of children. Key words bone tuberculosis, joint tuberculosis, tuberculosis of the spine, tuberculous osteomyelitis were used to search Pubmed and further references obtained by cross referencing and searching the indices of known papers. Results were tabulated regarding regimens, treatment duration, treatment failure, death and relapse. Twenty one papers described treatment of OATB with isoniazid (INH), streptomycin and para-aminosalicylic acid in 2466 patients; 2.1% failed treatment, 1.3% died due to tuberculosis (TB), 2.2% relapsed. Seventy seven papers provide details of 2950 patients receiving INH, rifampicin (RMP) and pyrazinamide (PZA) based regimens. Fifteen described six months treatment which failed in 2.5%, no patients died and 1.3% of patients followed up relapsed. Sixteen papers described 6-11 months treatment which failed in 4.3% of patients, 0.86% died due to TB and 0.86% relapsed. Forty six papers described treatment for ≥12 months; treatment failed in 0.74% of patients and death due to TB occurred in 0.84% and 0.51% relapsed. The majority of OATB cases in children (and adults) can be satisfactorily treated for 6 months with RMP and PZA based regimens; in spinal TB well documented cases of relapse and persistent signs of acute inflammatory response in some patients argue for caution with 6 month regimens at present. Dosages of INH (5-15 mg/kg), RMP (10-20 mg/kg), PZA (30-40 mg/kg), EMB (15-25 mg/kg) and SM (12-18 mg/kg) are recommended for treatment of children. Daily regimens are preferred. Copyright © 2011 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

  14. Optimising the in vitro and in vivo performance of oral cocrystal formulations via spray coating.

    Science.gov (United States)

    Serrano, Dolores R; Walsh, David; O'Connell, Peter; Mugheirbi, Naila A; Worku, Zelalem Ayenew; Bolas-Fernandez, Francisco; Galiana, Carolina; Dea-Ayuela, Maria Auxiliadora; Healy, Anne Marie

    2018-03-01

    Engineering of pharmaceutical cocrystals is an advantageous alternative to salt formation for improving the aqueous solubility of hydrophobic drugs. Although, spray drying is a well-established scale-up technique in the production of cocrystals, several issues can arise such as sublimation or stickiness due to low glass transition temperatures of some organic molecules, making the process very challenging. Even though, fluidised bed spray coating has been successfully employed in the production of amorphous drug-coated particles, to the best of our knowledge, it has never been employed in the production of cocrystals. The feasibility of this technique was proven using three model cocrystals: sulfadimidine (SDM)/4-aminosalicylic acid (4ASA), sulfadimidine/nicotinic acid (NA) and ibuprofen (IBU)/ nicotinamide (NAM). Design of experiments were performed to understand the critical formulation and process parameters that determine the formation of either cocrystal or coamorphous systems for SDM/4ASA. The amount and type of binder played a key role in the overall solid state and in vitro performance characteristics of the cocrystals. The optimal balance between high loading efficiencies and high degree of crystallinity was achieved only when a binder: cocrystal weight ratio of 5:95 or 10:90 was used. The cocrystal coated beads showed an improved in vitro-in vivo performance characterised by: (i) no tendency to aggregate in aqueous media compared to spray dried formulations, (ii) enhanced in vitro activity (1.8-fold greater) against S. aureus, (iii) larger oral absorption and bioavailability (2.2-fold higher C max ), (iv) greater flow properties and (v) improved chemical stability than cocrystals produced by other methods derived from the morphology and solid nature of the starter cores. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. 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

  16. Microbial sensor for drug susceptibility testing of Mycobacterium tuberculosis.

    Science.gov (United States)

    Zhang, Z-T; Wang, D-B; Li, C-Y; Deng, J-Y; Zhang, J-B; Bi, L-J; Zhang, X-E

    2018-01-01

    Drug susceptibility testing (DST) of clinical isolates of Mycobacterium tuberculosis is critical in treating tuberculosis. We demonstrate the possibility of using a microbial sensor to perform DST of M. tuberculosis and shorten the time required for DST. The sensor is made of an oxygen electrode with M. tuberculosis cells attached to its surface. This sensor monitors the residual oxygen consumption of M. tuberculosis cells after treatment with anti-TB drugs with glycerine as a carbon source. In principle, after drug pretreatment for 4-5 days, the response differences between the sensors made of drug-sensitive isolates are distinguishable from the sensors made of drug-resistant isolates. The susceptibility of the M. tuberculosis H37Ra strain, its mutants and 35 clinical isolates to six common anti-TB drugs: rifampicin, isoniazid, streptomycin, ethambutol, levofloxacin and para-aminosalicylic acid were tested using the proposed method. The results agreed well with the gold standard method (LJ) and were determined in significantly less time. The whole procedure takes approximately 11 days and therefore has the potential to inform clinical decisions. To our knowledge, this is the first study that demonstrates the possible application of a dissolved oxygen electrode-based microbial sensor in M. tuberculosis drug resistance testing. This study used the microbial sensor to perform DST of M. tuberculosis and shorten the time required for DST. The overall detection result of the microbial sensor agreed well with that of the conventional LJ proportion method and takes less time than the existing phenotypic methods. In future studies, we will build an O 2 electrode array microbial sensor reactor to enable a high-throughput drug resistance analysis. © 2017 The Authors. Journal of Applied Microbiology published by John Wiley & Sons Ltd on behalf of The Society for Applied Microbiology.

  17. Acetylsalicylic acid-tris-hydroxymethyl-aminomethane reduces colon mucosal damage without causing gastric side effects in a rat model of colitis.

    Science.gov (United States)

    Varga, Gabriella; Ugocsai, Melinda; Hartmann, Petra; Lajkó, Norbert; Molnár, Réka; Szűcs, Szilárd; Jász, Dávid Kurszán; Érces, Dániel; Ghyczy, Miklós; Tóth, Gábor; Boros, Mihály

    2018-02-01

    We have developed a novel compound from acetylsalicylic acid (ASA) and 2-amino-2-(hydroxymethyl)-1,3-propanediol (Tris) precursors with ASA-like anti-inflammatory efficacy and reduced the mucosa-damaging side-effects. Our aim was to examine local and remote consequences of ASA-Tris administration in 2-,4-,6-trinitrobenzene-sulfonic acid (TNBS)-induced colitis as compared to ASA or mesalamine (5-aminosalicylate) treatment. Sprague-Dawley rats were randomized to five groups (n = 6, each), and TNBS enemas were performed. Group 1 was the negative control; group 2 was the untreated colitis group. 12 hour after colitis induction repeated doses of ASA, ASA-Tris (both 0.55 mmol/kg) and mesalamine (0.77 mmol/kg) were given 3 times daily for 3 days to groups 3-5. On day 3 of colitis, the in vivo histology of the colon and stomach was investigated. Tissue xanthine-oxidoreductase, myeloperoxidase, nitrite/nitrate changes, and circulating TNF-alpha levels were measured. In addition, liver mitochondria were examined with high-resolution respirometry to analyze alterations in the electron transport chain. TNBS enema significantly elevated inflammatory enzyme activities, NO production, TNF-alpha concentration, and induced morphological damage in the colon. ASA-treatment reduced the inflammatory marker levels and mucosal injury in the colon, but gastric tissue damage was present. ASA-Tris- and mesalamine-treatments significantly reduced the cytokine levels, inflammatory enzyme activities, and colonic mucosal damage without inducing gastric injury. Also, ASA significantly reduced the Complex IV-linked respiration of liver mitochondria, which was not observed after ASA-Tris-treatment. As compared to ASA, ASA-Tris conjugation provides significant protection against the colonic injury and cytokine-mediated progression of inflammatory events in experimental colitis without influencing the gastric epithelial structure.

  18. The emotional and cognitive impact of unexpected simulated patient death: a randomized controlled trial.

    Science.gov (United States)

    Fraser, Kristin; Huffman, James; Ma, Irene; Sobczak, Matthew; McIlwrick, Joanne; Wright, Bruce; McLaughlin, Kevin

    2014-05-01

    Observational studies suggest that emotions experienced during simulation training may affect cognitive load and learning outcomes. The objective of this study was to manipulate emotions during simulation training and assess the impact on cognitive load and learning. In this prospective randomized trial, 116 final-year medical students received training in a simulated scenario of a 70-year-old woman presenting with reduced consciousness due to aminosalicylic acid ingestion. Training groups were randomly allocated to one of two endings for the scenario: The patient was transferred to another service, or she experienced a cardiorespiratory arrest and died. Participants rated their emotions and cognitive load after training. Three months later, we evaluated their performance on a simulation Objective Structured Clinical Examination station of a 60-year-old man presenting with reduced consciousness due to ethylene glycol ingestion. Emotions tended to be more negative for students in training groups where the simulated patient died. These students also reported a higher cognitive load (mean ± SD, 7.63 ± 0.97 vs 7.25 ± 0.84; P = .03; d = 0.42) and were less likely to be rated as competent to diagnose and manage a patient with reduced consciousness due to toxin ingestion (OR, 0.37; 95% CI, 0.14-0.95; P = 0.04) 3 months later. Students exposed to unexpected simulated patient death reported increased cognitive load and had poorer learning outcomes. Educators need to expose learners to negative experiences; therefore, further studies are needed on how best to use negative emotional experiences during simulation training.

  19. Pattern of Inflammation on Surveillance Colonoscopy Does Not Predict Development of Colitis-associated Neoplasia.

    Science.gov (United States)

    Jegadeesan, Ramprasad; Navaneethan, Udayakumar; Gutierrez, Norma G; Venkatesh, Preethi G K; Hammel, Jeffrey P; Sanaka, Madhusudhan R; Shen, Bo

    2016-09-01

    Identification of colonoscopic features which increase colitis-associated neoplasia risk in patients with ulcerative colitis (UC) may allow patient risk stratification. Our objective was to investigate whether colonoscopic features correlate with the risk of developing colitis-associated neoplasia in patients with UC on surveillance. In this retrospective case-control study, patients with UC who underwent surveillance colonoscopies from 1998 to 2011 were included. Patients with UC with neoplasia were compared with a matched control group of patients with UC without neoplasia in a 1:3 ratio. A total of 111 eligible patients with UC with colon neoplasia were compared with 356 patients with UC without colon neoplasia. On univariate analysis, colitis-associated neoplasia was associated with male gender (odds ratio [OR] = 2.58, 95% confidence interval [CI]: 1.71-3.89, P ≤ 0.001) and smoking history (OR = 1.62, 95% CI: 1.1-2.39, P = 0.045) but not with colonoscopic features, including tubular colon/shortened colon, scarring, segment of severe inflammation, inflammatory polyps, colonic stricture, or macroscopically normal appearance colonoscopy. In multivariate analysis, only male gender (OR = 2.68, 95% CI: 1.77-4.08, P ≤ 0.001) was found to be associated with an increased risk, whereas the use of 5-aminosalicylates was associated with a decreased risk for colitis-associated neoplasia (OR = 0.51, 95% CI: 0.31-0.84, P = 0.009). In patients with UC, colonoscopic features especially on standard-definition white-light colonoscopy did not appear to reliably predict the development of colitis-associated neoplasia. This will leave room for image-enhanced endoscopy technology and molecular markers for the early and accurate detection of colitis-associated neoplasia.

  20. Current approaches to the management of new-onset ulcerative colitis

    Science.gov (United States)

    Marchioni Beery, Renée; Kane, Sunanda

    2014-01-01

    Ulcerative colitis (UC) is an idiopathic, inflammatory gastrointestinal disease of the colon. As a chronic condition, UC follows a relapsing and remitting course with medical maintenance during periods of quiescent disease and appropriate escalation of therapy during times of flare. Initial treatment strategies must not only take into account current clinical presentation (with specific regard for extent and severity of disease activity) but must also take into consideration treatment options for the long-term. The following review offers an approach to new-onset UC with a focus on early treatment strategies. An introduction to the disease entity is provided along with an approach to initial diagnosis. Stratification of patients based on clinical parameters, disease extent, and severity of illness is paramount to determining course of therapy. Frequent assessments are required to determine clinical response, and treatment intensification may be warranted if expected improvement goals are not appropriately reached. Mild-to- moderate UC can be managed with aminosalicylates, mesalamine, and topical corticosteroids with oral corticosteroids reserved for unresponsive cases. Moderate-to-severe UC generally requires oral or intravenous corticosteroids in the short-term with consideration of long-term management options such as biologic agents (as initial therapy or in transition from steroids) or thiopurines (as bridging therapy). Patients with severe or fulminant UC who are recalcitrant to medical therapy or who develop disease complications (such as toxic megacolon) should be considered for colectomy. Early surgical referral in severe or refractory UC is crucial, and colectomy may be a life-saving procedure. The authors provide a comprehensive evidence-based approach to current treatment options for new-onset UC with discussion of long-term therapeutic efficacy and safety, patient-centered perspectives including quality of life and medication compliance, and future

  1. Comparação entre a composição química e capacidade antioxidante de diferentes extratos de própolis verde#

    Directory of Open Access Journals (Sweden)

    Fernanda B. Salgueiro

    Full Text Available In this work were determined the total phenolic contents, antioxidant activity and chemical composition of twelve samples of green propolis acquired from beekeepers and other twelve commercial extracts samples from different regions of Southeast Brazil. The phenolic contents and the antioxidant activity were evaluated by the Folin-Ciocalteau and DPPH, ABTS and FRAP methods, respectively. Both types of propolis showed significant radical scavenging properties. HPLC-PDA was applied for quantification of chlorogenic acid, caffeic acid, ferulic acid, para-coumaric acid, rosmarinic acid, vanillin, hesperidin, naringenin, pinobanksin, kaempferol, Artepillin-C (4-hydroxy-3,5-diprenyl cinnamic acid, kampheride and pinostrobin. Despite the chemical composition of both in natura and commercial propolis extracts were similar the multivariate analysis allowed the discrimination between them.

  2. Patient preferences for first-line oral treatment for mild-to-moderate ulcerative colitis: a discrete-choice experiment.

    Science.gov (United States)

    Hodgkins, Paul; Swinburn, Paul; Solomon, Dory; Yen, Linnette; Dewilde, Sarah; Lloyd, Andrew

    2012-01-01

    Patients with ulcerative colitis (UC) frequently require long-term therapy to prevent relapse. Treatments such as 5-aminosalicylic acid (5-ASA [mesalazine]) are efficacious and well tolerated, but adherence to treatment is often poor. This discrete-choice experiment (DCE) was conducted to estimate differences in patient preferences for 5-ASA treatment in mild-to-moderate UC based on levels of self-reported adherence. Inclusion of patients residing in the US, UK, Germany, and Canada allowed for assessment of possible cultural differences in patient preferences. DCE attributes were determined through literature review, clinician consultation, and patient interviews. Six treatment attributes were identified: ease of swallowing, time of day, quantity, extent of flare resolution, likelihood of flare occurrence, and cost. A total of 400 patients in four countries completed the DCE and adherence (Modified Morisky Scale) surveys. Data were analyzed using generalized estimating equations to estimate patient preference and willingness to pay (WTP) by levels of self-reported adherence and country of residence. All attributes had expected polarity and were significant predictors of patient preference. Self-reported 'good' versus 'poor' adherers significantly preferred symptom control (p = 0.0108) and mucosal healing (p = 0.0190) attributes. All patients stated preference for symptom control/mucosal healing and flare risk attributes; the latter attribute was significantly preferred across all countries. Country differences in patient preference for convenience versus clinical attributes were found. Overall, patients were willing to pay £29.24 ($US46.27) per month for symptom control and mucosal healing, and an additional £78.81 ($US124.70) per month for reduction in flare risk to 10% per year (WTP costs were equalized between each country using the published 2008 purchasing power parity). Those with flares in the past year significantly preferred avoiding future

  3. 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

  4. Cost-effectiveness of vedolizumab compared with conventional therapy for ulcerative colitis patients in the UK

    Directory of Open Access Journals (Sweden)

    Wilson MR

    2017-10-01

    Full Text Available Michele R Wilson,1 Ismail Azzabi Zouraq,2 Helene Chevrou-Severac,2 Ross Selby,3 Matthew C Kerrigan4 1RTI Health Solutions, Research Triangle Park, NC, USA; 2Takeda Pharmaceuticals International AG, Zurich, Switzerland; 3Takeda UK Ltd., Bucks, UK; 4PHMR Limited, London, UK Objective: To examine the clinical and economic impact of vedolizumab compared with conventional therapy in the treatment of moderately-to-severely active ulcerative colitis (UC in the UK based on results of the GEMINI I trial. Methods: A decision-analytic model in Microsoft Excel was used to compare vedolizumab with conventional therapy (aminosalicylates, corticosteroids, immunomodulators for the treatment of patients with UC in the UK. We considered the following three populations: the overall intent-to-treat population from the GEMINI I trial, patients naïve to anti-TNF therapy, and those who had failed anti-TNF-therapy. Population characteristics and efficacy data were obtained from the GEMINI I trial. Other inputs (eg, unit costs, probability of surgery, mortality were obtained from published literature. Time horizon was a lifetime horizon, with costs and outcomes discounted by 3.5% per year. One-way and probabilistic sensitivity analyses were conducted to measure the impact of parameter uncertainty. Results: Vedolizumab had incremental cost-effectiveness ratios of £4,095/quality-adjusted life-year (QALY, £4,423/QALY, and £5,972/QALY compared with conventional therapy in the intent-to-treat, anti-TNF-naïve, and anti-TNF-failure populations, respectively. Patients on vedolizumab accrued more QALYs while incurring more costs than patients on conventional therapy. The sensitivity analyses showed that the results were most sensitive to induction response and transition probabilities for each treatment. Conclusion: The results suggest that vedolizumab results in more QALYs and may be a cost-effective treatment option compared with conventional therapy for both anti

  5. Peculiarities of the course of ulcerative colitis in children at the present stage

    Directory of Open Access Journals (Sweden)

    M.F. Denisova

    2017-03-01

    Full Text Available Background. As to severity of the course, the incidence of complications and mortality rate, ulcerative colitis hold a position within the top of the gastrointestinal system diseases in children. Goal of research — to study peculiarities of the course of ulcerative colitis at the present stage. Materials and methods. The retrospective analysis was conducted of 184 clinical records of the children, who were on examination and treatment at the Department of the diseases of gastrointestinal system of the State Institution “Institute of Pediatrics, Obstetrics and Gynecology of the National Academy of Medical Sciences of Ukraine” between 2004 and 2014. Results and discussion. Ulcerative colitis is common in the children of all ages, among which the preschool children and teenagers are at greater risk than others. The risk factors include both the antenatal and the postnatal ones: gestational toxicosis and miscarriage threat, weight deficit at birth, artificial feeding, intestinal infections. Ulcerative colitis is characterized by chronic relapse, slow progression of the disease, and the typical clinical symptoms are: diarrhea, hemorrhagic colitis, abdominal pain syndrome, toxic syndrome, late physical development. In terms of localization, the inflammation process most often affects the entire large bowel (59.6 %, left-sided colitis (28.5 %, and proctosigmoiditis (accounts for 11.9 % are less common. The informative criteria of ulcerative colitis activity are the Pediatric Ulcerative Colitis Activity Index (PUCAI, fecal calprotectin level, a number of complete blood count values (hemoglobin, leucocytes, platelets, erythrocyte sedimentation rate and biochemical studies (C-reactive protein, alpha-2 globulins. The modern combined baseline therapy is efficient in 22 % of patients suffering from total colitis, in 42–58 % — from left-sided colitis according to the follow-up study results. Monotherapy with 5-aminosalicylic acid medications was

  6. Pediatric Crohn's disease: epidemiology and emerging treatment options

    Directory of Open Access Journals (Sweden)

    Kansal S

    2014-07-01

    Full Text Available Shivani Kansal,1–3 Anthony G Catto-Smith1,2 1Department of Paediatrics, University of Melbourne, 2Department of Gastroenterology, The Royal Children's Hospital Melbourne, 3Murdoch Children's Research Institute, Melbourne, VIC, Australia Abstract: There has been a dramatic increase in the incidence of Crohn's disease over the last two to three decades worldwide, which has affected both the developed world and increasingly also the developing world. Crohn's disease is a disease of youth and can have a profound effect on the growing child, both in terms of growth and skeletal health as well psychosocial maturation. Environmental risk factors appear to be crucially important, but it is not clear at present whether improved hygiene, especially in childhood, influences immunological conditioning, or whether there is a direct impact on the gut from a disturbed gut microbiota. Genetic variation appears to relate to how the host interacts with its microbiota, determining susceptibility rather than causation. The outcome is a sustained immune response, clinically presenting as a relapsing/remitting disease process. There is no current cure for Crohn's disease; treatments are designed to reduce symptoms and control inflammation, initially by inducing a remission, then trying to maintain it. Historical therapies have included 5-aminosalicylic acid-based drugs, corticosteroids, and immunomodulators. Two approaches which are gaining increasing interest are the use of exclusive enteral nutrition and biologicals. Enteral nutrition is a remarkably effective approach, though there is a limited understanding of its mechanism and difficulties in acceptance among the medical community. Biologicals are a class of drugs which specifically target molecules and pathways central to the inflammatory process; they are also very effective, but patients can develop a secondary loss of response as a result of antibodies to the biological agent. Infection and the development

  7. Cost effectiveness of ulcerative colitis treatment in Germany: a comparison of two oral formulations of mesalazine

    Directory of Open Access Journals (Sweden)

    Mittendorf Thomas

    2011-07-01

    Full Text Available Abstract Background The treatment of ulcerative colitis (UC can place a substantial financial burden on healthcare systems. The anti-inflammatory compound 5-aminosalicylic acid (5-ASA; mesalazine is the recommended first-line treatment for patients with UC. In this analysis, the incremental cost effectiveness ratio (ICER of two oral formulations of 5-ASA (Mezavant® and Asacol® is examined in the treatment of patients with mild-to-moderate, active UC in Germany. Methods A Markov cohort model was developed to assess the cost effectiveness of Mezavant compared with Asacol over a 5-year period in the German Statutory Health Insurance (SHI. Drug pricing details for 2009 were applied throughout the model, and overall resource use was determined and also fitted to 2009 from published results of a large cross sectional study of German SHI patients. Cost per quality adjusted life year (QALY was the primary endpoint for this study. Remission rates were obtained using data from a randomised, phase III trial of Mezavant with an active Asacol reference arm and a long-term, open label, safety and tolerability trial of Mezavant. Uncertainty in the study model was assessed using one-way and probabilistic sensitivity analyses applying a Monte Carlo simulation. Results Over a 5-year period, healthcare costs for patients receiving Mezavant were 624 Euro lower than for patients receiving Asacol. Additionally, patients receiving Mezavant gained 0.011 QALYs or 18 more days in remission compared with Asacol. One-way sensitivity analyses suggest that these results are driven by both differences in the acquisition cost between mesalazine formulations and differences in treatment efficacy. Furthermore, sensitivity analyses suggest a probability of 76% for cost savings and higher QALYs with Mezavant compared with Asacol. If adherence and its influence on the remission rates and the risk of developing colorectal cancer were included in the model, the results might have

  8. High Rate of Hypothyroidism in Multidrug-Resistant Tuberculosis Patients Co-Infected with HIV in Mumbai, India

    Science.gov (United States)

    Andries, Aristomo; Isaakidis, Petros; Das, Mrinalini; Khan, Samsuddin; Paryani, Roma; Desai, Chitranjan; Dalal, Alpa; Mansoor, Homa; Verma, Reena; Fernandes, Dolorosa; Sotgiu, Giovanni; Migliori, Giovanni B.; Saranchuk, Peter

    2013-01-01

    Background Adverse events (AEs) among HIV-infected patients with multidrug-resistant tuberculosis (MDR-TB) receiving anti-TB and antiretroviral treatments (ART) are under-researched and underreported. Hypothyroidism is a common AE associated with ethionamide, p-aminosalicylic acid (PAS), and stavudine. The aim of this study was to determine the frequency of and risk factors associated with hypothyroidism in HIV/MDR-TB co-infected patients. Methods This was a prospective, observational cohort study, using routine laboratory data in a Médecins Sans Frontières (MSF) clinic in collaboration with Sewri TB Hospital, Mumbai, India. Hypothyroidism was defined as a thyroid stimulating hormone (TSH) result >10 mIU/L at least once during treatment. Patients having a baseline result and one additional result after 3 months were eligible for enrolment. Results Between October 2006 and March 2013, 116 patients were enrolled, 69 of whom were included. The median (IQR) age was 38 years (34-43) and 61% were male. By March 2013, 37/69 (54%) had hypothyroidism after at least 90 days of treatment. Age, gender, CD4 counts and stavudine-based ART were not associated with the occurrence of hypothyroidism in multivariate models. The co-administration of PAS and ethionamide was found to double the risk of hypothyroidism (RR: 1.93, 95% CI: 1.06-3.54). Discussion High rate of hypothyroidism was recorded in a Mumbai cohort of MDR-TB/HIV co-infected patients on treatment. This is a treatable and reversible AE, however, it may go undiagnosed in the absence of regular monitoring. Care providers should not wait for clinical symptoms, as this risks compromising treatment adherence. Simple, affordable and reliable point-of-care tools for measuring TSH are needed, especially in high MDR-TB burden countries. Our findings suggest the need for TSH screening at baseline, three months, six months, and every six months thereafter for HIV-infected patients on MDR-TB treatment regimens containing PAS and

  9. Recurrence of Clostridium difficile Infection in Patients with Inflammatory Bowel Disease: The RECIDIVISM Study.

    Science.gov (United States)

    Razik, Roshan; Rumman, Amir; Bahreini, Zoya; McGeer, Allison; Nguyen, Geoffrey C

    2016-08-01

    Recurrent Clostridium difficile infection (rCDI) contributes to a significant burden of disease in patients with inflammatory bowel disease (IBD). In this study, we seek to identify risk factors for rCDI in a population of IBD patients at the Mount Sinai Hospital IBD Centre. In this retrospective cohort study, IBD patients with rCDI diagnosed between 2010 and 2013 were identified and compared with IBD patients with single-episode CDI. Multivariate regression was used to identify predictors of rCDI in IBD. Outcome analysis was performed for hospitalizations due to CDI, colectomy, and CDI-attributable mortality. A total of 503 patients were included, 110 (22%) of whom had IBD (49% CD, 51% ulcerative colitis). Recurrent CDI occurred in 32% of IBD patients compared with 24% of non-IBD patients (P<0.01). IBD patients with rCDI were more likely than those without rCDI to report recent antibiotic therapy (42.9 vs. 30.7%, P<0.01), 5-aminosalicylic acid (5-ASA) use (51.5 vs. 30.7%, P<0.001), steroid use (51.4 vs. 33.3%, P<0.001), and biologic therapy (48.6 vs. 40.0%, P<0.01). Infliximab (34.3 vs. 17.3%, P<0.01) but not adalimumab was associated with more rCDI events. Using a Cox model of predictors of rCDI in IBD, significant predictors included non-ileal Crohn's disease (hazard ratio (HR) 2.85, 95% confidence interval (CI) 1.30-6.30) and the use of 5-ASA (HR 2.15, 95% CI 1.11-4.18). Compared with the general population, IBD patients are 33% more likely to experience rCDI. Within the IBD cohort, exposure to certain drug classes (antibiotics, 5-ASA, steroids, certain biologics) and non-ileal Crohn's disease were found to be the predictors of rCDI.

  10. Heterogeneity in Definitions of Endpoints for Clinical Trials of Ulcerative Colitis: A Systematic Review for Development of a Core Outcome Set.

    Science.gov (United States)

    Ma, Christopher; Panaccione, Remo; Fedorak, Richard N; Parker, Claire E; Nguyen, Tran M; Khanna, Reena; Siegel, Corey A; Peyrin-Biroulet, Laurent; D'Haens, Geert; Sandborn, William J; Feagan, Brian G; Jairath, Vipul

    2017-08-24

    Advances in development of therapeutic agents for ulcerative colitis (UC) have been paralleled by innovations in trial design. It would be useful to identify a core outcome set, to standardize outcome definitions for efficacy and safety in clinical trials. We performed a systematic review of efficacy and safety outcomes reported in placebo-controlled randomized controlled trials of patients with UC. We searched MEDLINE, EMBASE, and the Cochrane Library from inception through March 1, 2017, for placebo-controlled randomized controlled trials of adult patients with UC treated with aminosalicylates, immunosuppressants, corticosteroids, biologics, and oral small molecules. We collected information on efficacy and safety outcomes, definitions, and measurement tools, stratified by decade of publication. We analyzed data from 83 randomized controlled trials (68 induction and 15 maintenance) comprising 17,737 patients. Clinical or composite-clinical efficacy outcomes were reported in all trials; the UC Disease Activity Index and Mayo Clinic Score were frequently used to determine clinical response or remission. We found substantial variation in definitions of clinical or composite-clinical endpoints, with more than 50 definitions of response or remission. Endoscopic factors, histologic features, and fecal or serum biomarkers were used to determine outcomes in 83.1% (69 of 83), 24.1% (20 of 83), and 24.1% (20 of 83) of trials, respectively. A greater proportion of trials published after 2007 reported objective outcomes (96.5% endoscopic, 26.3% histologic, and 36.8% biomarker outcomes), but no standardized definitions of histologic or biomarker endpoints were found. Patient-reported efficacy and quality-of-life outcomes were described in 25 trials (30.1%) and safety outcomes were reported in 77 trials (92.8%). In a systematic review, we found that despite recent advances in clinical trials methods, there is a great deal of variation in definitions of endpoints, including

  11. Pharmacokinetics of Second-Line Antituberculosis Drugs after Multiple Administrations in Healthy Volunteers.

    Science.gov (United States)

    Park, Sang-In; Oh, Jaeseong; Jang, Kyungho; Yoon, Jangsoo; Moon, Seol Ju; Park, Jong Sun; Lee, Jae Ho; Song, Junghan; Jang, In-Jin; Yu, Kyung-Sang; Chung, Jae-Yong

    2015-08-01

    Therapeutic drug monitoring (TDM) of second-line antituberculosis drugs would allow for optimal individualized dosage adjustments and improve drug safety and therapeutic outcomes. To evaluate the pharmacokinetic (PK) characteristics of clinically relevant, multidrug treatment regimens and to improve the feasibility of TDM, we conducted an open-label, multiple-dosing study with 16 healthy subjects who were divided into two groups. Cycloserine (250 mg), p-aminosalicylic acid (PAS) (5.28 g), and prothionamide (250 mg) twice daily and pyrazinamide (1,500 mg) once daily were administered to both groups. Additionally, levofloxacin (750 mg) and streptomycin (1 g) once daily were administered to group 1 and moxifloxacin (400 mg) and kanamycin (1 g) once daily were administered to group 2. Blood samples for PK analysis were collected up to 24 h following the 5 days of drug administration. The PK parameters, including the maximum plasma concentration (Cmax) and the area under the plasma concentration-time curve during a dosing interval at steady state (AUCτ), were evaluated. The correlations between the PK parameters and the concentrations at each time point were analyzed. The mean Cmax and AUCτ, respectively, for each drug were as follows: cycloserine, 24.9 mg/liter and 242.3 mg · h/liter; PAS, 65.9 mg/liter and 326.5 mg · h/liter; prothionamide, 5.3 mg/liter and 22.1 mg · h/liter; levofloxacin, 6.6 mg/liter and 64.4 mg · h/liter; moxifloxacin, 4.7 mg/liter and 54.2 mg · h/liter; streptomycin, 42.0 mg/liter and 196.7 mg · h/liter; kanamycin, 34.5 mg/liter and 153.5 mg · h/liter. The results indicated that sampling at 1, 2.5, and 6 h postdosing is needed for TDM when all seven drugs are administered concomitantly. This study indicates that PK characteristics must be considered when prescribing optimal treatments for patients. (This study has been registered at ClinicalTrials.gov under registration no. NCT02128308.). Copyright © 2015, American Society for

  12. Photodegradation of sulfasalazine and its human metabolites in water by UV and UV/peroxydisulfate processes.

    Science.gov (United States)

    Ji, Yuefei; Yang, Yan; Zhou, Lei; Wang, Lu; Lu, Junhe; Ferronato, Corinne; Chovelon, Jean-Marc

    2018-04-15

    The widespread occurrence of pharmaceuticals and their metabolites in natural waters has raised great concerns about their potential risks on human health and ecological systems. This study systematically investigates the degradation of sulfasalazine (SSZ) and its two human metabolites, sulfapyridine (SPD) and 5-aminosalicylic acid (5-ASA), by UV and UV/peroxydisulfate (UV/PDS) processes. Experimental results show that SPD and 5-ASA were readily degraded upon UV 254 nm direct photolysis, with quantum yields measured to be (8.6 ± 0.8) × 10 -3 and (2.4 ± 0.1) × 10 -2  mol Einstein -1 , respectively. Although SSZ was resistant to direct UV photolysis, it could be effectively removed by both UV/H 2 O 2 and UV/PDS processes, with fluence-based pseudo-first-order rate constants determined to be 0.0030 and 0.0038 cm 2  mJ -1 , respectively. Second-order rate constant between SO 4 •- and SSZ was measured as (1.33 ± 0.01) × 10 9  M -1 s -1 by competition kinetic method. A kinetic model was established for predicting the degradation rate of SSZ in the UV/PDS process. Increasing the dosage of PDS significantly enhanced the degradation of SSZ in the UV/PDS process, which can be well predicted by the developed kinetic model. Natural water constituents, such as natural organic matter (NOM) and bicarbonate (HCO 3 - ), influenced the degradation of SSZ differently. The azo functional group of SSZ molecule was predicted as the reactive site susceptible to electrophilic attack by SO 4 •- by frontier electron densities (FEDs) calculations. Four intermediate products arising from azo bond cleavage and SO 2 extrusion were identified by solid phase extraction-liquid chromatography-triple quadrupole mass spectrometry (SPE-LC-MS/MS). Based on the products identified, detailed transformation pathways for SSZ degradation in the UV/PDS system were proposed. Results reveal that UV/PDS could be an efficient approach for remediation of water

  13. Prevention of acute radiation-induced proctosigmoiditis by balsalazide: A randomized, double-blind, placebo controlled trial in prostate cancer patients

    International Nuclear Information System (INIS)

    Jahraus, Christopher D.; Bettenhausen, Doug Phar; Malik, Uzma M.B.B.S.; Sellitti, Marguerite; St Clair, William H.

    2005-01-01

    Purpose: A common complication of pelvic radiotherapy (RT) is acute radiation-induced proctosigmoiditis (RIPS), for which a multitude of therapies have been tried. The 5-aminosalicylates (5-ASA), which are traditionally used to treat inflammatory bowel disease, have been tested; however, all but one prior randomized attempt to limit or prevent RIPS with 5-ASA-type agents have failed. We sought to evaluate balsalazide, a new 5-ASA drug, for its potential to prevent or limit RIPS in patients undergoing RT for carcinoma of the prostate, as a representative sample of pelvic RT patients. Balsalazide has a unique delivery system in that 99% of ingested drug is delivered to and activated in the colon, a higher yield than all other oral agents currently available in this class. Furthermore, it lacks the antigenic sulfa moiety present in sulfasalazine, the only other 5-ASA with demonstrated benefit in this setting. Thus, it was deemed an ideal candidate for preventing or limiting RIPS. Methods and Materials: Eligible patients included prostate cancer patients, American Joint Committee on Cancer Stage T1-3, M0 being treated with external beam radiotherapy in University of Kentucky Department of Radiation Medicine. Between January 1, 2003 and July 1, 2004, 27 eligible patients were enrolled in the study. Patients were administered 2250 mg of balsalazide or an identical-appearing placebo twice daily beginning 5 days before RT and continuing for 2 weeks after completion. Toxicities were graded weekly according to National Cancer Institute Common Toxicity Criteria v. 2.0 for each of the following: proctitis, diarrhea, dysuria, weight loss, fatigue, nausea, and vomiting. A symptom index was formulated for each toxicity consisting of the toxicity's numeric grade multiplied by the number of days it was experienced, and summed for each grade experienced throughout the course of RT. Results: With the exception of nausea or vomiting, seen in 3 patients on balsalazide and 2 on placebo

  14. Role of fecal calprotectin testing to predict relapse in teenagers with inflammatory bowel disease who report full disease control.

    Science.gov (United States)

    van Rheenen, Patrick F

    2012-11-01

    Teenagers with inflammatory bowel disease undergo regular follow-up visits to watch for symptoms that may indicate relapse. Current disease activity is frequently estimated with the use of the Pediatric Ulcerative Colitis Activity Index (PUCAI) and the Pediatric Crohn's Disease Activity Index (PCDAI). We examined the capacity of fecal calprotectin and C-reactive protein (CRP) to predict relapse in teenagers who report no symptoms. Second, we examined whether calprotectin and CRP as an "add-on test" improve the specificity of PUCAI or PCDAI to predict relapse. We collected data of 62 consecutive teenagers (31 with Crohn's disease and 31 with ulcerative colitis) who scored their degree of disease control between 90 and 100% on two successive outpatient clinic visits. Calprotectin, PUCAI or PCDAI, and CRP were measured at baseline. Primary outcome was symptomatic relapse within 3 months of baseline, necessitating the introduction of steroids, exclusive enteral nutrition, or an aminosalicylate dose escalation. Fifteen teenagers (24%) developed symptomatic relapse within 3 months of baseline. Based on the receiver operating characteristic curve, the optimum calprotectin cutpoint to differentiate high from low risk patients was 500 μg/g. The PUCAI or PCDAI predicted relapse in 42% (11/26) of teenagers with a positive result (score ≥ 10 points), while a negative PUCAI or PCDAI result reduced the risk of relapse to 11% (4/36). Teenagers with a positive calprotectin test had a 53% (10/19) risk of progressing to symptomatic relapse within 3 months, whereas a negative calprotectin result gave a 12% (5/43) risk of symptomatic relapse. A positive CRP result (cutoff 10 mg/L) gave a 50% (4/8) risk of relapse, whereas a negative CRP result hardly reduced the risk compared with the pretest probability (from 24% to 21% (11/53)). As an add-on test after PUCAI or PCDAI, the calprotectin test limited the number of false positives and thus increased the specificity to detect

  15. 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)

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

    International Nuclear Information System (INIS)

    Gremy, O.

    2006-12-01

    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)

  17. Metabolic Engineering of the Shikimate Pathway for Production of Aromatics and Derived Compounds—Present and Future Strain Construction Strategies

    Directory of Open Access Journals (Sweden)

    Nils J. H. Averesch

    2018-03-01

    Full Text Available The aromatic nature of shikimate pathway intermediates gives rise to a wealth of potential bio-replacements for commonly fossil fuel-derived aromatics, as well as naturally produced secondary metabolites. Through metabolic engineering, the abundance of certain intermediates may be increased, while draining flux from other branches off the pathway. Often targets for genetic engineering lie beyond the shikimate pathway, altering flux deep in central metabolism. This has been extensively used to develop microbial production systems for a variety of compounds valuable in chemical industry, including aromatic and non-aromatic acids like muconic acid, para-hydroxybenzoic acid, and para-coumaric acid, as well as aminobenzoic acids and aromatic α-amino acids. Further, many natural products and secondary metabolites that are valuable in food- and pharma-industry are formed outgoing from shikimate pathway intermediates. (Reconstruction of such routes has been shown by de novo production of resveratrol, reticuline, opioids, and vanillin. In this review, strain construction strategies are compared across organisms and put into perspective with requirements by industry for commercial viability. Focus is put on enhancing flux to and through shikimate pathway, and engineering strategies are assessed in order to provide a guideline for future optimizations.

  18. Mesalamine (5-ASA) for the prevention of recurrent diverticulitis.

    Science.gov (United States)

    Carter, Flloyd; Alsayb, Majd; Marshall, John K; Yuan, Yuhong

    2017-10-03

    Diverticular disease is a common condition that increases in prevalence with age. Recent theories on the pathogenesis of diverticular inflammation have implicated chronic inflammation similar to that seen in ulcerative colitis. Mesalamine, or 5-aminosalicylic acid (5-ASA), is a mainstay of therapy for individuals with ulcerative colitis. Accordingly, 5-ASA has been studied for prevention of recurrent diverticulitis. To evaluate the efficacy of mesalamine (5-ASA) for prevention of recurrent diverticulitis. We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2017, Issue 8), in the Cochrane Library; Ovid MEDLINE (from 1950 to 9 September 2017); Ovid Embase (from 1974 to 9 September 2017); and two clinical trials registries for ongoing trials - Clinicaltrials.gov and the World Health Organization (WHO) International Clinical Trials Registry Platform database (9 September 2017).We also searched proceedings from major gastrointestinal conferences - Digestive Disease Week (DDW), United European Gastroenterology Week (UEGW), and the American College of Gastroenterology (ACG) Annual Scientific Meeting - from 2010 to September 2017. In addition, we scanned reference lists from eligible publications, and we contacted corresponding authors to ask about additional trials. We included randomised controlled clinical trials comparing the efficacy of 5-ASA versus placebo or another active drug for prevention of recurrent diverticulitis. We used standard methodological procedures as defined by Cochrane. Three review authors assessed eligibility for inclusion. Two review authors selected studies, extracted data, and assessed methodological quality independently. We calculated risk ratios (RRs) for prevention of diverticulitis recurrence using an intention-to-treat principle and random-effects models. We assessed heterogeneity using criteria for Chi 2 (P 50%). To explore sources of heterogeneity, we conducted a priori subgroup analyses. To assess the robustness of

  19. 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.

  20. 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

  1. Outcomes, infectiousness, and transmission dynamics of patients with extensively drug-resistant tuberculosis and home-discharged patients with programmatically incurable tuberculosis: a prospective cohort study

    KAUST Repository

    Dheda, Keertan

    2017-01-19

    Background: The emergence of programmatically incurable tuberculosis threatens to destabilise control efforts. The aim of this study was to collect prospective patient-level data to inform treatment and containment strategies. Methods: In a prospective cohort study, 273 South African patients with extensively drug-resistant tuberculosis, or resistance beyond extensively drug-resistant tuberculosis, were followed up over a period of 6 years. Transmission dynamics, infectiousness, and drug susceptibility were analysed in a subset of patients from the Western Cape using whole-genome sequencing (WGS; n=149), a cough aerosol sampling system (CASS; n=26), and phenotypic testing for 18 drugs (n=179). Findings: Between Oct 1, 2008, and Oct 31, 2012, we enrolled and followed up 273 patients for a median of 20·3 months (IQR 9·6-27·8). 203 (74%) had programmatically incurable tuberculosis and unfavourable outcomes (treatment failure, relapse, default, or death despite treatment with a regimen based on capreomycin, aminosalicylic acid, or both). 172 (63%) patients were discharged home, of whom 104 (60%) had an unfavourable outcome. 54 (31%) home-discharged patients had failed treatment, with a median time to death after discharge of 9·9 months (IQR 4·2-17·4). 35 (20%) home-discharged cases were smear-positive at discharge. Using CASS, six (23%) of 26 home-discharged cases with data available expectorated infectious culture-positive cough aerosols in the respirable range (<5 μm), and most reported inter-person contact with suboptimal protective mask usage. WGS identified 17 (19%) of the 90 patients (with available sequence data) that were discharged home before the diagnosis of 20 downstream cases of extensively drug-resistant tuberculosis with almost identical sequencing profiles suggestive of community-based transmission (five or fewer single nucleotide polymorphisms different and with identical resistance-encoding mutations for 14 drugs). 11 (55%) of these downstream

  2. Interventions to reduce acute and late adverse gastrointestinal effects of pelvic radiotherapy for primary pelvic cancers.

    Science.gov (United States)

    Lawrie, Theresa A; Green, John T; Beresford, Mark; Wedlake, Linda; Burden, Sorrel; Davidson, Susan E; Lal, Simon; Henson, Caroline C; Andreyev, H Jervoise N

    2018-01-23

    balloon and hydrogel spacers suggests that these interventions for prostate cancer RT may make little or no difference to GI outcomes.Pharmacological interventions: Evidence for any beneficial effects of aminosalicylates, sucralfate, amifostine, corticosteroid enemas, bile acid sequestrants, famotidine and selenium is of a low or very low certainty. However, evidence on certain aminosalicylates (mesalazine, olsalazine), misoprostol suppositories, oral magnesium oxide and octreotide injections suggests that these agents may worsen GI symptoms, such as diarrhoea or rectal bleeding.Non-pharmacological interventions: Low-certainty evidence suggests that protein supplements (RR 0.23, 95% CI 0.07 to 0.74; participants = 74; studies = 1), dietary counselling (RR 0.04, 95% CI 0.00 to 0.60; participants = 74; studies = 1) and probiotics (RR 0.43, 95% CI 0.22 to 0.82; participants = 923; studies = 5; I 2 = 91%) may reduce acute RT-related diarrhoea (grade 2+). Dietary counselling may also reduce diarrhoeal symptoms in the long term (at five years, RR 0.05, 95% CI 0.00 to 0.78; participants = 61; studies = 1). Low-certainty evidence from one study (108 participants) suggests that a high-fibre diet may have a beneficial effect on GI symptoms (mean difference (MD) 6.10, 95% CI 1.71 to 10.49) and quality of life (MD 20.50, 95% CI 9.97 to 31.03) at one year. High-certainty evidence indicates that glutamine supplements do not prevent RT-induced diarrhoea. Evidence on various other non-pharmacological interventions, such as green tea tablets, is lacking.Quality of life was rarely and inconsistently reported across included studies, and the available data were seldom adequate for meta-analysis. Conformal radiotherapy techniques are an improvement on older radiotherapy techniques. IMRT may be better than 3DCRT in terms of GI toxicity, but the evidence to support this is uncertain. There is no high-quality evidence to support the use of any other prophylactic intervention evaluated. However

  3. Uraemic toxins induce proximal tubular injury via organic anion transporter 1-mediated uptake

    Science.gov (United States)

    Motojima, Masaru; Hosokawa, Atsuko; Yamato, Hideyuki; Muraki, Takamura; Yoshioka, Toshimasa

    2002-01-01

    A direct effect of uraemic toxins in promoting progression of chronic renal disease has not been established. In this study, we investigated the toxic effects of organic anions which characteristically appeared in the patients with progressive renal disease on renal proximal tubular cells expressing human organic anion transporter (hOAT) 1. A renal proximal tubular cell line, opossum kidney (OK) cells, was transformed with hOAT1. Among the organic anions examined, hippuric acid, para-hydroxyhippuric acid, ortho-hydroxyhippuric acid, indoxyl sulphate and indoleacetic acid showed a high affinity for hOAT1 expressed in the OK cells. Indoxyl sulphate and indoleacetic acid concentration-dependently inhibited proliferation of the hOAT1-transformed cells. The h.p.l.c. analysis demonstrated that cellular uptake of these organic anions was significantly elevated in hOAT1-transformed cells. These organic anions also concentration-dependently stimulated cellular free radical production. The degrees of inhibition of cell proliferation and the stimulation of free radical production induced by the organic anions were significantly higher in the hOAT1-transformed cells than vector-transformed cells. The stimulatory effect of indoxyl sulphate on free radical production was abolished by anti-oxidants and probenecid. Less free radical production was observed in the hOAT1-transformed cells treated with p-hydroxyhippuric acid, o-hydroxyhippuric acid compared with indoxyl sulphate and indoleacetic acid. Hippuric acid had little effect on free radical production. Organic anions present in the serum of patients with progressive renal disease may cause proximal tubular injury via hOAT1-mediated uptake. The mechanism of cellular toxicity by these uraemic toxins involves free radical production. Thus, some uraemic toxins may directly promote progression of chronic renal disease. PMID:11815391

  4. [Osteogenic potential of bone marrow mesenchymal stem cells from ovariectomied osteoporotic rat].

    Science.gov (United States)

    Li, Dong-ju; Ge, Dong-xia; Wu, Wen-chao; Wu, Jiang; Li, Liang

    2005-05-01

    To investigate the difference of osteogenic potential of bone marrow mesenchymal stem cells (MSCs) between healthy rats and osteoporotic rats. We established the animal model of osteoporosis by performing ovariectom on the 3-month-old female Sprague-Dawley rats. Bone marrow mesenchymal stem cells(MSCs) were isolated from the rats of control group and of ovariectomized (ovx) group by means of the density-gradient centrifugation method, and the 3rd-4th passage MSCs were used in all the experiments. The experiments comprised 4 groups: (1) Marrow mesenchymal stem cells control group (MSCs control group); (2) Marrow mesenchymal stem cells ovx group (MSCs ovx group); (3) Osteogenesis induction control group (OSI control group); (4) Osteogenesis induction ovx group (OSI ovx group). Cell cycle and proliferation index (PI) of MSCs were detected by flow cytometry. The expression of alkaline phosphatase (ALP) was detected by dynamics method with substrate of phosphoric acid para-Nitro benzene. The levels of osteocalcin were detected with the isotope labelling method. (1) PI of MSCs was lower in MSCs ovx group than in MSCs control group. (2) The expression of alkaline phosphatase (ALP) was much higher in OSI control group than in the MSCs control group; the expression of alkaline phosphatase (ALP) was much higher in the OSI control group than in OSI ovx group after 7-day and 14-day osteogenic induction. (3) The level of osteocalcin was much higher in the OSI control group than in the MSCs control group after 14-day, 21-day, 28-day osteogenic induction. The level of osteocalcin was much higher in the OSI control group than in the OSI ovx group. Both the proliferative potential and the osteogenic potential of bone marrow mesenchymal stem cells (MSCs) from the ovariectomized osteoporotic rat are decreased.

  5. 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

  6. 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

  7. 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

  8. 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