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Sample records for aminosalicylic acid-para

  1. Synthesis of Chromium (Ⅲ) 5-aminosalicylate

    Institute of Scientific and Technical Information of China (English)

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

    2004-01-01

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

  2. Preparation and study of rare earth 4-aminosalicylates

    International Nuclear Information System (INIS)

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

  3. Synthesis of azo derivatives of 4-aminosalicylic acid

    Institute of Scientific and Technical Information of China (English)

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

    2007-01-01

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

  4. Absorption of 5-aminosalicylic acid from colon and rectum.

    OpenAIRE

    Bondesen, S; Schou, J B; Pedersen, V.; Rafiolsadat, Z; Hansen, S H; Hvidberg, E F

    1988-01-01

    In order to clarify the characteristics of absorption of 5-aminosalicylic acid (5-ASA) from the colon, a neutral solution was instilled into the right part of the colon and the rectum, respectively, in six volunteers. A laxative (bisacodyl) and liquid meals were given prior to each instillation. No significant difference could be demonstrated between the two parts of the large bowel, but the absorption was considerably restricted compared with previous results obtained from the jejunum. The r...

  5. Duration of treatment with 5-aminosalicylic acid compounds

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    The development of 5-aminosalicylic acid (5-ASA) therapy as a life long treatment for ulcerative colitis is reviewed from its origins in the 1940s to the present day. The drug was designed to treat rheumatoid arthritis, but was found helpful in the management of nine patients with ulcerative colitis. This discovery preceded the emergence of the clinical trial as a tool for assessing a new drug's efficacy; as a result it lacked scientific rigour and was selective in its presentation of results. Nevertheless it identified the future cornerstone of therapy in ulcerative colitis. In 1962, the first double blind controlled trial of sulphasalazine was conducted on 40 patients. Outcomemeasures were subjective and included symptoms and an assessment of the rectal mucosa. In 1973, the first two papers on the role of sulphasalazine in maintenance of remission were published. Both used placebo controls and had a stratified design. Outcomes were measuredusing "an intention to treat" approach. The British study of 64 patients used both subjective and objective criteria to assess outcomes. Patients on placebo had a relapse rate four times patients on active treatment and this founded the basis for a life long approach to therapy with 5-ASA compounds in ulcerative colitis. However, in 1985,a small "on demand" study of 32 patients suggested this approach might be as effective as continuous treatment.Some support for this view came from an Italian study which showed no benefit to continued treatment for those in remission for two years or more. The central problem these studies identify is that of adherence to treatment in the long-term. Few studies have considered patients' attitudes to continuous therapy and it is an area that needs further investigation.

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

    DEFF Research Database (Denmark)

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

    2010-01-01

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

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

    DEFF Research Database (Denmark)

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

    1992-01-01

    The formation of four major degradation products of 5-aminosalicylic acid (5-ASA) in buffered solutions at pH 7.0 was demonstrated by gradient HPLC analysis. The isolation and structural elucidation of the resulting degradation products showed that the degradation of 5-ASA led to the formation...

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

    International Nuclear Information System (INIS)

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

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

    OpenAIRE

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

    2015-01-01

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

  11. 5-Aminosalicylic acid protection against oxidative damage to synaptosomal membranes by alkoxyl radicals in vitro.

    Science.gov (United States)

    Kanski, J; Lauderback, C; Butterfield, D A

    2001-01-01

    The antioxidant properties of 5-aminosalicylic acid in vitro were evaluated in a synaptosomal membrane system prepared from gerbil cortical synaptosomes using EPR spin labeling and spectroscopic techniques. MAL-6 (2,2,6,6-tetramethyl-4-maleimidopiperidin-1-oxyl) and 5-NS (5-nitroxide stearate) spin labels were used to assess changes in protein oxidation and membrane lipid fluidity, respectively. Synaptosomal membranes were subjected to oxidative stress by incubation with 1 mM azo-bis(isobutyronitrile) (AIBN) or 1 mM 2,2'-azobis(amidino propane) dihydrochloride (AAPH) at 37 degrees C for 30 minutes. The EPR analyses of the samples showed significant oxidation of synaptosomal proteins and a decrease in membrane fluidity. 5-Aminosalicylic acid also was evaluated by means of FRAP (the ferric reducing ability of plasma) test as a potential antioxidant. 5-Aminosalicylic acid also showed protection against the oxidation in gerbil cortical synaptosomes system caused by AIBN and AAPH. These results are consistent with the notion of antioxidant protection against free radical induced oxidative stress in synaptosomal membrane system by this agent.

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

    Institute of Scientific and Technical Information of China (English)

    Javier P Gisbert; María Chaparro; Fernando Gomollón

    2011-01-01

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

  13. 3D printing of modified-release aminosalicylate (4-ASA and 5-ASA) tablets.

    Science.gov (United States)

    Goyanes, Alvaro; Buanz, Asma B M; Hatton, Grace B; Gaisford, Simon; Basit, Abdul W

    2015-01-01

    The aim of this study was to explore the potential of fused-deposition 3-dimensional printing (FDM 3DP) to produce modified-release drug loaded tablets. Two aminosalicylate isomers used in the treatment of inflammatory bowel disease (IBD), 5-aminosalicylic acid (5-ASA, mesalazine) and 4-aminosalicylic acid (4-ASA), were selected as model drugs. Commercially produced polyvinyl alcohol (PVA) filaments were loaded with the drugs in an ethanolic drug solution. A final drug-loading of 0.06% w/w and 0.25% w/w was achieved for the 5-ASA and 4-ASA strands, respectively. 10.5mm diameter tablets of both PVA/4-ASA and PVA/5-ASA were subsequently printed using an FDM 3D printer, and varying the weight and densities of the printed tablets was achieved by selecting the infill percentage in the printer software. The tablets were mechanically strong, and the FDM 3D printing was shown to be an effective process for the manufacture of the drug, 5-ASA. Significant thermal degradation of the active 4-ASA (50%) occurred during printing, however, indicating that the method may not be appropriate for drugs when printing at high temperatures exceeding those of the degradation point. Differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA) of the formulated blends confirmed these findings while highlighting the potential of thermal analytical techniques to anticipate drug degradation issues in the 3D printing process. The results of the dissolution tests conducted in modified Hank's bicarbonate buffer showed that release profiles for both drugs were dependent on both the drug itself and on the infill percentage of the tablet. Our work here demonstrates the potential role of FDM 3DP as an efficient and low-cost alternative method of manufacturing individually tailored oral drug dosage, and also for production of modified-release formulations.

  14. Para-aminosalicylic acid-induced hypoglycaemia in a patient with diabetic nephropathy.

    Science.gov (United States)

    Dandona, P; Greenbury, E; Beckett, A G

    1980-02-01

    A 62-year-old Indian with diabetic nephropathy controlled with metformin, developed miliary tuberculosis for which he was treated with rifampicin, isoniazid and ethambutol. Soon afterwards he developed cholestatic hepatitis and visual disturbance. Rifampicin and ethambutol were stopped. Streptomycin caused vertigo and had to be stopped. The introduction of para-aminosalicylic acid (PAS) led to hypoglycaemic coma. Metformin was stopped. Hypoglycaemic coma recurred. PAS was stopped and the patient's blood glucose concentrations became normal. Treatment with isoniazid and ethambutol led to total recovery from pulmonary tuberculosis. The induction of hypoglycaemia with PAS in this patient suggests a potential role for PAS in the treatment of diabetes mellitus.

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

    Directory of Open Access Journals (Sweden)

    Cristiana Perrotta

    2015-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

    Satinder Kakar; Deepa Batra; Ramandeep Singh

    2013-01-01

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

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

    Science.gov (United States)

    Dhaneshwar, Suneela S

    2014-04-01

    Despite the advent of biological products, such as anti-tumor necrosis factor-α monoclonal antibodies (infliximab and adalimumab), for treatment of moderate to severe cases of inflammatory bowel disease (IBD), most patients depend upon aminosalicylates as the conventional treatment option. In recent years, the increased knowledge of complex pathophysiological processes underlying IBD has resulted in development of a number of newer pharmaceutical agents like low-molecular-weight heparin, omega-3 fatty acids, probiotics and innovative formulations such as high-dose, once-daily multi-matrix mesalamine, which are designed to minimize the inflammatory process through inhibition of different targets. Optimization of delivery of existing drugs to the colon using the prodrug approach is another attractive alternative that has been utilized and commercialized for 5-aminosalicylic acid (ASA) in the form of sulfasalazine, balsalazide, olsalazine and ipsalazine, but rarely for its positional isomer 4-ASA - a well-established antitubercular drug that is twice as potent as 5-ASA against IBD, and more specifically, ulcerative colitis. The present review focuses on the complete profile of 4-ASA and its advantages over 5-ASA and colon-targeting prodrugs reported so far for the management of IBD. The review also emphasizes the need for reappraisal of this promising but unexplored entity as a potential treatment option for IBD. PMID:24707139

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

    NARCIS (Netherlands)

    Heap, Graham A.; So, Kenji; Weedon, Mike; Edney, Naomi; Bewshea, Claire; Singh, Abhey; Annese, Vito; Beckly, John; Buurman, Dorien; Chaudhary, Rakesh; Cole, Andrew T.; Cooper, Sheldon C.; Creed, Tom; Cummings, Fraser; de Boer, Nanne K.; D'Inca, Renata; D'Souza, Richard; Daneshmend, Tawfique K.; Delaney, Michael; Dhar, Anjan; Direkze, Natalie; Dunckley, Paul; Gaya, Daniel R.; Gearry, Richard; Gore, Steve; Halfvarson, Jonas; Hart, Ailsa; Hawkey, Chris J.; Hoentjen, Frank; Iqbal, Tariq; Irving, Peter; Lal, Simon; Lawrence, Ian; Lees, Charlie W.; Lewis, Steve; Lockett, Melanie; Mann, Stephen; Mansfield, John; Mowat, Craig; Mulgrew, Chris J.; Müller, Frank; Murray, Charles; Oram, Richard; Orchard, Tim; Parkes, Miles; Phillips, Rosemary; Pollok, Richard; Radford-Smith, Graham; Sebastian, Shaji; Sen, Sandip; Shirazi, Tarek; Silverberg, Mark; Solomon, Laurie; Sturniolo, Giacomo C.; Thomas, Mark; Tremelling, Mark; Tsianos, Epameinondas V.; Watts, David; Weaver, Sean; Weersma, Rinse K.; Wesley, Emma; Holden, Arthur; Ahmad, Tariq

    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

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

    Directory of Open Access Journals (Sweden)

    Nagpal Deepika

    2006-01-01

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

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

    DEFF Research Database (Denmark)

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

    1993-01-01

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

  1. 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.

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

    Science.gov (United States)

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

    2016-07-01

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

  3. 5-Aminosalicylic acid attenuates allergen-induced airway inflammation and oxidative stress in asthma.

    Science.gov (United States)

    Raju, K Rama Satyanarayana; Kumar, M N Sathish; Gupta, Saurabh; Naga, Srinivas T; Shankar, Jaya K; Murthy, Vishakantha; Madhunapanthula, Subba Rao V; Mulukutla, Shashank; Ambhore, Nilesh S; Tummala, Shashank; Vishnuvarthan, V J; Azam, Afzal; Elango, Kannan

    2014-12-01

    Pro-inflammatory cytokines regulate the magnitude of allergic reactions during asthma. Tumor necrosis factor--alpha (TNF-α), interleukin-6 (IL-6) and interleukin-13 (IL-13) play a crucial role in aggravating the inflammatory conditions during allergic asthma. In addition, oxidative stress contributes to the pathogenesis of asthma by altering the physiological condition resulting in the development of status asthmaticus. Anti-inflammatory corticosteroids are being widely used for treating allergic asthma. In the present study 5-aminosalicylic acid (5-ASA), a salicylic acid derivative, was evaluated, in vivo for its potential to suppress TNF-α, IL-6 and IL-13 using ovalbumin (OVA) induced allergic asthma in Balb/C mice. Oral administration of 65, 130 and 195 mg/kg 5-ASA significantly reduced the OVA induced total and differential leucocyte count, TNF-α, IL-6, IL-13, nitrite, nitrate, MDA, MPO and TPL levels in the lung lavage samples. Collectively, these findings suggest that 5-ASA is a potent immunomodulator and suppresses key Th2 cytokines production and oxidative stress in OVA-induced asthma.

  4. Co-crystal and crystal: Supramolecular arrangement obtained from 4-aminosalicylic acid, bpa ligand and cobalt ion

    Science.gov (United States)

    Garcia, Humberto C.; Cunha, Ronaldo T.; Diniz, Renata; de Oliveira, Luiz Fernando C.

    2012-02-01

    In this study, the synthesis, spectroscopic properties (infrared and Raman) and crystal structures of two new compounds co-crystal and crystal named HASbpa (1) and [Co(bpa)(H2O)4]AS2ṡ4H2O (2) have been reported, where bpa is trans-1,2-bis(4-pyridyl)ethane, HAS is 4-aminosalicylic acid and AS- is aminosalicylate anion. The crystalline arrangement of the compound 1 exhibits a triclinic system with space group P1¯. The formation of a structure known as co-crystal, composed by building blocks in their neutral form; being the first work of this type involving the HAS and nitrogen ligand as bpa. For compound 2, a monoclinic system was observed with P21/c space group. The crystalline arrangement of the structure consisted of a covalent one-dimensional cationic [Co(bpa)(H2O)4]2+ chain, which interacts by hydrogen bonding, π-stacking and electrostatic interactions with aminosalicylate anions and water molecules that were trapped in the crystal. These interactions form supramolecular cavities denominated as pseudo honeycombs. For compound 1, the infrared spectrum revealed the presence of bands at 1643 and 1601 cm-1 assigned to the stretching mode of CO [ν(CO)] and CC/CN groups [ν(CC/CN)]. For the Raman spectrum, these same modes appear around 1644 and 1602 cm-1 related to HAS and bpa blocks, respectively. For compound 2, the largest displacement of the bands compared to free ligand suggested the formation of covalent bonds between bpa ligand and metallic site and loss of the proton in HAS molecule. In the infrared spectrum we can observe the presence of bands around 1635 and 1618 cm-1 attributed to the stretching ν(COO-) and ν(CC/CN), for the Raman spectrum these same modes appear around 1631 and 1619 cm-1 related to AS- and bpa ligand respectively.

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

    International Nuclear Information System (INIS)

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

  6. 5-aminosalicylic acid in combination with nimesulide inhibits proliferation of colon carcinoma cells in vitro

    Institute of Scientific and Technical Information of China (English)

    Hai-Ming Fang; Qiao Mei; Jian-Ming Xu; Wei-Juan Ma

    2007-01-01

    AIM:To investigate the effects of 5-aminosalicylic acid (5-ASA) in combination with nimesulide on the proliferation of HT-29 colon carcinoma cells and its potential mechanisms.METHODS: Inhibitory effects of drugs (5-ASA,nimesulide and their combination) on HT-29 colon carcinoma cells were investigated by thiazolyl blue tetrazolium bromide (MTT) assay. Cellular apoptosis and proliferation were detected by TUNEL assay and immunocytochemical staining, respectively.RESULTS: Pretreatment with 5-ASA or nimesulide at the concentration of 10-1000 μmol/L inhibited proliferation of HT-29 colon carcinoma cells in a dose-dependent manner in vitro (t = 5.122, P < 0.05; t = 3.086, P <0.05, respectively). The inhibition rate of HT-29 colon carcinoma cell proliferation was also increased when pretreated with 5-ASA (100 μmol/L) or nimesulide (100μmol/L) for 12-96 h, which showed an obvious timeeffect relationship (t = 6.149, P < 0.05; t = 4.159, P< 0.05, respectively). At the concentration of 10-500μmol/L, the apoptotic rate of HT-29 colon carcinoma cells significantly increased (t = 18.156, P < 0.001; t =19.983, P < 0.001, respectively), while expression of proliferating cell nuclear antigen (PCNA) was remarkably decreased (t = 6.828, P < 0.05; t = 14.024, P < 0.05,respectively). 5-ASA in combination with nimesulide suppressed the proliferation of HT-29 colon carcinoma cells more than either of these agents in a dosedependent and time-dependent manner (t = 5.448, P <0.05; t = 4.428, P < 0.05, respectively).CONCLUSION: 5-ASA and nimesulide may inhibit the proliferation of HT-29 colon carcinoma cells and coadministration of these agents may have additional chemopreventive potential.

  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...... g/day) and placebo. Treatment was started 2 days before initiation of carrageenan administration. The drugs were administered through a chronic gastric fistula. At the end of the study concentrations of 5-ASA and acetylated 5-ASA (Ac-5-ASA) in cecal contents and in plasma were determined...... difference between the human ulcerative colitis and the carrageenan model may account for the lack of prophylactic effect of the slow-release 5-ASA in this experiment....

  8. Effect of 70-nm silica particles on the toxicity of acetaminophen, tetracycline, trazodone, and 5-aminosalicylic acid in mice.

    Science.gov (United States)

    Li, X; Kondoh, M; Watari, A; Hasezaki, T; Isoda, K; Tsutsumi, Y; Yagi, K

    2011-04-01

    Exposure to nano-sized particles is increasing because they are used in a wide variety of industrial products, cosmetics, and pharmaceuticals. Some animal studies indicate that such nanomaterials may have some toxicity, but their synergistic actions on the adverse effects of drugs are not well understood. In this study, we investigated whether 70-nm silica particles (nSP70), which are widely used in cosmetics and drug delivery, affect the toxicity of a drug for inflammatory bowel disease (5-aminosalicylic acid), an antibiotic drug (tetracycline), an antidepressant drug (trazodone), and an antipyretic drug (acetaminophen) in mice. Co-administration of nSP70 with trazodone did not increase a biochemical marker of liver injury. In contrast, co-administration increased the hepatotoxicity of the other drugs. Co-administration of nSP70 and tetracycline was lethal. These findings indicate that evaluation of synergistic adverse effects is important for the application of nano-sized materials.

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

    Science.gov (United States)

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

    2016-09-01

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

  11. Toxicity of 50-nm polystyrene particles co-administered to mice with acetaminophen, 5-aminosalicylic acid or tetracycline.

    Science.gov (United States)

    Isoda, K; Nozawa, T; Tezuka, M; Ishida, I

    2014-09-01

    We investigated whether nano-sized polystyrene particles affect drug-induced toxicity. The particles, which are widely used industrially, had diameters of 50 (NPP50), 200 (NPP200) or 1000 (NPP1000) nm. The toxic chemicals tested were acetaminophen (APAP), 5-aminosalicylic acid (5-ASA), tetracycline (TC), and sodium valproate (VPA). All treatments in the absence of the nanoparticles were non-lethal and did not result in severe toxicity. However, when mice were injected with APAP, 5-ASA or TC together with polystyrene particles, synergistic, enhanced toxicity was observed in mice injected with NPP50. These synergic effects were not observed in mice co-injected with NPP200 or NPP1000. On the other hand, co-administration of VPA and NPP50, NPP200 or NPP1000 did not elevate toxicity. The results show that NPP50 differs in hepatotoxicity depending on the drug co-administered. These findings suggest that further evaluation of the interactions between polystyrene nanoparticles and drugs is a critical prerequisite to the pharmaceutical application of nanotechnology.

  12. 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.

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

    Directory of Open Access Journals (Sweden)

    Saifullah B

    2014-07-01

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

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

    Directory of Open Access Journals (Sweden)

    Chinhwa Cheng

    2014-06-01

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

  15. 5-aminosalicylic acid is an attractive candidate agent for chemoprevention of colon cancer in patients with inflammatory bowel disease

    Institute of Scientific and Technical Information of China (English)

    Yang Cheng; Pierre Desreumaux

    2005-01-01

    Inflammatory bowel disease (IBD) is classically subdivided into ulcerative colitis (UC) and Crohn's disease (CD). Patients with IBD have increased risk for colorectal cancer. Because the pathogenesis of colorectal carcinoma has not been entirely defined yet and there is no ideal treatment for colon cancer, cancer prevention has become increasingly important in patients with IBD. The two adopted methods to prevent the development of colon cancer in clinical practice include the prophylactic colectomy and colonoscopic surveillance.But patients and physicians seldom accept colectomy as a routine preventive method and most patients do not undergo appropriate colonoscopic surveillance. Chemoprevention refers to the use of natural or synthetic chemical agents to reverse, suppress, or to delay the process of carcinogenesis.Chemoprevention is a particularly useful method in the management of patients at high risk for the development of specific cancers based on inborn genetic susceptibility, the presence of cancer-associated disease, or other known risk factors. Prevention of colorectal cancer by administration of chemopreventive agents is one of the most promising options for IBD patients who are at increased risks of the disease. The chemopreventive efficacy of nonsteroidal antiinflammatory drugs (NSAIDs) against intestinal tumors has been well established. But with reports that NSAIDs aggravated the symptoms of colitis, their sustained use for the purpose of cancer chemoprevention has been relatively contraindicated in IBD patients. Another hopeful candidate chemoprevention drug for IBD patients is 5-aminosalicylic acid (5-ASA), which is well tolerated by most patients and has limited systemic adverse effects, and no gastrointestinal toxicity. 5-ASA lacks the well-known side effects of longterm NSAIDs use. Retrospective correlative studies have suggested that the long-term use of 5-ASA in IBD patients may significantly reduce the risk of development of colorectal cancer

  16. 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

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

    OpenAIRE

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

    2014-01-01

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

  18. Effects of humic acids, para-aminobenzoic acid and ascorbic acid on the N-nitrosation of the carbamate insecticide propoxur and on the mutagenicity of nitrosopropoxur.

    Science.gov (United States)

    Gichner, T; Badaev, S A; Pospísil, F; Velemínský, J

    1990-03-01

    Nitrosation of the carbamate insecticide propoxur at pH 3 and 37 degrees C was determined colorimetrically and found to be time- and sodium nitrite concentration-dependent. Nitrosated propoxur was mutagenic when exposed to the seeds of the higher plant Arabidopsis thaliana but the formation of nitrosopropoxur, the presumed mutagen, was inhibited by humic acids, para-aminobenzoic acid and ascorbic acid. These agents also reduced the mutagenicity of preformed nitrosopropoxur.

  19. Use of new once-daily 5-aminosalicylic acid preparations in the treatment of ulcerative colitis: Is there anything new under the sun?

    Institute of Scientific and Technical Information of China (English)

    Peter Laszlo Lakatos

    2009-01-01

    5-aminosalicylate (5-ASA) agents remain the mainstay treatment in ulcerative colitis (UC). A number of oral 5-ASA agents are commercially available, including azobond pro-drugs, as well as delayed- and controlledrelease forms of mesalazine. However, poor adherence due to frequent daily dosing and a large number of tablets has been shown to be an important barrier to successful management of patients with UC. Recently, new, once-daily formulations of mesalazine, including the unique multi-matrix delivery system and mesalazine granules, were proven to be efficacious in inducing and maintaining remission in mild-to-moderate UC, with a good safety profile comparable to that of other oral mesalazine formulations. In addition, they offer the advantage of a low pill burden and might contribute to increased long-term compliance and treatment success in clinical practice. This editorial summarizes the available literature on the short- and medium-term efficacy and safety of the new once-daily mesalazine formulations.

  20. Effects of p-Aminosalicylic acid on the Neurotoxicity of Manganese and Levels of Dopamine and Serotonin in the Nervous System and Innervated Organs of Crassostrea virginica.

    Science.gov (United States)

    King, Candice; Myrthil, Marie; Carroll, Margaret A; Catapane, Edward J

    2008-01-01

    Manganese is a neurotoxin causing Manganism in individuals chronically exposed to elevated levels in their environment. Toxic manganese exposure causes mental and emotional disturbances, and a movement disorder similar to Idiopathic Parkinsons Disease. Manganese interferes with dopamine neurons involved in control of body movements. Recently, p-aminosalicylic acid (PAS) is being used to alleviate symptoms of Manganism, but its mechanism of action is unknown. The eastern oyster, Crassostrea virginica, possesses a dopaminergic innervation of its gill. Oysters exposed to manganese have reduced levels of dopamine in the cerebral ganglia, visceral ganglia and gill, but not of norepinephrine, octopamine or serotonin. Those results are consistent with reported mechanisms of action of manganese in human and mammalian systems. In this study we determined the effects of PAS treatments on dopamine and serotonin levels in oysters exposed to manganese. Adult C. virginica were exposed to 500 µM and 1 mM of manganese with and without 500 µM and 1 mM of PAS by removing one shell and maintaining the animals in individual containers of aerated artificial sea water at 18° C for 3 days. Control animals were similarly treated without manganese or PAS. Dopamine and serotonin levels were measured by HPLC with fluorescence detection. PAS protected the ganglia and gill against the effects of 500 µM manganese, but not against the 1 mM manganese treatments. Serotonin levels were not affected by the treatments. The study demonstrates PAS can protect against reductions in dopamine levels caused by neurotoxic manganese exposure, but is concentration dependent. These findings may provide insights into the actions of PAS in therapeutic treatments of Manganism.

  1. Time-and pH-dependent colon-specific drug delivery for orally administered diclofenac sodium and 5-aminosalicylic acid

    Institute of Scientific and Technical Information of China (English)

    Gang Cheng; Feng An; Mei-Juan Zou; Jin Sun; Xiu-Hua Hao; Yun-Xia He

    2004-01-01

    AIM: To investigate Time- and pH-dependent colon-specific drug delivery systems (CDDS) for orally administered diclofenac sodium (DS) and 5-aminosalicylic acid (5-ASA), respectively.METHODS: DS tablets and 5-ASA pellets were coated by ethylcellulose (EC) and methacrylic acid copolymers (Eudragit[] L100 and S100), respectively. The in vitro release behavior of the DS coated tablets and 5-ASA coated pellets were examined, and then in vivo absorption kinetics of DS coated tablets in dogs were further studied.RESULTS: Release profile of time-dependent DS coated tablets was not influenced by pH of the dissolution medium,but the lag time of DS release was primarily controlled by the thickness of the coating layer. The thicker the coating layer, the longer the lag time of DS release is. On the contrary, in view of the pH-dependent 5-ASA coated pellets,5-ASA release was significantly governed by pH. Moreover,the 5-ASA release features from the coated pellets depended upon both the combination ratio of the Eudragit[] L100 and S100 pH-sensitive copolymers in the coating formulation and the thickness of the coating layer. The absorption kinetic studies of the DS coated tablets in dogs demonstrated that in vivo lag time of absorption was in a good agreement with in vitro lag time of release.CONCLUSION: Two types of CDDS, prepared herein by means of the regular coating technique, are able to achieve site-specific drug delivery targeting at colon following oral administration, and provide a promising strategy to control drug release targeting the desired lower gastrointestinal region.

  2. 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].

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

    Science.gov (United States)

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

    2016-01-01

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

  4. 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

    -formamidosalicylic acid) using H-1- and C-13-n.m.r. spectrometry and mass spectroscopy and the structure was confirmed by chemical synthesis. 3. N-Formyl-5-ASA is stable in human plasma and in potassium phosphate buffers between pH 3.0 and 9.0. It is hydrolysed below pH 3.0. 4. N-Formyl-5-ASA was readily formed...... in rat liver homogenate when 5-ASA and N-formyl-L-kynurenine were added. Thus N-formyl-5-ASA might be formed by the actions of formamidase in vivo. 5. N-Formyl-5-ASA has been found in human plasma from healthy volunteers dosed i.v. with 5-ASA (250 mg). N-beta-D-glucopyranosyl-5-ASA, N-acetyl-5-ASA and N...

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

    DEFF Research Database (Denmark)

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

    2010-01-01

    fibres is related to disease activity in patients with ulcerative colitis (UC) treated with 5-ASA. METHODS: In vitro: 15 g of Ispaghula Husk, wheat bran, citrus-pectin, or wheat flour were incubated in a 37°C buffered solutions of 5-ASA (1 g/l) for 3 hours at pH 6 and 7. The concentrations of 5-ASA were...... determined before and after the incubation using HPLC. In vivo: patients with UC were interviewed two to three times during 6 months. The fibre consumption was estimated and related to the disease activity (CAI, CRP, Faecal-calprotectin) and quality of life (IBDQ). RESULTS: In vitro: 5-ASA was bound...... to Ispaghula Husk (5.3-10.0 mg/g) and wheat bran (4.6-5.5 mg/g), and to a minor degree to citrus-pectin. No differences were found in relation to pH. In vivo: 29 patients completed the scheduled interviews. No significant changes in fibre consumption were observed over time; however, patients consuming a diet...

  6. 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.

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

    Institute of Scientific and Technical Information of China (English)

    Zhang Xiuying; Li Shujing; Lei Xuefeng; Ma Junxian

    2005-01-01

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

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

    OpenAIRE

    2004-01-01

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

  9. Indications for 5-aminosalicylate in inflammatory bowel disease: IS the body of evidence complete?

    Institute of Scientific and Technical Information of China (English)

    Ad A van Bodegraven; Chris JJ Mulder

    2006-01-01

    Mesalazine is a safe drug, although adverse events may be seen in a minority of patients. This applies also to pregnant women and children. The role of mesalazine in combination therapy to improve efficacy and concomitant drug pharmacolinetics, or in chemoprevention againstinflammatory bowel disease (IBD)-related colonic carcinoma has not yet been completely elucidated.Therapeutic success of mesalazine may be optimized by a combination of high dose and low frequency of dosage to improve compliance. Therefore, due to its superior safety profile and pharmacokinetic characteristics,mesalazine is preferable to sulphasalazine. This paper reviews the literature concerning mechanisms of action,indications and off-label use, pharmacokinetic properties and formulations, therapeutic efficacy, compliance, paediatric indications, chemoprevention, and safety issues and adverse event profile of mesalazine treatment versus sulphasalazine. It also highlights these controversies in order to clarify the potential benefits of mesalazines in IBD therapy and evidence for its use.

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

    Institute of Scientific and Technical Information of China (English)

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

    2010-01-01

    New once daily mesalamine formulations may improve adherence to medication usage.Response to Asacol and other forms of 5-aminosalicyclic acid(5-ASA)is better correlated with tissue concentrations and best predicted by concentrations of the drug within the lumen of the colon.Our group used computer simulation to predict colonic 5-ASA levels after Asacol administration.In our study,the model simulated Asacol distribution in the healthy colon,and during quiescent and active ulcerative colitis.An Asacol dosage ...

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

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    Severe reactions to mesalamine products are rarely seen in pediatric patients. We report a case of a 12-year-old boy who had a severe cardiac reaction to a mesalamine product Asacol. Past medical history is significant for ulcerative colitis (UC) diagnosed at 9 years of age. Colo- noscopy one week prior to admission revealed pancoli- tis. He was treated with Asacol 800 mg three times per day and prednisone 20 mg/d. He was subsequently ad- mitted to the hospital for an exacerbation of his UC and started on intravenous solumedrol. He had improvement of his abdominal pain and diarrhea. The patient com- plained of new onset of chest pain upon initiating Asacol therapy. Electrocardiogram (ECG) revealed non-specific ST-T wave changes with T-wave inversion in the lateral leads. Echocardiogram (ECHO) revealed low-normal to mildly depressed left ventricular systolic function. The left main coronary artery and left anterior descending artery were mildly prominent measuring 5 mm and 4.7 mm, respectively. His chest pain completely resolved within 24-36 h of discontinuing Asacol. A repeat echo- cardiogram performed two days later revealed normal left ventricular function with normal coronary arteries (< 3.5 mm). Onset of chest pain after Asacol and im- mediate improvement of chest pain, as well as improve- ment of echocardiogram and ECG findings after discon- tinuing Asacol suggests that our patient suffered from a rare drug-hypersensitivity reaction to Asacol.

  12. 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

    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...

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

    DEFF Research Database (Denmark)

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

    1993-01-01

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

  14. 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...... and validation of the Web-based 'Constant-Care' concept. METHODS: A Web-based treatment program (www.constant-care.dk) and a Patient Educational Centre for UC patients were developed. The feasibility and acceptance of the concept was validated before (group A) and 6 months after (group B) the start...

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

    Institute of Scientific and Technical Information of China (English)

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

    2005-01-01

    AIM: To investigate the release of cyclodextrin-5-amino salicylic acid (CyD-5-ASA) in cecum and colon.METHODS: An anti-inflammatory drug 5-ASA was conjugated onto the hydroxyl groups of α-, β- and γ-cyclodextrins (CyDs) through an ester linkage, and the in vivo drug release behavior of these prodrugs in rat' s gastrointestinal tract after the oral administration was investigated.RESULTS: The 5-ASA concentration in the rat's stomach and small intestine after the oral administration of CyD5-ASA conjugate was much lower than that after the oral administration of 5-ASA alone. The lower concentration was attributable to the passage of the conjugate throughthe stomach and small intestine without significant degradation or absorption, followed by the degradation of the conjugate site-specific in the cecum and colon. The oral administration of CyD-5-ASA resulted in lower plasma and urine concentration of 5-ASA than that of 5-ASA alone.CONCLUSION: CyD-5-ASA conjugates may be used as prodrugs for colon-specific drug delivery system.

  16. 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.

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

    OpenAIRE

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

    2014-01-01

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

  18. Identification de filtres solaires dérivés de l'acide para-aminobenzoique par spectroscopie RMN et par CPG/SM.

    Science.gov (United States)

    Masse, M O; Delporte, C; Bervelt, E

    2001-10-01

    Gas chromatography coupled with mass spectrometry and protonic nuclear magnetic resonance used directly or on fractions obtained by preparative thin layer chromatography, allow identification of the main molecule in commercial samples of PABA (Cas RN 150-13-0), PEG-25 PABA (Cas RN 116242-27-4), glyceryl PABA (Cas RN136-44-7), ethyl dihydroxypropyl PABA (Cas RN 58882-17-0) or octyl dimethyl PABA (Cas RN 21245-02-3).

  19. Synthesis of 4-Aminosalicylglycine

    Institute of Scientific and Technical Information of China (English)

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

    2005-01-01

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

  20. Drug: D02715 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available osalicylic acid and similar agents A07EC04 Balsalazide D02715 Balsalazide disodium (USAN) USP drug classification [BR:br08302] Inflam...matory Bowel Disease Agents Aminosalicylates Balsalazide D02715 Balsalazide disodiu

  1. 甘氨酸及5-氨基水杨酸改性淀粉对Cd(Ⅱ)的吸附性能研究%ADSORPTION OF Cd(Ⅱ) BY GLYCINE-AND 5-AMINOSALICYLIC ACIDS-MODIFIED STARCH

    Institute of Scientific and Technical Information of China (English)

    曹玮; 吕彤; 崔莉; 杜晓; 王君

    2016-01-01

    以淀粉(Starch)为基体,接枝甲基丙烯酸缩水甘油酯(GMA)后得到starch-g-GMA,再分别将甘氨酸(Gly)或5-氨基水杨酸(ASA)修饰在starch-g-GMA上,形成2种对Cd(Ⅱ)具有优良吸附效果的新型改性淀粉螯合剂starch-g-GMA-Gly和starch-g-GMA-ASA.借助红外光谱、扫描电镜、元素分析仪等表征了改性淀粉螯合剂的结构,通过原子吸收光谱仪测试了改性淀粉螯合剂对Cd(Ⅱ)的静态吸附性能.结果表明,上述改性淀粉螯合剂对Cd(Ⅱ)的吸附过程均符合准二级动力学方程,且吸附等温线用Freundlich模型拟合效果优于Langmuir模型.starch-g-GMA-Gly和starch-g-GMA-ASA对Cd(Ⅱ)的平衡吸附量均较大,分别达到130mg/g和149mg/g.

  2. Cyclodextrin-based drug stabilizing system

    Science.gov (United States)

    Roik, N. V.; Belyakova, L. A.

    2011-02-01

    UV spectroscopy study of para-aminosalicylic acid behaviour in the presence of β-cyclodextrin and without it in buffer solutions was realized. Influence of duration of contact, acidity of solution, temperature, and content of reagents in the binary solutions on the complex formation between β-cyclodextrin and para-aminosalicylic acid was examined. The stability constants of the supramolecular complexes formed at pH = 1.00 and pH = 6.86 were calculated by the Ketelar equation at various temperatures. It was found that the inclusion interaction of β-cyclodextrin with protonated type of para-aminosalicylic acid is superior to that for its anionic one. From the temperature dependence of stability constants the thermodynamic parameters involved in the complex formation (ΔG, ΔH, ΔS) were calculated. It was proved that complex formation between β-cyclodextrin and para-aminosalicylic acid is spontaneous process accompanied by the release of heat and decrease of entropy. To characterize the solid product of para-aminosalicylic acid inclusion into the cavity of β-cyclodextrin supramolecular complex with a 1:1 mole ratio of components have been prepared by kneading method and studied by IR spectroscopy and X-ray diffraction.

  3. Utilization of aminoaromatic acids by a methanogenic enrichment culture and by a novel Citrobacter freundii strain

    NARCIS (Netherlands)

    Savelieva, O.; Kotova, I.; Roelofsen, W.; Stams, A.J.M.; Netrusov, A.

    2004-01-01

    Following incubation of mesophilic methanogenic floccular sludge from a lab-scale upflow anaerobic sludge bed reactor used to treat cattle manure wastewater, a stable 5-aminosalicylate-degrading enrichment culture was obtained. Subsequently, a Citrobacter freundii strain, WA1, was isolated from the

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

    Science.gov (United States)

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

    2000-01-01

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

  5. Fluorescent carbon dot–molecular salt hydrogels

    OpenAIRE

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

    2015-01-01

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

  6. Optical and thermal properties of azo derivatives of salicylic acid thin films

    Science.gov (United States)

    Ghoneim, M. M.; El-Ghamaz, N. A.; El-Sonbati, A. Z.; Diab, M. A.; El-Bindary, A. A.; Serag, L. S.

    2015-02-01

    N-acryloyl-4-aminosalicylic acid (4-AMSA), monomer (HL) and 5-(4‧-alkyl phenylazo)-N-acryloyl-4-aminosalicylic acid (HLn) are synthesized and characterized with various physico-chemical techniques. Thin films of 5-(4‧-alkyl phenylazo)-N-acryloyl-4-aminosalicylic acid (HLn) are prepared by spin coating technique. The X-ray diffraction (XRD) patterns of 4-aminosalicylic acid (4-ASA) and its derivatives are investigated in powder and thin film forms. Thermal properties of the compounds are investigated by thermogravemetric analysis (TGA). The optical energy gap and the type of optical transition are investigated in the wavelength range (200-2500 nm) for 4-ASA, HL and HLn. The values of fundamental energy gap (Eg) are in the range 3.60-3.69 eV for all compounds and the type of optical transition is found to be indirect allowed. The onset energy gap Eg∗ appeared only for azodye compounds is found to be in the range 0.95-1.55 eV depending on the substituent function groups. The refractive index, n, shows a normal dispersion in the wavelength range 650-2500 nm, while shows anomalous dispersion in the wavelength rang 200-650 nm. The dispersion parameters ε∞, εL, Ed, Eo and N /m∗ are calculated. The photoluminescence phenomena (PL) appear for thin films of 4-ASA and its derivatives show three main emission transitions.

  7. 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) t......) 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.......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...

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

    DEFF Research Database (Denmark)

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

    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......334, and amiselimod), as well as anti-sense therapy (mongersen) targeting SMAD7, drugs which directly target intracellular pathways of relevance for intestinal inflammation. EXPERT OPINION: A new avenue using easily administered oral therapies for the management of IBD is being introduced. While...

  9. Update in the treatment of paediatric ulcerative colitis.

    Science.gov (United States)

    Greifer, Melanie K; Markowitz, James F

    2006-10-01

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

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

    OpenAIRE

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

    2011-01-01

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

  11. Understanding of chemoprophylaxis and concordance in inflammatory bowel disease

    Institute of Scientific and Technical Information of China (English)

    Adam; Low; Melanie; Love; Robert; Walt; Katherine; Kane; Bertus; Eksteen; Jason; Goh

    2010-01-01

    AIM:To assess patients' understanding for the reasons for taking 5-aminosalicylic acid or ursodeoxycholic acid as chemoprophylaxis against colorectal carcinoma associated with in? ammatory bowel disease (IBD). METHODS: A questionnaire-based study using a 5 point opinion scale was performed. One hundred and ninety-two patients with colitis only and 74 patients with primary sclerosing cholangitis and IBD were invited to take part. RESULTS: Overall response rate was 58%. Sixtyfour percent of patients claimed f...

  12. NATURAL AGENTS FOR INFLAMMATORY BOWEL DISEASE

    OpenAIRE

    Darji Vinay Chhanalal; Bariya Aditi Hemrajbhai; Deshpande Shrikalp Shrikant

    2011-01-01

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

  13. Immunomodulators and Immunosuppressants for Japanese Patients with Ulcerative Colitis

    OpenAIRE

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

    2011-01-01

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

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

    OpenAIRE

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

    2014-01-01

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

  15. Microspheres for drug-delivery to the colon

    OpenAIRE

    Watts, Peter James

    1992-01-01

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

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

    OpenAIRE

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

    2007-01-01

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

  17. 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.

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

    International Nuclear Information System (INIS)

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

  19. Mesalamine hypersensitivity and Kounis syndrome in a pediatric ulcerative colitis patient

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    5-aminosalicylic acid (mesalamine) rarely induces hyper-sensitivity reactions. If chest pain associated with atypical electrocardiographic changes are seen during its adminis-tration, one should always bear in mind type I variant of Kounis syndrome. This variant includes patients, of any age, with normal coronary arteries, without predisposing factors for coronary artery disease, in whom the acute release of inflammatory mediators from mast cells can induce either sudden coronary artery narrowing, without increase of cardiac enzymes and troponins, or coronary artery spasm that progresses to acute myocardial infarc-tion, with elevated cardiac enzymes and troponins.

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

    International Nuclear Information System (INIS)

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

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

    Institute of Scientific and Technical Information of China (English)

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

    2005-01-01

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

  2. Anti tuberculosis drug resistance in west of Iran

    Directory of Open Access Journals (Sweden)

    Parviz Mohajeri

    2014-01-01

    Full Text Available Background and Objective: Mycobacterium tuberculosis has developed resistance to antituberculosis drugs and becoming a major and alarming public health problem in worldwide. This study was aimed to determine antituberculosis drug resistance rate and to identify multidrug resistant tuberculosis (MDR-TB in West of Iran. Materials and Methods: Of 130 samples were included between December 2011 and July 2012 in the study from that 112 cases were M. tuberculosis. The proportional method was carried out according to the Clinical and Laboratory Standards Institute on Lowenstein-Jensen against isoniazid, rifampicin, streptomycin, ethambutol, pyrazinamide, para aminosalicylic acid, ethionamide, cycloserine (CYC. The microdilution method was carried out using 7H9 broth with 96 well-plates. Results: From 112 isolates, resistance was observed to isoniazid 18 (16.07%, rifampicin 16 (14.28%, streptomycin 25 (22.32%, ethambutol 15 (13.39%, pyrazinamide 27 (24.10%, para aminosalicylic acid 19 (16.96%, CYC 4 (3.57%, and ethionamide 14 (12.5% cases. 16 isolates were MDR. Conclusion: The high prevalence of MDR-TB in our study is assumed to be due to recent transmission of drug-resistant strains. Overall, the rate of drug resistance in our study was high, which is in line with findings of some high-burden countries. Hence that early case detection, rapid drug susceptibility testing, and effective anti-TB treatment is necessary.

  3. 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.

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

    International Nuclear Information System (INIS)

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

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

    Institute of Scientific and Technical Information of China (English)

    Bei; Ye; Daniel; R; van; Langenberg

    2015-01-01

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

  6. Review article: the incidence and prevalence of colorectal cancer in inflammatory bowel disease

    DEFF Research Database (Denmark)

    Munkholm, P

    2003-01-01

    Although colorectal cancer (CRC), complicating ulcerative colitis and Crohn's disease, only accounts for 1-2% of all cases of CRC in the general population, it is considered a serious complication of the disease and accounts for approximately 15% of all deaths in inflammatory bowel disease (IBD......) patients. The magnitude of the risk was found to differ, even in population-based studies. Recent figures suggest that the risk of colon cancer for people with IBD increases by 0.5-1.0% yearly, 8-10 years after diagnosis. The magnitude of CRC risk increases with early age at IBD diagnosis, longer duration...... explanations have to be investigated. One possible cancer-protective factor could be treatment with 5-aminosalicylic acid preparations (5-ASAs). Adenocarcinoma of the small bowel is extremely rare, compared with adenocarcinoma of the large bowel. Although only few small bowel cancers have been reported...

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

    International Nuclear Information System (INIS)

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

  8. [Crohn's disease--standards of treatment 2004].

    Science.gov (United States)

    Kruis, W

    2005-10-12

    In Crohn's disease therapeutic concepts are according to distinct conditions. Course of the disease, the individual disease pattern and the aim of treatment are of particular significance. Care of patients with Crohn's disease requires interdisciplinary cooperation between gastroenterologists and surgeons. Primary therapy in mild to moderate disease comprises aminosalicylates and budesonide. Treatment of refractory or severe cases are corticosteroids. Immunosuppressive therapy is indicated in all kinds of complicated disease. First line immunosuppressants are Azathioprine and 6-Mercaptopurine while Methotrexate, Infliximab, Mycophenolatmofetil and other compounds represent alternative or rescue medications. Maintenance of remission should not be done on a regular basis but rather regarding the individual patients' situation. Risks have to be carefully balanced with possible benefits. The most important aim of treatment is quality of life.

  9. NATURAL AGENTS FOR INFLAMMATORY BOWEL DISEASE

    Directory of Open Access Journals (Sweden)

    Darji Vinay Chhanalal

    2011-02-01

    Full Text Available Inflammatory bowel disease (IBD is a chronic inflammatory disease of gastrointestinal tract. It comprises the two conditions, Crohn’s disease and ulcerative colitis, characterized by chronic recurrent ulceration of the bowel. Conventional drugs for colitis treatment include aminosalicylate, corticosteroids,antibiotics & immunomodulators. 5- Amino salicylic acid having side effects in 30% of the patients. Systemic corticosteroids producing incidence of complication is 4.3%. Antibiotic therapy is beneficial in 70% of the patients & Immunomodulators having 50 to 70% beneficial effects. This report shows that there is no any appropriate treatment available to treat IBD without side effects. A natural agent with reduced or no toxicity is therefore essential. In nature there are so many types of natural agents which are used as protective agents in IBD. This article emphasizes many natural products obtained from plant & other sources, which possess potent activity against experimentally induced IBD.

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

    Institute of Scientific and Technical Information of China (English)

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

    2013-01-01

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

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

    DEFF Research Database (Denmark)

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

    2010-01-01

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

  12. 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.

  13. Presence of phthalates in gastrointestinal medications: is there a hidden danger?

    Science.gov (United States)

    Gallinger, Zane R; Nguyen, Geoffrey C

    2013-11-01

    Pharmaceutical companies that produce gastrointestinal (GI) medications often utilize phthalates for their ability to localize medication release. Commonly prescribed GI medications that may utilize phthalates are 5-Aminosalicylates, proton pump inhibitors, and pancreatic enzymes. Our understanding of the cumulative health effects of phthalates from medications remains unclear, and there is increasing evidence that phthalates are not harmless. Experimental studies in animals have shown that phthalates, specifically dibutyl phthalate and Di-(2-ethyl-hexyl) phthalate, have the potential to alter and/or inhibit reproductive biology and in utero development. Despite the lack of definitive human data, many cohort and cross-sectional studies demonstrate concerning associations between phthalates and poor health status, specifically developmental problems. Longitudinal studies and studies with larger sample sizes are required to determine whether phthalates actually cause negative health consequences. It is also important that physicians regularly review and discuss with patients the medicinal ingredients in their medications and supplements, specifically in pregnant woman with inflammatory bowel disease.

  14. Innovative therapeutics for inflammatory bowel disease

    Institute of Scientific and Technical Information of China (English)

    Jesus K Yamamoto-Furusho

    2007-01-01

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

  15. 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

  16. Segmental colitis associated with diverticulosis syndrome

    Institute of Scientific and Technical Information of China (English)

    Hugh James Freeman

    2008-01-01

    An inflammatory process that involves the sigmoid colonic segment associated with diverticular disease (SCAD) appears to be a distinct clinical and pathological disorder. It has been described in older adults, often presenting with rectal bleeding. Host of the patients seem to respond to treatment only with a 5-aminosalicylate, but some spontaneously resolve with no treatment. Endoscopic evaluation usually shows a non-specific inflammatory process localized in the sigmoid colon alone that may resolve completely with histologically normal colonic mucosa. Repeated symptomatic events with discrete episodes of segmental colitis may occur, but most patients have an entirely benign clinical course. Definition of the underlying molecular events that occur with SCAD may be critically important in understanding the critical elements present in a colonic inflammatory process that can completely resolve without pharmacological or biological treatment.

  17. Infliximab to treat severe ulcerative colitis

    Institute of Scientific and Technical Information of China (English)

    Dídia Bisamra Cury; Marcelo de Souza Cury; Geraldo Vinicius Hemerly Elias; Sender Jankiel Mizsputen

    2009-01-01

    A 48-year-old female with severe ulcerative colitis refractory to conventional therapy was referred to our facility for management. The patient showed extensive ulcerative colitis since the age of 20 years and had failed therapy with 5-aminosalicylic acid agents and azathioprine. The disease remained active despite treatment with steroids and cyclosporine. The clinical and endoscopic parameters were consistent with severe disease. Infectious precipitants were ruled out. Given the severity of the disease and in order to avoid a colectomy, we started the patient on infliximab therapy. A dramatic clinical and endoscopic response was observed and she remained in remission at the end of a 1-year follow-up period. We discuss findings in the literature regarding the use of infliximab therapy in patients with ulcerative colitis who have failed steroids and cyclosporine.

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

    Institute of Scientific and Technical Information of China (English)

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

    2010-01-01

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

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

    Science.gov (United States)

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

    2014-10-21

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

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

    DEFF Research Database (Denmark)

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

    2010-01-01

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

  1. Treatment of Tuberculosis. A Historical Perspective.

    Science.gov (United States)

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

    2015-12-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2012-11-15

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

  3. Inflammatory bowel disease in India - Past, present and future.

    Science.gov (United States)

    Ray, Gautam

    2016-09-28

    There is rising incidence and prevalence of inflammatory bowel disease (IBD) in India topping the Southeast Asian (SEA) countries. The common genes implicated in disease pathogenesis in the West are not causal in Indian patients and the role of "hygiene hypothesis" is unclear. There appears to be a North-South divide with more ulcerative colitis (UC) in north and Crohn's disease (CD) in south India. IBD in second generation Indian migrants to the West takes the early onset and more severe form of the West whereas it retains the nature of its country of origin in migrants to SEA countries. The clinical presentation is much like other SEA countries (similar age and sex profile, low positive family history and effect of smoking, roughly similar disease location, use of aminosalicylates for CD, low use of biologics and similar surgical rates) with some differences (higher incidence of inflammatory CD, lower perianal disease, higher use of aminosalicylates and azathioprine and lower current use of corticosteroids). UC presents more with extensive disease not paralleled in severity clinically or histologically, follows benign course with easy medical control and low incidence of fulminant disease, cancer, complications, and surgery. UC related colorectal cancer develop in an unpredictable manner with respect to disease duration and site questioning the validity of strict screening protocol. About a third of CD patients get antituberculosis drugs and a significant number presents with small intestinal bleed which is predominantly afflicted by aggressive inflammation. Biomarkers have inadequate diagnostic sensitivity and specificity for both. Pediatric IBD tends to be more severe than adult. Population based studies are needed to address the lacunae in epidemiology and definition of etiological factors. Newer biomarkers and advanced diagnostic techniques (in the field of gastrointestinal endoscopy, molecular pathology and genetics) needs to be developed for proper disease

  4. Treatment of Tuberculosis. A Historical Perspective.

    Science.gov (United States)

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

    2015-12-01

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

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

    International Nuclear Information System (INIS)

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

  6. Inflammatory bowel disease in India - Past, present and future.

    Science.gov (United States)

    Ray, Gautam

    2016-09-28

    There is rising incidence and prevalence of inflammatory bowel disease (IBD) in India topping the Southeast Asian (SEA) countries. The common genes implicated in disease pathogenesis in the West are not causal in Indian patients and the role of "hygiene hypothesis" is unclear. There appears to be a North-South divide with more ulcerative colitis (UC) in north and Crohn's disease (CD) in south India. IBD in second generation Indian migrants to the West takes the early onset and more severe form of the West whereas it retains the nature of its country of origin in migrants to SEA countries. The clinical presentation is much like other SEA countries (similar age and sex profile, low positive family history and effect of smoking, roughly similar disease location, use of aminosalicylates for CD, low use of biologics and similar surgical rates) with some differences (higher incidence of inflammatory CD, lower perianal disease, higher use of aminosalicylates and azathioprine and lower current use of corticosteroids). UC presents more with extensive disease not paralleled in severity clinically or histologically, follows benign course with easy medical control and low incidence of fulminant disease, cancer, complications, and surgery. UC related colorectal cancer develop in an unpredictable manner with respect to disease duration and site questioning the validity of strict screening protocol. About a third of CD patients get antituberculosis drugs and a significant number presents with small intestinal bleed which is predominantly afflicted by aggressive inflammation. Biomarkers have inadequate diagnostic sensitivity and specificity for both. Pediatric IBD tends to be more severe than adult. Population based studies are needed to address the lacunae in epidemiology and definition of etiological factors. Newer biomarkers and advanced diagnostic techniques (in the field of gastrointestinal endoscopy, molecular pathology and genetics) needs to be developed for proper disease

  7. Inflammatory bowel disease in India - Past, present and future

    Science.gov (United States)

    Ray, Gautam

    2016-01-01

    There is rising incidence and prevalence of inflammatory bowel disease (IBD) in India topping the Southeast Asian (SEA) countries. The common genes implicated in disease pathogenesis in the West are not causal in Indian patients and the role of “hygiene hypothesis” is unclear. There appears to be a North-South divide with more ulcerative colitis (UC) in north and Crohn’s disease (CD) in south India. IBD in second generation Indian migrants to the West takes the early onset and more severe form of the West whereas it retains the nature of its country of origin in migrants to SEA countries. The clinical presentation is much like other SEA countries (similar age and sex profile, low positive family history and effect of smoking, roughly similar disease location, use of aminosalicylates for CD, low use of biologics and similar surgical rates) with some differences (higher incidence of inflammatory CD, lower perianal disease, higher use of aminosalicylates and azathioprine and lower current use of corticosteroids). UC presents more with extensive disease not paralleled in severity clinically or histologically, follows benign course with easy medical control and low incidence of fulminant disease, cancer, complications, and surgery. UC related colorectal cancer develop in an unpredictable manner with respect to disease duration and site questioning the validity of strict screening protocol. About a third of CD patients get antituberculosis drugs and a significant number presents with small intestinal bleed which is predominantly afflicted by aggressive inflammation. Biomarkers have inadequate diagnostic sensitivity and specificity for both. Pediatric IBD tends to be more severe than adult. Population based studies are needed to address the lacunae in epidemiology and definition of etiological factors. Newer biomarkers and advanced diagnostic techniques (in the field of gastrointestinal endoscopy, molecular pathology and genetics) needs to be developed for proper

  8. Effect of Cyperus Rotundus on Cytokine Gene Expression in Experimental Inflammatory Bowel Disease

    Science.gov (United States)

    Johari, Sarika; Joshi, Chaitanya; Gandhi, Tejal

    2016-01-01

    Background: The protective effect of the chloroform extract of Cyperus rotundus (CHCR) is attributed to its anti-inflammatory and antioxidant activities. Cytokines, important regulators of inflammation and repair, play a key role in the pathogenesis of inflammatory bowel disease (IBD). Targeting these cytokines can effectively ameliorate the symptoms of IBD. The aim of the present study was to unravel the molecular mechanism through cytokine regulation in rats in experimental IBD. Methods: Sprague Dawley rats were randomly allocated to 5 groups (n=6). Group I served as the normal control. Group II served as the vehicle control and received 50% ethanol intracolonically on day 11 of the study. Group III served as the model control. Group IV and Group V were given standard drug 5-aminosalicylic acid (100 mg/kg) and CHCR (800 mg/kg), respectively, for 18 days once a day orally. Colitis was induced with dinitrobenzene sulfonic acid (180 mg/kg in 50% ethanol) intracolonically in groups III–V on day 11 of the study. On day 18, the rats were euthanized and colon tissues were removed for IL-4, IL-6, IL-12, and IFN-gamma gene expression studies using quantitative RT-PCR. Results: The expression levels of proinflammatory cytokines IL-4, IL-6, IL-12, and IFN-gamma were upregulated in the model control rats. Pretreatment with 5-aminosalicylic acid (100 mg/kg) and CHCR (800 mg/kg) significantly decreased the fold of the expression of the above cytokines. Conclusion: CHCR acts as a molecular brake and downregulates the expression of proinflammatory cytokine genes; this is beneficial for reducing the severity of the experimental IBD. Thus, Cyperus rotundus is a safe, economical, and effective alternative for the treatment of patients with IBD. PMID:27582588

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

    Institute of Scientific and Technical Information of China (English)

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

    2008-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

    宋军民; 战玉华; 李岩

    2012-01-01

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

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

    OpenAIRE

    Viciano Delibano, Elena

    2015-01-01

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

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

    OpenAIRE

    Geara-Matta, Darine

    2012-01-01

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

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

    Science.gov (United States)

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

    2015-01-01

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

  14. 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.

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

    Institute of Scientific and Technical Information of China (English)

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

    2015-01-01

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

  16. Serum Fatty Acids Are Correlated with Inflammatory Cytokines in Ulcerative Colitis.

    Directory of Open Access Journals (Sweden)

    Dawn M Wiese

    Full Text Available Ulcerative colitis (UC is associated with increased dietary intake of fat and n-6 polyunsaturated fatty acids (PUFA. Modification of fat metabolism may alter inflammation and disease severity. Our aim was to assess differences in dietary and serum fatty acid levels between control and UC subjects and associations with disease activity and inflammatory cytokines.Dietary histories, serum, and colonic tissue samples were prospectively collected from 137 UC subjects and 38 controls. Both histologic injury and the Mayo Disease Activity Index were assessed. Serum and tissue cytokines were measured by Luminex assay. Serum fatty acids were obtained by gas chromatography.UC subjects had increased total fat and oleic acid (OA intake, but decreased arachidonic acid (AA intake vs controls. In serum, there was less percent saturated fatty acid (SFA and AA, with higher monounsaturated fatty acids (MUFA, linoleic acid, OA, eicosapentaenoic acid (EPA, and docosapentaenoic acid (DPA in UC. Tissue cytokine levels were directly correlated with SFA and inversely correlated with PUFA, EPA, and DPA in UC subjects, but not controls. 5-aminosalicylic acid therapy blunted these associations.In summary, we found differences in serum fatty acids in UC subjects that correlated with pro-inflammatory tissue cytokines. We propose that fatty acids may affect cytokine production and thus be immunomodulatory in UC.

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

    Science.gov (United States)

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

    2001-09-01

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

  18. Ischemic colitis due to obstruction of mesenteric and splenic veins: A case report

    Institute of Scientific and Technical Information of China (English)

    Seong-Su Hwang; Woo-Chul Chung; Kang-Moon Lee; Hyun-Jin Kim; Chang-Nyol Paik; Jin-Mo Yang

    2008-01-01

    Ischemic injury to the bowel is a well known disease entity that has a wide spectrum of pathological and clinical findings. A sudden drop in the colonic blood supply is essential to its development. We encountered a 41-year-old male patient, who presented with abdominal pain and bloody diarrhea. A colonoscopy showed markedly edematous mucosa with tortuous dilatation of the veins and a deep ulceration at the rectosigmoid junction. On an abdominal computed tomography (CT) scan and CT angiography, the mesenteric and splenic veins were absent with numerous venous collaterals for drainage. The patient gradually responded to oral aminosalicylate therapy, and was in remission after nine months. In most cases, non-occlusive ischemic injury is caused by idiopathic form and occlusive ischemia is caused by abnormalities of arteries and acute venous thrombosis. However, chronic venous insufficiency due to obstruction of macrovascular mesenteric vein rarely causes ischemia of the bowel. This report describes the first case of ischemic colitis caused by obstruction of the mesenteric and splenic veins.

  19. Colon-specific drug delivery behavior of pH-responsive PMAA/perlite composite.

    Science.gov (United States)

    Mahkam, Mehrdad; Vakhshouri, Laleh

    2010-04-12

    The preparation, characterization, and in vitro release of 5-aminosalicylic acid (5-ASA) from methacrylic acid (MAA)/perlite composites (APC) prepared via a sol-gel route are reported. The free-radical graft polymerization of methacrylic acid (MAA) onto perlite particles was studied experimentally. The grafting procedure consisted of surface activation with 3-(trimethoxysilyl) propyl methacrylate (TSPA), followed by free-radical graft polymerization of methacrylic acid (MAA) in ethyl acetate with 2,2'-azobisisobutyronitrile (AIBN) initiator. The composition of the composites hybrid materials was determined by FTIR spectroscopy. Equilibrium swelling studies were carried out in enzyme-free simulated gastric and intestinal fluids (SGF and SIF, respectively). The dried composites were immersed in a saturated solution of 5-ASA in water overnight and dried over a period of three days at room temperature and the in vitro release profiles were established separately in both (SGF, pH 1) and (SIF, pH 7.4). The 5-ASA concentration of the solution was measured using a UV-Vis spectrophotometer (205 nm) at different time intervals. The in vitro drug release test revealed that the release rate of 5-ASA in buffer solutions increased with the silica content in the composites; on the contrary, the increase of the content of 3-(trimethoxysilyl)propyl methacrylate (TSPA), a coupling agent, decreased the drug release rate.

  20. Colon-Specific Drug Delivery Behavior of pH-Responsive PMAA/Perlite Composite

    Directory of Open Access Journals (Sweden)

    Mehrdad Mahkam

    2010-04-01

    Full Text Available The preparation, characterization, and in vitro release of 5-aminosalicylic acid (5-ASAfrom methacrylic acid (MAA/perlite composites (APC prepared via a sol–gel route are reported. The free-radical graft polymerization of methacrylic acid (MAA onto perlite particles was studied experimentally. The grafting procedure consisted of surface activation with 3-(trimethoxysilyl propyl methacrylate (TSPA, followed by free-radical graft polymerization of methacrylic acid (MAA in ethyl acetate with 2,2΄-azobis-isobutyronitrile (AIBN initiator. The composition of the composites hybrid materials was determined by FTIR spectroscopy. Equilibrium swelling studies were carried out in enzyme-free simulated gastric and intestinal fluids (SGF and SIF, respectively. The dried composites were immersed in a saturated solution of 5-ASA in water overnight and dried over a period of three days at room temperature and the in vitro release profiles were established separately in both (SGF, pH 1 and (SIF, pH 7.4. The 5-ASA concentration of the solution was measured using a UV-Vis spectrophotometer (205 nm at different time intervals. The in vitro drug release test revealed that the release rate of 5-ASA in buffer solutions increased with the silica content in the composites; on the contrary, the increase of the content of 3-(trimethoxysilylpropyl methacrylate (TSPA, a coupling agent, decreased the drug release rate.

  1. [Resistance to second-line drugs in migrants with multidrug-resistant tuberculosis in the Berlin region].

    Science.gov (United States)

    Otto-Knapp, R; Bös, L; Schönfeld, N; Wagner, S; Starzacher, A K; Weiss, T; Vesenbeckh, S; Glaser-Paschke, G; Mauch, H; Rüssmann, H; Bauer, T T

    2014-07-01

    The empiric therapy of multidrug-resistant (MDR) tuberculosis (TB) after rapid molecular testing is rendered difficult by an often several weeks-long period of uncertainty, because results of susceptibility testing for second-line TB drugs are pending. The analysis of regional resistance patterns could lead to a more targeted empiric treatment for migrants depending on their country of origin. The results of the susceptibility testing from 2008 to 2013 of all mycobacteria sent to the Institute of Microbiology, working with the department of Pneumology, Heckeshorn Lung Clinic, Berlin, were reanalysed and tested for regional differences. We found 39 multidrug-resistant Mycobacterium tuberculosis strains among the examined strains. More than half of these strains tested susceptible to the following second line drugs namely, linezolid (97%), clofazimine (95%), cycloserine (95%), capreomycin (90%), p-aminosalicylic acid (82%), moxifloxacin (79%) and amikacin (79%). The proportion of strains susceptible to pyrazinamide (44%), ethambutol (28%), prothionamide (15%), rifabutin (8%) and streptomycin (8%) was lower. The mycobacterial cultures of the Chechen patients (n = 14) showed significantly different susceptibilities to amikacin (57%) and prothionamide (36%) compared to the strains from migrants of other regions. In this study, the regional differences in mycobacterial susceptibility to second line drugs suggest that the initial MDR TB therapy of migrants should be tailored to their country of origin.

  2. Quantification of fumaric acid in liver, spleen and urine by high-performance liquid chromatography coupled to photodiode-array detection.

    Science.gov (United States)

    Baati, Tarek; Horcajada, Patricia; Gref, Ruxandra; Couvreur, Patrick; Serre, Christian

    2011-12-01

    Quantification of fumaric acid, an endogenous dicarboxylic acid with interesting biomedical applications either through its own biological activity or as a linker constitutive of the porous iron(III) fumarate metal organic framework (MOF) MIL-88A based drug nanocarrier (MIL stands for Material from Institut Lavoisier), has been developed in different rat biological complex media (liver, spleen and urine). After a liquid-liquid extraction procedure, fumaric acid concentration was determined by a simple and accurate high-performance liquid chromatography (HPLC) method coupled to a photodiode-array detector (PDA) using aminosalicylic acid as internal standard (IS) and a gradient elution. The recovery of fumaric acid reaches 89% and 92% for urine (for concentrations of 0.05 and 1μgml(-1), respectively) and 90% for liver and spleen tissues, exceeding 89% in all instances in comparison with the IS. Linearity has been kept from 0.05 to 1μgml(-1) and from 0.5 to 10μgg(-1) of fumaric acid in urine and tissues, respectively. The limit of detection of the method was 0.01μg per injection. This method has finally allowed the quantification of fumaric acid in rat urine and tissue samples after the intravenous administration of MIL-88A nanoparticles.

  3. Quantification of tetramethyl-terephthalic acid in rat liver, spleen and urine matrices by liquid-liquid phase extraction and HPLC-photodiode array detection.

    Science.gov (United States)

    Baati, Tarek; Horcajada, Patricia; David, Olivier; Gref, Ruxandra; Couvreur, Patrick; Serre, Christian

    2012-01-01

    Tetramethyl-terephthalate (TMT) is the constitutive linker of the flexible porous iron(III) carboxylate Metal Organic Framework (MOF) MIL-88B_4CH₃ based drug nanocarrier (MIL stands for Material from Institut Lavoisier). A method for the determination of the concentration of tetramethyl-terephthalic acid has been developed in different biological rat matrices (liver, spleen and urine) using a liquid-liquid phase extraction and high-performance liquid chromatography (HPLC) coupled to photodiode array detection with 4-aminosalicylic acid as internal standard. The extraction conditions of TMT have been varied from urine to tissue depending on the complexity of the biological matrices. The chromatographic separation was performed with a gradient elution. In all matrices, the limits of detection and quantification of TMT was 0.01 and 0.05 μg ml⁻¹, respectively. The recovery of the TMT reached 86, 89 and 97% for urine, spleen and liver tissues, respectively. The linearity of the calibration curves in urine and tissues was satisfactory in all cases as evidenced by correlation coefficients >0.990. The within-day and between-day precisions were <15% (n=6) and the accuracy ranged in all cases between 86 and 103%. This method has finally allowed the quantification of TMT in rat urine and in tissue samples of rats administered intravenously with iron(III) tetramethyltherepthalate MIL-88B_4CH₃ nanoparticles.

  4. 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.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1991-01-01

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

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

    Science.gov (United States)

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

    2016-04-30

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

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

    Science.gov (United States)

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

    2014-06-01

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

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

    Directory of Open Access Journals (Sweden)

    Anita Annaházi

    2015-01-01

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

  9. Changes in immunohistochemical levels and subcellular localization after therapy and correlation and colocalization with CD68 suggest a pathogenetic role of Hsp60 in ulcerative colitis.

    Science.gov (United States)

    Tomasello, Giovanni; Rodolico, Vito; Zerilli, Monica; Martorana, Anna; Bucchieri, Fabio; Pitruzzella, Alessandro; Marino Gammazza, Antonella; David, Sabrina; Rappa, Francesca; Zummo, Giovanni; Damiani, Provvidenza; Accomando, Salvatore; Rizzo, Manfredi; de Macario, Everly Conway; Macario, Alberto J L; Cappello, Francesco

    2011-12-01

    In an earlier work, the role of heat shock protein (Hsp60) in the pathogenesis of ulcerative colitis (UC) was suggested by its significant increase in the pathological mucosa parallel with an increase in inflammatory cells. More data in this direction are reported in this work. We analyzed by immunohistochemistry biopsies of colon tissue from 2 groups of patients with UC and treated with either 5-aminosalicylic acid (5-ASA) alone or in combination with a probiotic. We looked for inflammatory markers and Hsp60. Both the treatments were effective in reducing symptoms but the group treated with both 5-ASA and probiotics showed better clinical results. Amelioration of symptoms was associated with reduction of both inflammation and Hsp60, a reduction that was most marked in the group treated with 5-ASA and probiotics. The levels of Hsp60 positively correlated with those of CD68-positive cells, and double immunofluorescence showed a high index of colocalization of the chaperonin and CD68 in lamina propria. Immunoelectron microscopy showed that Hsp60-classically a mitochondrial protein-was abundantly also present in cytosol in biopsies taken at the time of diagnosis, but not after the treatment. Our data suggest that Hsp60 is an active player in pathogenesis of UC and it can be hypothesized that the chaperonin is responsible, at least in part, for initiation and maintenance of disease.

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

    Science.gov (United States)

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

    2016-01-01

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

  11. Current therapy of pediatric Crohn’s disease

    Institute of Scientific and Technical Information of China (English)

    Avishay; Lahad; Batia; Weiss

    2015-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

    Christian P Selinger; Rupert WL Leong; Simon Lal

    2012-01-01

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

  13. 炎症性肠病联合治疗中的药物相互作用

    Institute of Scientific and Technical Information of China (English)

    武丽娜; 张波; 鲁重美

    2015-01-01

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

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

    Science.gov (United States)

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

    2016-04-30

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

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

    Science.gov (United States)

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

    2016-02-01

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

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

    Directory of Open Access Journals (Sweden)

    Gilroy L

    2014-05-01

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

  17. Gynecomastia caused by ethionamide

    Directory of Open Access Journals (Sweden)

    Parveen K Sharma

    2012-01-01

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

  18. Higher platelet P-selectin in male patients with inflammatory bowel disease compared to healthy males

    Institute of Scientific and Technical Information of China (English)

    J Patrik F(a)gerstam; Per A Whiss

    2006-01-01

    AIM: To observe if the total amount of platelet P-selectin (tP-selectin) in patients with inflammatory bowel disease (IBD) was related to disease entity or activity, 5-ami-nosalicylic acid (5-ASA) medication or gender.METHODS: tP-selectin was measured by immunoassay in seventeen IBD patients and twelve healthy controls.RESULTS: Compared to controls, there was no difference of tP-selectin in patients related to disease entity or activity and 5-ASA medication. When the groups were split according to gender the male patient group showed higher levels of tP-selectin compared to male controls (153 ng/mL vs 94 ng/mL, P< 0.05).CONCLUSION: Increased tP-selectin levels may alter the inflammatory response and susceptibility to throm-boembolic disease. As previously shown with soluble P-selectin, tP-selectin shows gender dependent differences important to consider in future studies.

  19. Arachidonic acid metabolism in TNS-induced chronic and immunologic enteritis in rats, and the effect of 5-ASA

    Directory of Open Access Journals (Sweden)

    F. J. Zijlstra

    1993-01-01

    Full Text Available Inflammation of the rat distal intestine was induced by intradermal sensitization and subsequent multiple intrajejunal challenge with the hapten 2,4,6-trinitrobenzenesulphonic acid (TNBS via an implanted catheter. The time course of the inflammatory reaction was followed by determination of the enteritis score and measurement of in vitro eicosanoid formation of homogenates of the gut after 0, 1, 2, 4, 7, 14 and 21 days of local daily challenge with 0.08% TNBS. There was a small initial increase of eicosanoid formation, reached at days 1 and 2, followed by a significant increase in metabolism of arachidonic acid on day 21. Although at day 1 a four-fold increase in inflammation score was reached, no further significant changes were observed during the following 3 weeks. The greatest increase in metabolite formation was observed in prostanoids TxB2, PGE2. and PGD2 and the 5-lipoxygenase product LTC4, whereas minor changes were found for LTB4 and other lipoxygenase products such as 12- and 15-HETE. The formation of these metabolites was already inhibited by low-dose 5-aminosalicylic acid (5-ASA, given orally twice daily during the 3 weeks challenge period, while the enteritis score was affected dosedependently.

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

    Institute of Scientific and Technical Information of China (English)

    魏润新; 李敏

    2014-01-01

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

  1. Identification of sucrose binding, membrane proteins using a photolyzable sucrose analog. [P. saccharophila

    Energy Technology Data Exchange (ETDEWEB)

    Ripp, K.G.; Liu, D.F.; Viitanen, P.; Hitz, W.D.

    1986-04-01

    The sucrose derivative 6'-deoxy-6'-(2-hydroxy-4-azido)benzamidosucrose (6'-HABS) was prepared from sucrose (via 6'-deoxy-6'-aminosucrose) and 4-amino-salicylic acid. 6'-HABS is a competitive inhibitor of sucrose influx into protoplasts from developing soybean cotyledons and of sucrose binding to membranes from the bacteria P. saccharophila. The Ki for inhibition in the soybean protoplasts was 75..mu..M. 6'-Deoxy-6'-(2-hydroxy-3-/sup 125/Iodo-4-azido)benzamidosucrose was prepared by lactoperoxidase iodination of 6'-HABS. Upon photolysis in the presence of membranes from P saccharophila, label from the photoprobe is incorporated into a sucrose inducible polypeptide of mass 84 KD in SDS-PAGE. The polypeptide is protected from labeling by the inclusion of sucrose in the photolysis mixture. Photolysis conditions which lead to specific labeling of the sucrose protectable polypeptide in bacterial membranes also give sucrose protectable labeling of a 66 KD polypeptide in microsomal preparations made from developing soybeans. The possibility that this is a sucrose transporting protein is being tested.

  2. Cancer in inflammatory bowel disease

    Institute of Scientific and Technical Information of China (English)

    Jianlin Xie; Steven H Itzkowitz

    2008-01-01

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

  3. Current treatment of ulcerative colitis

    Institute of Scientific and Technical Information of China (English)

    JohannesMeier; AndreasSturm

    2011-01-01

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

  4. Current treatment of ulcerative colitis

    Institute of Scientific and Technical Information of China (English)

    Johannes Meier; Andreas Sturm

    2011-01-01

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

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

    Science.gov (United States)

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

    2012-10-01

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

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

    Directory of Open Access Journals (Sweden)

    Bruno Rafael Ramos de Mattos

    2015-01-01

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

  7. Long-term efficacy and safety of once-daily mesalazine granules for the treatment of active ulcerative colitis

    Directory of Open Access Journals (Sweden)

    Böhm SK

    2014-09-01

    Full Text Available Stephan Karl Böhm,1 Wolfgang Kruis2 1Kantonsspital Baselland, Medizinische Universitätsklinik, Bruderholz, Switzerland; 2Evangelisches Krankenhaus Kalk, University of Cologne, Cologne, Germany Abstract: In 1977, 5-aminosalicylic acid (5-ASA was discovered as a therapeutically active moiety of sulfasalazine (SASP and was launched for topical and oral therapy of ulcerative colitis (UC in 1984. As a first-step, delivery systems had to be developed to protect 5-ASA against absorption in the upper gastrointestinal tract, resulting in different and competing strategies (azo compounds, controlled release, and pH-dependent release. In a second step, at the beginning of the new century, coinciding with the expiration of patent protection for the first 5-ASA formulations, two component composite release mechanisms (pH-dependent and controlled release were developed. Furthermore, the drug was formulated as granules instead of tablets, allowing higher unit strengths compared with tablets. Neither Salofalk Granu-Stix®, nor MMX 5-ASA, nor Pentasa® granules have initially been developed for once-daily (OD dosing. A review of the achievements of 20 years of 5-ASA development has demonstrated that 5-ASA has equal efficacy compared with SASP at best, that there are no measurable differences in efficacy between various 5-ASA preparations, and that in a group of patients tolerating SASP, adverse event profiles of SASP and 5-ASA did not differ significantly, with SASP being the far cheaper substance. Therefore, drug adherence came into focus as a new goal for improving UC therapy. Although adherence is a complex and multifactorial construct, a simple dosing schedule may contribute to higher drug adherence and better efficacy of treatment. Simultaneously, the US 5-ASA market, estimated to be worth US$1.4 billion, is expected to grow continuously. Naturally, this very competitive market is not only driven by scientific progress but also by commercial interests

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

    Institute of Scientific and Technical Information of China (English)

    Selwvn Odes

    2008-01-01

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

  9. Progress in the Application of Biological Agents in Inlfammatory Bowel Disease%炎症性肠病生物制剂应用进展

    Institute of Scientific and Technical Information of China (English)

    李宇

    2016-01-01

    Inflammatory bowel disease (IBD) in traditional medicine include aminosalicylic acid, hormone and immunosuppressive agents, For some refractory inflammatory bowel disease, biological agents have important application prospects. Biological agents IBD mainly include:tumor necrosis factor (TNF) alpha antagonists such as infliximab, adalimumab (Inlfiximab) (Adalimumab), race trastuzumab (Certolizumab), golimumab (Golimumab), integrin antagonists such as natalizumab (Natalizumab), Weiduozhu monoclonal antibody (Vedolizumab), tyrosine kinase (JAK) antagonist (Tofacitinib), interleukin (IL) antibody, monoclonal antibody (Ustekinumab). This paper brielfy introduces the therapeutic effect and side effects of the biological agents.%炎症性肠病(IBD)传统用药包括氨基水杨酸类、激素、免疫抑制剂,而对于一些难治性炎症性肠病,生物制剂有着重要应用前景。IBD的生物制剂主要包括:肿瘤坏死因子(TNF)-α拮抗剂如英夫利昔单抗(Infliximab)、阿达木单抗(Adalimumab)、赛妥珠单抗(Certolizumab)、戈利木单抗(Golimumab);整合素拮抗剂如那他珠单抗(Natalizumab)、维多珠单抗(Vedolizumab);酪氨酸激酶(JAK)拮抗剂托法替尼(Tofacitinib);白细胞介素(IL)抗体优斯它单抗(Ustekinumab)。本文就上述生物制剂疗效、副作用等做简要介绍。

  10. 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

  11. Drug elimination function of rat small intestine: metabolism and intraluminal excretion.

    Science.gov (United States)

    Yasuhara, M; Kurosaki, Y; Kimura, T; Sezaki, H

    1984-10-15

    The metabolic and excretory function of the small intestine was investigated after oral and intravenous administration of drugs having an aromatic amino group to rats. After administration of drugs into the intestinal loop at the initial concentration of 0.1 mM, significant excretion of their N-acetylated forms into the lumen was observed. The amount of N-acetyl forms excreted in the lumen were 39.3 +/- 3.5, 63.5 +/- 20.9 and 18.0 +/- 13.8% of disappeared drugs from the lumen for p-aminobenzoic acid (PABA), p-aminosalicylic acid and sulfanilic acid, respectively. The excretion of p-acetamidobenzoic acid (Ac-PABA) after the absorption of PABA was reduced by the coadministration with salicylic acid, benzoic acid and 2,4-dinitrophenol. Salicylic acid noncompetitively inhibited the acetylation of PABA by the intestinal N-acetyltransferase. A good correlation was found between the intestinal N-acetyltransferase activities for drugs and the intraluminal excretion of N-acetyl derivatives after intestinal absorption of drugs. These results indicate that a drug having a higher susceptibility to intestinal N-acetyltransferase would undergo a greater excretion into the lumen in its N-acetyl form after intestinal absorption. After intravenous administration of PABA at a dose of 100 mumole/kg, 4.02 +/- 0.51% of dose was excreted in the lumen as Ac-PABA in 30 min. On the other hand, a significantly smaller fraction (2.72 +/- 0.68% of dose) was excreted in the lumen after intravenous injection of 100 mumole/kg of Ac-PABA. The larger excretion of Ac-PABA after administration of PABA indicates the contribution of intestinal metabolism on the transfer of PABA not only after oral, but also after intravenous administration.

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

    Institute of Scientific and Technical Information of China (English)

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

    2008-01-01

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

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

    Science.gov (United States)

    Lei, Qingjuan; Gao, Baojiao; Zhang, Dandan

    2016-01-01

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

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

    Science.gov (United States)

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

    2016-01-01

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

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

    Science.gov (United States)

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

    2016-09-01

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

  16. Multidrug-resistant tuberculosis treatment outcomes in Karakalpakstan, Uzbekistan: treatment complexity and XDR-TB among treatment failures.

    Directory of Open Access Journals (Sweden)

    Helen S Cox

    Full Text Available BACKGROUND: A pilot programme to treat multidrug-resistant TB (MDR-TB was implemented in Karakalpakstan, Uzbekistan in 2003. This region has particularly high levels of MDR-TB, with 13% and 40% among new and previously treated cases, respectively. METHODOLOGY: This study describes the treatment process and outcomes for the first cohort of patients enrolled in the programme, between October 2003 and January 2005. Confirmed MDR-TB cases were treated with an individualised, second-line drug regimen based on drug susceptibility test results, while suspected MDR-TB cases were treated with a standardised regimen pending susceptibility results. PRINCIPAL FINDINGS: Of 108 MDR-TB patients, 87 were started on treatment during the study period. Of these, 33 (38% were infected with strains resistant to at least one second-line drug at baseline, but none had initial ofloxacin resistance. Treatment was successful for 54 (62% patients, with 13 (15% dying during treatment, 12 (14% defaulting and 8 (8% failing treatment. Poor clinical condition and baseline second-line resistance contributed to treatment failure or death. Treatment regimens were changed in 71 (82% patients due to severe adverse events or drug resistance. Adverse events were most commonly attributed to cycloserine, ethionamide and p-aminosalicylic acid. Extensively drug resistant TB (XDR-TB was found among 4 of the 6 patients who failed treatment and were still alive in November 2006. CONCLUSIONS: While acceptable treatment success was achieved, the complexity of treatment and the development of XDR-TB among treatment failures are important issues to be addressed when considering scaling up MDR-TB treatment.

  17. 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

  18. Recent progress in treatment of inflammatory bowel disease%炎症性肠病治疗的新进展

    Institute of Scientific and Technical Information of China (English)

    高树娟; 施瑞华

    2012-01-01

    Inflammatory bowel disease (IBD) comprises two main types, namely, Crohn's disease (CD) and ulcerative colitis (UC). The etiology of IBD is not clear, and there is no effective cure so far. Currently available agents for IBD mainly consist of traditional drugs (including aminosalicy-lates, corticosteroids, and immunosuppressants) and new biological preparations (mainly TNF-α monoclonal antibody). The treatment of IBD evolves with the progress of clinical research and pharmaceutical techniques, such as new dosage forms, different routes of administration, and the application of new biological preparations. This article reviews recent progress in the treatment of IBD.%炎症性肠病(inflammatory bowel disease,IBD)主要包括溃疡性结肠炎(ulcerative colitis,UC)和克罗恩病(Crohn's disease,CD),其病因尚不明确,迄今也无有效的治愈方法.目前临床上的药物治疗包括传统药物治疗及新型生物制剂.传统药物主要有氨基水杨酸类、肾上腺糖皮质激素和免疫抑制剂;用于临床的新型生物制剂主要为肿瘤坏死因子(tumor necrosis factor-α,TNF-α)的单克隆抗体.随着研究的深入及制药的进步,IBD的治疗有了新的进展,如传统药物新剂型的出现及新的给药方式,新型治疗药物的问世.本文就IBD治疗新进展作一综述.

  19. Endoscopic and non-endoscopic approaches for the management of radiation-induced rectal bleeding.

    Science.gov (United States)

    Weiner, Joseph Paul; Wong, Andrew Thomas; Schwartz, David; Martinez, Manuel; Aytaman, Ayse; Schreiber, David

    2016-08-21

    Pelvic radiation is a commonly utilized treatment for malignancy of the genitourinary and lower gastrointestinal tract. Radiation proctitis and the resultant clinical picture varies from asymptomatic to potentially life threatening. Similarly, treatment options also vary greatly, from medical therapy to surgical intervention. Commonly utilized medical therapy includes sucralfate enemas, antibiotics, 5-aminosalicylic acid derivatives, probiotics, antioxidants, short-chain fatty acids, formalin instillation and fractionated hyperbaric oxygen. More invasive treatments include endoscopic-based, focally ablative interventions such as dilation, heater and bipolar cautery, neodymium/yttrium aluminum garnet argon laser, radiofrequency ablation or argon plasma coagulation. Despite its relatively common frequency, there is a dearth of existing literature reporting head-to-head comparisons of the various treatment options via a randomized controlled approach. The purpose of our review was to present the reader a consolidation of the existing evidence-based literature with the goal of highlighting the comparative effectiveness and risks of the various treatment approaches. Finally, we outline a pragmatic approach to the treatment of radiation proctitis. In light of the lack of randomized data, our goal is to pursue as least invasive an approach as possible, with escalation of care tailored to the severity of the patient's symptoms. For those cases that are clinically asymptomatic or only mildly symptomatic, observation or medical management can be considered. Once a patient fails such management or symptoms become more severe, invasive procedures such as endoscopically based focal ablation or surgical intervention can be considered. Although not all recommendations are supported by level I evidence, reported case series and single-institutional studies in the literature suggest that successful treatment with cessation of symptoms can be obtained in the majority of cases. PMID

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

    Institute of Scientific and Technical Information of China (English)

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

    2011-01-01

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

  1. 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.

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

    Science.gov (United States)

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

    2016-09-10

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

  3. Recent advances in the management of distal ulcerative colitis

    Institute of Scientific and Technical Information of China (English)

    Ioannis; E; Koutroubakis

    2010-01-01

    The most frequent localization of ulcerative colitis(UC) is the distal colon.In treating patients with active distal UC,efficacy and targeting of the drug to the distal colon are key priorities.Oral and rectal 5-aminosalicylic acid(5-ASA) preparations represent the first line therapy of mild-to-moderate distal UC for both induction and maintenance treatment.It has been reported that many UC patients are not adherent to therapy and that noncompliant patients had a 5-fold risk of experiencing a relapse.These findings led to the introduction of oncedaily oral regimens of 5-ASA as better therapeutic options in clinical practice due to improved adherence.New formulations of mesalazine,including the multimatrix delivery system,and mesalazine granules,which allow once-daily administration,have been developed.They have been demonstrated to be efficacious in inducing and maintaining remission in mild-to-moderate distal UC in large clinical trials.However,existing data for distal UC are rather insufficient to make a comparison between new and classical 5-ASA formulations.It seems that the new formulations are at least as effective as classical oral 5-ASA formulations.Other treatment options,in the case that 5-ASA therapy is not effective,include systemic corticosteroids,thiopurines(azathioprine or 6-mercaptopurine),cyclosporine,infliximab and surgery.The combination of a prompt diagnostic work-up,a correct therapeutic approach and an appropriate follow-up schedule is important in the management of patients with distal UC.This approach can shorten the duration of symptoms,induce a prolonged remission,improve patient’s quality of life,and optimize the use of health resources.

  4. 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.

  5. Overview of 5-ASA in Therapy of Inflammatory Bowel Disease

    Directory of Open Access Journals (Sweden)

    CN Williams

    1994-01-01

    Full Text Available There are two forms of 5-aminosalicylic acid (5-ASA drug delivery. First, a pro-drug form in which 5-ASA, the active principal, is attached to a c.arrier molecule and released in the intestine by bacterial cleavage. An example of this is sulfasalazine, originally developed in the 1940s and found to be effective, cheap, but limited by side effects due to the sulfapyridine component. The second drug delivery system depends on an enteric coating for delayed pH-dependent release or for a timed-released mechanism. 5-ASA inhibits 5-lipoxygenase, modulates leukocyte function and inhibits soluble mediator release, and is an effective scavenger action of free oxygen radicals, the relative importance of which is unknown. The multiplicity of action is probably its strength because drugs that have only one of these actions are relatively ineffective in inflammatory bowel disease. 5-ASA compounds are effective in treating mild to moderate acute ulcerative colitis and in maintaining remission, and are equivalent to sulfasalazine in this regard. 5-ASA used topically in enema or suppository form is highly efficient in both acute disease and in maintaining remission. 5-ASA is also effective in active Crohn’s disease, but not as effective as in maintenance therapy compared with ulcerative colitis. The pro-drugs tend to have more side effects. Slow release compounds are well tolerated with few side effects, allowing increases to effective dosage. In patients intolerant of sulfasalazine, switching to a 5-ASA preparation usually results in tolerance and therapeutic benefit, with an occasional allergic reaction to the 5-ASA molecule limiting its use.

  6. Drug therapy for ulcerative colitis

    Institute of Scientific and Technical Information of China (English)

    Chang-Tai Xu; Shu-Yong Meng; Bo-Rong Pan

    2004-01-01

    Ulcerative colitis (UC) is an inflammatory destructive disease of the large intestine occurred usually in the rectum and lower part of the colon as well as the entire colon. Drug therapy is not the only choice for UC treatment and medical management should be as a comprehensive whole.Azulfidine, Asacol, Pentasa, Dipentum, and Rowasa all contain 5-aminosalicylic acid (5-ASA), which is the topical anti-inflammatory ingredient. Pentasa is more commonly used in treating Crohn's ileitis because Pentasa capsules release more 5-ASA into the small intestine than Asacol tablets. Pentasa can also be used for treating mild to moderate UC. Rowasa enemas are safe and effective in treating ulcerative proctitis and proctosigmoiditis. The sulfafree 5-ASA agents (Asacol, Pentasa, Dipentum and Rowasa) have fewer side effects than sulfa-containing Azulfidine. In UC patients with moderate to severe disease and in patients who failed to respond to 5-ASA compounds,systemic (oral) corticosteroids should be used. Systemic corticosteroids (prednisone, prednisolone, cortisone, etc.)are potent and fast-acting drugs for treating UC, Crohn's ileitis and ileocolitis. Systemic corticosteroids are not effective in maintaining remission in patients with UC.Serious side effects can result from prolonged corticosteroid treatment. To minimize side effects, corticosteroids should be gradually reduced as soon as the disease remission is achieved. In patients with corticosteroid-dependent or unresponsive to corticosteroid treatment, surgery or immunomodulator is considered. Immunomodulators used for treating severe UC include azathioprine/6-MP,methotrexate, and cyclosporine. Integrated traditional Chinese and Western medicine is safe and effective in maintaining remission in patients with UC.

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

    Institute of Scientific and Technical Information of China (English)

    Pilar Nos; Eugeni Domènech

    2008-01-01

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

  8. Concomitant herpes simplex virus colitis and hepatitis in a man with ulcerative colitis

    Science.gov (United States)

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

    2016-01-01

    Abstract Background: Herpesvirus infections often complicate the clinical course of patients with inflammatory bowel disease; however, invasive disease due to herpes simplex virus is distinctly uncommon. Methods: 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. Results: 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. Conclusions: 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. PMID:27759636

  9. DECISION TREE CONSTRUCTION AND COST-EFFECTIVENESS ANALYSIS OF TREATMENT OF ULCERATIVE COLITIS WITH PENTASA® MESALAZINE 2 G SACHET

    Directory of Open Access Journals (Sweden)

    Alvaro Mitsunori NISHIKAWA

    2013-12-01

    Full Text Available Context Unspecified Ulcerative Rectocolitis is a chronic disease that affects between 0.5 and 24.5/105 inhabitants in the world. National and international clinical guidelines recommend the use of aminosalicylates (including mesalazine as first-line therapy for induction of remission of unspecified ulcerative rectocolitis, and recommend the maintenance of these agents after remission is achieved. However, multiple daily doses required for the maintenance of disease remission compromise compliance with treatment, which is very low (between 45% and 65%. Use of mesalazina in granules (2 g sachet once daily - Pentasa® sachets 2 g - can enhance treatment adherence, reflecting in an improvement in patients' outcomes. Objective To evaluate the evidence on the use of mesalazine for the maintenance of remission in patients with unspecified ulcerative rectocolitis and its effectiveness when taken once versus more than once a day. From an economic standpoint, to analyze the impact of the adoption of this dosage in Brazil's public health system, considering patients' adherence to treatment. Methods A decision tree was developed based on the Clinical Protocol and Therapeutic Guidelines for Ulcerative Colitis, published by the Ministry of Health in the lobby SAS/MS n° 861 of November 4 th, 2002 and on the algorithms published by the Associação Brasileira de Colite Ulcerativa e Doença de Crohn, aiming to get the cost-effectiveness of mesalazine once daily in granules compared with mesalazine twice daily in tablets. Results The use of mesalazine increases the chances of remission induction and maintenance when compared to placebo, and higher doses are associated with greater chance of success without increasing the risk of adverse events. Conclusion The use of a single daily dose in the maintenance of remission is effective and related to higher patient compliance when compared to the multiple daily dose regimens, with lower costs.

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

  11. 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.

  12. In vitro and in vivo inhibitory activity of 6-amino-2,4,5-trimethylpyridin-3-ols against inflammatory bowel disease.

    Science.gov (United States)

    Banskota, Suhrid; Kang, Han-Eol; Kim, Dong-Guk; Park, Sang Won; Jang, Hyeonjin; Karmacharya, Ujjwala; Jeong, Byeong-Seon; Kim, Jung-Ae; Nam, Tae-Gyu

    2016-10-01

    Although the pathogenesis of inflammatory bowel disease (IBD) is complex, attachment and infiltration of leukocytes to gut epithelium induced by pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α) represents the initial step of inflammation in IBD. Previously, we have reported that some 6-amino-2,4,5-trimethylpyridin-3-ols have significant levels of antiangiogenic activity via PI3K inhibition. Based on the reports that angiogenesis is involved in the aggravation of IBD and that PI3K is a potential target for IBD therapy, we investigated whether the scaffold has inhibitory activity against in vitro and in vivo models of colitis. Many analogues showed >80% inhibition against TNF-α-induced monocyte adhesion to colon epithelial cells at 1μM. Compound 8m showed IC50=0.19μM, which is about five orders of magnitude better than that of 5-aminosalicylic acid (5-ASA, IC50=18.1mM), a positive control. In a rat model of 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis, orally administered 8m dramatically ameliorated TNBS-induced colon inflammation. It was demonstrated by a high level of suppression in myeloperoxidase (MPO), a surrogate marker of colitis, as well as almost perfect recovery of colon and body weights in a dose-dependent manner. Compared to sulfasalazine, a prodrug of 5-ASA, compound 8m showed >300-fold better efficacy in those parameters. Taken together, 6-amino-2,4,5-trimethylpyridin-3-ols can provide a novel platform for anti-IBD drug discovery. PMID:27597248

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

    Directory of Open Access Journals (Sweden)

    Dorofeyev AE

    2011-06-01

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

  14. {{text{C}}_{α }} - {text{C}} Bond Cleavage of the Peptide Backbone in MALDI In-Source Decay Using Salicylic Acid Derivative Matrices

    Science.gov (United States)

    Asakawa, Daiki; Takayama, Mitsuo

    2011-07-01

    The use of 5-formylsalicylic acid (5-FSA) and 5-nitrosalicylic acid (5-NSA) as novel matrices for in-source decay (ISD) of peptides in matrix-assisted laser desorption/ionization (MALDI) is described. The use of 5-FSA and 5-NSA generated a- and x-series ions accompanied by oxidized peptides [M - 2 H + H]+. The preferential formation of a- and x-series ions was found to be dependent on the hydrogen-accepting ability of matrix. The hydrogen-accepting ability estimated from the ratio of signal intensity of oxidized product [M - 2 H + H]+ to that of non-oxidized protonated molecule [M + H]+ of peptide was of the order 5-NSA > 5-FSA > 5-aminosalicylic acid (5-ASA) ≒ 2,5-dihydroxyl benzoic acid (2,5-DHB) ≒ 0. The results suggest that the hydrogen transfer reaction from peptide to 5-FSA and 5-NSA occurs during the MALDI-ISD processes. The hydrogen abstraction from peptides results in the formation of oxidized peptides containing a radical site on the amide nitrogen with subsequent radical-induced cleavage at the {{{C}}_{α }} - {{C}} bond, leading to the formation of a- and x-series ions. The most significant feature of MALDI-ISD with 5-FSA and 5-NSA is the specific cleavage of the {{{C}}_{α }} - {{C}} bond of the peptide backbone without degradation of side-chain and post-translational modifications (PTM). The matrix provides a useful complementary method to conventional MALDI-ISD for amino acid sequencing and site localization of PTMs in peptides.

  15. 单耐异烟肼或利福平肺结核患者的治疗方案选取及效果分析%Treating scheme choice and effect analysis of single isoniazid or rifampin therapy for patients with pulmonary tuberculosis

    Institute of Scientific and Technical Information of China (English)

    李颖

    2016-01-01

    目的:研究单耐异烟肼或利福平肺结核患者的治疗方案选取及效果分析。方法抽选2013年7月至2014年7月在我院接受异烟肼、利福平治疗2月后痰菌仍阳性的肺结核患者82例,随机法将上述患者分为观察组和对照组,每组41例,观察组以莫西沙星、对氨基水杨酸异烟肼、利福喷丁、乙胺丁醇口服治疗;对照组以左氧氟沙星、对氨基水杨酸异烟肼、利福喷丁、乙胺丁醇口服治疗,持续治疗6个月。检测两组患者治疗前后免疫球蛋白(IgG、IgM、IgA)含量,计算每月痰菌转阴率,观察记录两组患者治疗期间不良反应发生情况。结果两组患者治疗后 IgG、IgM、IgA 水平均显著上升,且观察组 IgG(12.26±2.11)g/L 水平明显高于对照组(10.34±2.07)g/L,差异均有统计学意义(P0.05)。治疗6月时观察组痰菌转阴率78.05%显著高于对照组46.34%,差异有统计学意义(P0.05)。结论莫西沙星联合对氨基水杨酸异烟肼、利福喷丁、乙胺丁醇治疗单耐异烟肼或利福平肺结核患者疗效显著,安全性高。%ABSTRAC:Objective To study the selection of therapeutic regimen for pulmonary tuberculosis patients with single isoniazid or rifampicin resistance and to analyze the effects. Methods 82 cases of pulmonary tuberculosis patients whose sputum bacteria were still positive and who received 2 months of treatment with isoniazid and rifampicin in our hospital between July 2013 and July 2014 were selected and were randomly divided into the observation group and the control group, 41 cases in each group. The observation group were treated with moxifloxacin, isoniazid aminosalicylate, rifapentine and ethambutol, oral medication; The control group were treated with levofloxacin, isoniazid aminosalicylate, rifapentin and ethambutol, oral medication and the treatment lasted for 6 months. The contents of immunoglobulin (IgG, IgM, IgA) in the two groups

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

    Science.gov (United States)

    Leitner, Gerda C; Vogelsang, Harald

    2016-02-01

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

  17. Analysis of antibiotics resistance of Mycobacterium tuberculosis during 2008-2010%2008-2010年结核分枝杆菌的耐药性分析

    Institute of Scientific and Technical Information of China (English)

    王湘,; 张丽霞

    2011-01-01

    摘要:目的 了解2008-2010年结核患者分离出的结核分枝杆菌对常用抗结核药物的耐药性变迁.方法 采用罗氏培养系统进行结核分枝杆菌培养,药敏试验采用绝对浓度法,回顾性分析天津市海河医院分离的455株痰结核分枝杆菌的耐药性.结果455株结核分枝杆菌对链霉素、左氧氟沙星、利福平、乙胺丁醇、异烟肼、阿米卡星、对氨基水杨酸的总耐药率分别为29.2%、24.6%、23.1%、18.2%、18.5%、13.4%、9.2%.结论结核分枝杆菌的耐药率仍然较高,规范、足量、联合用药,是减缓耐药率的主要途径.%OBJECTIVE To investigate the variance of antimicrobial resistance and drug susceptibility of seven anti-TB drugs in hospitalized tuberculosis patients during 2008 - 2010. METHODS Roche system was used to culture Mycobacterium tuberculosis and absolute concentration method was used to test the drug susceptibility. Drug resistance and variance of antimicrobial resistance rates of 455 strains were retrospectively analyzed. RESULTS Of 455 strains, the total drug resistance rates of streptomycin, levofloxacin, rifampicin, ethambutol, isoniazid, amikacin, para-aminosalicylic acid were 29. 2%, 24. 6%, 23. 1%, 18. 2%, 18. 5%, 13. 4% and 9. 2%, respectively. CONCLUSION The resistance rate of M. Tuberculosis is still high. Standard, united, full course of treatment medication is still the main way to reduce the drug resistance.

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

    Institute of Scientific and Technical Information of China (English)

    田玲玲; 刘丽娜

    2016-01-01

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

  19. 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

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

    Science.gov (United States)

    Leitner, Gerda C; Vogelsang, Harald

    2016-02-01

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

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

    Science.gov (United States)

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

    2007-01-01

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

  2. Lactobacillus crispatus M206119 exacerbates murine DSS-colitis by interfering with inflammatory responses

    Institute of Scientific and Technical Information of China (English)

    Fu-Xi Zhou; Lu Chen; Xiao-Wei Liu; Chun-Hui Ouyang; Xiao-Ping Wu; Xue-Hong Wang; Chun-Lian Wang

    2012-01-01

    saline or 5-aminosalicylic-acid-treated DSS-colitis mice.Next,CCTCC M206119 strain was characterized as L.crispatus by microscopic morphology,biochemical tests and 16S rRNA gene level.CONCLUSION:Not all lactobacilli are beneficial for intestinal inflammation,and L.crispatus CCTCC M206119 strain is involved in exacerbation of intestinal inflammation in DSS-colitis mice.

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

    Institute of Scientific and Technical Information of China (English)

    吴颖

    2015-01-01

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

  4. 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

  5. Systematic review: treatment pattern and clinical effectiveness and safety of pharmaceutical therapies for Crohn’s disease in Europe

    Directory of Open Access Journals (Sweden)

    Lelli F

    2016-10-01

    Full Text Available Filippo Lelli,1 Solomon Nuhoho,2 Xin Ying Lee,3 Weiwei Xu4 1EMEA Hemar, Janssen, Milan, Italy; 2Health Economics, Market Access and Reimbursement, Johnson & Johnson Middle East FZ LLC, Dubai, United Arab Emirates; 3EMEA Hemar, Janssen, Birkerød, Denmark; 4Pharmerit International, Rotterdam, the Netherlands Background: Although many clinical trials have been conducted in treatments of Crohn’s ­disease (CD, whether the trial results were representative of daily practice needs to be supported by studies conducted in real-world settings. Aim: This study aims to identify how CD is treated and what are the clinical effectiveness and safety of the pharmaceutical therapies of CD in real-world settings. Methods: A systematic literature review was conducted based on Medline®, Embase®, and Cochrane. All publications were assessed for title/abstract and full-text according to a predefined study protocol. Data were extracted and reported.Results: A total of 1,998 publications were identified. Fifty studies including six publications reporting treatment pattern and 44 studies reporting clinical effectiveness and safety of pharmaceutical therapies in CD management in Europe were included. 5-Aminosalicylic acid and corticosteroids were reported to be used among 14%–74% of CD patients. Immunomodulators were used by 14%–25% and 29%–31% of CD patients as an initial and follow-up treatment, respectively. Biological therapies were used by 25%–33% of CD patients. A trend toward an increasing use of immunomodulators and biological therapies in Europe has been reported in recent years. Approximately 50% of patients achieved remission on immunomodulator or biologic treatment, although a relapse rate of up to 23% has been reported.Conclusion: There is a trend of treatment shift to immunomodulators and biologics in CD management. Clinical effectiveness of immunomodulators and biologics has been demonstrated, though with a lack of sustainability of the

  6. 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)

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

    International Nuclear Information System (INIS)

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

  8. Association between oral 5-ASA adherence and health care utilization and costs among patients with active ulcerative colitis

    Directory of Open Access Journals (Sweden)

    Mitra Debanjali

    2012-09-01

    Full Text Available Abstract Background Observational cohort study to assess the association between adherence to oral 5-aminosalicylates (5-ASAs and all-cause costs and health care utilization among patients with active ulcerative colitis (UC in the United States. Methods Retrospective analysis of insurance claims from June 1997 to August 2006 in the LifeLink Database. Patient criteria: aged 18 or older with one or more claim(s between June 1997 and August 2005 for a UC diagnosis and at least one oral 5-ASA prescription on or after the first observed UC diagnosis; continuous enrollment for at least 6 months prior to and 12 months following 5-ASA initiation (index date. As a proxy for active disease, patients needed to have at least two UC-specific non-pharmacy claims, at least 30 days of 5-ASA treatment and at least one corticosteroid prescription within the 12-month post-index period. Cumulative exposure to oral 5-ASAs over the 12-month period was calculated using the medication possession ratio (MPR. Patients with an MPR of at least 0.80 were classified as adherent. All-cause medical and pharmacy resource utilization and costs were computed over the 12-month post-index period and compared between adherent and nonadherent patients. Results 1,693 UC patients met study inclusion criteria: 72% were nonadherent to 5-ASA treatment (n = 1,217 and 28% were adherent (n = 476 in the 12-month study period. Compared with nonadherent patients, adherent patients had 31% fewer hospitalizations (P = 0.0025 and 34% fewer emergency department admissions (P = 0.0016. Adherent patients had 25% more pharmacy prescriptions overall (P P P = 0.0002. After adjusting for covariates, total all-cause costs were 29% higher for nonadherent patients than for adherent patients (mean [95% confidence interval]: $13,465 [$13,094, $13,835] vs $17,339 [$17,033, $17,645]. Conclusions Approximately three-quarters of patients with active UC were not adherent with their

  9. Site-Specific Labeling of Protein Kinase CK2: Combining Surface Display and Click Chemistry for Drug Discovery Applications.

    Science.gov (United States)

    Nienberg, Christian; Retterath, Anika; Becher, Kira-Sophie; Saenger, Thorsten; Mootz, Henning D; Jose, Joachim

    2016-06-27

    Human CK2 is a heterotetrameric constitutively active serine/threonine protein kinase and is an emerging target in current anti-cancer drug discovery. The kinase is composed of two catalytic CK2α subunits and two regulatory CK2β subunits. In order to establish an assay to identify protein-protein-interaction inhibitors (PPI) of the CK2α/CK2β interface, a bioorthogonal click reaction was used to modify the protein kinase α-subunit with a fluorophore. By expanding the genetic code, the unnatural amino acid para azidophenylalanine (pAzF) could be incorporated into CK2α. Performing the SPAAC click reaction (Strain-Promoted Azide-Alkyne Cycloaddition) by the use of a dibenzylcyclooctyne-fluorophore (DBCO-fluorophore) led to a specifically labeled human protein kinase CK2α. This site-specific labeling does not impair the phosphorylation activity of CK2, which was evaluated by capillary electrophoresis. Furthermore a dissociation constant (KD) of 631 ± 86.2 nM was determined for the substrate αS1-casein towards CK2α. This labeling strategy was also applied to CK2β subunit on Escherichia coli, indicating the site-specific modifications of proteins on the bacterial cell surface when displayed by Autodisplay.

  10. Site-Specific Labeling of Protein Kinase CK2: Combining Surface Display and Click Chemistry for Drug Discovery Applications

    Directory of Open Access Journals (Sweden)

    Christian Nienberg

    2016-06-01

    Full Text Available Human CK2 is a heterotetrameric constitutively active serine/threonine protein kinase and is an emerging target in current anti-cancer drug discovery. The kinase is composed of two catalytic CK2α subunits and two regulatory CK2β subunits. In order to establish an assay to identify protein-protein-interaction inhibitors (PPI of the CK2α/CK2β interface, a bioorthogonal click reaction was used to modify the protein kinase α-subunit with a fluorophore. By expanding the genetic code, the unnatural amino acid para azidophenylalanine (pAzF could be incorporated into CK2α. Performing the SPAAC click reaction (Strain-Promoted Azide-Alkyne Cycloaddition by the use of a dibenzylcyclooctyne-fluorophore (DBCO-fluorophore led to a specifically labeled human protein kinase CK2α. This site-specific labeling does not impair the phosphorylation activity of CK2, which was evaluated by capillary electrophoresis. Furthermore a dissociation constant (KD of 631 ± 86.2 nM was determined for the substrate αS1-casein towards CK2α. This labeling strategy was also applied to CK2β subunit on Escherichia coli, indicating the site-specific modifications of proteins on the bacterial cell surface when displayed by Autodisplay.

  11. Site-Specific Labeling of Protein Kinase CK2: Combining Surface Display and Click Chemistry for Drug Discovery Applications †

    Science.gov (United States)

    Nienberg, Christian; Retterath, Anika; Becher, Kira-Sophie; Saenger, Thorsten; Mootz, Henning D.; Jose, Joachim

    2016-01-01

    Human CK2 is a heterotetrameric constitutively active serine/threonine protein kinase and is an emerging target in current anti-cancer drug discovery. The kinase is composed of two catalytic CK2α subunits and two regulatory CK2β subunits. In order to establish an assay to identify protein-protein-interaction inhibitors (PPI) of the CK2α/CK2β interface, a bioorthogonal click reaction was used to modify the protein kinase α-subunit with a fluorophore. By expanding the genetic code, the unnatural amino acid para azidophenylalanine (pAzF) could be incorporated into CK2α. Performing the SPAAC click reaction (Strain-Promoted Azide-Alkyne Cycloaddition) by the use of a dibenzylcyclooctyne-fluorophore (DBCO-fluorophore) led to a specifically labeled human protein kinase CK2α. This site-specific labeling does not impair the phosphorylation activity of CK2, which was evaluated by capillary electrophoresis. Furthermore a dissociation constant (KD) of 631 ± 86.2 nM was determined for the substrate αS1-casein towards CK2α. This labeling strategy was also applied to CK2β subunit on Escherichia coli, indicating the site-specific modifications of proteins on the bacterial cell surface when displayed by Autodisplay. PMID:27355959

  12. Hepatic and intestinal blood flow following thermal injury

    International Nuclear Information System (INIS)

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

  13. Study and analysis on the prophylaxis and treatment of manganism among ferromanganese alloy smelting workers during 35 years%高炉锰铁冶炼工人锰中毒的三十五年防治研究与分析

    Institute of Scientific and Technical Information of China (English)

    潘举升; 王晓江; 方梅芳; 魏泽荣; 林萍; 钟莹; 汤锦龙; 刘武; 龚茶秀

    2001-01-01

    Objective To seek the measures for prophylaxis and treatment of occupational manganism among high furnace ferromanganese-smelting workers. Methods Data of 35 year occupational health supervision,and clinical therapy and prevention of manganism among workers exposed to manganese were analyzed with the method of occupational epidemiology. Results In the workplace,the maximum manganese content in the air was 199.4 mg/m3,minimum 0.034 mg/m3 and average 2.046 mg/m3.As the techology continuously improved,the manganese content in the air was gradually decreasing.Of 1*!555 followed up Mn exposed workers,the incidence was 2.508%.The shortest diseased work-year was 3 a,the longest 34 a,average 14 a.Using disodium coolium ethylene diamine tetraacetate(CaNa2EDTA),2,3-dimercaptosuccinic acid(DMSA),p-aminosalicylic acid(PAS) etc to scavenge Mn,supplemented with ATP mixture,vitamin,procaine block,traditional Chinese medicine and moving the patients away from the manganese exposed spot etc were effective therapy.Rheoencephalography(REG),transcranial doppler(TCD) and neurobehavioral function were of certain reference value for diagnosis. Conclusion Improving the workplace environment,strengthenning health monitor and actively treating manganism patients,will help prevent the occurrence of manganism and recover from manganism.%目的 寻求高炉锰铁冶炼致职业暴露人群锰中毒的防治对策。 方法 用职业流行病学的方法对某公司高炉锰铁冶炼的职业卫生监督监测和职业暴露人群追踪35年的资料进行分析研究。 结果 车间空气中锰浓度最高199.4 mg/m3,最低0.034 mg/m3,平均2.046 mg/m3。随着技术改造的不断深入,车间空气中锰浓度呈显著下降趋势。累计追踪观察1 555例锰暴露人群,共诊断锰中毒39例,患病率2.508%。发病工龄最短3年,最长34年,平均14年。采取依地酸二钠钙(CaNa2EDTA)、二巯基丁二酸(DMSA)、对氨基水杨酸(PAS)等驱锰,

  14. 左氧氟沙星与莫西沙星治疗耐药性肺结核的疗效和安全性比较%Comparison of Efficacy and Safety of Levofloxacin and Moxifloxacin in the Treatment of Patients with Drug-resistant Tuberculosis

    Institute of Scientific and Technical Information of China (English)

    朱刚

    2016-01-01

    OBJECTIVE:To compare the efficacy and safety of levofloxacin and moxifloxacin in the treatment of patients with drug-resistant tuberculosis. METHODS:148 patients with drug-resistant tuberculosis were divided into observation group(74 cases) and control group(74 cases). All patients were treated with 300 mg Aminosalicylic acid isoniazid tablet+250 mg Ethambutol hydro-chloride tablet+200 mg Pyrazinamide tablet+200 mg Protionamide tablet,3 times a day,treatment for 3 months;based on it,obser-vation group was orally given 0.4 g Moxifloxacin hydrochloride tablet,once a day;control group was orally given 0.5 g Levofloxa-cin hydrochloride tablet,once a day. They were treated for 12 months. The total efficacy,sputum negative convevsion rate after 1, 4,8 and 12 months,X-ray cavities lesion improvement and incidence of ADR in 2 groups were observed. RESULTS:The total effi-cacy,sputum negative conversion rate after 1,4,8 and 12 months,and cavity closure and reduced proportion in observation group were significantly higher than control group,the empty change and increase proportion,incidence of ADR were significantly lower control group,the differences were statistically significant (P<0.05). CONCLUSIONS:Based on conventional treatment, moxifloxacin shows better efficacy and safety than levofloxacin in the treatment of patients with drug-resistant tuberculosis.%目的:比较左氧氟沙星与莫西沙星治疗耐药性肺结核的疗效和安全性。方法:148例耐药性肺结核患者随机分为观察组(74例)和对照组(74例)。两组患者均给予氨基水杨酸异烟肼片300 mg+盐酸乙胺丁醇片250 mg+吡嗪酰胺片200 mg+丙硫异烟胺片200 mg,均为每日3次,连用3个月。在此基础上,观察组患者口服盐酸莫西沙星片0.4 g,每日1次;对照组患者口服盐酸左氧氟沙星片0.5 g,每日1次。两组均治疗12个月。比较两组患者的临床疗效,治疗1、4、8、12个月后痰菌转阴率,X线空洞病

  15. A comparative study of proportion method and absolute concentration method on drug susceptibility testing of M. tuberculosis%比例法和绝对浓度法对结核分支杆菌药物敏感性测定的对比研究

    Institute of Scientific and Technical Information of China (English)

    陈裕; 刘建民; 张华伟; 苗永红

    2001-01-01

    Objective To study the susceptibility to drugs of proportion method and absolute concentration method of M. tuberculosis ( MTB ). Methods According to the Laboratory Science Procedure of Diagnostic Bacteriology in Tuberculosis Published by Chinese Antituberculosis Association, drug sensitivity test( DST)was performed to 104 strains of MTB using proportion method and absolute concentration method at the same time. Results By proportion method and absolute concentration method, the rates of drug resistance and multidrug resistance of tuberculosis were 84.6% 、50.0% and 53.8%、40.4%, respectively. It was signficanfly higher in proportion method than that of absolute concentration method ( P < 0.01 ). The sensitivity accordance rates to Streptomycin ( SM )、 Isoniazid ( INH )、 Rifampicin ( RFP ), Ethambutol( EMB) and Para- aminosalicylic acid( PAS) of proportion method compared to absolute comcentrtion method were 88.2%、 100.0%、95.0% and 96.8%, respectively. The accordance rates to SM、 INH、 RFP、 EMB and PAS between two methods were 88.5 %、 84.6 %、 80.8 %、 63.5 % and 73.1%, respectively, Conclusions The results of proportion method were accurate and could be compared.%目的对比研究比例法和绝对浓度法测定结核分支杆菌的药物敏感性。方法按照中国防痨协会《结核病诊断细菌学检验规程》,对104株结核分支杆菌分别采用比例法和绝对浓度法检测药物敏感性。结果比例法及绝对浓度法对耐药病例检出率及耐多药结核(MDR-TB)检出率分别为84.6%、50.O%及53.8%、40.4%,(P<O.01)。比例法对链霉素(SM)、异菸肼(INH)、利福平(RFP)、乙胺丁醇(EMB)、对氨基水杨酸钠(PAS)等敏感与绝对浓度法符合率分别为88.2%、100.O%、100.O%、95.0%、96.8%。两种检测方法对SM、INH、RFP、EMB、PAS各药的符合率分别为88.5%、84.6%、80.8%、63.5%、73.1%。结论比例法结果精确,具有可比性。

  16. Long-term efficacy and safety of once-daily mesalazine granules for the treatment of active ulcerative colitis.

    Science.gov (United States)

    Böhm, Stephan Karl; Kruis, Wolfgang

    2014-01-01

    In 1977, 5-aminosalicylic acid (5-ASA) was discovered as a therapeutically active moiety of sulfasalazine (SASP) and was launched for topical and oral therapy of ulcerative colitis (UC) in 1984. As a first-step, delivery systems had to be developed to protect 5-ASA against absorption in the upper gastrointestinal tract, resulting in different and competing strategies (azo compounds, controlled release, and pH-dependent release). In a second step, at the beginning of the new century, coinciding with the expiration of patent protection for the first 5-ASA formulations, two component composite release mechanisms (pH-dependent and controlled release) were developed. Furthermore, the drug was formulated as granules instead of tablets, allowing higher unit strengths compared with tablets. Neither Salofalk Granu-Stix(®), nor MMX 5-ASA, nor Pentasa(®) granules have initially been developed for once-daily (OD) dosing. A review of the achievements of 20 years of 5-ASA development has demonstrated that 5-ASA has equal efficacy compared with SASP at best, that there are no measurable differences in efficacy between various 5-ASA preparations, and that in a group of patients tolerating SASP, adverse event profiles of SASP and 5-ASA did not differ significantly, with SASP being the far cheaper substance. Therefore, drug adherence came into focus as a new goal for improving UC therapy. Although adherence is a complex and multifactorial construct, a simple dosing schedule may contribute to higher drug adherence and better efficacy of treatment. Simultaneously, the US 5-ASA market, estimated to be worth US$1.4 billion, is expected to grow continuously. Naturally, this very competitive market is not only driven by scientific progress but also by commercial interests. Thus, patents for minor changes to the formulation may serve as protection against drug companies trying to launch generic versions. Randomized controlled trials performed on OD dosing in induction of remission have

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

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

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

    2005-01-01

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

  19. Copper complex of 5-methyl-amino salicylic acid salicylaldehyde Schiff base:synthesis, characterization and antitumor activity in vitro%5-甲基水杨醛缩对氨基水杨酸希夫碱铜配合物合成表征与体外抗肿瘤活性研究

    Institute of Scientific and Technical Information of China (English)

    郭永胜; 陈红林; 刘文; 孙体健

    2016-01-01

    Objective To synthesize the copper complex of 5-methyl-amino salicylic acid Schiff base and de-termine its anti-tumor effect in vitro. Methods The conventional heating under reflux method was used for synthesis of the target compound. Ultraviolet absorption, elemental analysis and infrared spectroscopy were employed to charac-terize the synthesized product. MTT assay was used to investigate the inhibitory effect of the copper complex against proliferation of human cervical cancer SiHa and HeLa cell lines. AO/EB double staining fluorescence microscopy was used to study the change in SiHa cell morphology as induced by the copper complex. Results The molecular formula of the target compound was found to be [C30H24N2O8Na2Cu]·2H2O. The copper complex exhibited varying degrees of in-hibitory effects on SiHa and HeLa cell lines in a significant dose-response manner. The anti-tumor effect was more ac-tive against SiHa than HeLa cells. The compound was found to induce obvious changes in tumor cell morphology, apoptosis or necrosis of the tumor cell lines. Conclusion The copper complex of 5-methyl-aminosalicylic acid Schiff base may inhibit the proliferation of HeLa and SiHa cell lines of cervical cancer, and thereby shows satisfactory anti-tumor activity in vitro.%目的:合成5-甲基水杨醛缩对氨基水杨酸希夫碱铜配合物药物并研究其体外抗肿瘤作用。方法采用常规加热回流法合成目标化合物,利用紫外吸收、元素分析和红外光谱等方法对其进行表征研究。采用四甲基偶氮唑盐(MTT)法考察药物对人宫颈癌细胞SiHa和HeLa增殖的抑制作用,并采用吖啶橙/溴乙锭(AO/EB)双染色荧光显微镜观察药物对SiHa细胞形态的变化。结果目标化合物的组成为[C30H24N2O8Na2Cu ]·2H2O;对SiHa和HeLa细胞都有不同程度的抑制作用,呈现良好的剂量-效应关系,对SiHa的活性优于HeLa;并且可使肿瘤细胞的形态发生显著变化,引起细胞株

  20. 阿莫西林/克拉维酸钾联合左氧氟沙星治疗耐多药肺结核临床疗效分析%Clinical Efficacy Analysis of Amoxicillin/clavulanic Potassium Combined Levofloxacin in the treatment of multi-drug resistant tuberculosis (MDR-TB)

    Institute of Scientific and Technical Information of China (English)

    王晓; 刘幸; 王璐

    2011-01-01

    Objective To observe and evaluate the clinical effect of amoxicillin/clavulanate potassium combined lev- ofloxacin in multi-drug resistant tuberculosis(MDR-TB). Methods 101 cases of retreatment smear-positive MDR-TB patients were randomly divided into treatment group (52 patients) and control group (49 patients); chemotherapy: the treatment group based on amoxicillin/clavulanate potassium and levofloxacin, associated with pyrazinamide, ethambutol, aminosalicylic acid isoniazid and rifampicin spray bite; The control group based on levofloxacin, combination therapy is same with the treatment group; The treatment course of all cases is 12 months. Results 5 patients were terminated because of adverse drug reactions In the course of treatment, the treatment group actually completed 50 patients, the control group actually completed 46 patients. To the end of treatment, sputum conversion rate of treatment group and control group Separately was 78.0% and 56.5%, sputum conversion rate in the treated group was significantly higher than the control group(P <0.05); foci effective rate of treatment group was 78.0%, cavity closure rate was 82.0%, foci effective rate and cavity closure rate in treatment group were significantly higher than the control group(P <0.05). Conclusion amoxicillin/clavulanate potassium combined levofloxacin in the treatment of MDR-TB was contribute to sputum conversion and Absorption of the lesion, adverse drug reactions was low, worthy of clinical application.%目的 观察并评价阿莫西林/克拉维酸钾联合左氧氟沙星在耐多药肺结核(MDR-TB)治疗中的效果.方法 将101例复治涂阳耐多药肺结核患者随机分为治疗组52例和对照组49例;化疗方案:治疗组以阿莫西林/克拉维酸钾、左氧氟沙星为主,联合吡嗪酰胺、盐酸乙胺丁醇、对氨基水杨酸异烟肼、利福喷叮;对照组以左氧氟沙星为主,联合用药同治疗组;所有病例疗程均为12个月.结果 治疗中途因

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

    Institute of Scientific and Technical Information of China (English)

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

    2012-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

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

    2012-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

    陈松华; 王晓萌; 柳正卫; 何海波; 陈彬; 黄玉

    2011-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Lauran Vogelaar

    2009-09-01

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

  5. 4-Chloro-α-cyanocinnamic acid is an efficient soft matrix for cyanocobalamin detection in foodstuffs by matrix-assisted laser desorption/ionization mass spectrometry (MALDI MS).

    Science.gov (United States)

    Calvano, Cosima Damiana; Ventura, Giovanni; Palmisano, Francesco; Cataldi, Tommaso R I

    2016-09-01

    4-Chloro-α-cyanocinnamic acid (ClCCA) is a very useful matrix able to give the protonated adduct [M+H](+) of intact cyanocobalamin (CNCbl) as the base peak (m/z 1355.58) in matrix-assisted laser desorption/ionization (MALDI) mass spectrometry (MS). The only fragment observed is [M-CN + H](+•) formed through the facile (•) CN neutral loss reflecting the fairly low Co-C bond energy. All other investigated proton transfer matrices, including α-cyano-4-hydroxycinnamic acid, para-nitroaniline and 2,5-dihydroxybenzoic acid, give rise to a complete decyanation of CNCbl with concomitant formation of [M-CN + H](+•) , [M-CN + Na](+•) and [M-CN + K](+•) adducts at m/z 1329.57, 1351.55 and 1367.51, respectively. Depending on the matrix used, a variable degree of fragmentation involving the α-side axial ligand was observed. A plausible explanation of the specific behaviour of 4-chloro-α-cyanocinnamic acid as a soft matrix is discussed. Tandem mass spectra of both [M + H](+) and [M-CN + H](+•) ions were obtained and product ions successfully assigned. The possibility of detecting the protonated adduct of intact CNCbl was exploited in foodstuff samples such as cow milk and hen egg yolk by MALDI tandem MS upon sample extraction. We believe that our data provide strong basis for the application of MALDI tandem MS in the qualitative analysis of natural CNCbl, including fish, liver and meat samples. Copyright © 2016 John Wiley & Sons, Ltd. PMID:27468135

  6. 4-Chloro-α-cyanocinnamic acid is an efficient soft matrix for cyanocobalamin detection in foodstuffs by matrix-assisted laser desorption/ionization mass spectrometry (MALDI MS).

    Science.gov (United States)

    Calvano, Cosima Damiana; Ventura, Giovanni; Palmisano, Francesco; Cataldi, Tommaso R I

    2016-09-01

    4-Chloro-α-cyanocinnamic acid (ClCCA) is a very useful matrix able to give the protonated adduct [M+H](+) of intact cyanocobalamin (CNCbl) as the base peak (m/z 1355.58) in matrix-assisted laser desorption/ionization (MALDI) mass spectrometry (MS). The only fragment observed is [M-CN + H](+•) formed through the facile (•) CN neutral loss reflecting the fairly low Co-C bond energy. All other investigated proton transfer matrices, including α-cyano-4-hydroxycinnamic acid, para-nitroaniline and 2,5-dihydroxybenzoic acid, give rise to a complete decyanation of CNCbl with concomitant formation of [M-CN + H](+•) , [M-CN + Na](+•) and [M-CN + K](+•) adducts at m/z 1329.57, 1351.55 and 1367.51, respectively. Depending on the matrix used, a variable degree of fragmentation involving the α-side axial ligand was observed. A plausible explanation of the specific behaviour of 4-chloro-α-cyanocinnamic acid as a soft matrix is discussed. Tandem mass spectra of both [M + H](+) and [M-CN + H](+•) ions were obtained and product ions successfully assigned. The possibility of detecting the protonated adduct of intact CNCbl was exploited in foodstuff samples such as cow milk and hen egg yolk by MALDI tandem MS upon sample extraction. We believe that our data provide strong basis for the application of MALDI tandem MS in the qualitative analysis of natural CNCbl, including fish, liver and meat samples. Copyright © 2016 John Wiley & Sons, Ltd.

  7. 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

  8. Design and characterization of artificial extracellular matrix proteins for use as small-diameter vascular grafts

    Science.gov (United States)

    Heilshorn, Sarah

    , isoleucine. Replacing 82% of the isoleucines results in a twofold reduction in degradation rate without compromising sequence-specific HUVEC adhesion. Incorporation of another noncanonical amino acid, para-azidophenylalanine, allows synthesis of photoreactive proteins that can be patterned using photolithography. These protein patterns retain their ability to adhere HUVEC and produce stable cell patterns after 48 hours in medium supplemented with serum.

  9. Prevalence and risk factors on the resistance related to second-line drugs among multi-drug resistant tuberculosis cases in Shanghai, China%上海市耐多药结核病患者二线药物耐药情况及危险因素分析

    Institute of Scientific and Technical Information of China (English)

    李静; 张阳奕; 桂晓虹; 袁政安; 潘启超; 梅建; 沈鑫

    2012-01-01

    目的 分析上海市耐多药结核病(MDR-TB)患者二线药物耐药分布情况及危险因素.方法 收集2009年上海市各区(县)结核病定点医院痰培养阳性菌株,进行菌型鉴定和一线抗结核药物(异烟肼、利福平、链霉素及乙胺丁醇)敏感性检测,对耐多药菌株进行二线抗结核药物(卡那霉素、阿米卡星、卷曲霉素、氧氟沙星、对氨基水杨酸及丙硫异烟胺)敏感性检测,结合患者特征及实验室信息,采用多因素分析上海市MDR-TB患者二线药物耐药的危险因素.结果 2009年上海市确诊的1867例结核病病例中,112例(6.0%)为MDR-TB患者,其中58例(51,8%)至少耐1种二线抗结核药物,10例为广泛耐药结核病.多因素分析显示,MDR-TB患者中,45 ~ 59岁年龄组(aOR=4.76,P=0.001)及痰涂片阳性(aOR=6.51,P=0.026)与二线药物耐药相关.结论 上海市MDR-TB患者二线抗结核药物耐药情况严重,45~59岁年龄组和痰涂片阳性是MDR-TB患者二线药物耐药相关的危险因素.%Objective To determine the prevalence and risk factors on second-line drug resistance in patients with multidrug resistant tuberculosis (MDR-TB) in Shanghai,China.Methods All pulmonary TB patients with sputum culture positivity detected in Shanghai during January to December,2009,were enrolled.All of the pretreatment sputum-positive cultures samples were tested for routine specimen identification and routine drug susceptibility testing for first-line drugs (Isoniazid,Rrifampin,Ethambutol and Streptomycin).Drug susceptibility testing on second-line anti-TB drugs (Ofloxcin,Amikacin,Kanamycin,Capreomycin,P-aminosalicylic acid and Prothionamide) was routinely performed on isolates of Mycobacterium (M.) TB with MDR.Logistic regression analysis was conducted to determine the risk factors regarding second-line drug resistance.Results A total of 1867 patients infected with M.TB isolates were diagnosed at the TB hospitals/clinics in Shanghai during the

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

    Institute of Scientific and Technical Information of China (English)

    周伟杰; 窦泽燕

    2014-01-01

    41.4%,ethambutol 24.2%,paraaminosalicylicacid 4.5%,amikacin 0.7%, prothionamide 5.6%,levofloxacin 9.4%,isoniazid aminosalicylate 0.7%;Among 425 primary drug-resistant cases, there were 253 cases of drug-resistant tuberculosis(59.5%),101 cases of polydrug-resistant tuberculosis(23.7%),71 cases of multidrug-resistant tuberculosis(16.4%).Conclusion The data obtained strongly suggests that the present situation of resistant tuberculosis in the hospital is still very serious.It is imperative to strengthen the management of tuberculosis prevention and control,and expand the testing points of Mycobacterium tuberculosis drug resistance,and supervise pulmonary tuberculosis under full-course management of the tuberculosis.

  11. 抗结核药物致皮疹的临床分析%Clinical Analysis of the Durg Eruptions Caused by Anti-tuberculosis Drugs

    Institute of Scientific and Technical Information of China (English)

    侍羽; 赵丽

    2015-01-01

    of isoniazid (INH), pasiniazid (DIP) in 4 cases, 3 cases of levofloxacin hydrochloride, 3 cases of gatifloxacin, protionamide 1 case. 10 cases were al ergic to ifampicin, but weren't al ergic to rifapentine. 1 cases was al ergic to both rifampin and rifapentine. There were dif erent types of skin rash, urticaria, erythema polymorphe, eczema eruption, scarlet rash, erythema polymorphe etc. Conclusion There were dif erent types of skin rash casued by anti-tuberculosis drugs. The incidence rates wre (from high to low) rifampicin, hydrochloride ethambutol, pyrazinamide, rifapentine, isoniazid, isoniazid aminosalicylate respectively. The cross al ergy of rifampin and rifapentine is less. The prognosis is excel ent after termimtion the anti-tuberculosis drugs and with anti-al ergic treatment.

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

    Directory of Open Access Journals (Sweden)

    Juan Carlos Rodríguez D

    2012-06-01

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

  13. 阿莫西林/克拉维酸钾联合常规抗结核药治疗耐多药肺结核的疗效观察%Observation of Amoxycillin/Clavulanate Potassium Combined with Conventional Anti-TB Drugs in Treatment of Multidrug Resistance Tuberculosis

    Institute of Scientific and Technical Information of China (English)

    郭蕊; 焦雪峰; 陈爽; 罗琳

    2015-01-01

    OBJECTIVE:To probe into the clinical efficacy and adverse drug reaction of amoxycillin /clavulanate potassium combined with conventional anti-TB drugs in treatment of multidrug resistance tuberculosis ( MDR-TB ) . METHODS:205 MDR-TB patients were divided into treatment group (103 patients) and control group (102 patients) by random number table .The control group was given amoxycillin , ethambutol , isoniazid aminosalicylate , rifapentine and levofloxacin , the observation group received amoxycillin/clavulanate potassiumthe based on the same treatment regimen of the control group .The treatment course of 2 groups was 12 months.The changes of sputum negative conversion, focal absorption, cavity, the improved clinical symptoms and negative ADR consequences were closely observed in two groups .RESULTS:After the treatment of 3 months, there was no statistically significant difference of the sputum negative conversion rate in 2 groups ( P>0.05 ) .In the treatment group , the sputum negative rate at the sixth, ninth and twelfth month were respectively 68.93%(71/103), 74.76%(77/103) and 81.55%(84/103), which was significantly higher than that in the control group 50.98%( 52/102 )、55.88%( 57/102 ) and 60.78%(62/102) respectively, with statistically significant difference ( P >0.05).At the end of the treatment, the focal absorption rate of treatment group and control group was respectively 88.35%(91/103) and 66.67%(68/102), the cavity closure rate of treatment group and control group were respectively 84.47%(87/103) and 64.71%(66/102);the above-mentioned indexes in the treatment group were all significantly better than that in the control group , with significant difference ( P<0.05 ) .CONCLUSIONS:It is safe and effective to use amoxycillin/clavulanate potassium in the treatment of MDR-TB, but still have few significant advantages in the short-term efficacy.%目的:探讨阿莫西林/克拉维酸钾联合常规抗结核药治疗耐多药肺结核( multidrug

  14. 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

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

    Institute of Scientific and Technical Information of China (English)

    韩玲玲; 苑兆和; 冯立娟; 杨尚尚; 朱峰

    2012-01-01

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

  16. 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

  17. 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