6,314 results on '"Aminosalicylic acid"'
Search Results
202. A review on 5-aminosalicylic acid colon-targeted oral drug delivery systems
- Author
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Abbas Akhgari, Hossein Shahdadi Sardo, Hadi Afrasiabi Garekani, Sara Bagheri, Farinaz Saremnejad, and Fatemeh Sadeghi
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Drug ,Aminosalicylic acid ,Colon ,media_common.quotation_subject ,Pharmaceutical Science ,02 engineering and technology ,Pharmacology ,030226 pharmacology & pharmacy ,Inflammatory bowel disease ,Dosage form ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Drug Delivery Systems ,medicine ,Animals ,Humans ,Colitis ,Mesalamine ,media_common ,Gastrointestinal tract ,business.industry ,Anti-Inflammatory Agents, Non-Steroidal ,Prodrug ,021001 nanoscience & nanotechnology ,medicine.disease ,digestive system diseases ,chemistry ,Drug delivery ,0210 nano-technology ,business - Abstract
Site-specific colon drug delivery is a practical approach for the treatment of local diseases of the colon with several advantages such as rapid onset of action and reduction of the dosage of the drug as well as minimization of harmful side effects. 5-aminosalicylic acid (5-ASA) is a drug of choice in the treatment of inflammatory bowel disease and colitis. For the efficient delivery of this drug, it is vital to prevent 5-ASA release in the upper part of the gastrointestinal tract and to promote its release in the proximal colon. Different approaches including chemical manipulation of drug molecule for production of prodrugs or modification of drug delivery systems using pH-dependent, time-dependent and/or bacterially biodegradable materials have been tried to optimize 5-ASA delivery to the colon. In the current review, the different strategies utilized in the design and development of an oral colonic delivery dosage form of 5-ASA are presented and discussed.
- Published
- 2018
203. Methionine Antagonizes para-Aminosalicylic Acid Activity via Affecting Folate Precursor Biosynthesis in Mycobacterium tuberculosis
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Allison A. Bauman, Yusuke Minato, Courtney C. Aldrich, Malcolm S. Cole, Michael D. Howe, Anthony D. Baughn, and Shannon Lynn Kordus
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0301 basic medicine ,Microbiology (medical) ,030106 microbiology ,Immunology ,lcsh:QR1-502 ,Antitubercular Agents ,Biotin ,Microbial Sensitivity Tests ,Microbiology ,lcsh:Microbiology ,Mycobacterium ,Methionine transport ,Mycobacterium tuberculosis ,03 medical and health sciences ,chemistry.chemical_compound ,Cellular and Infection Microbiology ,Folic Acid ,Biosynthesis ,Bacterial Proteins ,Drug Resistance, Bacterial ,Amino acid transporter ,para-aminosalicylic acid ,Original Research ,methionine ,para-aminobenzoic acid ,Methionine ,biology ,Metabolism ,biology.organism_classification ,methionine transport ,Aminosalicylic Acid ,antagonism ,anti-folate drug ,030104 developmental biology ,Infectious Diseases ,chemistry ,Biochemistry ,Antagonism ,4-Aminobenzoic Acid ,Drug Antagonism - Abstract
para-Aminosalicylic acid (PAS) is a second-line anti-tubercular drug that is used for the treatment of drug-resistant tuberculosis (TB). PAS efficacy in the treatment of TB is limited by its lower potency against Mycobacterium tuberculosis relative to many other drugs in the TB treatment arsenal. It is known that intrinsic metabolites, such as, para-aminobenzoic acid (PABA) and methionine, antagonize PAS and structurally related anti-folate drugs. While the basis for PABA-mediated antagonism of anti-folates is understood, the mechanism for methionine-based antagonism remains undefined. In the present study, we used both targeted and untargeted approaches to identify factors associated with methionine-mediated antagonism of PAS activity. We found that synthesis of folate precursors as well as a putative amino acid transporter, designated MetM, play crucial roles in this process. Disruption of metM by transposon insertion resulted in a ≥30-fold decrease in uptake of methionine in M. bovis BCG, indicating that metM is the major facilitator of methionine transport. We also discovered that intracellular biotin confers intrinsic PAS resistance in a methionine-independent manner. Collectively, our results demonstrate that methionine-mediated antagonism of anti-folate drugs occurs through sustained production of folate precursors.
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- 2018
204. Investigation of 5-aminosalicylic acid (Mesalazine Drug) as a Corrosion Inhibitor for Carbon Steel in Sulfuric Acid Solution
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Hossein Movahedinia
- Subjects
Drug ,Aminosalicylic acid ,Carbon steel ,media_common.quotation_subject ,Sulfuric acid ,engineering.material ,Corrosion inhibitor ,chemistry.chemical_compound ,chemistry ,Mesalazine ,Electrochemistry ,engineering ,media_common ,Nuclear chemistry - Published
- 2021
205. Solubility of 3-aminosalicylic acid in ethanol + water mixtures at different temperatures
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Fleming Martínez, Abolghasem Jouyban, Martin Kuentz, Milad Moradi, Salar Hemmati, and Elaheh Rahimpour
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Ethanol ,Aminosalicylic acid ,Thermodynamics ,02 engineering and technology ,Atmospheric temperature range ,010402 general chemistry ,021001 nanoscience & nanotechnology ,Condensed Matter Physics ,01 natural sciences ,Atomic and Molecular Physics, and Optics ,0104 chemical sciences ,Electronic, Optical and Magnetic Materials ,chemistry.chemical_compound ,1-Propanol ,chemistry ,Materials Chemistry ,Molecule ,Local environment ,Physical and Theoretical Chemistry ,Solubility ,0210 nano-technology ,Dissolution ,Spectroscopy - Abstract
Temperature-dependent solubility data of 3-aminosalicylic acid (3-ASA) are scarce in the literature and there is a particular need to explore cosolvency for this compound. Therefore, in the current study, the solubilization profile of 3-ASA along with density data in the mixtures of ethanol and water were measured at a temperature range of 293.2–313.2 K. The generated data were described by using some previously reported linear or non-linear mathematical models and their accuracies were investigated by calculating the mean relative deviations (MRD%). The apparent thermodynamic analysis for 3-ASA dissolution process was performed by the Gibbs and van't Hoff equations. Moreover, molecular insights in the local environment of the solute was obtained based on the inverse Kirkwood-Buff integrals, as it was observed that 3-ASA is preferentially solvated by water molecules from neat water to the mixture x1 = 0.24 and from x1 = 0.35 to neat ethanol. The experimental data and thermodynamic properties provide helpful information for the separation and purification of 3-ASA.
- Published
- 2020
206. Topical Aminosalicylic Acid Improves Keratinocyte Differentiation in an Inducible Mouse Model of Harlequin Ichthyosis
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Lynelle K. Jones, Denny L Cottle, Allara K. Zylberberg, Gloria M. A. Ursino, Ian M. Smyth, and Ming Shen Tham
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Keratinocytes ,Aminosalicylic acid ,medicine.drug_class ,Gene Expression ,Inflammation ,Pharmacology ,Article ,mesalamine ,4ASA ,General Biochemistry, Genetics and Molecular Biology ,Acitretin ,Mice ,chemistry.chemical_compound ,Downregulation and upregulation ,Animals ,Medicine ,Retinoid ,ABCA12 ,harlequin ichthyosis ,Skin ,Mice, Knockout ,biology ,business.industry ,5ASA ,Cell Differentiation ,Harlequin Ichthyosis ,Aminosalicylic Acid ,Up-Regulation ,Disease Models, Animal ,Phenotype ,chemistry ,skin barrier function ,Mutation ,biology.protein ,ATP-Binding Cassette Transporters ,Epidermis ,medicine.symptom ,Salicylic Acid ,business ,epidermal differentiation ,Ichthyosis, Lamellar ,Salicylic acid ,medicine.drug - Abstract
Summary Mutations in the lipid transport protein ABCA12 cause the life-threatening skin condition harlequin ichthyosis (HI), which is characterized by the loss of skin barrier function, inflammation, and dehydration. Inflammatory responses in HI increase disease severity by impairing keratinocyte differentiation, suggesting amelioration of this phenotype as a possible therapy for the condition. Existing treatments for HI are based around the use of retinoids, but their value in treating patients during the neonatal period has been questioned relative to other improved management regimens, and their long-term use is associated with side effects. We have developed a conditional mouse model to demonstrate that topical application of the aminosalicylic acid derivatives 5ASA or 4ASA considerably improves HI keratinocyte differentiation without the undesirable side effects of the retinoid acitretin and salicylic acid (aspirin). Analysis of changes in gene expression shows that 4ASA in particular elicits compensatory upregulation of a large family of barrier function-related genes, many of which are associated with other ichthyoses, identifying this compound as a lead candidate for developing topical treatments for HI., Graphical Abstract, Highlights Inflammation impairs keratinocyte differentiation and worsens harlequin ichthyosis Harlequin ichthyosis mice can be used to assess therapies for this disease Aminosalicylic acids may be therapeutic treatments for harlequin ichthyosis 4ASA improves skin differentiation and barrier function in harlequin ichthyosis models, Harlequin ichthyosis arises because of the loss of lipid transport in the skin. Cottle et al. demonstrate that the treatment of mouse models of this disease with anti-inflammatory aminosalicylic acid drugs improves skin differentiation and protective barrier function.
- Published
- 2020
207. Quantitative determination of sulfisoxazole and its three N-acetylated metabolites using HPLC–MS/MS, and the saturable pharmacokinetics of sulfisoxazole in mice
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Moon-Chang Baek, Kyungsoo Oh, and Wonku Kang
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Clinical Biochemistry ,Administration, Oral ,Pharmaceutical Science ,02 engineering and technology ,Absorption (skin) ,Pharmacology ,01 natural sciences ,Analytical Chemistry ,Excretion ,Mice ,Pharmacokinetics ,Tandem Mass Spectrometry ,Oral administration ,Drug Discovery ,medicine ,Animals ,Humans ,Chromatography, High Pressure Liquid ,Spectroscopy ,Acetaminophen ,Chromatography ,Chemistry ,010401 analytical chemistry ,Sulfisoxazole ,Metabolism ,021001 nanoscience & nanotechnology ,Aminosalicylic Acid ,Rats ,0104 chemical sciences ,Acetylation ,0210 nano-technology ,medicine.drug - Abstract
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.
- Published
- 2016
208. Mucoadhesive microparticulates based on polysaccharide for target dual drug delivery of 5-aminosalicylic acid and curcumin to inflamed colon
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Haogang Duan, Hongyan Qin, Yuhui Wei, Xinan Wu, Xiao Bai, Chunmei Gao, Shaoyu Lü, and Mingzhu Liu
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Curcumin ,Aminosalicylic acid ,Colon ,02 engineering and technology ,Pharmacology ,030226 pharmacology & pharmacy ,Inflammatory bowel disease ,Chitosan ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Colloid and Surface Chemistry ,Polymethacrylic Acids ,In vivo ,Mucoadhesion ,medicine ,Animals ,Physical and Theoretical Chemistry ,Colitis ,Mesalamine ,Drug Carriers ,Surfaces and Interfaces ,General Medicine ,Inflammatory Bowel Diseases ,021001 nanoscience & nanotechnology ,medicine.disease ,Rats ,chemistry ,Drug delivery ,0210 nano-technology ,Ex vivo ,Biotechnology - Abstract
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.
- Published
- 2016
209. Inflammatory bowel disease in India - Past, present and future
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Gautam Ray
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Crohn’s disease ,medicine.medical_specialty ,Antitubercular Agents ,India ,Disease ,Review ,Southeast asian ,Inflammatory bowel disease ,History, 21st Century ,Endoscopy, Gastrointestinal ,03 medical and health sciences ,0302 clinical medicine ,Hygiene hypothesis ,Internal medicine ,Epidemiology ,Azathioprine ,medicine ,Humans ,Asia, Southeastern ,Inflammation ,Crohn's disease ,Biological Products ,business.industry ,Incidence (epidemiology) ,Gastroenterology ,General Medicine ,History, 20th Century ,medicine.disease ,Inflammatory Bowel Diseases ,Ulcerative colitis ,Aminosalicylic Acid ,030220 oncology & carcinogenesis ,Immunology ,030211 gastroenterology & hepatology ,Colitis, Ulcerative ,business ,Colorectal Neoplasms ,Gastrointestinal Hemorrhage ,Biomarkers - Abstract
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 definition and treatment.
- Published
- 2016
210. Sodium P-Aminosalicylic Acid Improved Manganese-Induced Learning and Memory Dysfunction via Restoring the Ultrastructural Alterations and γ-Aminobutyric Acid Metabolism Imbalance in the Basal Ganglia
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Chao-Yan Ou, Yi-Ni Luo, Hai-Lan Luo, Yueming Jiang, Sheng-Nan He, Shao-Jun Li, Zong-Xiang Yuan, Yu-Huan Mo, Xiang-Fa Deng, and Hao-Yang Meng
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Male ,0301 basic medicine ,GABA Plasma Membrane Transport Proteins ,medicine.medical_specialty ,Neuropil ,Time Factors ,Endocrinology, Diabetes and Metabolism ,Blotting, Western ,Clinical Biochemistry ,Gene Expression ,Glutamic Acid ,Biochemistry ,Aminobutyric acid ,Basal Ganglia ,GABA transporter 1 ,Muscle hypertrophy ,Rats, Sprague-Dawley ,Inorganic Chemistry ,03 medical and health sciences ,0302 clinical medicine ,Microscopy, Electron, Transmission ,Memory ,Internal medicine ,Basal ganglia ,medicine ,Animals ,Maze Learning ,gamma-Aminobutyric Acid ,Neurons ,Manganese ,biology ,Reverse Transcriptase Polymerase Chain Reaction ,GABAA receptor ,Biochemistry (medical) ,Neurotoxicity ,General Medicine ,Metabolism ,medicine.disease ,Aminosalicylic Acid ,030104 developmental biology ,Endocrinology ,medicine.anatomical_structure ,Astrocytes ,biology.protein ,030217 neurology & neurosurgery - Abstract
Excessive intake of manganese (Mn) may cause neurotoxicity. Sodium para-aminosalicylic acid (PAS-Na) has been used successfully in the treatment of Mn-induced neurotoxicity. The γ-aminobutyric acid (GABA) is related with learning and memory abilities. However, the mechanism of PAS-Na on improving Mn-induced behavioral deficits is unclear. The current study was aimed to investigate the effects of PAS-Na on Mn-induced behavioral deficits and the involvement of ultrastructural alterations and γ-aminobutyric acid (GABA) metabolism in the basal ganglia of rats. Sprague-Dawley rats received daily intraperitoneally injections of 15 mg/kg MnCl2.4H2O, 5d/week for 4 weeks, followed by a daily back subcutaneously (sc.) dose of PAS-Na (100 and 200 mg/kg), 5 days/week for another 3 or 6 weeks. Mn exposure for 4 weeks and then ceased Mn exposure for 3 or 6 weeks impaired spatial learning and memory abilities, and these effects were long-lasting. Moreover, Mn exposure caused ultrastructural alterations in the basal ganglia expressed as swollen neuronal with increasing the electron density in the protrusions structure and fuzzed the interval of neuropil, together with swollen, focal hyperplasia, and hypertrophy of astrocytes. Additionally, the results also indicated that Mn exposure increased Glu/GABA values as by feedback loops controlling GAT-1, GABAA mRNA and GABAA protein expression through decreasing GABA transporter 1(GAT-1) and GABA A receptor (GABAA) mRNA expression, and increasing GABAA protein expression in the basal ganglia. But Mn exposure had no effects on GAT-1 protein expression. PAS-Na treatment for 3 or 6 weeks effectively restored the above-mentioned adverse effects induced by Mn. In conclusion, these findings suggest the involvement of GABA metabolism and ultrastructural alterations of basal ganglia in PAS-Na’s protective effects on the spatial learning and memory abilities.
- Published
- 2016
211. 5-Aminosalicylic Acid Azo-Linked to Procainamide Acts as an Anticolitic Mutual Prodrug via Additive Inhibition of Nuclear Factor kappaB
- Author
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Joon Nam, Sun-Young Lee, Yunjin Jung, Wooseong Kim, and Seongkeun Jeong
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Male ,0301 basic medicine ,Aminosalicylic acid ,Colon ,Pharmaceutical Science ,Procainamide ,Pharmacology ,030226 pharmacology & pharmacy ,Rats, Sprague-Dawley ,Intracolonic ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Sulfasalazine ,Drug Discovery ,medicine ,Animals ,Prodrugs ,Large intestine ,Colitis ,Mesalamine ,Chemistry ,NF-kappa B ,Prodrug ,medicine.disease ,digestive system diseases ,Rats ,surgical procedures, operative ,030104 developmental biology ,medicine.anatomical_structure ,Trinitrobenzenesulfonic Acid ,Molecular Medicine ,Azo Compounds ,Salicylic acid ,medicine.drug - Abstract
To improve the anticolitic efficacy of 5-aminosalicylic acid (5-ASA), a colon-specific mutual prodrug of 5-ASA was designed. 5-ASA was coupled to procainamide (PA), a local anesthetic, via an azo bond to prepare 5-(4-{[2-(diethylamino)ethyl]carbamoyl}phenylazo)salicylic acid (5-ASA-azo-PA). 5-ASA-azo-PA was cleaved to 5-ASA and PA up to about 76% at 10 h in the cecal contents while remaining stable in the small intestinal contents. Oral gavage of 5-ASA-azo-PA and sulfasalazine, a colon-specific prodrug currently used in clinic, to rats showed similar efficiency in delivery of 5-ASA to the large intestine, and PA was not detectable in the blood after 5-ASA-azo-PA administration. Oral gavage of 5-ASA-azo-PA alleviated 2,4,6-trinitrobenzenesulfonic acid-induced rat colitis. Moreover, combined intracolonic treatment with 5-ASA and PA elicited an additive ameliorative effect. Furthermore, combined treatment with 5-ASA and PA additively inhibited nuclear factor-kappaB (NFκB) activity in human colon carcinoma cells and inflamed colonic tissues. Finally, 5-ASA-azo-PA administered orally was able to reduce inflammatory mediators, NFκB target gene products, in the inflamed colon. 5-ASA-azo-PA may be a colon-specific mutual prodrug acting against colitis, and the mutual anticolitic effects occurred at least partly through the cooperative inhibition of NFκB activity.
- Published
- 2016
212. Metabolic investigation on ZL006 for the discovery of a potent prodrug for the treatment of cerebral ischemia
- Author
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Fei Li, Kaidong Ni, Yang Lei, Chen Dongyin, Dai Peng, Ting Zhao, and Yi Xu
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0301 basic medicine ,Benzylamines ,Aminosalicylic acid ,Stereochemistry ,Clinical Biochemistry ,Ischemia ,Pharmaceutical Science ,Blood–brain barrier ,Biochemistry ,Brain Ischemia ,Brain ischemia ,Mice ,03 medical and health sciences ,chemistry.chemical_compound ,Glucuronides ,0302 clinical medicine ,Drug Discovery ,medicine ,Animals ,Prodrugs ,Molecular Biology ,Esterification ,Chemistry ,Organic Chemistry ,Metabolism ,Prodrug ,medicine.disease ,Glucuronic acid ,Aminosalicylic Acids ,Neuroprotective Agents ,030104 developmental biology ,medicine.anatomical_structure ,Blood-Brain Barrier ,Molecular Medicine ,Amine gas treating ,030217 neurology & neurosurgery - Abstract
4-((3,5-Dichloro-2-hydroxybenzyl)amino)-2-hydroxybenzoic acid (ZL006, 1) is a small-molecular inhibitor of the nNOS/PSD-95 interaction, that is under preclinical evaluation stage for cerebral ischemia. However, the fast metabolism and low permeability across the blood brain barrier (BBB) have restricted its further use. In this manuscript, the mass spectroscopy analysis showed that ZL006 mainly combined with glucuronic acid in mice plasma, which accelerated its metabolism and elimination. Hence, six ZL006 analogs were designed according to the probable metabolism sites of ZL006, and featured the alkylation at phenolic hydroxyl, secondary amine and carboxyl groups. These compounds were synthesized in moderate to good yields, and fully characterized with (1)H NMR and MS. Further metabolism investigation of ZL006 analogs showed that phenolic hydroxyl group of aromatic ring A was the major conjugation site with glucuronic acid, and ZL006 cyclohexyl ester (6) had a better permeability across BBB, which was a potent prodrug for cerebral ischemia.
- Published
- 2016
213. Stereolithographic (SLA) 3D printing of oral modified-release dosage forms
- Author
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Abdul Basit, Alvaro Goyanes, Simon Gaisford, and Jie Wang
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Materials science ,Administration, Oral ,Pharmaceutical Science ,3D printing ,02 engineering and technology ,Polyethylene glycol ,010402 general chemistry ,01 natural sciences ,Dosage form ,Polyethylene Glycols ,law.invention ,chemistry.chemical_compound ,law ,PEG ratio ,Technology, Pharmaceutical ,Dissolution ,Stereolithography ,Acetaminophen ,business.industry ,021001 nanoscience & nanotechnology ,Aminosalicylic Acid ,Controlled release ,0104 chemical sciences ,Drug Liberation ,Monomer ,chemistry ,Chemical engineering ,Printing, Three-Dimensional ,0210 nano-technology ,business ,Tablets - Abstract
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.
- Published
- 2016
214. Timing for dose-down of 5-ASA depends on mucosal status with ulcerative colitis
- Author
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Takeshi Sugaya, Fumiaki Takahashi, Akira Kanamori, Hideyuki Hiraishi, Keiichi Tominaga, Masakazu Nakano, Kazuhiro Takenaka, and Atsushi Hoshino
- Subjects
Male ,0301 basic medicine ,medicine.medical_specialty ,Aminosalicylic acid ,Gastroenterology ,Endoscopy, Gastrointestinal ,03 medical and health sciences ,Remission induction ,chemistry.chemical_compound ,0302 clinical medicine ,Intestinal mucosa ,Internal medicine ,medicine ,Humans ,Intestinal Mucosa ,business.industry ,Remission Induction ,Middle Aged ,medicine.disease ,Aminosalicylic Acid ,Ulcerative colitis ,digestive system diseases ,030104 developmental biology ,chemistry ,Colitis, Ulcerative ,Female ,030211 gastroenterology & hepatology ,business - Abstract
Although aminosalicylic acid (ASA) preparations have been used as first-line drugs for the treatment of ulcerative colitis (UC), no consistent view has been established regarding the ASA dose during the remission-maintenance phase of the disease. In this study, we examined whether the ASA dose should be reduced during the remission-maintenance phase.This study included 203 patients in the remission-maintenance phase of UC. The Mayo endoscopic subscore (MES) was used to evaluate mucosa. Comparison and analysis were performed between patients whose ASA dose had been unchanged and whose dose had been reduced, between patients with endoscopic healing (EH) group and those without endoscopic healing (WEH) group, and between patients with an MES of 0 and 1.Comparison between the unchanged-ASA and reduced-ASA groups revealed that the remission-maintenance rate was higher in the unchanged-ASA group (p 0.001). Next, the remission-maintenance rate was higher in the EH/unchanged-ASA group than in the EH/reduced-ASA group (p = 0.042). Comparison between the MES 0 and 1 groups revealed that the remission-maintenance rate was higher in the MES 0 group (p = 0.007). In addition, no significant difference in remission-maintenance rates was observed between the MES 0/unchanged-ASA group and the MES 0/reduced-ASA group (p = 0.108).When the same ASA dose is maintained regardless of the presence or absence of EH, remission is more likely to be maintained. If the ASA dose must be reduced, dose reduction is more advantageous after an MES of 0 is achieved.
- Published
- 2016
215. Controlled release kinetics of p-aminosalicylic acid from biodegradable crosslinked polyesters for enhanced anti-mycobacterial activity
- Author
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Kaushik Chatterjee, Queeny Dasgupta, and Giridhar Madras
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Materials science ,Polyesters ,Biomedical Engineering ,Biodegradable Plastics ,02 engineering and technology ,010402 general chemistry ,Xylitol ,01 natural sciences ,Biochemistry ,Mycobacterium ,Biomaterials ,Mice ,chemistry.chemical_compound ,Polymer degradation ,Animals ,Organic chemistry ,Molecular Biology ,chemistry.chemical_classification ,Mycobacterium Infections ,Materials Engineering (formerly Metallurgy) ,General Medicine ,Polymer ,Chemical Engineering ,021001 nanoscience & nanotechnology ,Aminosalicylic Acid ,Biodegradable polymer ,Controlled release ,Anti-Bacterial Agents ,0104 chemical sciences ,Polyester ,Monomer ,chemistry ,Polymerization ,Delayed-Action Preparations ,NIH 3T3 Cells ,0210 nano-technology ,Biotechnology - Abstract
Unlike conventional polymeric drug delivery systems, where drugs are entrapped in polymers, this study focuses on the incorporation of the drug into the polymer backbone to achieve higher loading and sustained release. Crosslinked, biodegradable, xylitol based polyesters have been synthesized in this study. The bioactive drug moiety, p-aminosalicylic acid (PAS), was incorporated in xylitol based polyesters to impart its anti-mycobacterial activity. To understand the influence of the monomer chemistry on the incorporation of PAS and its subsequent release from the polymer, different diacids have been used. Controlled release profiles of the drug from these polyesters were studied under normal physiological conditions. The degradation of the polyesters varied from 48% to 76% and the release of PAS ranged from 54% to 65% of its initial loading in 7 days. A new model was developed to explain the release kinetics of PAS from the polymer that accounted for the polymer degradation and drug concentration. The thermal, mechanical, drug release and cytocompatibility properties of the polymers indicate their suitability in biomedical applications. The released products from these polymers were observed to be pharmacologically active against Mycobacteria. The high drug loading and sustained release also ensured enhanced efficacy. These polymers form biocompatible, biodegradable polyesters where the sustained release of PAS may be tailored for potential treatment of mycobacterial infections. Statement of significance In the present work, we report on novel polyesters with p-aminosalicylic acid (PAS) incorporated in the polymer backbone. The current work aims to achieve controlled release of PAS and ensures the delivered PAS is stable and pharmacologically active. The novelty of this work primarily involves the synthetic chemistry of polymerization and detailed analysis and efficacy of active PAS delivery. A new kinetic model has been developed to explain the PAS release profiles. These polymers are biodegradable, cytocompatible and anti-mycobacterial in nature. (C) 2015 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
- Published
- 2016
216. Sodium para-aminosalicylate protected cultured basal ganglia astrocytes from manganese-induced DNA damages and alteration of amino acid neurotransmitter levels
- Author
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Shiyan Ou, Yu-Huan Mo, Yi-Ni Luo, Yong Li, Xiang-Fa Deng, Zong-Xiang Yuan, Shao-Jun Li, Jing-Wen Chen, Yueming Jiang, and Chao-Yan Ou
- Subjects
0301 basic medicine ,medicine.medical_specialty ,Glutamine ,Sodium ,Glycine ,Glutamic Acid ,chemistry.chemical_element ,Biology ,Protective Agents ,Toxicology ,Basal Ganglia ,Rats, Sprague-Dawley ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Chlorides ,Internal medicine ,Basal ganglia ,medicine ,Manganism ,Animals ,Cells, Cultured ,chemistry.chemical_classification ,Dose-Response Relationship, Drug ,Manganese Poisoning ,Neurotoxicity ,medicine.disease ,Aminosalicylic Acid ,Amino acid ,Dose–response relationship ,030104 developmental biology ,Endocrinology ,medicine.anatomical_structure ,Animals, Newborn ,Manganese Compounds ,chemistry ,Biochemistry ,Cytoprotection ,Astrocytes ,Amino acid neurotransmitter ,030217 neurology & neurosurgery ,DNA Damage ,Astrocyte - Abstract
Sodium para-aminosalicylate (PAS-Na) was first applied successfully in clinical treatment of two manganism patients with good prognosis. However, the mechanism of how PAS-Na protects against Mn-induced neurotoxicity is still elusive. The current study was conducted to explore the effects of PAS-Na on Mn-induced basal ganglia astrocyte injury, and the involvement of amino acid neurotransmitter in vitro. Basal ganglia astrocytes were exposed to 500 μM manganese chloride (MnCl2) for 24 hr, following by 50, 150, or 450 μM PAS-Na treatment for another 24 hr. MnCl2 significantly decreased viability of astrocytes and induced DNA damages via increasing the percentage of tail DNA and Olive tail moment of DNA. Moreover, Mn interrupted amino acid neurotransmitters by decreasing Gln levels and increasing Glu, Gly levels. In contrast, PAS-Na treatment reversed the aforementioned Mn-induced toxic effects on basal ganglia astrocytes. Taken together, our results demonstrated that excessive Mn exposure may induce toxic effects on basal ganglia astrocytes, while PAS-Na could protect basal ganglia astrocytes from Mn-induced neurotoxicity.
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- 2016
217. A Novel Para-Amino Salicylic Acid Magnesium Layered Hydroxide Nanocomposite Anti-Tuberculosis Drug Delivery System with Enhanced in vitro Therapeutic and Anti-Inflammatory Properties.
- Author
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Saifullah B, Arulselvan P, El Zowalaty ME, Tan WS, Fakurazi S, Webster TJ, Baby R, and Hussein MZ
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- Anti-Inflammatory Agents pharmacology, Antitubercular Agents, Humans, Hydroxides, Magnesium, Magnesium Hydroxide, Aminosalicylic Acid, Nanocomposites
- Abstract
Introduction: Mycobacterium tuberculosis infections are associated with severe local inflammatory reactions, which may be life-threatening and lead to tuberculosis pathogenesis and associated complications. Inorganic nanolayers have been vastly exploited for biomedical applications (especially in drug delivery) because of their biocompatible and biodegradable nature with the ability to release a drug in a sustained manner. Herein, we report a new nanodelivery system of inorganic nanolayers based on magnesium layered hydroxides (MgLH) and a successfully intercalated anti-tuberculosis drug para-aminosalicylic acid (PAS)., Methods: The designed anti-tuberculosis nanodelivery composite, MgLH-PAS, was prepared by a novel co-precipitation method using MgNO
3 as well MgO as starting materials., Results: The designed nano-formulation, PAS-MgLH, showed good antimycobacterial and antimicrobial activities with significant synergistic anti-inflammatory effects on the suppression of lipopolysaccharide (LPS) stimulated inflammatory mediators in RAW 264.7 macrophages. The designed nano-formulation was also found to be biocompatible with human normal lung cells (MRC-5) and 3T3 fibroblast cells. Furthermore, the in vitro release of PAS from PAS-MgLH was found to be sustained in human body simulated phosphate buffer saline (PBS) solutions of pH 7.4 and pH 4.8., Discussion: The results of the present study are highly encouraging for further in vivo studies. This new nanodelivery system, MgLH, can be exploited in the delivery of other drugs and in numerous other biomedical applications as well., Competing Interests: The authors report no conflicts of interest for this work., (© 2021 Saifullah et al.)- Published
- 2021
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218. Modulation of base hydroxylation by bile acids and salicylates in a model of human colonic mucosal DNA: putative implications in colonic cancer.
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Allgayer, H., Kolb, M., Stuber, V., and Kruis, W.
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COLON tumor prevention ,DNA metabolism ,ANIMAL experimentation ,CATTLE ,COMPARATIVE studies ,DNA ,GAS chromatography ,GASTROINTESTINAL agents ,HYDROXYLATION ,INTESTINAL mucosa ,MASS spectrometry ,RESEARCH methodology ,MEDICAL cooperation ,NONSTEROIDAL anti-inflammatory agents ,NUCLEAR magnetic resonance spectroscopy ,RESEARCH ,SALICYLATES ,THYMUS ,EVALUATION research ,PHARMACODYNAMICS - Abstract
Bile acids are believed to be involved in the formation of colonic cancer, and 5-aminosalicylic acid and other salicylates may have a protective role. The precise mechanisms of both actions are not known, but modifications (stimulation or inhibition) of basal or oxygen-radical induced DNA base hydroxylation as potential early events in tumor formation by these compounds may be involved in such actions. We, therefore, investigated whether: (1) bile acids in concentrations as they occur systemically or intraluminally are able to enhance basal or OH*-radical-stimulated base hydroxylation in DNA from calf thymus; (2) 5-aminosalicylic acid, its main intestinal metabolite N-acetyl-aminosalicylic acid and salicylate, the main aspirin metabolite, are able to inhibit this hydroxylation; and (3) DNA from calf thymus can be used as a model by comparing its base composition and hydroxylation with DNA from normal human colonic mucosa. We found an enhancement of the OH*-radical-induced DNA hydroxylation especially 8-OH adenine with 214.0%. On the other hand 5-ASA, N-acetyl-ASA, and salicylate showed a concentration-dependent inhibition of OH*-stimulated hydroxylation with IC50 between 0.04 +/- 0.01 mM (X +/- SD) and 1.3 +/- 0.1 mM. No effects were observed on basal hydroxylation. Electron spin resonance spectroscopy studies showed reduction of the corresponding base signals pointing to a scavenger mechanism. In DNA isolated from normal human colonic mucosa (N = 7) a similar base distribution was found as in calf thymus; hydroxylation was < or = 1.0% in both systems. From our results we conclude that DNA from calf thymus may serve as a model for human colonic mucosal DNA and that one of the carcinogenic actions of bile acids may be enhancement of oxygen-radical-induced DNA base hydroxylation, especially 8-OH adenine. The absence of effects under unstimulated conditions supports their role as cocarcinogens. The concentration-dependent inhibition of OH*-stimulated DNA hydroxylation by 5-ASA, salicylate, and N-acetyl-ASA may be a possible mechanism of chemoprevention. [ABSTRACT FROM AUTHOR]
- Published
- 1999
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219. Cocrystalline Solids of Telaprevir with Enhanced Oral Absorption
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Yuegang Zhang, Steve Johnston, Patricia Hurter, Bhisetti Govinda Rao, Michael Hurrey, Stavropoulos Kathy, Elizabeth M. Topp, and Irina Nikolaevna Kadiyala
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Male ,Models, Molecular ,Chemistry, Pharmaceutical ,Molecular Conformation ,Biological Availability ,Pharmaceutical Science ,Calorimetry ,Absorption (skin) ,Viral Nonstructural Proteins ,Antiviral Agents ,Cocrystal ,Telaprevir ,Rats, Sprague-Dawley ,medicine ,Animals ,Organic chemistry ,Desiccation ,Solubility ,Calorimetry, Differential Scanning ,Chemistry ,Aminosalicylic Acid ,Combinatorial chemistry ,Nanocrystalline material ,Rats ,Amorphous solid ,Bioavailability ,Crystallization ,Oligopeptides ,Powder Diffraction ,medicine.drug - Abstract
A combination of coformer screening and modeling, followed by characterization using calorimetry, structure elucidation, and solubility led to the identification of novel crystalline forms of the hepatitis C protease inhibitor, telaprevir. The lead crystalline form, a cocrystalline solid of telaprevir with 4-aminosalycilic acid, was identified among the list of possible cocrystals via modeling and confirmed by initial screening. It displayed the most significant aqueous solubility improvement over the neat crystalline form. Enhancement of in vivo performance was further demonstrated: a 10-fold increase in bioavailability was achieved for the cocrystal in comparison to the neat nanocrystalline telaprevir and it was found to be not statistically different from the lead amorphous spray-dried formulation.
- Published
- 2015
220. The protective effect of Lactobacillus versus 5-aminosalicylic acid in ulcerative colitis model by modulation of gut microbiota and Nrf2/Ho-1 pathway
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Mohamed Mohamed Adel El-Sokkary, Ahmed Shata, Ahmed M. El-Baz, and Ahmed E. Khodir
- Subjects
Male ,0301 basic medicine ,medicine.medical_specialty ,Aminosalicylic acid ,NF-E2-Related Factor 2 ,Inflammation ,Gut flora ,Protective Agents ,medicine.disease_cause ,030226 pharmacology & pharmacy ,Gastroenterology ,Antioxidants ,General Biochemistry, Genetics and Molecular Biology ,Rats, Sprague-Dawley ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Internal medicine ,Lactobacillus ,Escherichia coli ,medicine ,Animals ,Humans ,General Pharmacology, Toxicology and Pharmaceutics ,Colitis ,Mesalamine ,biology ,Tumor Necrosis Factor-alpha ,business.industry ,General Medicine ,Fusobacterium ,biology.organism_classification ,medicine.disease ,Ulcerative colitis ,Gastrointestinal Microbiome ,Rats ,Oxidative Stress ,030104 developmental biology ,chemistry ,Colitis, Ulcerative ,medicine.symptom ,business ,Heme Oxygenase-1 ,Oxidative stress - Abstract
Aims Ulcerative colitis (UC) has many complications, from colonic damage to colorectal cancer. The mystery of both etiology and effective treatment of UC still challenging process. The role of gut microbiota in UC is still unclear. In the current study we compare the difference in gut microbiota abundance in both UC and normal colon besides the therapeutic effect of Lactobacillus spp. in treating UC versus the standard drug. Materials and methods The experimental panel included five group of rats; normal control, UC diseased rats, sterilizing rats, ASA treated and Lactobacillus treated. The change in the microbiota abundance was investigated using conventional and real time PCR. In parallel, clinical evaluation of UC and macroscopic examination scoring was also done. Colonic oxidants/antioxidant stress biomarkers; MDA, GSH, catalase, myeloperoxidase activity, and SOD activity were assessed. Colon Nrf2, HO-1 contents and TNF-α was evaluated. Key findings The current study revealed a significant difference in the relative abundance of microbiota where, UC is associated with massive increase of E. coli and Fusobacterium spp., while enormous decrease in Bifidobacteria spp. in contrast with negative control. Both 5-ASA and Lactobacillus show a significant amelioration of all antioxidant enzymes and marked decline of inflammatory and oxidative stress markers. Both Lactobacillus and 5-ASA show significant increase of NrF2 and HO-1 and marked decrease of TNF-α. Significance Lactobacillus spp. exerted a beneficial effect on the inflammation, oxidative stress and the symbiosis of gut microbiota that improve structural intestinal defect and promote healing in UC.
- Published
- 2020
221. Chitosan-5-aminosalicylic acid conjugates for colon-specific drug delivery: Methods of preparation and in vitro evaluations
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Chitchamai Ovatlarnporn and Sirinporn Nalinbenjapun
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Aminosalicylic acid ,Chromatography ,Pharmaceutical Science ,Hydrochloric acid ,02 engineering and technology ,Sulfapyridine ,021001 nanoscience & nanotechnology ,030226 pharmacology & pharmacy ,digestive system diseases ,Chitosan ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,chemistry ,Sulfasalazine ,Drug delivery ,medicine ,0210 nano-technology ,Drug carrier ,Salicylic acid ,medicine.drug - Abstract
Increasing the efficiency and specificity of drug delivery to the colon is recognized as advantageous for improving the treatment of inflammatory bowel diseases. Novel colon-specific delivery systems for 5-aminosalicylic acid (5-ASA) were developed by conjugating the active to chitosan as a drug carrier via a 4-aminobenzoyl spacer. Chitosan-5-ASA azoconjugates were synthesized from N-(4-aminobenzoyl)-chitosan by diazotization reaction with salicylic acid producing a 55–66% yield. FT-IR and UV–visible spectroscopy confirmed that the chitosan-5ASA azoconjugates were stable and did not release 5-ASA in simulated gastric fluid (SGF, hydrochloric acid pH 1.2), simulated intestinal fluid (SIF, phosphate buffer pH 6.8) and simulated colon fluid (SCF, phosphate buffer pH 7.4) for 24 h at 37 °C. The release of 5-ASA from the chitosan-5-ASA azoconjugates in SGF, SIF and SCF containing rat gastrointestinal contents was determined using HPLC and compared with 5-ASA release from sulfasalazine which employs sulfapyridine as the azoreductable carrier. Sulfasalazine released approximately 70% of the 5-ASA load in simulated colonic fluid containing rat colon content in 24 h, whereas the chitosan-5-ASA azoconjugates released around 25% of the drug load over the same time period. Although the colon targeting potential of chitosan-5-ASA azoconjugates has been demonstrated, improving the drug delivery efficiency suggests a requirement for formulation of the chitosan-5-ASA azoconjugate as nanoparticles to increase the specific surface area and azo bond exposure to bacterial enzymes.
- Published
- 2020
222. 5‐Aminosalicylic Acid Treatment Affects the Rate of Caloric Intake in Fattening Ground Squirrels
- Author
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Rachel Bradley, Nathan Witman, Courtney C. Kurtz, Emily Roberts, Ivanna Kovalenko, and Khrystyne N. Duddleston
- Subjects
chemistry.chemical_compound ,Animal science ,Aminosalicylic acid ,Chemistry ,Genetics ,Molecular Biology ,Biochemistry ,Caloric intake ,Biotechnology - Published
- 2020
223. P671 Natural history and clinical outcomes of patients with ulcerative colitis who are intolerant to 5-aminosalicylic acid agents: A multi-centre cohort study
- Author
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K Araki, Y Izumi, A Hirayama, Y Nakamori, A Fuji, T Yamaguchi, R Suzuki, Hiroto Kinoshita, S Shonai, Akira Madarame, Y Nishikawa, M Tatsuno, Hideaki Kimura, Aya Ikeda, T Ogashiwa, Katsuki Yaguchi, Reiko Kunisaki, and Y Ishii
- Subjects
medicine.medical_specialty ,Aminosalicylic acid ,business.industry ,medicine.medical_treatment ,Gastroenterology ,General Medicine ,medicine.disease ,Ulcerative colitis ,Inflammatory bowel disease ,Vedolizumab ,Natural history ,chemistry.chemical_compound ,chemistry ,Internal medicine ,medicine ,business ,Survival rate ,medicine.drug ,Colectomy ,Cohort study - Abstract
Background Five-aminosalicylic acid (5-ASA) compounds are used as the primary treatment for ulcerative colitis (UC); however, some patients are intolerant to this drug. There have been few studies on the natural history and clinical outcomes of 5-ASA intolerant patients. The aim of this study was to elucidate the clinical outcomes of 5-ASA intolerant patients in terms of colectomy, immunomodulator use, and biologic (anti-tumour necrosis factor (TNF) and Vedolizumab) therapy. Methods Data were obtained by a retrospective review of the charts of 2065 consecutive patients with UC who were treated with 5-ASA compounds at our tertiary referral inflammatory bowel disease (IBD) centre and a related IBD clinic from 2010 to 2020. Patients were considered to be intolerant to 5-ASA if they discontinued the drug because of any type of adverse effect. The cumulative rates of immunomodulator-, biologic- and colectomy-free survival rates in 5-ASA tolerant and intolerant patients were calculated using the Kaplan–Meier method. Additionally, Cox regression was used to analyse other factors besides 5-ASA intolerance contributing to clinical outcomes. Results Intolerance to 5-ASA was identified in 268 patients. The cumulative probability of colectomy within 10 years in 5-ASA intolerant patients was 23%, which is significantly higher than that in tolerant patients, 10% (log-rank test < 0.0001). Within 10 year, 63% of 5-ASA intolerant and 20% of tolerant patients received immunomodulators (log-rank test < 0.0001); and 37% of 5-ASA intolerant and 11% of tolerant patients received biologic therapy (log-rank test < 0.0001). Cox regression multivariate analysis identified that younger age, disease extent and 5-ASA intolerance were predictors of colectomy. Conclusion In this retrospective cohort study, 5-ASA intolerant patients had worse clinical outcomes than those who tolerated 5-ASA treatment. This is the first report on the long-term prognosis of 5-ASA intolerant patients.
- Published
- 2020
224. Controlled trial of 4-ASA in ulcerative colitis.
- Author
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Beeken, W., Howard, D., Bigelow, J., Trainer, T., Roy, M., Thayer, W., and Wild, G.
- Subjects
ANTITUBERCULAR agents ,BIOPSY ,CLINICAL trials ,COMPARATIVE studies ,FECES ,RESEARCH methodology ,MEDICAL cooperation ,RECTUM ,RESEARCH ,ULCERATIVE colitis ,EVALUATION research ,RANDOMIZED controlled trials - Abstract
A six-week placebo-controlled trial of the efficacy and safety of 6 g per day of 4-aminosalicylic acid (4-ASA) was conducted in 30 subjects with mild to moderately severe ulcerative colitis. Subjects were stratified into groups having distal (< 60 cm) or more extensive (> 60 cm) disease. Diarrhea, bleeding, sigmoidoscopic and biopsy appearance, and physician global assessment were scored to judge efficacy. Safety was evaluated by monitoring untoward symptoms and laboratory values. Median percent improvement was significantly greater (P < 0.05) in the 4-ASA > 60-cm group (42.7%) than in the placebo > 60-cm group (21.2%), but 4-ASA was not better than placebo for the < 60-cm group or the total study group. Severe dyspepsia (one subject), abnormal AST (transient in five, persistent in one) and elevated lipase without pancreatitis (six subjects) were noted. Thus 6 g 4-ASA for six weeks was more effective than placebo in mild to moderate ulcerative colitis extending more than 60 cm above the anus, but not in distal disease, and the drug was generally well tolerated. [ABSTRACT FROM AUTHOR]
- Published
- 1997
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225. Role of neutrophil-derived oxidants in the pathogenesis of intestinal inflammation.
- Author
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Yamada, T. and Grisham, M.
- Abstract
There is a growing body of experimental data to suggest that the chronically inflamed intestine and/or colon may be subjected to considerable oxidative stress. The most probable sources of these oxidants are the phagocytic leukocytes since these cells are known to be present in large numbers in the inflamed mucosa and are known to produce significant amounts of reactive oxygen species in response to certain inflammatory stimuli. Because the colonic mucosa contains relatively small amounts of antioxidant enzymes (e.g. SOD, catalase, GSH peroxidase) it is possible that the gut mucosa may be overwhelmed during times of active inflammation which could result in intestinal injury. If reactive oxygen species play an important role in mediating mucosal injury in IBD then it should be possible to attenuate this injury by the use of antioxidants. One such drug is the sulfasalazine metabolite 5-ASA. It may not be coincidence that this potent antiinflammatory metabolite is a potent antioxidant that possesses multiple mechanisms of action including nitrogen, carbon and oxygen-centered free radical scavenging properties as well as the ability to decompose HOCl and scavenge hemoprotein-associated oxidants. In addition 5-ASA has the additional property of being able to chelate iron and render it poorly redox active. The reason that 5-ASA is so effective in vivo may be due to this multitude of antioxidant properties. This would also suggest that other, more potent antioxidants may prove beneficial in the treatment of IBD. [ABSTRACT FROM AUTHOR]
- Published
- 1991
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226. Factors associated with low adherence to oral 5-aminosalicylic acid in patients with ulcerative colitis
- Author
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Jin Lee, Sam Ryong Jee, Hyung Wook Kim, Dong Hoon Baek, Geun Am Song, Won Moon, Seun Ja Park, Hyun Jin Kim, Jong Hoon Lee, Jong Ha Park, Tae Oh Kim, and Busan Ulsan Gyeongnam Intestinal Study Group Society (BIGS)
- Subjects
Male ,Questionnaires ,Cross-sectional study ,Administration, Oral ,Social Sciences ,chemistry.chemical_compound ,Habits ,0302 clinical medicine ,Medicine and Health Sciences ,Smoking Habits ,Psychology ,Ethnicities ,030212 general & internal medicine ,Mesalamine ,education.field_of_study ,Multidisciplinary ,Alcohol Consumption ,Pharmaceutics ,Anti-Inflammatory Agents, Non-Steroidal ,Middle Aged ,Colitis ,Ulcerative colitis ,Research Design ,Korean People ,Medicine ,Population study ,030211 gastroenterology & hepatology ,Female ,Research Article ,Adult ,medicine.medical_specialty ,Aminosalicylic acid ,Patients ,Science ,Population ,Gastroenterology and Hepatology ,Research and Analysis Methods ,Medication Adherence ,03 medical and health sciences ,Pharmacotherapy ,Drug Therapy ,Internal medicine ,medicine ,Humans ,Ulcerative Colitis ,education ,Nutrition ,Behavior ,Survey Research ,business.industry ,Inflammatory Bowel Disease ,Biology and Life Sciences ,Odds ratio ,medicine.disease ,Confidence interval ,Diet ,Health Care ,Cross-Sectional Studies ,chemistry ,People and Places ,Colitis, Ulcerative ,Population Groupings ,business - Abstract
Background/Aims It is well known that 5-aminosalicylic acid (5-ASA) is the standard first-line treatment for ulcerative colitis (UC). Medication adherence is an important factor in the treatment of UC. We aimed to identify predictors of low adherence to oral 5-ASA in Koreans with UC. Methods Between July 2017 and January 2018, we performed a multicenter, cross-sectional study across 6 University Hospitals in Korea. Medication adherence was assessed using the modified Morisky Medication Adherence Scale (MMAS-8) questionnaire. Our study included 264 patients with UC. Patients were requested to complete the self-reported MMAS-8 questionnaire and a survey assessing sociodemographic data. Adherence was categorized as low (scores
- Published
- 2018
227. Improving the anti-inflammatory activity of 5-aminosalicylic acid by combination with cyanidin-3-glucoside: An in vitro study
- Author
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Leonor M. Almeida, Sónia R. Pereira, and Teresa C.P. Dinis
- Subjects
0301 basic medicine ,Aminosalicylic acid ,medicine.drug_class ,p38 mitogen-activated protein kinases ,Medicine (miscellaneous) ,Pharmacology ,Synergistic interaction ,Anti-inflammatory ,Anti-inflammatory activity ,03 medical and health sciences ,chemistry.chemical_compound ,Ingredient ,0404 agricultural biotechnology ,medicine ,TX341-641 ,Cyanidin-3-glucoside ,030109 nutrition & dietetics ,Nutrition and Dietetics ,AP-1 activation ,Nutrition. Foods and food supply ,Biological activity ,5-aminosalicylic acid ,04 agricultural and veterinary sciences ,040401 food science ,In vitro ,chemistry ,Anthocyanin ,Phosphorylation ,Food Science - Abstract
This study investigated the anti-inflammatory action of cyanidin-3-glucoside (Cy3glc), an anthocyanin widely spread in diet, in comparison and in association with 5-aminosalicylic acid (5-ASA), an anti-inflammatory reference drug for ulcerative colitis. The efficacy, action mechanism and interaction between Cy3glc and 5-ASA were assessed in vitro, in an LPS-activated macrophage cell line. Our data showed a higher effectiveness of Cy3glc in counteracting inflammatory mediators as compared to 5-ASA at the same concentration. In addition, the mixture afforded a better protection than Cy3glc and a much better than 5-ASA, showing a synergistic effect in terms of reducing NO and ROS cellular production. Although neither Cy3glc nor the mixture counteracted LPS-induced NF-κB activation, the mixture strongly inhibited AP-1 translocation to the nucleus and prevented p38 MAPK and JNK phosphorylation suggesting that, the co-administration of a biologically active food ingredient and a medicine could be a potential strategy to increase the medicine therapeutic effect.
- Published
- 2019
228. High-dimensional single-cell proteomics analysis identifies immune checkpoint signatures and therapeutic targets in ulcerative colitis
- Author
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David A. Schubert, Sebastian Fuchs, Nicolas Staedler, Andreas P. Frei, Nadia Sawas, Annalisa D’Andrea, Luca Piali, Robert Zeiser, and Petr Hruz
- Subjects
0301 basic medicine ,Adult ,Male ,Proteomics ,Immunology ,Cell ,Inflammation ,Biology ,medicine.disease_cause ,Antibodies, Monoclonal, Humanized ,Autoimmunity ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,TIGIT ,Gastrointestinal Agents ,T-Lymphocyte Subsets ,medicine ,Immunology and Allergy ,Humans ,Mass cytometry ,Receptors, Immunologic ,Aged ,Autoimmune disease ,Aged, 80 and over ,Middle Aged ,medicine.disease ,Aminosalicylic Acid ,Immune checkpoint ,Infliximab ,Killer Cells, Natural ,030104 developmental biology ,medicine.anatomical_structure ,Colitis, Ulcerative ,Female ,medicine.symptom ,Single-Cell Analysis ,Immunosuppressive Agents ,030215 immunology - Abstract
Immune checkpoints are regulators of immune cells and play key roles in the modulation of immune responses. The role of checkpoints in autoimmune disease is poorly understood but likely to be central since checkpoint inhibition during cancer treatment can cause autoimmunity. We generated a high-dimensional single-cell proteomics data set from PBMCs of healthy individuals and patients with ulcerative colitis (UC) by mass cytometry, enabling systems-wide analyses of immune cell frequencies and cell type-specific expression patterns of 12 immune checkpoints. Subtle but significant changes in immune cell frequencies and checkpoint expression were observed between UC patients on different treatment regimens and between patients and healthy controls. Most strikingly, UC patients showed a reduced number of peripheral NK-cells and those cells showed an altered phenotype including increased TIGIT expression. Based on these results, we modulated NK-cell function ex vivo through targeting of TIGIT pathway members. In summary, we describe a pattern of changes in immune cell abundance and checkpoint expression as a basis for UC patient stratification and we show modulation of a corresponding immune cell subset through checkpoint targeting. Our approach can be used for the identification of pathogenic immune cell subsets and guide target selection in autoimmunity and chronic inflammation.
- Published
- 2018
229. Efficacy and safety of bifid triple viable plus aminosalicylic acid for the treatment of ulcerative colitis
- Author
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Qing-qun Cai, Kun-hai Zhuang, Xinlin Chen, Hui-biao Li, Hong-mei Tang, Mu-yuan Chen, and Zhen-wen Qiu
- Subjects
medicine.medical_specialty ,Aminosalicylic acid ,Cochrane Library ,law.invention ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Randomized controlled trial ,law ,Internal medicine ,medicine ,Humans ,030212 general & internal medicine ,Adverse effect ,Randomized Controlled Trials as Topic ,ulcerative colitis ,medicine.diagnostic_test ,business.industry ,Probiotics ,General Medicine ,Aminosalicylic Acid ,Combined Modality Therapy ,meta-analysis ,Clinical trial ,Treatment Outcome ,chemistry ,030220 oncology & carcinogenesis ,Meta-analysis ,Relative risk ,Erythrocyte sedimentation rate ,bifid triple viable ,Colitis, Ulcerative ,business ,Systematic Review and Meta-Analysis ,Research Article - Abstract
Objective: Ulcerative colitis (UC), one of the most stubborn diseases, is mainly treated by aminosalicylic acid (ASA). However, the side effects of ASA include vomiting, nausea, rash, diarrhea, headache, etc, which seriously affect life-quality of UC patients. Probiotics such as bifid triple viable (BTV) could reduce drug-induced adverse reactions and has a good clinical effect on UC. Therefore, we aimed to evaluate the clinical efficacy and safety of BTV plus ASA in treating UC. Methods: PubMed, Cochrane Library, Embase, Chinese Biomedical Literature Database, Chinese Scientific Journal Database, Chinese National Knowledge Infrastructure, and Wanfang databases were searched from the inception dates to October 12, 2018. Randomized controlled trials (RCTs) were included by comparing BTV plus ASA programs with ASA alone in patients with UC. Methodological quality was assessed by 2 independent researchers according to the inclusion criteria and exclusion criteria. Meta-analysis was performed by using the Review Manager 5.3 Software. Risk ratios (RRs), 95% confidence interval (CI), and standardized mean difference were calculated. Results: Sixty RCTs involving 4954 participants were selected for final review. Compared with ASA, BTV plus ASA significantly improved the clinical effect rate [RR = 1.23, 95% CI (1.20, 1.26), P < .00001]; reduced the relapse rate [RR = 0.34, 95% CI (0.18, 0.62), P = .0005]; and adverse effect rate [RR = 0.66, 95% CI (0.53, 0.82), P = .0002]. Compared with the controls, levels of tumor necrosis factor-α, interleukin-6 (IL-6), IL-8, C-reactive protein (CRP), hypersensitive CRP, erythrocyte sedimentation rate, and malondialdehyde were reduced; levels of IL-10, CD3+, CD4+, and superoxide dismutase were increased in BTV plus ASA group. Conclusions: BTV plus ASA has positive therapeutic effects on UC, and it might be a safe way to treat UC. However, comprehensive clinical trials are needed to obtain high level of clinical evidence.
- Published
- 2019
230. No Benefit of Concomitant 5-Aminosalicylates in Patients with Ulcerative Colitis Escalated to Biologic Therapy: Pooled Analysis of Individual Participant Data from Clinical Trials
- Author
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Brian G. Feagan, Vipul Jairath, Mathurin Fumery, Siddharth Singh, Ronghui Xu, James A. Proudfoot, William J. Sandborn, and Parambir S. Dulai
- Subjects
medicine.medical_specialty ,Clinical Trials and Supportive Activities ,Clinical Sciences ,Ulcerative ,Autoimmune Disease ,Antibodies ,Oral and gastrointestinal ,Article ,03 medical and health sciences ,0302 clinical medicine ,Pharmacotherapy ,Maintenance therapy ,Drug Therapy ,Prednisone ,Clinical Research ,Internal medicine ,Monoclonal ,medicine ,Humans ,Randomized Controlled Trials as Topic ,Hepatology ,Gastroenterology & Hepatology ,business.industry ,Tumor Necrosis Factor-alpha ,Inflammatory Bowel Disease ,Gastroenterology ,Antibodies, Monoclonal ,Evaluation of treatments and therapeutic interventions ,medicine.disease ,Colitis ,Ulcerative colitis ,Aminosalicylic Acid ,Infliximab ,Golimumab ,Clinical trial ,Biological Therapy ,Treatment Outcome ,030220 oncology & carcinogenesis ,Concomitant ,6.1 Pharmaceuticals ,Combination ,Colitis, Ulcerative ,Drug Therapy, Combination ,030211 gastroenterology & hepatology ,business ,Digestive Diseases ,medicine.drug - Abstract
Objectives5-aminosalicylates (5-ASA) are frequently continued in patients with moderate-severe ulcerative colitis (UC), even after escalation to biologic agents, without evaluation of the benefit of this approach. We conducted an individual participant data (IPD) pooled analysis of trials of infliximab and golimumab in UC, to evaluate whether concomitant use of 5-ASA modifies clinical outcomes among anti-tumor necrosis factor (TNF)-α-treated patients.MethodsWe included IPD from five trials of infliximab and golimumab in patients with moderate-severe UC (ACT-1 and -2, PURSUIT-SC, PURSUIT-M, NCT00336492). Patients treated with infliximab or golimumab were categorized as receiving concomitant 5-ASA or not at time of trial entry. Primary outcome was clinical remission (Mayo Clinic Score
- Published
- 2018
231. 5-Aminosalicylic Acid Alters the Gut Bacterial Microbiota in Patients With Ulcerative Colitis
- Author
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Jun Xu, Ning Chen, Zhe Wu, Yang Song, Yifan Zhang, Na Wu, Feng Zhang, Xinhua Ren, and Yulan Liu
- Subjects
0301 basic medicine ,Microbiology (medical) ,Validation study ,medicine.medical_specialty ,Aminosalicylic acid ,Firmicutes ,lcsh:QR1-502 ,Microbial dysbiosis ,Microbiology ,Gastroenterology ,lcsh:Microbiology ,03 medical and health sciences ,chemistry.chemical_compound ,Internal medicine ,mucosal microbiota ,Medicine ,In patient ,Original Research ,ulcerative colitis ,bacterial dysbiosis ,biology ,business.industry ,bacterial correlation ,5-aminosalicylic acid ,medicine.disease ,biology.organism_classification ,Ulcerative colitis ,030104 developmental biology ,chemistry ,Enterococcus ,Proteobacteria ,business - Abstract
Background: The aim of this study was to clarify the effect of 5-aminosalicylic acid (5-ASA) treatment on gut bacterial microbiota in patients with ulcerative colitis (UC). Methods: A total of 57 UC patients, including 20 untreated and 37 5-ASA-treated, were recruited into an exploration cohort. We endoscopically collected both non-inflamed and inflamed mucosal samples from all patients, and compared the gut bacterial profiles using 16S rDNA sequencing. Ten untreated UC patients were then treated with 5-ASA and subsequently recruited for an independent validation study to confirm the acquired data. Results: In untreated UC patients, compared with those in non-inflamed mucosae, Firmicutes (such as Enterococcus) were decreased and Proteobacteria (e.g., Escherichia–Shigella) were increased in the inflamed mucosae. Compared with the inflamed mucosae of untreated UC patients, there was a higher abundance of Firmicutes (e.g., Enterococcus) and lower Proteobacteria (Escherichia–Shigella) in the inflamed mucosae of 5-ASA treated UC patients. In the validation cohort, after administration of 5-ASA, bacterial alteration was consistent with these data. Furthermore, there was a skewed negative correlation between Escherichia–Shigella and bacterial genera of Firmicutes in the inflamed mucosae. 5-ASA treatment decreased the strength of bacterial correlation and weakened the skewed negative correlation pattern. Conclusion: The microbial dysbiosis (mainly characterized by an increased abundance in the Escherichia–Shigella genus) and the skewed negative correlation between Escherichia–Shigella and bacterial genera of Firmicutes are two characteristics of the inflamed mucosae of UC patients. 5-ASA treatment decreases Escherichia–Shigella and weakens the skewed correlations, which may be related to its treatment efficiency.
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- 2018
232. Controversies in Inflammatory Bowel Disease: Exploring Clinical Dilemmas Using Cochrane Reviews
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John K MacDonald, Claire E Parker, Joana Torres, Brian G. Feagan, Nilesh Chande, Ray Boyapati, and James E. East
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medicine.medical_specialty ,Colorectal cancer ,Colonoscopy ,Administration, Oral ,Disease ,Inflammatory bowel disease ,Aminosalicylate ,03 medical and health sciences ,Drug withdrawal ,0302 clinical medicine ,Crohn Disease ,Internal medicine ,medicine ,Immunology and Allergy ,Humans ,030212 general & internal medicine ,Crohn's disease ,medicine.diagnostic_test ,business.industry ,Gastroenterology ,medicine.disease ,Prognosis ,Ulcerative colitis ,Aminosalicylic Acid ,digestive system diseases ,Withholding Treatment ,Colonic Neoplasms ,030211 gastroenterology & hepatology ,Colitis, Ulcerative ,business - Abstract
A symposium organized by the Cochrane IBD Group and presented at the 2017 Digestive Disease Week annual meeting reviewed the recent literature on several controversial topics in inflammatory bowel disease (IBD) management including the efficacy of oral aminosalicylates for induction and maintenance of Crohn's disease (CD), the feasibility of drug withdrawal in patients with quiescent CD, and strategies for detecting colon cancer in patients with IBD. This article summarizes the data presented at that session.
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- 2018
233. Efficacy and safety of Kangfuxin liquid combined with aminosalicylic acid for the treatment of ulcerative colitis
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Li, Hui-biao, Chen, Mu-yuan, Qiu, Zhen-wen, Cai, Qing-qun, Li, De-tang, Tang, Hong-mei, and Chen, Xin-lin
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Remission Induction ,Antitubercular Agents ,Aminosalicylic Acid ,Kangfuxin liquid ,meta-analysis ,Treatment Outcome ,Materia Medica ,ComputingMethodologies_DOCUMENTANDTEXTPROCESSING ,Cytokines ,Humans ,Colitis, Ulcerative ,Drug Therapy, Combination ,Systematic Review and Meta-Analysis ,Research Article ,ulcerative colitis ,Drugs, Chinese Herbal - Abstract
Supplemental Digital Content is available in the text, Background: To systematically evaluate the clinical efficacy and safety of Kangfuxin liquid (KFXL) combined with aminosalicylic acid (ASA) in treating ulcerative colitis (UC). Methods: The PubMed, Cochrane Library, Embase, CBM, Wan fang, the Chinese Scientific Journal Database (VIP), and Chinese National Knowledge Infrastructure (CNKI) databases were systematically searched for randomized controlled trials of KFXL combined with ASA for UC from the inception dates to March 3, 2017. Two researchers independently screened the literature, extracted data, and evaluated the methodological quality according to the inclusion criteria. The meta-analysis was performed using Review Manager software (RevMan, Version 5.3, Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, 2014), and the risk of bias was assessed using the Cochrane Collaboration Tool. Results: A total of 39 randomized controlled trials (RCTs) involving 3204 patients fulfilled the inclusion criteria. Compared with ASA alone, KFXL combined with ASA significantly improved the clinical effectiveness rate [RR = 1.19, 95% CI: (1.16, 1.23), P
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- 2018
234. CLA-supplemented diet accelerates experimental colorectal cancer by inducing TGF-β-producing macrophages and T cells
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T G, Moreira, L S, Horta, A C, Gomes-Santos, R P, Oliveira, N M G P, Queiroz, D, Mangani, B, Daniel, A T, Vieira, S, Liu, A M, Rodrigues, D A, Gomes, G, Gabriely, E, Ferreira, H L, Weiner, R M, Rezende, L, Nagy, and A M C, Faria
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Mice, Knockout ,Carcinogenesis ,Macrophages ,T-Lymphocytes ,Dextran Sulfate ,Colitis ,Inflammatory Bowel Diseases ,Aminosalicylic Acid ,Mice, Inbred C57BL ,PPAR gamma ,Disease Models, Animal ,Mice ,Transforming Growth Factor beta ,Dietary Supplements ,Animals ,Humans ,Female ,Linoleic Acids, Conjugated ,Colorectal Neoplasms ,Cells, Cultured - Abstract
Conjugated linoleic acid (CLA) has been shown to activate the nuclear receptor PPAR-γ and modulate metabolic and immune functions. Despite the worldwide use of CLA dietary supplementation, strong scientific evidence for its proposed beneficial actions are missing. We found that CLA-supplemented diet reduced mucosal damage and inflammatory infiltrate in the dextran sodium sulfate (DSS)-induced colitis model. Conditional deletion of PPAR-γ in macrophages from mice supplemented with CLA diet resulted in loss of this protective effect of CLA, suggesting a PPAR-γ-dependent mechanism mediated by macrophages. However, CLA supplementation significantly worsened colorectal tumor formation induced by azoxymethane and DSS by inducing macrophage and T-cell-producing TGF-β via PPAR-γ activation. Accordingly, either macrophage-specific deletion of PPAR-γ or in vivo neutralization of latency-associated peptide (LAP, a membrane-bound TGF-β)-expressing cells abrogated the protumorigenic effect of CLA. Thus, the anti-inflammatory properties of CLA are associated with prevention of colitis but also with development of colorectal cancer.
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- 2018
235. Treatment Adherence in Patients with Ulcerative Colitis Is Dependent on the Formulation of 5-Aminosalicylic Acid
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Yasutaka Hijikata, Masahide Ebi, Yasuhiro Tamura, Tomoya Sugiyama, Makoto Sasaki, Shoko Nakagawa, Shinya Izawa, Yasushi Funaki, Noriko Okaniwa, Kunio Kasugai, Yoshiharu Yamaguchi, Naotaka Ogasawara, and Mari Mizuno
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Adult ,Male ,medicine.medical_specialty ,Aminosalicylic acid ,Adolescent ,Treatment adherence ,Drug Compounding ,Administration, Oral ,Drug formulations ,Medication Adherence ,03 medical and health sciences ,chemistry.chemical_compound ,Young Adult ,0302 clinical medicine ,Internal medicine ,Clinical endpoint ,Medicine ,Humans ,In patient ,Prospective Studies ,Prospective cohort study ,Mesalamine ,business.industry ,Anti-Inflammatory Agents, Non-Steroidal ,Gastroenterology ,Middle Aged ,medicine.disease ,Ulcerative colitis ,Regimen ,chemistry ,030220 oncology & carcinogenesis ,Delayed-Action Preparations ,030211 gastroenterology & hepatology ,Colitis, Ulcerative ,Female ,Self Report ,business ,Tablets - Abstract
Background/Aims: It is unclear whether 5-aminosalicylic acid (5-ASA) formulation is associated with treatment adherence in ulcerative colitis (UC). Thus, we aimed to investigate the adherence rate after switching from 5-ASA tablets to granules. Methods: This prospective study included 121 UC outpatients treated using 5-ASA tablets. They were grouped based on choice: Group 1 (continued with tablets) and Group 2 (switched to granules without regimen change). Group 2 was further divided into Group 3 (returned to tablets) and Group 4 (continued with granules). The patients completed a self-administered questionnaire regarding the treatment. The primary endpoint was change in adherence after switching to granules. Results: Seventy-nine patients continued with tablets, while 42 patients switched to granules. The adherence rate to the tablet was not significantly different between Group 1 and 2 before switching. In Group 2, switching to granules did not affect adherence. However, in Group 4, adherence significantly improved after switching to granules. Group 3 showed no significant change in adherence before and after switching from tablets. Full-time work and difficulty taking tablets were significant predictors of continuing with granules in Group 4. Conclusion: Patients who continued with 5-ASA granules showed significantly increased adherence, suggesting that patient-tailored drug formulations improved treatment adherence.
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- 2018
236. Molecular Modeling of Adsorption of 5-Aminosalicylic Acid in the Halloysite Nanotube
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Claro Ignacio Sainz Diaz, Mahmoud ElSayed Awad, Ana Borrego-Sánchez, Mahmoud Awad, Junta de Andalucía, and Ministerio de Economía y Competitividad (España)
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Nanotube ,Aminosalicylic acid ,Materials science ,lcsh:QE351-399.2 ,Molecular model ,02 engineering and technology ,engineering.material ,halloysite ,5-aminosalicylic acid ,surface adsorption ,DFT calculations ,force fields ,nanotubes ,010402 general chemistry ,01 natural sciences ,Halloysite ,chemistry.chemical_compound ,Adsorption ,Surface adsorption ,Conformational isomerism ,lcsh:Mineralogy ,Nanotubes ,Geology ,Force fields ,021001 nanoscience & nanotechnology ,Geotechnical Engineering and Engineering Geology ,0104 chemical sciences ,chemistry ,Chemical engineering ,Drug delivery ,engineering ,Density functional theory ,0210 nano-technology - Abstract
Halloysite nanotubes are becoming interesting materials for drug delivery. The knowledge of surface interactions is important for optimizing this application. The aim of this work is to perform a computational study of the interaction between 5-aminosalicylic acid (5-ASA) drug and halloysite nanotubes for the development of modified drug delivery systems. The optimization of this nanotube and the adsorption of different conformers of the 5-ASA drug on the internal surface of halloysite in the presence and absence of water were performed using quantum mechanical calculations by using Density Functional Theory (DFT) and methods based on atomistic force fields for molecular modeling, respectively., This work is funded by the Andalusian Government projects (RNM1897) and the MINECO project FIS2016-77692-C2-2P. It also supported by the Egyptian Cultural Affairs and Missions Sector (Plan 2013-2014), Ministry of Higher Education.
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- 2018
237. Chronic use of statins and aminosalicylic acid and incidence of post-ERCP acute pancreatitis. Preliminary data from the STARK study, a prospective international, multicenter, cohort study
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Alberto Mariani, Marianne Udd, Paolo Giorgio Arcidiacono, Giuseppe Vanella, Davor Štimac, Goran Hauser, Goran Poropat, Juan Antonio Casellas, Karina Cárdenas Jaén, Livia Archibugi, Taija Korpela, Gabriele Capurso, José Ramón Aparicio, Leena Kylänpää, Emilio Di Giulio, and Enrique de-Madaria
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medicine.medical_specialty ,Aminosalicylic acid ,Hepatology ,business.industry ,Endocrinology, Diabetes and Metabolism ,Incidence (epidemiology) ,Post-ERCP acute pancreatitis ,Gastroenterology ,ERCP ,Digestive Endoscopy ,Acute Pancreatitis ,Chemioprevention ,Biliopancreatic diseases ,chemistry.chemical_compound ,chemistry ,Internal medicine ,medicine ,business ,Cohort study - Published
- 2018
238. Sodium P-aminosalicylic Acid Inhibits Manganese-Induced Neuroinflammation in BV2 Microglial Cells via NLRP3-CASP1 Inflammasome Pathway.
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Fang Y, Peng D, Liang Y, Lu L, Li J, Zhao L, Ou S, Li S, Aschner M, and Jiang Y
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- Inflammasomes, Manganese toxicity, Microglia, NLR Family, Pyrin Domain-Containing 3 Protein, Sodium, Aminosalicylic Acid, Pharmaceutical Preparations
- Abstract
Background: Sodium p-aminosalicylic acid (PAS-Na) was reported to exhibit anti-inflammatory effect in the nervous system. However, the mechanism by which PAS-Na exhibits anti-inflammatory effects on manganese (Mn)-stimulated BV2 microglia cells remains unclear. Thus, this study investigated the role of PAS-Na in Mn-stimulated BV2 microglial cells., Methods: Microglia-like BV2 were treated with MnCl
2 with or without the non-steroidal anti-inflammatory drug PAS-Na for 12 or 24 h to examine cell viability using MTT; for 24 or 48 h to examine levels of NLRP3, CASP1, IL-1β, and IL-18 mRNA using Real-Time quantitative PCR; for 48 h to examine levels of NLRP3 and CASP1 inflammasomes, measured by western blot analysis; and for 48 h to examine levels of inflammatory cytokines, measured by enzyme-linked immunosorbent assay., Results: The MTT assay showed that PAS-Na produced significant neuroprotective effect by preventing Mn-induced inflammation in BV2 microglial cells. PAS-Na significantly concentration and time dependently inhibited Mn-induced production of NLRP3, CASP1, IL-1β, and IL-18., Conclusion: Taken together, our results suggest that PAS-Na exerts anti-inflammatory effects in Mn-stimulated BV2 microglial cells via downregulation of NLRP3, CASP1, IL-1β, and I L-18. Furthermore, a high concentration and prolonged PAS-Na treatment appear necessary for its therapeutic efficacy. Taken together, we conclude that PAS-Na affords therapeutic efficacy in mitigating neurological conditions associated with neuroinflammation.- Published
- 2021
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239. Dextran-5-(4-ethoxycarbonylphenylazo)salicylic acid ester, a polymeric colon-specific prodrug releasing 5-aminosalicylic acid and benzocaine, ameliorates TNBS-induced rat colitis
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Sun-Young Lee, Joon Nam, Seongkeun Jeong, Jin-Wook Yoo, Wooseong Kim, Min-Soo Kim, and Yunjin Jung
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Male ,Aminosalicylic acid ,Colon ,Polymers ,Benzocaine ,Administration, Oral ,Pharmaceutical Science ,02 engineering and technology ,Pharmacology ,030226 pharmacology & pharmacy ,Rats, Sprague-Dawley ,03 medical and health sciences ,chemistry.chemical_compound ,Cecum ,0302 clinical medicine ,Oral administration ,hemic and lymphatic diseases ,medicine ,Animals ,Prodrugs ,Large intestine ,Colitis ,Mesalamine ,Dextrans ,Prodrug ,021001 nanoscience & nanotechnology ,medicine.disease ,digestive system diseases ,Rats ,medicine.anatomical_structure ,Trinitrobenzenesulfonic Acid ,chemistry ,Inflammation Mediators ,0210 nano-technology ,Salicylic acid ,medicine.drug - Abstract
Local anesthetics have beneficial effects on colitis. Dextran-5-(4-ethoxycarbonylphenylazo)salicylic acid ester (Dex-5-ESA), designed as a polymeric colon-specific prodrug liberating 5-ASA and benzocaine in the large intestine, was prepared and its therapeutic activity against colitis was evaluated using a TNBS-induced rat colitis model. Dex-5-ESA liberated 5-ASA and benzocaine in the cecal contents while (bio)chemically stable in the small intestinal contents and mucosa. Oral administration of Dex-5-ESA (equivalent to 10 mg 5-ASA/kg, twice a day) alleviated colonic injury and reduced MPO activity in the inflamed colon. In parallel, pro-inflammatory mediators, COX-2, iNOS and CINC-3, elevated by TNBS-induced colitis, were substantially diminished in the inflamed colon. Dex-5-ESA was much more effective for the treatment of colitis than 5-(4-ethoxycarbonylphenylazo)salicylic acid (5-ESA) that may not deliver benzocaine to the large intestine. Our data suggest that Dex-5-ESA is a polymeric colon-specific prodrug, liberating 5-ASA and benzocaine in the target site (large intestine), probably exerting anti-colitic effects by combined action of 5-ASA and benzocaine.
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- 2015
240. Mycobacterium tuberculosis Folate Metabolism and the Mechanistic Basis for para -Aminosalicylic Acid Susceptibility and Resistance
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Shannon Lynn Kordus, Joshua M. Thiede, Yusuke Minato, Edward J. McKlveen, Anthony D. Baughn, and Breanna J. Turman
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Drug ,Tuberculosis ,Aminosalicylic acid ,Folate Metabolism ,media_common.quotation_subject ,Antitubercular Agents ,Microbial Sensitivity Tests ,Pharmacology ,Mycobacterium tuberculosis ,chemistry.chemical_compound ,Folic Acid ,Tuberculosis, Multidrug-Resistant ,medicine ,Pharmacology (medical) ,media_common ,biology ,business.industry ,Prodrug ,medicine.disease ,biology.organism_classification ,Antimicrobial ,Aminosalicylic Acid ,Multiple drug resistance ,Infectious Diseases ,chemistry ,Minireview ,business - Abstract
para -Aminosalicylic acid (PAS) entered clinical use in 1946 as the second exclusive drug for the treatment of tuberculosis (TB). While PAS was initially a first-line TB drug, the introduction of more potent antitubercular agents relegated PAS to the second-line tier of agents used for the treatment of drug-resistant Mycobacterium tuberculosis infections. Despite the long history of PAS usage, an understanding of the molecular and biochemical mechanisms governing the susceptibility and resistance of M. tuberculosis to this drug has lagged behind that of most other TB drugs. Herein, we discuss previous studies that demonstrate PAS-mediated disruption of iron acquisition, as well as recent genetic, biochemical, and metabolomic studies that have revealed that PAS is a prodrug that ultimately corrupts one-carbon metabolism through inhibition of the formation of reduced folate species. We also discuss findings from laboratory and clinical isolates that link alterations in folate metabolism to PAS resistance. These advancements in our understanding of the basis of the susceptibility and resistance of M. tuberculosis to PAS will enable the development of novel strategies to revitalize this and other antimicrobial agents for use in the global effort to eradicate TB.
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- 2015
241. Synthesis, bioactivity evaluation, and docking study of 5-aminosalicylic acid’s fatty acid derivatives
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Intan Safinar Ismail, Elnaz Saki, Emilia Abdulmalek, Mohd Basyaruddin Abdul Rahman, Sze Wei Leong, Samira Yousefi, and Saadi Bayat
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Aminosalicylic acid ,biology ,Linoleic acid ,General Chemistry ,medicine.disease_cause ,biology.organism_classification ,Lauric acid ,chemistry.chemical_compound ,Oleic acid ,chemistry ,Biochemistry ,Docking (molecular) ,medicine ,Antibacterial activity ,Escherichia coli ,Bacteria - Abstract
Some new oleic acid, linoleic acid, lauric acid derivatives of 5-aminosalicylic acid were produced in order to enhance bioactivity properties of 5-aminosalicylic acid. All new compounds’ structures were confirmed by spectroscopic methods. Moreover, in vitro antibacterial, anticancer, and anti-inflammatory activities of new synthesized compounds were investigated. Antibacterial activity was studied against pathogenic Gram-negative bacteria, Escherichia coli and Gram-positive bacteria, Staphylococcus aureus via disc diffusion method. Additionally, all derivatives’ anti-inflammatory activity were evaluated through NO suppression assay using interferon gamma (IFN-γ)/lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. Furthermore, in vitro cytotoxicity assay was probed using MTT test against 3T3 and HT-29 cell lines. In another effort, docking studies were performed to predict the possible interactions and binding energy of new compounds against cyclooxygenase (COX-1/COX-2) and lipoxygenase (5-LOX) proteins. In conclusion, all new compounds exhibited moderate to better bioactivity improvements in comparison with parent drug. Also study of interactions between the new derivatives with active sites of proteins presented greater binding affinities than 5-aminosalicylic acid.
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- 2015
242. Pharmacokinetics of Second-Line Antituberculosis Drugs after Multiple Administrations in Healthy Volunteers
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Kyung Sang Yu, Seol Ju Moon, Jae Ho Lee, Jongsun Park, In-Jin Jang, Kyungho Jang, Jangsoo Yoon, Jaeseong Oh, Sang In Park, Jae Yong Chung, and Junghan Song
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Adult ,Male ,Moxifloxacin ,Antitubercular Agents ,Levofloxacin ,Clinical Therapeutics ,Pharmacology ,Young Adult ,Pharmacokinetics ,Kanamycin ,medicine ,Humans ,Pharmacology (medical) ,medicine.diagnostic_test ,business.industry ,Cycloserine ,Liter ,Pyrazinamide ,Aminosalicylic Acid ,Healthy Volunteers ,Infectious Diseases ,Therapeutic drug monitoring ,Area Under Curve ,Prothionamide ,Streptomycin ,Drug Monitoring ,business ,Fluoroquinolones ,medicine.drug - Abstract
Therapeutic drug monitoring (TDM) of second-line antituberculosis drugs would allow for optimal individualized dosage adjustments and improve drug safety and therapeutic outcomes. To evaluate the pharmacokinetic (PK) characteristics of clinically relevant, multidrug treatment regimens and to improve the feasibility of TDM, we conducted an open-label, multiple-dosing study with 16 healthy subjects who were divided into two groups. Cycloserine (250 mg), p -aminosalicylic acid (PAS) (5.28 g), and prothionamide (250 mg) twice daily and pyrazinamide (1,500 mg) once daily were administered to both groups. Additionally, levofloxacin (750 mg) and streptomycin (1 g) once daily were administered to group 1 and moxifloxacin (400 mg) and kanamycin (1 g) once daily were administered to group 2. Blood samples for PK analysis were collected up to 24 h following the 5 days of drug administration. The PK parameters, including the maximum plasma concentration ( C max ) and the area under the plasma concentration-time curve during a dosing interval at steady state (AUC τ ), were evaluated. The correlations between the PK parameters and the concentrations at each time point were analyzed. The mean C max and AUC τ , respectively, for each drug were as follows: cycloserine, 24.9 mg/liter and 242.3 mg · h/liter; PAS, 65.9 mg/liter and 326.5 mg · h/liter; prothionamide, 5.3 mg/liter and 22.1 mg · h/liter; levofloxacin, 6.6 mg/liter and 64.4 mg · h/liter; moxifloxacin, 4.7 mg/liter and 54.2 mg · h/liter; streptomycin, 42.0 mg/liter and 196.7 mg · h/liter; kanamycin, 34.5 mg/liter and 153.5 mg · h/liter. The results indicated that sampling at 1, 2.5, and 6 h postdosing is needed for TDM when all seven drugs are administered concomitantly. This study indicates that PK characteristics must be considered when prescribing optimal treatments for patients. (This study has been registered at ClinicalTrials.gov under registration no. NCT02128308.)
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- 2015
243. Antibiotic Susceptibility Patterns ofMycobacterium tuberculosisIsolates from Guizhou Province of China Against 13 Antituberculosis Drugs
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Mei Liu, Ling Chen, Xiaoqin Liao, Nana Li, Hong Zhang, and Jianhua Wang
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Microbiology (medical) ,China ,Tuberculosis ,Capreomycin ,Extensively Drug-Resistant Tuberculosis ,Immunology ,Antitubercular Agents ,Microbial Sensitivity Tests ,Microbiology ,Mycobacterium tuberculosis ,Levofloxacin ,Moxifloxacin ,Drug Resistance, Multiple, Bacterial ,medicine ,Humans ,Tuberculosis, Pulmonary ,Pharmacology ,biology ,business.industry ,Incidence ,medicine.disease ,biology.organism_classification ,Aminosalicylic Acid ,Gatifloxacin ,Aminoglycosides ,Amikacin ,Prothionamide ,business ,Fluoroquinolones ,medicine.drug - Abstract
A total of 92 Mycobacterium tuberculosis isolates were collected from patients with pulmonary tuberculosis (TB) in the Zunyi region between 2011 and 2012. Collected isolates were used to determine antibiotic susceptibility patterns against 13 anti-TB drugs: 4 first-line and 9 second-line (ciprofloxacin, gatifloxacin, levofloxacin, moxifloxacin, para-aminosalicylic acid, amikacin, capreomycin, kanamycin, and prothionamide) drugs. Results showed that among 57 new cases of TB only 66.7% were susceptible to all four first-line anti-TB drugs and 64.9% were susceptible to fluoroquinolones and second-line injectables; 10.5% of new and 22.9% of previously treated cases were multidrug-resistant TB (MDR-TB); and 1.8% of new and 2.9% of previously treated cases were extensively drug-resistant TB (XDR-TB). In addition, 14.3% of MDR-TB cases (2 out of 14) were XDR-TB, which is higher than the average numbers in China (about 8%) and in the world (9.6%). This study confirms that primary transmission of drug-resistant TB, including MDR/XDR-TB, is a real threat to achieving effective control of drug-resistant TB in the Guizhou Province and indicates the necessity to determine antibiotic susceptibility patterns in patients with TB to improve treatment outcomes.
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- 2015
244. Release of 5-Aminosalicylic Acid (5-ASA) from Mesalamine Formulations at Various pH Levels
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Srini Tenjarla and Adeyinka Abinusawa
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Drug ,Aminosalicylic acid ,Chemistry, Pharmaceutical ,media_common.quotation_subject ,Pharmacology toxicology ,5-Aminosalicylic acid ,Administration, Oral ,Absorption (skin) ,Pharmacology ,chemistry.chemical_compound ,Intestinal mucosa ,medicine ,Humans ,Pharmacology (medical) ,Intestinal Mucosa ,Colitis ,Mesalamine ,Original Research ,media_common ,Medicine(all) ,business.industry ,Anti-Inflammatory Agents, Non-Steroidal ,Gastroenterology ,General Medicine ,Hydrogen-Ion Concentration ,medicine.disease ,Ulcerative colitis ,digestive system diseases ,chemistry ,Colitis, Ulcerative ,business ,Dissolution - Abstract
Introduction Oral formulations of 5-aminosalicylic acid (5-ASA) for treatment of ulcerative colitis have been developed to minimize absorption prior to the drug reaching the colon. In this study, we investigate the release of 5-ASA from available oral mesalamine formulations in physiologically relevant pH conditions. Methods Release of 5-ASA from 6 mesalamine formulations (APRISO®, Salix Pharmaceuticals, Inc., USA; ASACOL® MR, Procter & Gamble Pharmaceuticals UK Ltd.; ASACOL® HD, Procter & Gamble Pharmaceuticals, USA; MEZAVANT XL®, Shire US Inc.; PENTASA®, Ferring Pharmaceuticals, Ltd., UK; SALOFALK®, Dr. Falk Pharma UK Ltd.) was evaluated using United States Pharmacopeia apparatus I and II at pH values of 1.0 (2 h), 6.0 (1 h), and 6.8 (8 h). Dissolution profiles were determined for each formulation, respectively. Results Of the tested formulations, only the PENTASA formulation demonstrated release of 5-ASA at pH 1.0 (48%), with 56% cumulative release after exposure to pH 6.0 and 92% 5-ASA release after 6–8 h at pH 6.8. No other mesalamine formulation showed >1% drug release at pH 1.0. The APRISO formulation revealed 36% 5-ASA release at pH 6.0, with 100% release after 3 h at pH 6.8. The SALOFALK formulation revealed 11% 5-ASA release at pH 6.0, with 100% release after 1 h at pH 6.8. No 5-ASA was released by the ASACOL MR, ASACOL HD, and MEZAVANT XL formulations at pH 6.0. At pH 6.8, the ASACOL MR and ASACOL HD formulations exhibited complete release of 5-ASA after 4 and 2 h, respectively, and the MEZAVANT XL formulation demonstrated complete 5-ASA release over 6–7 h. Conclusion 5-Aminosalicylic acid release profiles were variable among various commercially available formulations. Funding Shire Development LLC. Electronic supplementary material The online version of this article (doi:10.1007/s12325-015-0206-4) contains supplementary material, which is available to authorized users.
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- 2015
245. Allopurinol and 5-aminosalicylic acid influence thiopurine-induced hepatotoxicity in vitro
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Geert J. A. Wanten, Mark M. T. J. Broekman, Dennis R Wong, Wilbert H.M. Peters, Frank Hoentjen, Alex Leijten, Mariska Kerstholt, Hennie M.J. Roelofs, and Dirk J. de Jong
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6-Mercaptopurine ,HepG2 ,Aminosalicylic acid ,Antimetabolites ,Allopurinol ,Cytotoxicity ,Health, Toxicology and Mutagenesis ,lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4] ,5-Aminosalicylic acid ,Other Research Radboud Institute for Molecular Life Sciences [Radboudumc 0] ,Azathioprine ,Pharmacology ,Toxicology ,Article ,chemistry.chemical_compound ,Cell Line, Tumor ,medicine ,Humans ,Mesalamine ,Thioguanine ,IC50 ,Thiopurines ,Thiopurine methyltransferase ,biology ,Mercaptopurine ,Chemistry ,Anti-Inflammatory Agents, Non-Steroidal ,Cell Biology ,Huh7 ,Apoptosis ,Toxicity ,Hepatocytes ,biology.protein ,HepaRG ,Inflammatory diseases Radboud Institute for Molecular Life Sciences [Radboudumc 5] ,medicine.drug - Abstract
Contains fulltext : 153788.pdf (Publisher’s version ) (Open Access) 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-1 (WST-1) cytotoxicity assays were used to calculate cell survival curves and half maximal inhibitory concentrations (IC50). Combination experiments with thiopurines with a fixed dose of 200 muM 5-ASA or 100 muM allopurinol were conducted in HepaRG cells. Caspase-3/7 activation was evaluated, and single cell electrophoresis analysis was performed. RESULTS: A time- and dose-related cytotoxic effect was seen with azathioprine (AZA) in all hepatoma cells, whereas Huh7 and HepG2 cells did not show toxicity to 6-mercaptopurine (6-MP). HepaRG cells expressed the highest levels of drug metabolising enzymes, and therefore, combination experiments were conducted in HepaRG cells. Addition of a non-toxic dose of allopurinol resulted in a twofold to threefold increased cytotoxicity of all thiopurines, which seemed to be mediated by apoptosis/DNA damage. CONCLUSION: The addition of allopurinol to thiopurines leads to a two-threefold increased cytotoxicity in HepaRG cells.
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- 2015
246. 5-Aminosalicylic acid, a specific drug for ulcerative colitis
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Tom C. Martinsen, Øyvind Hauso, and Helge L. Waldum
- Subjects
Drug ,medicine.medical_specialty ,Aminosalicylic acid ,Colon ,media_common.quotation_subject ,Inflammation ,Gastroenterology ,chemistry.chemical_compound ,Internal medicine ,medicine ,Animals ,Humans ,Mesalamine ,media_common ,business.industry ,Anti-Inflammatory Agents, Non-Steroidal ,Remission Induction ,Inflammatory Bowel Diseases ,medicine.disease ,Ulcerative colitis ,Sulfasalazine ,chemistry ,Etiology ,Colitis, Ulcerative ,medicine.symptom ,business - Abstract
The etiology of the inflammatory bowel diseases is unknown, although genetic factors play a role, and tobacco smoking has opposite effect on the two entities. Inflammation is central in the pathogenesis, and treatment is aiming to suppress it. The active part of salazopyrin, the oldest drug in use in the treatment of ulcerative colitis, is 5-aminosalicylic acid (5-ASA). In the present paper, we wanted to discuss the etiology and pathogenesis of ulcerative colitis in relation to the beneficial effects of 5-ASA and particularly whether this compound has a specific effect on ulcerative colitis.5-ASA seems to have a selective positive effect on ulcerative colitis in inducing remission, preventing relapse and possibly reducing the risk of cancer. In contrast to other agents used in the treatment of ulcerative colitis, 5-ASA does not have any known anti-inflammatory effect on other organs or other colonic inflammatory diseases like diverticulitis. Moreover, the effect on experimental colitis in rodents is not convincing.5-ASA seems to have a specific effect on the inflammation in ulcerative colitis. Research on the mechanism of its action may give information on the etiology of ulcerative colitis. 5-ASA is a first-line treatment that should be given once daily in high doses and for long term to reduce the possibility of recurrence and risk of colonic cancer. Side effects with 5-ASA are rare, and every patient with ulcerative colitis who tolerate this drug, should be treated with 5-ASA.
- Published
- 2015
247. 5-Aminosalicylic Acid attenuates allergen-induced airway inflammation and oxidative stress in asthma
- Author
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Srinivas T. Naga, Saurabh Gupta, Jaya K. Shankar, M.N. Sathish Kumar, Shashank Tummala, Shashank Mulukutla, V.J. Vishnuvarthan, Vishakantha Murthy, Nilesh Sudhakar Ambhore, Afzal Azam, Subba Rao V. Madhunapanthula, K. Rama Satyanarayana Raju, and K. Elango
- Subjects
Male ,Pulmonary and Respiratory Medicine ,Aminosalicylic acid ,Ovalbumin ,medicine.disease_cause ,Pathogenesis ,chemistry.chemical_compound ,Allergen ,In vivo ,Malondialdehyde ,medicine ,Animals ,Pharmacology (medical) ,Mesalamine ,Lung ,Nitrites ,Peroxidase ,Asthma ,Inflammation ,Mice, Inbred BALB C ,Interleukin-13 ,Nitrates ,biology ,Interleukin-6 ,Tumor Necrosis Factor-alpha ,Chemistry ,Anti-Inflammatory Agents, Non-Steroidal ,Biochemistry (medical) ,medicine.disease ,Oxidative Stress ,Immunology ,biology.protein ,Tumor necrosis factor alpha ,Bronchoalveolar Lavage Fluid ,Oxidative stress - Abstract
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.
- Published
- 2014
248. Roles of P-glycoprotein and multidrug resistance protein in transporting para-aminosalicylic acid and its N-acetylated metabolite in mice brain
- Author
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Su Zeng, Min Huang, Wei Zheng, Hui-chang Bi, Stefanie L. O’Neal, Lan Hong, and Cong Xu
- Subjects
Male ,ATP Binding Cassette Transporter, Subfamily B ,Aminosalicylic acid ,Metabolite ,ATP-binding cassette transporter ,Transfection ,Blood–brain barrier ,Madin Darby Canine Kidney Cells ,Capillary Permeability ,chemistry.chemical_compound ,Dogs ,Membrane Transport Modulators ,medicine ,Animals ,Tissue Distribution ,Pharmacology (medical) ,ATP Binding Cassette Transporter, Subfamily B, Member 1 ,Biotransformation ,P-glycoprotein ,Mice, Knockout ,Pharmacology ,biology ,business.industry ,Brain ,Acetylation ,General Medicine ,Aminosalicylic Acid ,Multiple drug resistance ,Aminosalicylic Acids ,medicine.anatomical_structure ,chemistry ,Biochemistry ,Blood-Brain Barrier ,Injections, Intravenous ,biology.protein ,Original Article ,Multidrug Resistance-Associated Proteins ,business - Abstract
Para-aminosalicylic acid (PAS) is effective in the treatment of manganism-induced neurotoxicity (manganism). In this study we investigated the roles of P-glycoprotein (MDR1a) and multidrug resistance protein (MRP) in transporting PAS and its N-acetylated metabolite AcPAS through blood-brain barrier.MDR1a-null or wild-type mice were intravenously injected with PAS (200 mg/kg). Thirty minutes after the injection, blood samples and brains were collected, and the concentrations of PAS and AcPAS in brain capillaries and parenchyma were measured using HPLC. Both MDCK-MDR1 and MDCK-MRP1 cells that overexpressed P-gp and MRP1, respectively, were used in two-chamber Transwell transport studies in vitro.After injection of PAS, the brain concentration of PAS was substantially higher in MDR1a-null mice than in wild-type mice, but the brain concentration of AcPAS had no significant difference between MDR1a-null mice and wild-type mice. Concomitant injection of PAS with the MRP-specific inhibitor MK-571 (50 mg/kg) further increased the brain concentration of PAS in MDR1a-null mice, and increased the brain concentration of AcPAS in both MDR1a-null mice and wild-type mice. Two-chamber Transwell studies with MDCK-MDR1 cells demonstrated that PAS was not only a substrate but also a competitive inhibitor of P-gp, while AcPAS was not a substrate of P-gp. Two-chamber Transwell studies with the MDCK-MRP1 cells showed that MRP1 had the ability to transport both PAS and AcPAS across the BBB.P-gp plays a major role in the efflux of PAS from brain parenchyma into blood in mice, while MRP1 is involved in both PAS and AcPAS transport in the brain.
- Published
- 2014
249. On the Colonic Bacterial Metabolism of Azo-Bonded Prodrugsof 5-Aminosalicylic Acid
- Author
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Vanessa Zann, Abdul Basit, Vipul Yadav, Anders Borde, Tiago Sousa, and Bertil Abrahamsson
- Subjects
Olsalazine ,Aminosalicylic acid ,Bacteria ,Colon ,business.industry ,Pharmaceutical Science ,Balsalazide ,Prodrug ,Pharmacology ,medicine.disease ,Inflammatory bowel disease ,Ulcerative colitis ,chemistry.chemical_compound ,Mesalazine ,chemistry ,Sulfasalazine ,medicine ,Humans ,Prodrugs ,Mesalamine ,business ,Azo Compounds ,Chromatography, High Pressure Liquid ,medicine.drug - Abstract
Azo-bonded prodrugs of 5-aminosalicylic acid (mesalazine)-sulfasalazine, balsalazide, and olsalazine, which are used in the treatment of ulcerative colitis, rely on colonic bacteria to cleave the azo bond and liberate the active drug in the large intestine. The aim of this study was to use an in vitro colonic simulator to determine the rates of metabolism of these three prodrugs in the presence of colonic bacteria, and to link the data to results obtained previously in humans. In individual fecal slurries prepared from five different donors, sulfasalazine degradation was rapid and virtually complete within 4 h, confirming the ubiquitous nature of azo-reduction between individuals. In pooled fecal slurry, the rate of degradation of sulfasalazine was faster (t1/2 , 32.8 min) than balsalazide (t1/2 , 80.9 min) and olsalazine (t1/2 , 145.1 min). These results are in agreement with data in humans, where it was found that sulfasalazine was more extensively metabolized on passage through the human colon than the other two drugs. These findings indicate that other than the azo bond itself, the broader chemical structure of the molecules play a role in the degradation of this class of compound, and highlight the utility of this in vitro model to evaluate the metabolism of drugs in the presence of colonic microbiota.
- Published
- 2014
250. Deletion of sigB Causes Increased Sensitivity to para-Aminosalicylic Acid and Sulfamethoxazole in Mycobacterium tuberculosis
- Author
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Shiyun Chen, Wang Xude, Yangbo Hu, Jiao-Yu Deng, Jing Gu, Xian-En Zhang, Yang Shanshan, Kun Li, Tianyu Zhang, and Y.X. Gao
- Subjects
0301 basic medicine ,Aminosalicylic acid ,Sulfamethoxazole ,030106 microbiology ,Antitubercular Agents ,Lyases ,Sigma Factor ,Microbial Sensitivity Tests ,Microbiology ,Mycobacterium tuberculosis ,03 medical and health sciences ,chemistry.chemical_compound ,Folic Acid ,Downregulation and upregulation ,Bacterial Proteins ,Sigma factor ,Gene expression ,4-Aminobenzoic acid ,Pharmacology (medical) ,Gene ,Pharmacology ,biology ,biochemical phenomena, metabolism, and nutrition ,biology.organism_classification ,Aminosalicylic Acid ,030104 developmental biology ,Infectious Diseases ,chemistry ,Susceptibility ,bacteria ,4-Aminobenzoic Acid ,Bacteria ,Gene Deletion - Abstract
Although the de novo folate biosynthesis pathway has been well studied in bacteria, little is known about its regulation. In the present study, the sigB gene in Mycobacterium tuberculosis was deleted. Subsequent drug susceptibility tests revealed that the M. tuberculosis Δ sigB strain was more sensitive to para -aminosalicylic acid (PAS) and sulfamethoxazole. Comparative transcriptional analysis was performed, and downregulation of pabB was observed in the Δ sigB strain, which was further verified by a quantitative reverse transcription-PCR and Western blot assay. Then, the production levels of para -aminobenzoic acid ( p ABA) were compared between the sigB deletion mutant and wild-type strain, and the results showed that sigB deletion resulted in decreased production of p ABA. In addition, SigB was able to recognize the promoter of pabB in vitro . Furthermore, we found that deleting pabC also caused increased susceptibility to PAS. Taken together, our data revealed that, in M. tuberculosis , sigB affects susceptibility to antifolates through multiple ways, primarily by regulating the expression of pabB . To our knowledge, this is the first report showing that SigB modulates p ABA biosynthesis and thus affecting susceptibility to antifolates, which broadens our understanding of the regulation of bacterial folate metabolism and mechanisms of susceptibility to antifolates.
- Published
- 2017
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