Rheumatoid arthritis(RA) is a chronic degenerative joint disease characterized by inflammation. Due to the complex causes, no specific therapy is available. Non-steroidal anti-inflammatory agents and corticosteroids are often used(long-term, oral/injection) to interfere with related pathways for reducing inflammatory response and delaying the progression of RA, which, however, induce many side effects. Microneedle, an emerging transdermal drug delivery system, is painless and less invasive and improves drug permeability. Thus, it is widely used in the treatment of RA and is expected to be a new strategy in clinical treatment. This paper summarized the application of microneedles in the treatment of RA, providing a reference for the development of new microneedles and the expansion of its clinical application.
Humans ; Drug Delivery Systems ; Administration, Cutaneous ; Pharmaceutical Preparations ; Anti-Inflammatory Agents, Non-Steroidal/therapeutic use* ; Arthritis, Rheumatoid/drug therapy* ; Needles

OBJECTIVE: To investigate the effectiveness of preemptive analgesia with loxoprofen sodium orally, which was a kind of non-steroid anti-inflammatory drugs, in extractions of mandibular impacted third teeth. METHODS: There were questionnaires about postoperative pain for patients whose mandibular impacted third teeth were extracted from July 2017 to August 2017 in First Clinical Division of Peking University School and Hospital of Stomatology. All the patients did their routine clinical examinations and imaging examinations. After their mandibular impacted third teeth were extracted, the questionnaires were sent to them. The questionnaires were filled in by the patients on their own and returned one week later. There were 120 questionnaires that were sent and 105 questionnaires returned, of which 98 questionnaires were filled in completely. According to the inclusive criteria and exclusion criteria, 66 questionnaires were totally selected in this study. According to the time when the patients took their loxoprofen sodium orally firstly, the patients were divided into 3 groups. The first group was for patients who didn't take loxoprofen sodium during their extractions (non-medicine group). The second group was for patients who took 60 mg loxoprofen sodium 30 min before their extractions (preoperative group). The third group was for patients who took 60 mg loxoprofen sodium 30 min after their extractions (postoperative group). The operation time among the 3 groups was analyzed by Kruskal-Wallis method. The postoperative time points were 2, 4, 12,24 and 48 h after operation. The scores of visual analogue scales (VAS) for postoperative pain in each group at different postoperative time points were analyzed by Friedman method. At each postoperative time point, VAS scores in the different groups were analyzed by Kruskal-Wallis me-thod. The numbers of the patients taking loxoprofen sodium home and drug adverse reactions were also analyzed. RESULTS: The operation time of the 3 groups was 15.0 (5.0,30.0) min and had no significant differences (P=0.848).VAS scores of non-medicine group 2,4, 12,24 and 48 h after operation were 1.75 (0.1,10.0), 6.25 (1.5,10.0), 2.00 (0.1,8.0), 2.00 (0.1,6.0) and 0.5 (0.1,5.5) separately and had significant differences (P<0.001).The VAS score at 4 h after operation was higher than the VAS scores at other time points after operation (P<0.005). Four hours after the operations, the VAS scores of preoperative group [2.0 (0.1,10.0)] and postoperative group [2.0 (0.1,5.0)] were lower significantly than those of non-medicine group [6.25 (1.5,10.0)] (P<0.001).The numbers of the patients taking loxoprofen sodium home were 9(40.9%) in non-medicine group,5(21.8%) in preoperative group and 7(33.3%) in postoperative group. The number of the patients who had drug adverse reactions in preoperative group (n=3,13.0%) and in postoperative group (n=4,19.0%) was less than the number of the patients who had drug adverse reactions in non-medicine group (n=8,36.4%). CONCLUSION There were two protocols of preemptive analgesia with loxoprofen sodium orally in extractions of mandibular impacted third teeth, which were taking 60 mg loxoprofen sodium orally 30 min before the extractions and taking 60 mg loxoprofen sodium orally 30 min after the extractions. Both of the two preemptive analgesia protocols could decrease the postoperative pain significantly.
Analgesia ; Anti-Inflammatory Agents, Non-Steroidal/administration & dosage* ; Humans ; Pain, Postoperative/prevention & control* ; Phenylpropionates/administration & dosage* ; Tooth Extraction/adverse effects* ; Tooth, Impacted

OBJECTIVETo observe effects and mechanism of Dinggui gel paste analgesic anti-inflammatory.

METHODSEighty-four male KM mice weighted from 18 to 22 g and aged 4 to 5 weeks were randomly divided into 7 groups, named blank group, model group, matrix control group, Votalin group, high dosage of Dinggui gel paste group with group, equivalent dosage of Dinggui gel paste group, Dinggui gel paste group, 12 mice in each group. Except blank and model group, the other groups were paste ointment for 7 days, and one time a day, matrix control group were pasted isodose blank matrix gel patch. Pain threshold were tested at 30, 60, 90 and 120 min after the last ad-ministration. Hot plate test were performed by injection of 5% formalin for 20 µL on right hindfoot sole after the last administration. The cumulative time of mice licking right rear foot were observed at stage of I and II, and content of IL-1, TNF-α were tested by ELISA method. Differences of weight between right and left ears were measured by ear swelling method and anti-inflammation experiment.

RESULTSIn hot plate test at 90 min, pain threshold in equivalent dosage of Dinggui gel paste group was (24.87 ± 14.67) s and (15.28 ± 8.23) s in model group; (26.33 ± 15.45) s in high dosage of Dinggui gel paste group and (15.31 ± 5.02) s in model group at 120 min in hot plate test, there were no statistical differences between two groups. Pain period at stage I, licking cumulative time in high dosage of Dinggui gel paste group was (66.70 ± 22.83) s and (101.80 ± 33.65) s in model group,and had significant differences between two groups; there were statistical differences in licking cumulative time at stage I of pain period among high dosage of Dinggui gel paste group (51.30 ± 43.60)s, equivalent dosage of Dinggui gel paste group (64.00 ± 47.27) sand model group (109.50 ± 36.78) s. Content of IL-1 in model group was (28.70 ± 8.24) ng/L and (13.33 ± 2.20) ng/L in high dosage of Dinggui gel paste group, there was obvious meaning between two groups; There were significant differences in TNF-α content among model group (93.60 ± 23.65) ng/L,high dosage of Dinggui gel paste group (63.21 ± 10.54)ng/L and equivalent dosage of Dinggui gel paste group (72.69 ± 16.26) ng/L; while there were no statistical meaning in ear swelling degree among model group (5.73 ± 0.80) mg,high dosage of Dinggui gel paste group (5.42 ± 0.68) mg and equivalent dosage of Dinggui gel paste group (4.98 ± 1.52) mg.

CONCLUSIONDinggui gel paste could increase pain threshold, reduce licking accumulative time, and decrease ear swelling degree, and relief pain by regulating level of TNF-α and IL-1.

Analgesics ; administration & dosage ; Animals ; Anti-Inflammatory Agents, Non-Steroidal ; administration & dosage ; Dosage Forms ; Drugs, Chinese Herbal ; administration & dosage ; Humans ; Interleukin-1beta ; genetics ; immunology ; Interleukin-6 ; genetics ; immunology ; Male ; Mice ; Ointments ; Pain ; genetics ; immunology ; Pain Management ; Tumor Necrosis Factor-alpha ; genetics ; immunology

BACKGROUND/AIMS: Acute pancreatitis is a common complication of endoscopic retrograde cholangiopancreatography (ERCP). Combination therapy w ith ora l udenafil and aceclofenac may reduce the occurrence of post-ERCP pancreatitis by targeting different pathophysiological mechanisms. We investigated whether combining udenafil and aceclofenac reduced the rates of post-ERCP pancreatitis. METHODS: A prospective, randomized, double-blind, placebo-controlled, multicenter study was conducted in four academic medical centers. Between January 2012 and June 2013, a total of 216 patients who underwent ERCP were analyzed for the occurrence of post-ERCP pancreatitis. Patients were determined to be at high risk for pancreatitis based on validated patient and procedure-related risk factors. RESULTS: Demographic features, indications for ERCP, and therapeutic procedures were similar in each group. There were no significant differences in the rate (15.8% [17/107] vs. 16.5% [18/109], p = 0.901) and severity of post-ERCP pancreatitis between the udenafil/aceclofenac and placebo groups. One patient in each group developed severe pancreatitis. Multivariate analyses indicated that suspected dysfunction of the sphincter of Oddi and endoscopic papillary balloon dilation without sphincterotomy were associated with post-ERCP pancreatitis. CONCLUSIONS: Combination therapy with udenafil and aceclofenac is not effective for the prevention of post-ERCP pancreatitis.
Acute Disease ; Administration, Oral ; Adult ; Aged ; Aged, 80 and over ; Anti-Inflammatory Agents, Non-Steroidal/*administration & dosage/adverse effects ; Cholangiopancreatography, Endoscopic Retrograde/*adverse effects ; Diclofenac/administration & dosage/adverse effects/*analogs & derivatives ; Double-Blind Method ; Drug Therapy, Combination ; Female ; Humans ; Male ; Middle Aged ; Multivariate Analysis ; Pancreatitis/diagnosis/etiology/*prevention & control ; Phosphodiesterase 5 Inhibitors/*administration & dosage/adverse effects ; Prospective Studies ; Pyrimidines/*administration & dosage/adverse effects ; Republic of Korea ; Risk Factors ; Sulfonamides/*administration & dosage/adverse effects ; Treatment Outcome ; Young Adult

PURPOSE: To compare the additive effects of two types of non-steroidal anti-inflammatory drugs (NSAIDs), bromfenac 0.1% or ketorolac 0.45%, relative to topical steroid alone in cataract surgery. MATERIALS AND METHODS: A total 91 subjects scheduled to undergo cataract operation were randomized into three groups: Group 1, pre/postoperative bromfenac 0.1%; Group 2, pre/postoperative preservative-free ketorolac 0.45%; and Group 3, postoperative steroid only, as a control. Outcome measures included intraoperative change in pupil size, postoperative anterior chamber inflammation control, change in macular thickness and volume, and ocular surface status after operation. RESULTS: Both NSAID groups had smaller intraoperative pupil diameter changes compared to the control group (p<0.05). There was significantly less ocular inflammation 1 week and 1 month postoperatively in both NSAID groups than the control group. The changes in central foveal subfield thickness measured before the operation and at postoperative 1 month were 4.30+/-4.25, 4.87+/-6.03, and 12.47+/-12.24 microm in groups 1 to 3, respectively. In the control group, macular thickness and volume increased more in patients with diabetes mellitus (DM), compared to those without DM. In contrast, in both NSAID groups, NSAIDs significantly reduced macular changes in subgroups of patients with or without DM. Although three ocular surface parameters were worse in group 1 than in group 2, these differences were not significant. CONCLUSION: Adding preoperative and postoperative bromfenac 0.1% or ketorolac 0.45% to topical steroid can reduce intraoperative miosis, postoperative inflammation, and macular changes more effectively than postoperative steroid alone.
Aged ; Anti-Inflammatory Agents, Non-Steroidal/*administration & dosage/pharmacology ; Benzophenones/*administration & dosage/pharmacology ; Bromobenzenes/*administration & dosage/pharmacology ; *Cataract ; *Cataract Extraction ; Female ; Humans ; Inflammation/prevention & control ; Ketorolac/*administration & dosage/pharmacology ; Lens Implantation, Intraocular ; Macular Edema/*prevention & control ; Male ; Middle Aged ; Miosis/*prevention & control ; Phacoemulsification ; Postoperative Complications/drug therapy ; Postoperative Period ; Premedication ; Treatment Outcome

This study investigated the toxicity of commercial non-steroid anti-inflammatory drug (NSAID) eye solutions against corneal epithelial cells in vitro. The biologic effects of 1/100-, 1/50-, and 1/10-diluted bromfenac sodium, pranoprofen, diclofenac sodium, and the fluorometholone on corneal epithelial cells were evaluated after 1-, 4-, 12-, and 24-hr of exposure compared to corneal epithelial cell treated with balanced salt solution as control. Cellular metabolic activity, cellular damage, and morphology were assessed. Corneal epithelial cell migration was quantified by the scratch-wound assay. Compared to bromfenac and pranoprofen, the cellular metabolic activity of diclofenac and fluorometholone significantly decreased after 12-hr exposure, which was maintained for 24-hr compared to control. Especially, at 1/10-diluted eye solution for 24-hr exposure, the LDH titers of fluorometholone and diclofenac sodium markedly increased more than those of bromfenac and pranoprofen. In diclofenac sodium, the Na+ concentration was lower and amount of preservatives was higher than other NSAIDs eye solutions tested. However, the K+ and Cl- concentration, pH, and osmolarity were similar for all NSAIDs eye solutions. Bromfenac and pranoprofen significantly promoted cell migration, and restored wound gap after 48-hr exposure, compared with that of diclofenac or fluorometholone. At 1/50-diluted eye solution for 48-hr exposure, the corneal epithelial cellular morphology of diclofenac and fluorometholone induced more damage than that of bromfenac or pranoprofen. Overall, the corneal epithelial cells in bromfenac and pranoprofen NSAID eye solutions are less damaged compared to those in diclofenac, included fluorometholone as steroid eye solution.
Anti-Inflammatory Agents, Non-Steroidal/administration & dosage/*toxicity ; Benzophenones/administration & dosage/toxicity ; Benzopyrans/administration & dosage/toxicity ; Bromobenzenes/administration & dosage/toxicity ; Cell Movement/drug effects ; Cells, Cultured ; Diclofenac/administration & dosage/toxicity ; Epithelial Cells/drug effects/metabolism/ultrastructure ; Epithelium, Corneal/cytology/*drug effects/metabolism ; Fluorometholone/administration & dosage/toxicity ; Humans ; L-Lactate Dehydrogenase/metabolism ; Microscopy, Electron, Transmission ; Ophthalmic Solutions ; Propionates/administration & dosage/toxicity

BACKGROUND/AIMS: The use of proton pump inhibitors or misoprostol is known to prevent the gastrointestinal complications of nonsteroidal anti-inflammatory drugs (NSAIDs). Rebamipide is known to increase the mucosal generation of prostaglandins and to eliminate free oxygen radicals, thus enhancing the protective function of the gastric mucosa. However, it is unknown whether rebamipide plays a role in preventing NSAID-induced gastropathy. The aim of this study was to determine the effectiveness of rebamipide compared to misoprostol in preventing NSAID-induced gastrointestinal complications in patients requiring continuous NSAID treatment. METHODS: We studied 479 patients who required continuous NSAID treatment. The patients were randomly assigned to groups that received 100 mg of rebamipide three times per day or 200 microg of misoprostol three times per day for 12 weeks. The primary endpoint of the analysis was the occurrence rate of gastric ulcers, as determined by endoscopy after 12 weeks of therapy. RESULTS: Of the 479 patients in the study, 242 received rebamipide, and 237 received misoprostol. Ultimately, 44 patients (18.6%) withdrew from the misoprostol group and 25 patients (10.3%) withdrew from the rebamipide group. There was a significant difference in withdrawal rate between the two groups (p=0.0103). The per protocol analysis set was not valid because of the dropout rate of the misoprostol group; thus, the intention to treat (ITT) analysis set is the main set for the efficacy analysis in this study. After 12 weeks, the occurrence rate of gastric ulcers was similar in the rebamipide and misoprostol groups (20.3% vs 21.9%, p=0.6497) according to ITT analysis. In addition, the therapeutic failure rate was similar in the rebamipide and misoprostol groups (13.6% vs 13.1%, p=0.8580). The total severity score of the gastrointestinal symptoms was significantly lower in the rebamipide group than in the misoprostol group (p=0.0002). The amount of antacid used was significantly lower in the rebamipide group than in the misoprostol group (p=0.0258). CONCLUSIONS: Rebamipide can prevent gastric ulcers when used with NSAIDs and can decrease the gastrointestinal symptoms associated with NSAID administration. When the possibility of poor compliance and the potential adverse effects of misoprostol are considered, rebamipide appears to be a clinically effective and safe alternative.
Adult ; Aged ; Alanine/administration & dosage/adverse effects/*analogs & derivatives ; Anti-Inflammatory Agents, Non-Steroidal/*adverse effects ; Anti-Ulcer Agents/*administration & dosage/adverse effects ; Arthritis/drug therapy ; Butanones/adverse effects ; Diclofenac/adverse effects/analogs & derivatives ; Double-Blind Method ; Drug Administration Schedule ; Gastric Mucosa ; Humans ; Middle Aged ; Misoprostol/*administration & dosage/adverse effects ; Quinolones/*administration & dosage/adverse effects ; Stomach Ulcer/chemically induced/*prevention & control ; Thiazines/adverse effects ; Thiazoles/adverse effects ; Treatment Outcome

Aspirin and nonsteroidal anti-inflammatory drugs (NSAIDs) are the most widely used medications, based on their antipyretic, analgesic, and anti-inflammatory effects. However, both aspirin and NSAIDs cause hypersensitivity reactions through immunologic as well as non-immunologic mechanisms. Except for the rare single-NSAID-induced reaction, most hypersensitivity reactions show cross-reactive features to other NSAIDs regardless of their chemical structure. An accurate correct medical history is the most important diagnostic approach, whereas the roles of blood and skin tests are limited in the majority of cases of NSAIDs hypersensitivity. Although able to confirm the presence of a hypersensitivity reaction, an oral or bronchial provocation test should be performed only under the supervision of a skilled physician at a well-equipped institution. Avoidance of the causative NSAID and all cross-reactive NSAIDs is the cornerstone of management. Patients who require treatment with aspirin or NSAIDs can undergo aspirin desensitization. Genetic predisposition to hypersensitivity to NSAIDs have been demonstrated, but a clear understanding of the pathophysiologic and phenotypic diversity of these hypersensitivity reactions requires further studies, including functional ones.
Anti-Inflammatory Agents, Non-Steroidal ; Aspirin* ; Bronchial Provocation Tests ; Genetic Predisposition to Disease ; Humans ; Hypersensitivity* ; Organization and Administration ; Skin Tests

OBJECTIVETo study the effect of ethyl acetate fraction of Blumea balsamifera (BBE) residue on treating rats of adjuvant arthritis (AA) and its mechanism.

METHODThe rats were immunized with the Freund's complete adjuvant (FCA). After modeling, 28 days' treatment with BBE was performed. During the experimental process, rat mass, toe girth, arthritic index (AI), proliferation of immune organs and pathological section were measured. After treatment, blood samples were collected through fossa orbitalis vein for detection of serum SOD, MDA, GSH, NO, OH*, ALP, AST, ALT, NAG and SA content using colorimetric method and IL-1, IL-6, TNF-α content using ELISA method.

RESULTAdministration with BBE (high dose) could significantly ameliorate joint swelling and arthritis index, effectively inhibit synovial hyperplasia, down-regulate the levels of MDA, NO, OH*, ALP, AST, ALT, NAG, SA, IL-1, IL-6, TNF-α and up-regulate the SOD and GSH levels in serum.

CONCLUSIONThe results suggested BBE possesses substantial anti-arthritis and antioxidant activities.

Acetates ; Animals ; Anti-Inflammatory Agents, Non-Steroidal ; administration & dosage ; isolation & purification ; Arthritis, Experimental ; blood ; drug therapy ; metabolism ; Asteraceae ; chemistry ; Drugs, Chinese Herbal ; administration & dosage ; isolation & purification ; Humans ; Interleukin-1 ; blood ; Interleukin-6 ; blood ; Male ; Malondialdehyde ; blood ; Oxidative Stress ; drug effects ; Rats ; Rats, Sprague-Dawley ; Tumor Necrosis Factor-alpha ; blood

5-aminosalicylic acid (5-ASA) is drug of choice for the treatment of ulcerative colitis (UC). In this study, the efficacy of topical versus oral 5-ASA for the treatment of UC was examined as well as the action mechanism of this medication. A flexible tube was inserted into the rat cecum to establish a topical administration model of 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced UC. A total of 60 rats were divided into sham operation group (receiving an enema of 0.9% saline solution instead of the TNBS solution via the tube), model group, topical 5-ASA group, oral Etiasa group (a release agent of mesalazine used as positive control) and oral 5-ASA group (n=12 each). Different treatments were administered 1 day after UC induction. The normal saline (2 mL) was instilled twice a day through the tube in the sham operation group and model group. 5-ASA was given via the tube in the topical 5-ASA group (7.5 g/L, twice per day, 100 mg/kg), and rats in the oral Etiasa group and oral 5-ASA group intragastrically received Etiasa (7.5 g/L, twice per day, 100 mg/kg) and 5-ASA (7.5 g/L, twice per day, 100 mg/kg), respectively. The body weight was recorded every day. After 7 days of treatment, blood samples were drawn from the heart to harvest the sera. Colonic tissues were separated and prepared for pathological and related molecular biological examinations. The concentrations of 5-ASA were detected at different time points in the colonic tissues, feces and sera in different groups by using the high pressure liquid chromatography (HPLC). The results showed that the symptoms of acute UC, including bloody diarrhea and weight loss, were significantly improved in topical 5-ASA-treated rats. The colonic mucosal damage, both macroscopical and histological, was significantly relieved and the myeloperoxidase activity was markedly decreased in rats topically treated with 5-ASA compared with those treated with oral 5-ASA or Etiasa. The mRNA and protein expression of IL-1β, IL-6, and TNF-α was down-regulated in the colonic tissue of rats topically treated with 5-ASA, significantly lower than those from rats treated with oral 5-ASA or Etiasa. The concentrations of 5-ASA in the colonic tissue were significantly higher in the topical 5-ASA group than in the oral 5-ASA and oral Etiasa groups. It was concluded that the topical administration of 5-ASA can effectively increase the concentration of 5-ASA in the colonic tissue, decrease the expression of proinflammatory cytokines, alleviate the colonic pathological damage and improve the symptoms of TNBS-induced acute UC in rats.
Administration, Oral ; Administration, Topical ; Animals ; Anti-Inflammatory Agents, Non-Steroidal ; administration & dosage ; pharmacology ; Colitis, Ulcerative ; chemically induced ; drug therapy ; Colon ; drug effects ; metabolism ; pathology ; Down-Regulation ; drug effects ; Drug Administration Schedule ; Gene Expression ; drug effects ; Immunohistochemistry ; Interleukin-1beta ; genetics ; metabolism ; Interleukin-6 ; genetics ; metabolism ; Intestinal Mucosa ; drug effects ; metabolism ; pathology ; Male ; Mesalamine ; administration & dosage ; pharmacology ; Peroxidase ; metabolism ; Rats ; Rats, Wistar ; Reverse Transcriptase Polymerase Chain Reaction ; Time Factors ; Treatment Outcome ; Trinitrobenzenesulfonic Acid ; Tumor Necrosis Factor-alpha ; genetics ; metabolism