BACKGROUND: NSAIDs and methotrexate induce gut damage and bacterial translocation (BT). However, there is no study examining the combined effects of methotrexate and NSAID on gut damage and BT. We examined the combined effects of methotrexate and NSAID-induced enteropathy and bacterial translocation in an experimental animal model. METHODS: Rats received either no drug, NSAID alone (diclofenac 80 mg/kg and 120 mg/kg per os), methorexate alone (20 mg/kg per os) or NSAID with methotrexate. Gut barrier dysfunction, the degree of intestinal adhesion, stool pellet number, bacterial number of total aerobes and Gram negatives in the distal ileal and cecal contents and the number of Gram negatives in the mesenteric lymph nodes, liver, spleen, kidney and heart were measured. RESULTS: Administration of diclofenac or methotrexate alone caused an increase in gut barrier dysfunction and intestinal adhesion and a decrease in stool pellet number. Administration of diclonfenac alone induced enteric bacterial overgrowth and increased BT to the mesenteric lymph nodes, liver, spleen, kidney and heart. Administration of methotrexate alone induced enteric bacterial undergrowth and BT to the mesenteric lymph nodes, liver, spleen but not to the kidney and heart. The supplements with methotrexate increased the NSAID-induced gut barrier dysfunction and intestinal adhesion, and decreased the stool pellet number. However, the reduced NSAID-induced enteric Gram negative bacterial overgrowth (with a dose of diclofenac of 80 mg/kg) and BT to the liver, spleen, kidney and heart. COCNLUSION: Methotrexate increases NSAID-induced intestinal damage, but reduces NSAID-induced BT to the liver, spleen, kidney and heart in experimental animals.
Administration, Oral* ; Animals ; Anti-Inflammatory Agents ; Anti-Inflammatory Agents, Non-Steroidal ; Bacterial Translocation* ; Diclofenac* ; Heart ; Kidney ; Liver ; Lymph Nodes ; Methotrexate* ; Models, Animal* ; Rats* ; Spleen

Administration, Oral ; Anti-Inflammatory Agents, Non-Steroidal ; adverse effects ; Female ; Hematuria ; chemically induced ; Humans ; Infant ; Male ; Sulfonamides ; adverse effects

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

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

Two different salts of diclofenac, diclofenac sodium and diclofenac potassium, in tablet dosage form were tested for their bioavailability and disposition kinetics in a group of eighteen rabbits in normal and experimentally induced dehydrated conditions with a wash out period of 7 days between both stages of study. Biochemical and physiological parameters were also measured in both normal and dehydrated states. Diclofenac levels in plasma were determined using a validated reversed phase HPLC method. Primary kinetic parameters i.e. AUC(0-infinity), Cmax, Tmax and other disposition kinetics were obtained with non-compartmental procedure. Biochemical parameters i.e. packed cell volume, plasma glucose and total lipid concentration in dehydrated rabbits increased significantly. Plasma concentration of diclofenac sodium and diclofenac potassium decreased significantly in water deprived rabbits. In comparison, diclofenac potassium in normal and dehydrated state of the same group of rabbits showed a significantly increased plasma concentration when compared with diclofenac sodium.
Administration, Oral ; Animals ; Anti-Inflammatory Agents, Non-Steroidal ; administration & dosage ; blood ; pharmacokinetics ; Area Under Curve ; Biological Availability ; Dehydration ; metabolism ; Diclofenac ; administration & dosage ; analogs & derivatives ; blood ; pharmacokinetics ; Rabbits ; Tablets

Acute pancreatitis remains the most frequent complication of endoscopic retrograde cholangiopancreatography (ERCP), with reported incidence rates that have changed little over several decades. Patient- and procedure-related risk factors for post-ERCP pancreatitis (PEP) are well-defined. Effective measures to prevent PEP have been identified, including improvements in cannulation techniques and pancreatic stenting, as well as pharmacological intervention. Pharmacotherapy has been widely studied in the prevention of PEP, but the effect in averting PEP has been inconclusive. Although pharmacological prophylaxis is appealing, attempts to find an ideal drug are incomplete. Most available data on the efficacy of pharmacological agents for PEP prophylaxis have been obtained from patients at average risk for PEP. However, recently, a randomized prospective controlled trial of rectal nonsteroidal anti-inflammatory drugs (NSAIDs) to prevent PEP in high-risk patients was published. The results revealed that rectal indomethacin reduced the incidence of PEP significantly. Thus, rectal administration of diclofenac or indomethacin immediately before or after ERCP is used routinely to prevent PEP. However, additional studies with NSAIDs using large numbers of subjects are necessary to confirm the prophylactic effect of these drugs and to establish whether they act synergistically with other prophylactic interventions, including pancreatic stenting.
Acute Disease ; Administration, Rectal ; Animals ; Anti-Inflammatory Agents, Non-Steroidal/administration & dosage/*therapeutic use ; Cholangiopancreatography, Endoscopic Retrograde/*adverse effects ; Humans ; Pancreatitis/etiology/*prevention & control ; Treatment Outcome

BACKGROUND/AIMS: Lymphoid follicular proctitis (LFP) is an uncommon inflammatory condition confined to the rectum. Patients with LFP constitute a special group with clinical, endoscopic, and histological features unrelated to other types of inflammatory bowel diseases, and have been reported to be refractory to local steroid and/or oral sulfasalazine therapy. The aim of this study was to clarify whether mesalazine suppositories have a therapeutic effect in LFP. METHODS: The histologic slides of 8 cases indexed in our pathology files as "lymphoid follicular proctitis of the rectal mucosa" from January 2001 to November 2003 were reviewed retrospectively. RESULTS: The most common symptom in the patients with LFP was rectal bleeding. The endoscopic mucosal changes were discontinuous, sparing whole circumferential involvement, and were strictly confined to the rectum. Average period of medication was 12 months. All the symptomatic patients with LFP responded to mesalazine suppository therapy. In addition, these patients did not progress to other disease including ulcerative proctitis or lymphoma. CONCLUSIONS: Mesalazine suppository treatment is a useful therapeutic option for symptomatic patients with LFP.
Adult ; Aged ; Anti-Inflammatory Agents, Non-Steroidal/*administration & dosage ; Female ; Humans ; Male ; Mesalamine/*administration & dosage ; Middle Aged ; Proctitis/*drug therapy/pathology ; Rectum/pathology ; Suppositories

BACKGROUND/AIMS: Lymphoid follicular proctitis (LFP) is an uncommon inflammatory condition confined to the rectum. Patients with LFP constitute a special group with clinical, endoscopic, and histological features unrelated to other types of inflammatory bowel diseases, and have been reported to be refractory to local steroid and/or oral sulfasalazine therapy. The aim of this study was to clarify whether mesalazine suppositories have a therapeutic effect in LFP. METHODS: The histologic slides of 8 cases indexed in our pathology files as "lymphoid follicular proctitis of the rectal mucosa" from January 2001 to November 2003 were reviewed retrospectively. RESULTS: The most common symptom in the patients with LFP was rectal bleeding. The endoscopic mucosal changes were discontinuous, sparing whole circumferential involvement, and were strictly confined to the rectum. Average period of medication was 12 months. All the symptomatic patients with LFP responded to mesalazine suppository therapy. In addition, these patients did not progress to other disease including ulcerative proctitis or lymphoma. CONCLUSIONS: Mesalazine suppository treatment is a useful therapeutic option for symptomatic patients with LFP.
Adult ; Aged ; Anti-Inflammatory Agents, Non-Steroidal/*administration & dosage ; Female ; Humans ; Male ; Mesalamine/*administration & dosage ; Middle Aged ; Proctitis/*drug therapy/pathology ; Rectum/pathology ; Suppositories

OBJECTIVETo investigate the therapeutic effect of Lugua polypeptide on active rheumatoid arthritis (RA).

METHODSFifty patients with active RA were selected for the study and were randomly divided into study group and control group. Patients in study group were treated with Lugua polypeptide intravenously at a dose of 16 mg per day and those in control group were given Celecoxib 200 mg twice a day for successive 2 weeks. Two groups were given the same basic treatment. Tenderness and swelling of joints, morning stiffness, erythrocyte sedimentation rate, C-reactive protein,rheumatoid factor and so on were recorded before and after treatment.

RESULTSThe above index on joints in study group was significantly improved compared with that in control group and the level before treament. No apparent side effects were observed.

CONCLUSIONLugua polypeptide is effective and safe on active RA. It is a promising agent in the treatment of RA.

Adult ; Aged ; Anti-Inflammatory Agents, Non-Steroidal ; administration & dosage ; Arthritis, Rheumatoid ; drug therapy ; Female ; Humans ; Injections ; Male ; Middle Aged ; Peptides ; administration & dosage

AIMTo investigate the in vitro recovery and influencing factors of ketoprofen in microdialysis probe, and study the pharmacokinetic of unbound ketoprofen in rat after iv administration.

METHODSThe recovery of ketoprofen was detected by a concentration difference method. After microdialysis probe was inserted into the jugular vein of male Wistar rats, the probe was infused with various concentrations perfusate. The in vivo recovery and the pharmacokinetics of unbound ketoprofen in rat were investigated. Dialysate samples were determined by HPLC.

RESULTSThe recovery detected by gain was as the same as that by loss; the recovery was independent of the drug concentration surrounding the probe. The in vitro recovery was 28.75% by concentration difference method and the in vivo recovery was (40.3 +/- 2.7) % by retrodialysis method. After i.v. administration of ketoprofen in rat, T 1/2, AUC and CL of unbound ketoprofen were (181 +/- 16) min, (112 +/- 27) microg x min x mL(-1) and (0.22 +/- 0.05) L x min(-1), respectively.

CONCLUSIONMicrodialysis sampling can be used for the pharmacokinetic study of unbound ketoprofen in rat.

Animals ; Anti-Inflammatory Agents, Non-Steroidal ; administration & dosage ; pharmacokinetics ; Area Under Curve ; Chromatography, High Pressure Liquid ; Injections, Intravenous ; Ketoprofen ; administration & dosage ; pharmacokinetics ; Male ; Microdialysis ; methods ; Rats ; Rats, Wistar