BACKGROUND: High on-treatment platelet reactivity (HTPR) is the phenomenon wherein patients exhibit normal platelet activity in laboratory testing despite adequate adherence to anti-platelet treatment. We investigated the detection rates of Platelet Function Analyzer (PFA)-100 (Dade Behring AG, Düdingen, Switzerland) for drug-induced platelet dysfunction and analyzed potential contributors to HTPR with practical PFA-100 data over six years. METHODS: We used data from 6,957 patients who underwent PFA-100 testing after receiving aspirin, clopidogrel, or non-steroidal anti-inflammatory drugs (NSAIDs). Of these, 6,163 patients were tested with only the collagen/epinephrine cartridge (Col/EPI) of PFA-100; 794 were tested with both Col/EPI and the collagen/ADP cartridge (Col/ADP). We calculated PFA-100 closure time (CT) for each drug and compared the clinical and laboratory characteristics of the patients with prolonged CTs and normal CTs (i.e., HTPR). RESULTS: In Col/EPI, 73.2% (365/499), 72.6% (390/537), and 55.3% (3,442/6,228) patients showed prolonged CTs for aspirin, clopidogrel, and NSAIDs, respectively. In Col/ADP, prolonged CTs were observed in 37.4% (34/91), 43.2% (35/81), and 29.6% (200/676) of patients receiving aspirin, clopidogrel, and NSAIDs, respectively. Of the patients tested with both cartridges, 88.9% (48/54), 95.3% (41/43), and 89.0% (577/648) of the patients receiving aspirin, clopidogrel, and NSAIDs had prolonged CTs, and 10.0% (79/794) showed normal CTs regardless of drugs. For clopidogrel users (both cartridges), there were more patients with malignancies in the normal CT than prolonged CT group. CONCLUSIONS: PFA-100 is not sufficiently effective for laboratory screening of drug-induced platelet dysfunction. Malignancy may contribute to clopidogrel-related HTPR in PFA-100.
Anti-Inflammatory Agents, Non-Steroidal ; Aspirin ; Blood Platelets* ; Humans ; Mass Screening

A 5-year-old, 2.7 kg, spayed female Scottish Fold cat presented with hematemesis after administration of oral zaltoprofen, a non-steroidal anti-inflammatory drug, by the owner. Diagnostic imaging and blood analyses indicated development of acute kidney injury (AKI) resulting from zaltoprofen ingestion. To correct dehydration and anemic conditions, the cat received intravenous fluid therapy with whole blood transfusion and peroral N-acetylcysteine. Clinical signs resolved, but persistent azotemia was unresolved indicating that AKI could progress to chronic kidney disease. This case suggests that although zaltoprofen may have low adverse effects on humans, administration of zaltoprofen in cats can have serious adverse effects.
Acetylcysteine ; Acute Kidney Injury* ; Animals ; Anti-Inflammatory Agents, Non-Steroidal ; Azotemia ; Blood Transfusion ; Cats* ; Child, Preschool ; Dehydration ; Diagnostic Imaging ; Eating ; Female ; Fluid Therapy ; Hematemesis ; Humans ; Renal Insufficiency ; Renal Insufficiency, Chronic

Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a rare and severe drug-induced hypersensitivity syndrome characterized by hematological abnormalities and multiorgan involvement. Liver involvement is the most common visceral manifestation. However, renal failure has been rarely described. The common culprit drugs are anticonvulsants and allopurinol. We experienced a patient with DRESS syndrome with acute interstitial nephritis caused by concomitant administration of quinolone and non-steroidal anti-inflammatory drugs (NSAIDs). A 41-year-old man presented with a diffuse erythematous rash and fever which developed after administration of quinolone and NSAIDs for a month due to prostatitis. He was diagnosed with DRESS syndrome. Skin rash, fever, eosinophilia, and elevations of liver enzymes improved with conservative treatment and discontinuation of the causative drugs. However, deterioration of his renal function occurred on day 8 of admission. The levels of blood urea nitrogen and serum creatinine increased and oliguria, proteinuria and urinary eosinophils were observed. Ultrasonography showed diffuse renal enlargement. The clinical features were compatible with acute interstitial nephritis. Despite intravenous rehydration and diuretics, renal function did not improve. After hemodialysis, his renal function recovered completely within 2 weeks without administration of systemic corticosteroid.
Adult ; Allopurinol ; Anti-Inflammatory Agents, Non-Steroidal ; Anticonvulsants ; Blood Urea Nitrogen ; Creatinine ; Diuretics ; Drug Hypersensitivity ; Drug Hypersensitivity Syndrome* ; Eosinophilia ; Eosinophils ; Exanthema ; Fever ; Fluid Therapy ; Humans ; Hypersensitivity ; Liver ; Nephritis, Interstitial* ; Oliguria ; Prostatitis ; Proteinuria ; Renal Dialysis ; Renal Insufficiency ; Ultrasonography

Refractory peptic ulcers are defined as ulcers that do not heal completely after 8 to 12 weeks of standard anti-secretory drug treatment. The most common causes of refractory ulcers are persistent Helicobacter pylori infection and use of nonsteroidal anti-inflammatory drugs (NSAIDs). Simultaneous use of two or more H. pylori diagnostic methods are recommended for increased sensitivity. Serologic tests may be useful for patients currently taking proton pump inhibitors (PPIs) or for suspected false negative results, as they are not affected by PPI use. NSAID use should be discontinued when possible. Platelet cyclooxygenase activity tests can confirm surreptitious use of NSAIDs or aspirin. Cigarette smoking can delay ulcer healing. Therefore, patients who smoke should be encouraged to quit. Zollinger-Ellison syndrome (ZES) is a rare but important cause of refractory gastroduodenal ulcers. Fasting plasma gastrin levels should be checked if ZES is suspected. If an ulcer is refractory despite a full course of standard PPI treatment, the dose should be doubled and administration of another type of PPI considered.
Anti-Inflammatory Agents, Non-Steroidal ; Aspirin ; Blood Platelets ; Fasting ; Gastrins ; Helicobacter pylori ; Humans ; Peptic Ulcer* ; Plasma ; Prostaglandin-Endoperoxide Synthases ; Proton Pump Inhibitors ; Serologic Tests ; Smoke ; Smoking ; Ulcer ; Zollinger-Ellison Syndrome

Thyroid antibodies are frequently observed in urticaria patients, but their roles in urticaria are not clearly elucidated. We investigated the role of serum specific IgE to thyroid peroxidase (TPO) in patients with aspirin intolerant acute urticaria (AIAU) and aspirin intolerant chronic urticaria (AICU). We recruited 59 AIAU and 96 AICU patients with 69 normal controls (NC). Serum specific IgE to TPO was measured by manual direct ELISA, and CD203c expressions on basophil with additions of TPO were measured to prove a direct role of TPO in effector cells. The prevalences of serum specific IgE to TPO were significantly higher in AIAU (15.2%) and AICU groups (7.5%) compared to NC (0%, P=0.018: P=0.013, respectively). Flow cytometry showed CD203c induction in a dose dependent manner with serial additions of TPO in some AIAU and AICU patients having high specific IgE to TPO. Our findings show that the prevalence of serum specific IgE to TPO was significantly higher in both AIAU and AICU patients than in NC. It is suggested that specific IgE to TPO play a pathogenic role in AIAU and AICU.
Adult ; Anti-Inflammatory Agents, Non-Steroidal/adverse effects ; Aspirin/*adverse effects ; Autoantibodies/immunology ; Basophils/drug effects/*immunology ; Humans ; Immunoglobulin E/blood/*immunology ; Iodide Peroxidase/blood/*immunology ; Urticaria/*chemically induced/*immunology/pathology

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

The present research was aimed to develop a high performance liquid chromatography (HPLC) method to determine oxaprozin in plasma and to evaluate the bioavailability of two oxaprozin enteric coated tablets. A C18 column was used to separate the plasma after protein precipitation and the mobile phase was methanol-12. 5mmol/L ammonium acetate buffer solution (pH=3.0)(71:29). The calibration curve was linear in the concentration range of 0. 50-70. 56 microg . mL-1, and the intra and inter-day RSDs were less than 12. 33% and 10. 42% respectively. A single dose of 0. 4 g reference preparation or test preparation of oxaprozin enteric coated tablets was administered to 20 healthy volunteers according to a randomized crossover study. AUC0-->264h were (4 917. 44 +/- 629. 57) microg . h . mL-1 and (4 604. 30+/-737. 83) microg . h . mL-1, respectively; Cmax were (52. 34+/-7. 68) microg . mL-1 and (48. 66+/-4. 87) microg . mL-1, respectively; Tmax were (18. 70+/-2.27) h and (19. 30+/-1. 63) h, respectively; The relative bioavailability of test preparation was 94.0% +/- 13. 7%. The method is simple, rapid and selective for oxaprozin determination. There is no significant difference in the main pharmacokinetic parameters between the test formulation and reference formulation and the two formulations are in bioequivalence.
Anti-Inflammatory Agents, Non-Steroidal ; blood ; pharmacokinetics ; Biological Availability ; Chromatography, High Pressure Liquid ; Cross-Over Studies ; Humans ; Propionates ; administration & dosage ; blood ; pharmacokinetics ; Tablets, Enteric-Coated

An improved method to determine meloxicam (MEL) concentrations in koala plasma using reversed phase high performance liquid chromatography equipped with a photo diode array detector was developed and validated. A plasma sample clean-up step was carried out with hydrophilic-lipophilic copolymer solid phase extraction cartridges. MEL was separated from an endogenous interference using an isocratic mobile phase [acetonitrile and 50 mM potassium phosphate buffer (pH 2.15), 45:55 (v:v)] on a Nova-Pak C18 4-microm (300 x 3.9 mm) column. Retention times for MEL and piroxicam were 8.03 and 5.56 min, respectively. Peak area ratios of MEL to the internal standard (IS) were used for regression analysis of the calibration curve, which was linear from 10 to 1,000 ng/mL (r2 > 0.9998). Average absolute recovery rates were 91% and 96% for MEL and the IS, respectively. This method had sufficient sensitivity (lower quantitation limit of 10 ng/mL), precision, accuracy, and selectivity for routine analysis of MEL in koala plasma using 250-microL sample volumes. Our technique clearly resolved the MEL peak from the complex koala plasma matrix and accurately measured MEL concentrations in small plasma volumes.
Animals ; Anti-Inflammatory Agents, Non-Steroidal/*blood ; Chromatography, High Pressure Liquid/methods/*veterinary ; Molecular Structure ; Phascolarctidae/*blood ; Piroxicam/chemistry ; Quality Control ; Reproducibility of Results ; Sensitivity and Specificity ; Thiazines/*blood ; Thiazoles/*blood

An improved method to determine meloxicam (MEL) concentrations in koala plasma using reversed phase high performance liquid chromatography equipped with a photo diode array detector was developed and validated. A plasma sample clean-up step was carried out with hydrophilic-lipophilic copolymer solid phase extraction cartridges. MEL was separated from an endogenous interference using an isocratic mobile phase [acetonitrile and 50 mM potassium phosphate buffer (pH 2.15), 45:55 (v:v)] on a Nova-Pak C18 4-microm (300 x 3.9 mm) column. Retention times for MEL and piroxicam were 8.03 and 5.56 min, respectively. Peak area ratios of MEL to the internal standard (IS) were used for regression analysis of the calibration curve, which was linear from 10 to 1,000 ng/mL (r2 > 0.9998). Average absolute recovery rates were 91% and 96% for MEL and the IS, respectively. This method had sufficient sensitivity (lower quantitation limit of 10 ng/mL), precision, accuracy, and selectivity for routine analysis of MEL in koala plasma using 250-microL sample volumes. Our technique clearly resolved the MEL peak from the complex koala plasma matrix and accurately measured MEL concentrations in small plasma volumes.
Animals ; Anti-Inflammatory Agents, Non-Steroidal/*blood ; Chromatography, High Pressure Liquid/methods/*veterinary ; Molecular Structure ; Phascolarctidae/*blood ; Piroxicam/chemistry ; Quality Control ; Reproducibility of Results ; Sensitivity and Specificity ; Thiazines/*blood ; Thiazoles/*blood

OBJECTIVETo study whether effect of aspirin plus low-dose diethylstilbestrol is more effective and safer than high diethylstilbestrol dose alone on prevention of ovariectomy-induced osteopenia and dyslipidemia.

METHODSThirty-eight 4-month-old female SD rats were divided into baseline (BAS) group (n=6), sham operation group (n=8) and ovariectomy (OVX) group (n=24). The OVX group was further divided into vehicle treatment group (n=8), diethylstilbestrol (30 μg/kg•d) treatment group (OVX+D30 group, n=8), and aspirin (9 mg/kg•d) plus diethylstilbestrol (10 μg/kg•d) treatment group (OVX+A-D10 group, n=8). Their left tibiae were collected for the bone histomorphometric analysis in undecalcified sections. Left femurs were collected for the bone mineral density measurement.

RESULTSThe body weight and serum cholesterol were increased, while uterine weight and cancellous bone mass were decreased in OVX rats compared with the SHAM group. Cancellous bone mass was significantly increased, while body weight and bone resorption parameters were decreased in both A-D10 and D30 treatment group compared with OVX group. The rats treated with A-D10 showed significantly increased in bone formation parameters and decreased in serum triglyceride compared with the D30-treated rats.

CONCLUSIONAspirin plus low-dose diethylstilbestrol can effectively prevent osteopenia by reducing bone resorption, and is thus a better treatment modality for preventing dyslipidemia than high-dose diethylstilbestrol alone.

Animals ; Anti-Inflammatory Agents, Non-Steroidal ; pharmacology ; therapeutic use ; Aspirin ; pharmacology ; therapeutic use ; Biomarkers ; blood ; Body Weight ; drug effects ; Bone Density ; Bone Diseases, Metabolic ; blood ; prevention & control ; Bone and Bones ; drug effects ; Diethylstilbestrol ; pharmacology ; therapeutic use ; Drug Evaluation, Preclinical ; Drug Therapy, Combination ; Dyslipidemias ; blood ; prevention & control ; Estrogens, Non-Steroidal ; pharmacology ; therapeutic use ; Female ; Organ Size ; drug effects ; Ovariectomy ; Rats ; Uterus ; drug effects