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

This report describes the successful treatment of spontaneous intracranial hypotension (SIH) with multiple cerebrospinal fluid (CSF) leaks using 10 applications of epidural blood patches (EBP). A forty year old female who suffered with a postural headache was diagnosed as having SIH. On the cisternography, multiple CSF leaks were noted at the thoracic and lumbar area. Her headache was not improved with conservative treatments such as bed rest, hydration and NSAIDS. So, she underwent treatment with EBPs. After 10 applications of site-directed EBPs, her headache was resolved gradually and completely without any complications.
Anti-Inflammatory Agents, Non-Steroidal ; Bed Rest ; Blood Patch, Epidural* ; Cerebrospinal Fluid ; Female ; Headache ; Humans ; Intracranial Hypotension*

OBJECTIVETo investigate the effect of antibiotics and a nonsteroidal anti-inflammatory agent on the level of total prostate specific antigen (PSA) and free PSA ratio (F-PSAR) in patients with chronic prostatitis IIIA.

METHODSA total of 228 outpatients diagnosed as with chronic prostatitis III A received 4-week antibiotic and anti-inflammatory treatment. The PSA level and F-PSAR were determined before and after the treatment, and the changes analyzed.

RESULTSSignificant variations were observed in the median PSA concentrations (3.51 microg/L and 2.75 microg/L) and F-PSAR (0.25% and 0.27%) 4 weeks after the treatment. Sixty-five of the patients (28.5%) presented with serum PSA greater than 4 ng/ml, the mean PSA decreased by 32.9%, from 6.24 microg/L before the treatment to 4.58 microg/L 4 weeks after the treatment (P < 0.05), and the serum PSA was normalized in 18 of the 65 patients (27.7%). The median variation of F-PSAR (0.16% and 0.22%) was greater than that of PSA. The variation indexes obtained 4 weeks after the treatment showed no statistical difference from those observed 8 weeks after the treatment.

CONCLUSIONChronic prostatitis IIIA appears to contribute to increased serum PSA levels in some men. Antibiotic and anti-inflammatory treatment could significantly reduce the PSA level and increase F-PSAR.

Adult ; Aged ; Anti-Bacterial Agents ; therapeutic use ; Anti-Inflammatory Agents, Non-Steroidal ; therapeutic use ; Chronic Disease ; Humans ; Male ; Middle Aged ; Prostate-Specific Antigen ; blood ; Prostatitis ; blood ; drug therapy

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

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

BACKGROUND: There is controversy regarding whether COX-2 specific inhibitors are associated with elevation of blood pressure. We compared the effects of aspirin, indomethacin, and celecoxib for vascular reactivity induced by phenylephrine. We also tested the effects of indomethacin and NO donor on COX-1 and COX-2 protein expression, as well as nitrite production in culture medium of vascular smooth muscle cells. MATERILAS AND METHODS: In this experiment, we used the isometric tension study for vascular reactivity. After 45 minutes of pretreatment with aspirin, indomethacin, celecoxib, and phenylephrine induced contractions were tested. COX-1 and COX-2 protein expressions were analyzed by Western blot and nitrite production by the Griess reaction. RESULTS: Although celecoxib pretreatment caused enhanced arterial contraction, aspirin pretreatment induced more potent arterial contraction than celecoxib in the isometric tension study of rabbit femoral artery. COX-1 protein expression was unchanged by indomethacin, SNP and NOR-3; COX-2 protein expression was increased by the addition of indomethacin, SNP, and NOR-3. Especially, NOR-3, a NO donor, significantly increased COX-2 protein expression with unstimulated conditions as well as LPS stimulation. Induction of nitrite production was higher with NOR-3 treatment than SNP treatment with LPS stimulation. CONCLUSION: These results suggest that aspirin caused more potent vascular contraction than celecoxib and indomethacin. COX-2 expression in VSMC depended on the types of NO donor and LPS stimulation.
Anti-Inflammatory Agents, Non-Steroidal ; Aspirin ; Blood Pressure ; Blotting, Western ; Cyclooxygenase Inhibitors* ; Femoral Artery ; Humans ; Indomethacin ; Muscle, Smooth, Vascular ; Phenylephrine ; Prostaglandin-Endoperoxide Synthases* ; Tissue Donors ; Celecoxib

This study examined in vitro effect of lipoxin A(4) (LXA(4)) on interleukin-1β (IL-1β) production of monocytes and its possible mechanism in severe preeclampsia (PE). Peripheral venous blood was drawn from 15 patients with severe preeclampsia (PE group) and 20 normal pregnant women (control group) to prepare monocytes which were then treated with LXA(4) at different concentrations of 0, 10, 100 nmol/L respectively. IL-1β level in the supernatant of monocytes was detected by enzyme linked immunoassay. The [Ca(2+)](i) of monocytes was measured by laser scanning confocal microscopy. The results showed that the IL-1β level and the [Ca(2+)](i) of monocytes in the PE group were significantly higher than those in the control group. LXA(4) significantly decreased the generation of IL-1β in a dose-dependent manner in the PE group. After treatment with 100-nmol/L LXA(4), in the PE group, the [Ca(2+)](i) concentration of monocytes was significantly reduced. It was concluded that LXA(4) may inhibit the IL-1β production of monocytes from severe preeclampsia women by inhibiting extracellular calcium influx.
Adult ; Anti-Inflammatory Agents, Non-Steroidal ; pharmacology ; Calcium ; metabolism ; Cells, Cultured ; Female ; Humans ; Interleukin-1beta ; biosynthesis ; Lipoxins ; pharmacology ; Monocytes ; cytology ; metabolism ; Pre-Eclampsia ; blood ; physiopathology ; Pregnancy

Nonsteroidal anti-inflammatory drugs (NSAIDs), are characterized by their anti-inflammatory, analgesic, and antipyretic activities; they have been widely used for the management of acute pain and chronic inflammation. The mechanism of action of NSAIDs is inhibition of prostaglandin biosynthesis. Inflammatory prostaglandins are primarily derived from COX-2, while the prostaglandins formed by COX-1 have in general a more homeostatic role. Based on their selectivity for COX-1 or COX-2, NSAIDs are classified into non-selective NSAIDs and COX-2 selective NSAIDs. Non-selective NSAIDs and COX-2 selective NSAIDs have similar effects on pain relief and inflammation. One major problem associated with the use of non-selective NSAIDs is their adverse effects on the gastrointestinal tract, caused by inhibition of COX-1. Compared with non-selective NSAIDS, the main advantage of COX-2 selective NSAIDs is reduced gastrointestinal complications. Reviews have suggested that COX-2 selective NSAIDs increase the risk of cardiovascular events; however, cardiovascular risk may vary among the selective NSAIDs. Because of their anti-inflammatory properties, the use of NSAIDs is essential for the relief of pain and the symptoms associated with inflammatory conditions such as active osteoarthritis. When NSAIDs are prescribed, age, additional medication such as aspirin, gastrointestinal and cardiovascular status, and co-morbidity must be taken into account. COX-2 selective NSAIDs have minimal effects on platelet function and thus, can also be used for pre and postoperative pain control in patients with osteoarthritis waiting for the surgery.
Acute Pain ; Anti-Inflammatory Agents, Non-Steroidal ; Aspirin ; Blood Platelets ; Gastrointestinal Tract ; Humans ; Imidazoles ; Inflammation ; Nitro Compounds ; Osteoarthritis ; Pain, Postoperative ; Prostaglandins

BACKGROUND AND OBJECTIVES: Nonsteroidal anti-inflammatory durgs (NSAIDs) are now widely accepted analgesics for posttonsillectomy patients, but their ability to inhibit platelet cyclooxygenase (COX) may be associated with a risk of increased bleeding after tonsillectomy. Rofecoxib, the recently introduced selective COX-2 inhibitor, may have advantages for analgesics in tonsillectomy in that they produce minimal effects on platelet aggregation. But the analgesic efficacy of rofecoxib in tonsillectomy has not been made known yet. The aim of our randomized prospective study was to compare the analgesic efficacy of rofecoxib, the selective COX-2 inhibitor, and ibuprofen, the classic NSAID, for the posttonsillectomy pain management. We also evaluated the influence of both drugs on the posttonsillectomy bleeding. SUBJECTS AND METHOD: Thirty-eight adult patients undergoing tonsillectomy were randomly divided into either ibuprofen or rofecoxib group. Patients received either oral ibuprofen (600 mg, three times a day) or oral rofecoxib (25 mg, twice a day). Patients recorded pain levels twice daily for 7 days using a visual analogue scale. Posttonsillectomy hemorrhage was recorded in each groups. RESULTS: Pain scores for the 7 days were not significantly different between two groups, but the rofecoxib group reported less pain. Rofecoxib group felt more satisfactorily about early control of postoperative pain. There was no significant difference in the incidence of postoperative hemorrhage between two groups. CONCLUSION: Rofecoxib is as effective as ibuprofen for postoperative pain control in adult tonsillectomy, which might be beneficial for avoiding the adverse effects of NSAIDs.
Adult ; Analgesics ; Anti-Inflammatory Agents, Non-Steroidal ; Blood Platelets ; Hemorrhage* ; Humans ; Ibuprofen ; Incidence ; Pain Management ; Pain, Postoperative ; Platelet Aggregation ; Postoperative Hemorrhage ; Prospective Studies ; Prostaglandin-Endoperoxide Synthases ; Tonsillectomy*

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