PURPOSE: This study was performed to investigate the effects of intravesical instillation of cyclooxygenase-2 (COX-2) inhibitors on the cyclophosphamide-induced overactive bladder. MATERIALS AND METHODS: The 40 Sprague-Dawley rats were divided into 3 groups; the control group, the overactive group, and the COX-2 inhibitor treated group. Cystometrograms (CMG) were performed and the contraction interval, inter-contraction interval, contraction time and contraction pressure were measured. After CMG, the bladders of each group were dissected out, and weighed. RESULTS: On CMG, the contraction interval and inter-contraction interval for the overactive group were significantly decreased compared with the control group. After treatment with COX-2 inhibitor, the contraction interval and inter-contraction interval were significantly increased compared with the overactive group (p<0.05). The contraction time in the overactive group was significantly increased compared with the control group, and it was also decreased in the COX-2 inhibitor treated group compared with the overactive group (p<0.05). The contraction pressure in the overactive group and the COX-2 inhibitor treated group were significantly increased compared with the control group. There were no significant differences between the overactive and COX-2 inhibitor treated groups. The bladder weights of the overactive and COX-2 inhibitor treated groups were significantly increased compared with the control group (p<0.05). CONCLUSIONS: Intravesical instillation of COX-2 inhibitor can suppress cyclophosphamide-induced detrusor overactivity. Therefore, intravesical instillation of COX-2 inhibitor may be considered as a possible treatment for the overactive bladder.
Administration, Intravesical* ; Cyclooxygenase 2 Inhibitors ; Cyclooxygenase 2* ; Cyclophosphamide ; Rats, Sprague-Dawley ; Urinary Bladder ; Urinary Bladder, Overactive* ; Weights and Measures

PURPOSE: This study was performed to investigate the effects of intravesical instillation of cyclooxygenase-2 (COX-2) inhibitors on the cyclophosphamide-induced overactive bladder. MATERIALS AND METHODS: The 40 Sprague-Dawley rats were divided into 3 groups; the control group, the overactive group, and the COX-2 inhibitor treated group. Cystometrograms (CMG) were performed and the contraction interval, inter-contraction interval, contraction time and contraction pressure were measured. After CMG, the bladders of each group were dissected out, and weighed. RESULTS: On CMG, the contraction interval and inter-contraction interval for the overactive group were significantly decreased compared with the control group. After treatment with COX-2 inhibitor, the contraction interval and inter-contraction interval were significantly increased compared with the overactive group (p<0.05). The contraction time in the overactive group was significantly increased compared with the control group, and it was also decreased in the COX-2 inhibitor treated group compared with the overactive group (p<0.05). The contraction pressure in the overactive group and the COX-2 inhibitor treated group were significantly increased compared with the control group. There were no significant differences between the overactive and COX-2 inhibitor treated groups. The bladder weights of the overactive and COX-2 inhibitor treated groups were significantly increased compared with the control group (p<0.05). CONCLUSIONS: Intravesical instillation of COX-2 inhibitor can suppress cyclophosphamide-induced detrusor overactivity. Therefore, intravesical instillation of COX-2 inhibitor may be considered as a possible treatment for the overactive bladder.
Administration, Intravesical* ; Cyclooxygenase 2 Inhibitors ; Cyclooxygenase 2* ; Cyclophosphamide ; Rats, Sprague-Dawley ; Urinary Bladder ; Urinary Bladder, Overactive* ; Weights and Measures

OBJECTIVETo assess the effect of perioperative administration of a selective cyclooxygenase 2 inhibitor (celecoxib) on pain management and recovery of function after total knee arthroplasty (TKA).

METHODSRandomized, controlled trial conducted from January 2005 through February 2006, 60 patients underwent TKA for osteoarthritis or rheumatoid arthritis were randomly divided into group of perioperative, administration of celecoxib (Study group, n = 30) and postoperative administration of celecoxib (Control group, n = 30). Patients in Study group were given oral celecoxib 3 d before TKA, 200 mg twice daily, and extended to 5 d postoperatively; patients in Control group were given oral celecoxib 2 h after TKA, 200 mg twice daily, and extended to 5 d postoperatively. All operations were finished by the same surgeon group.

RESULTSThe postoperative patient-controlled analgesia (PCA) consumption was significantly less in Study group than in Control group [(43 +/- 12) ml vs. (53 +/- 12) ml, P < 0.05]. The pain scores of postoperative 4, 8, 12 h, 1, 2 d in Study group were 6.1 +/- 1.2, 5.0 +/- 1.3, 4.3 +/- 1.1, 3.4 +/- 1.2, significantly less than in Control group (P < 0.05); There were no intergroup significant differences in the pain scores of postoperative 3, 4, 5 d (P > 0.05). There were no intergroup significant differences in respect to the side-effect occurrence, operation time and postoperative drainage, postoperative analgesic consumption (P > 0.05). The time to achieve 90 degrees knee flexion was significantly shorter in Study group than in Control group [(6.2 +/- 1.7) d vs. (8.6 +/- 1.8) d, P < 0.05].

CONCLUSIONSPerioperative administration of the selective Celecoxib holds the effect of preemptive analgesia. Compared with postoperative administration, perioperative administration of celecoxib can alleviate the early postoperative pain score, reduce the consumption of postoperative analgesic, accelerate the recovery of joint motion and thus increase the patient satisfaction.

Aged ; Arthroplasty, Replacement, Knee ; Celecoxib ; Cyclooxygenase 2 Inhibitors ; administration & dosage ; Female ; Humans ; Male ; Middle Aged ; Pain, Postoperative ; drug therapy ; Perioperative Care ; Pyrazoles ; administration & dosage ; Sulfonamides ; administration & dosage

PURPOSE: Tumor invasion and metastasis are known to be extremely important factors in the prognosis of cancer patients. Although recent studies have demonstrated that cyclooxygenase-2 (COX-2) is overexpressed in various cancers including gastric cancer, the mechanisms underlying the contribution of COX-2 to tumorigenesis and tumor promotion remain unclear. METHODS: In order to determine the role of COX-2 in tumor growth and metastasis, we investigated COX-2 expression, apoptosis and the expression of E-cadherin, CD44v6, MMP-2 and TIMP-2 in gastric cancer xenografts treated with meloxicam (a selective COX-2 inhibitor). RESULTS: Cells from the MKN45 gastric cancer cell line that overexpress COX-2 were inoculated subcutaneously into athymic mice. Oral administration with meloxicam reduced the tumor volume (P<0.01), induced apoptosis of cancer cells (P<0.01), suppressed the proliferation rates (P<0.01), increased the expression of E-cadhrin (P<0.05) and reduced the expression of MMP-2 and TIMP-2. CONCLUSION: The above data showed that COX-2 inhibitors can inhibit tumor growth and suppress metastatic potential by expression of adhesion molecules and suppression of metalloproteinases, suggesting that this inhibitor can be used as an additive anti-cancer drug in cases of stomach cancer with radical resection, although further evaluation is required.
Administration, Oral ; Animals ; Apoptosis ; Cadherins ; Carcinogenesis ; Cell Line ; Cyclooxygenase 2 ; Cyclooxygenase 2 Inhibitors ; Heterografts* ; Humans ; Metalloproteases ; Mice ; Mice, Nude ; Neoplasm Metastasis* ; Prognosis ; Stomach Neoplasms* ; Tissue Inhibitor of Metalloproteinase-2 ; Tumor Burden

Meloxicam concentration in skin was determined following topical administration of meloxicam patches in hairless mouse. Samples were analysized by HPLC coupled with microdialysis sampling technique, in which in vivo recovery of probe was characterized by the retrodialysis method. It was indicated that the in vivo recovery of the probe was 14.0%. The range of steady state concentration of meloxicam in dialysate was 24-50 ng x mL(-1), and that was 170-360 ng x mL(-1) in the hairless mouse skin. Steady state concentration of meloxicam was reached shortly after the application of meloxicam patches, which was maintained during the period of experiment.
Administration, Cutaneous ; Animals ; Chromatography, High Pressure Liquid ; Cyclooxygenase 2 Inhibitors ; administration & dosage ; pharmacokinetics ; Isoenzymes ; antagonists & inhibitors ; Mice ; Mice, Hairless ; Mice, Inbred BALB C ; Microdialysis ; Skin ; metabolism ; Skin Absorption ; Thiazines ; administration & dosage ; pharmacokinetics ; Thiazoles ; administration & dosage ; pharmacokinetics

OBJECTIVETo evaluate the analgesic efficacy and systemic anti-inflammation of preoperative cyclooxygenase-2 nonsteroidal antiinflammatory drug, rofecoxib, after total knee replacement (TKR).

METHODSThirty patients underwent elective knee replacement were randomly given oral rofecoxib 25 mg (group RE, n = 15) or placebo (group E, n = 15) 1 hour prior to surgery. All patients received epidural combined isoflurane anesthesia during surgery and patient-controlled epidural analgesia after surgery for 72 hrs (0.1 mg/ml morphine + 1.2 mg/ml bupivacaine + 0.02 mg/ml droperidol). Modified verbal rate scale was used to evaluate postoperative pain intensity. The outcomes included pain scores during rest and movement of knee joints and analgesia satisfaction. Daily morphine consumption was recorded. Circulation leucocyte and serum cytokine concentrations (including interleukin 6, interleukin 8, interleukin 10, Tumor necrosis factor-alpha) were determined before surgery, at the end of surgery, 2 h, 6 h, 12 h, 24 h and 48 h after surgery in two groups using RIA. The amount of intraoperative blood loss and postoperative drainage from the knees were measured.

RESULTSThe pain scores were significantly less in the group RE than in group E during rest and knee joints movement on the first and second postoperative day, with an improvement in total analgesia satisfaction (P < 0.05). The mean dose of morphine for first 24 h was (8.1 +/- 1.5) mg in the E group and (6.8 +/- 0.7) mg in the RE group (t = -2.71, P < 0.01). Leucocyte and neutrophil counts were much higher in group E than in group RE at 12 h, 24 h post-operatively (P < 0.05). Serum TNF-alpha concentration was significantly lower in group RE than group E at the end of surgery, 6 h, 12 h postoperatively, as well as IL6 at 48 h, IL8 at 24h after surgery (P < 0.05). There were no significant differences in respect to the amount of intraoperative and postoperative blood loss between two groups (P > 0.05).

CONCLUSIONPreoperative cyclooxygenase-2-specific nonsteroidal anti-inflammatory drug rofecoxib increases analgesia satisfaction, reduces opioid requirement and demonstrates a systemic anti-inflammatory effect after TKR.

Administration, Oral ; Aged ; Analgesia, Epidural ; Anti-Inflammatory Agents ; Arthroplasty, Replacement, Knee ; Cyclooxygenase 2 Inhibitors ; administration & dosage ; Drug Therapy, Combination ; Female ; Humans ; Lactones ; administration & dosage ; Male ; Middle Aged ; Morphine ; administration & dosage ; Pain, Postoperative ; drug therapy ; prevention & control ; Premedication ; Sulfones ; administration & dosage

OBJECTIVETo investigate methods and therapeutic effects of sequential drugs treatment for central pain following spinal cord injury.

METHODSA total of 28 patients suffered from central pain following spinal cord injury were treated with sequential drugs from 1994 to 2008, including 23 males and 5 females, ranging in age from 25 to 59 years (mean 42 years). According to the patients' response to drugs, the therapy grade was adjusted step by step until the pain was relieved. Basing on VAS scores before and after drugs treatment, analgesic effect was evaluated. The first grade drugs: COX-2 inhibitors. The second grade drugs: Tricyclic antidepressant drugs (Amitriptyline) + COX-2 inhibitors + Carbamazepine. The third grade drugs: Tricyclic antidepressant drugs (Amitriptyline) + Gabapentin + Neurotropin/COX-2 inhibitors.

RESULTSThe pain of all of 28 patients was relieved to different extent. The VAS scores decreased by 23.3 +/- 1.2 in the first grade drugs treatment group. The VAS scores decreased by 54.5 +/- 3.8 in the second grade drugs treatment group. The VAS scores decreased by 65.8 +/- 5.1 in the third grade drugs treatment group (P<0.05).

CONCLUSIONThe sequential drugs treatment for central pain following spinal cord injury has a good analgesia effect and little adverse reaction.

Adult ; Amitriptyline ; administration & dosage ; Carbamazepine ; administration & dosage ; Cyclooxygenase 2 Inhibitors ; administration & dosage ; Drug Therapy, Combination ; Female ; Humans ; Male ; Middle Aged ; Pain ; drug therapy ; Pain Measurement ; Polysaccharides ; administration & dosage ; Spinal Cord Injuries ; complications ; drug therapy

BACKGROUNDMultimodal cocktail periarticular injection (MCPI) with a large volume of low concentration local anesthetics, adrenaline, and anti-inflammatory agents such as non-steroidal anti-inflammatory drug or steroids have shown good pain control and improvement in range of motion after surgery. This study compares the efficacy of pain control after total knee arthroplasty, using multimodal cocktail periarticular injection with steroid or without steroid.

METHODSThis is a prospective, double-blinded, randomized and control study. Seventy-two patients with osteoarthritis that met clinical criteria for total knee arthroplasty were recruited into the study, and were randomized to receive either multimodal cocktail periarticular injection with steroid or without steroid. Pain was assessed by visual analogue scale (VAS) at preoperative and postoperative at rest, and during activity. The range of motion was recorded preoperatively and postoperatively. The amount of daily and cumulative morphine consumption were measured by patient-controlled analgesia in the first 72 hours postoperatively. The duration of celecoxib usage was also recorded at the last follow-up.

RESULTSThere were no differences between the non-steroid and steroid groups with regard to VAS at rest and during activity, or range of motion, at any postoperative observation time. The postoperative Knee Society Knee Score in the steroid group improved significantly as compared with that in non-steroid group at the one-month (84.1±13.1 and 65.9±12.1; P < 0.0045), three-month follow-up (90.2±16.3 and 72.5±16.6; P < 0.0027), but after postoperative six-month the Knee Society Knee Score showed no significant difference between the groups. There was no significant difference in consumption of the morphine about daily or total consumption within 72 hours between the two groups. The duration of celecoxib usage in patients in the steroid group was significantly shorter than that in the non-steroid group ((7.2±0.7) compared with (10.5±1.9) weeks; P = 0.012).

CONCLUSIONThe patients who received the steroid injection had faster rehabilitation and less non-steroidal antiinflammatory drugs consumption.

Aged ; Arthroplasty, Replacement, Knee ; methods ; Celecoxib ; Cyclooxygenase 2 Inhibitors ; administration & dosage ; therapeutic use ; Female ; Humans ; Injections, Intra-Articular ; Male ; Pain Measurement ; Pyrazoles ; administration & dosage ; therapeutic use ; Steroids ; administration & dosage ; therapeutic use ; Sulfonamides ; administration & dosage ; therapeutic use

It has been proposed that the pro-inflammatory catalytic activity of cyclooxygenase-2 (COX-2) plays a key role in the aging process. However, it remains unclear whether the COX-2 activity is a causal factor for aging and whether COX-2 inhibitors could prevent aging. We here examined the effect of COX-2 inhibitors on aging in the intrinsic skin aging model of hairless mice. We observed that among two selective COX-2 inhibitors and one non-selective COX inhibitor studied, only NS-398 inhibited skin aging, while celecoxib and aspirin accelerated skin aging. In addition, NS-398 reduced the expression of p53 and p16, whereas celecoxib and aspirin enhanced their expression. We also found that the aging-modulating effect of the inhibitors is closely associated with the expression of type I procollagen and caveolin-1. These results suggest that pro-inflammatory catalytic activity of COX-2 is not a causal factor for aging at least in skin and that COX-2 inhibitors might modulate skin aging by regulating the expression of type I procollagen and caveolin-1.
Animals ; Aspirin/administration & dosage ; Catalysis ; Caveolin 1/genetics/metabolism ; Collagen Type I/genetics/metabolism ; *Cyclooxygenase 2/metabolism/physiology ; Cyclooxygenase 2 Inhibitors/*administration & dosage ; Gene Expression Regulation ; Mice ; Nitrobenzenes/*administration & dosage ; Pyrazoles/administration & dosage ; Skin Aging/*drug effects/physiology ; Sulfonamides/*administration & dosage ; Tumor Suppressor Protein p53/genetics/metabolism

This study involves mathematical simulation model such as in vitro-in vivo correlation (IVIVC) development for various extended release formulations of nimesulide loaded hydroxypropylmethylcellulose (HPMC) microparticles (M1, M2 and M3 containing 1, 2, and 3 g HPMC, respectively and 1 g drug in each) having variable release characteristics. In vitro dissolution data of these formulations were correlated to their relevant in vivo absorption profiles followed by predictability worth analysis of these Level A IVIVC. Nimaran was used as control formulation to validate developed formulations and their respective models. The regression coefficients of IVIVC plots for M1, M2, M3 and Nimaran were 0.834 9, 0.831 2, 0.927 2 and 0.898 1, respectively. The internal prediction error for all formulations was within limits, i.e., < 10%. A good IVIVC was found for controlled release nimesulide loaded HPMC floating M3 microparticles. In other words, this mathematical simulation model is best fit for biowaiver studies which involves study parameters as those adopted for M3 because the value of its IVIVC regression coefficient is the closest to 1 as compared to M1 and M2.
Anti-Inflammatory Agents, Non-Steroidal ; administration & dosage ; pharmacokinetics ; Cross-Over Studies ; Cyclooxygenase 2 Inhibitors ; administration & dosage ; pharmacokinetics ; Delayed-Action Preparations ; Humans ; Hypromellose Derivatives ; Methylcellulose ; analogs & derivatives ; Microspheres ; Models, Chemical ; Sulfonamides ; administration & dosage ; pharmacokinetics