Objective: To investigate whether the selective cyclooxygenase-2 enzyme inhibitors celecoxib has protective effect on the liver of rats with type 2 diabetes mellitus (T2DM) combined with nonalcoholic steatohepatitis (NASH) via inhibiting the expression of Rho/ROCK pathway. Methods: Forty male SD rats were randomly divided into four groups: type 2 diabetes mellitus combined with nonalcoholic steatohepatitis (T2DM-NASH) group, T2DM-NASH + celecoxib group, control group, and control+celecoxib group. The T2DM-NASH and T2DM-NASH + celecoxib groups were fed with high-sugar and fat diet, and the control group and control + celecoxib group were fed with basal diet (25 kJ/kg). Four weeks later, streptozotocin (STZ, 30 mg/kg) was intraperitoneally injected into the NASH group and T2DM-NASH + celecoxib group to induce T2DM model, and the control group and control + celecoxib group were intraperitoneally injected with isovolumic citric acid-sodium citrate buffer. Four weeks after STZ injection, the T2DM-NASH + celecoxib group and the control + celecoxib group were gavaged with celecoxib (10 mg·kg·d) dissolved in normal saline for 4 weeks, and the remaining two groups of rats were gavaged with isovolumic normal saline for 4 weeks. Animals were sacrificed at the end of the 12- weeks, and the liver tissue was collected. Liver pathological changes were observed by HE staining. The expressions of RhoA, RhoA, ROCK1 and ROCK2 proteins in liver were detected by immunohistochemistry and western blot. The expressional condition of RhoA, ROCK1 and ROCK2 mRNA in liver were detected by real-time quantitative PCR. The differences were compared between protein and mRNA expression among the groups by analysis of variance and t-test. Results: Compared with the control group and the control + celecoxib group, the liver tissue of the T2DM-NASH group and the T2DM-NASH + celecoxib group had severe steatosis, and there was partial inflammatory cell infiltration under the light microscope. The expression levels of RhoA, ROCK1 and ROCK2 protein and mRNA were significantly increased (P < 0.05) in each liver tissue, while liver steatosis was reduced to certain extent in T2DM-NASH + celecoxib group than T2DM-NASH group, and the expression levels of RhoA, ROCK1 and ROCK2 protein and mRNA were decreased in each liver tissue of T2DM-NASH group (P < 0.05). Conclusion: The selective cyclooxygenase-2 enzyme inhibitors celecoxib has a protective effect on the liver of rats with T2DM-NASH, and its effect may be achieved by inhibiting the expression of Rho/ROCK pathway.
Animals ; Cyclooxygenase 2/therapeutic use* ; Cyclooxygenase 2 Inhibitors/therapeutic use* ; Diabetes Mellitus, Type 2/drug therapy* ; Liver ; Male ; Non-alcoholic Fatty Liver Disease/drug therapy* ; Rats ; Rats, Sprague-Dawley

The opioid epidemic continues to be a serious public health concern. Many have pointed to prescription drug misuse as a nidus for patients to become addicted to opioids and as such, urologists and other surgical subspecialists must critically define optimal pain management for the various procedures performed within their respective disciplines. Controlling pain following penile prosthesis implantation remains a unique challenge for urologists, given the increased pain patients commonly experience in the postoperative setting. Although most of the existing urological literature focuses on interventions performed in the operating room, there are many studies that examine the role of preoperative adjunctive pain medicine in diminishing postoperative narcotic requirements. There are relatively few studies looking at postoperative strategies for managing pain in prosthetic surgery with follow-up past the immediate hospitalization. This review assess the various strategies employed for managing pain following penile implantation through the lens of the current state of the opioid crisis, thus examining how urologists can responsibly treat pain without contributing to the growing threat of opioid addiction.
Analgesics/therapeutic use* ; Analgesics, Opioid/therapeutic use* ; Anesthetics, Local/therapeutic use* ; Anti-Inflammatory Agents, Non-Steroidal/therapeutic use* ; Cyclooxygenase 2 Inhibitors/therapeutic use* ; Gabapentin/therapeutic use* ; Humans ; Intraoperative Care ; Male ; Nerve Block/methods* ; Opioid Epidemic ; Pain Management/methods* ; Pain, Postoperative/therapy* ; Penile Implantation/methods* ; Pregabalin/therapeutic use* ; Preoperative Care

OBJECTIVETo study the effect of cyclooxygenase -2 selective inhibitor celecoxib on the expression of major vault protein ( MVP) in the brain of rats with status epilepticus and its possible roles in the treatment of refractory epilepsy.

METHODSSixty adult male Sprague-Dawley rats were randomly assigned to blank control (n=16), epilepsy model (n=22) and celecoxib treatment groups (n=22). After the status epilepticus was induced in rats by injecting lithium and pilocarpine, each group had 16 rats enrolled as subjects. Immunohistochemical method and Western blot method were used to detect the expression of MVP in the frontal cortex and hippocampus.

RESULTSThe expression of MVP was significantly higher in the epilepsy model group than in the control group (P<0.01). The expression of MVP in the celecoxib treatment group was significantly decreased compared with the epilepsy model group, but it was still higher than in the control group (P<0.01).

CONCLUSIONSCelecoxib could decrease the expression of MVP in brain tissue of rats with status epilepticus, suggesting that it is promising for the treatment of intractable epilepsy.

Animals ; Blotting, Western ; Brain ; metabolism ; Celecoxib ; pharmacology ; therapeutic use ; Cyclooxygenase 2 Inhibitors ; pharmacology ; Immunohistochemistry ; Male ; Rats ; Rats, Sprague-Dawley ; Status Epilepticus ; drug therapy ; metabolism ; Vault Ribonucleoprotein Particles ; analysis

PURPOSE: The purpose of this study was to define the role of cyclooxygenase-2 inhibitors (COX-2i) in reducing hepatic fibrosis in pediatric patients with chronic liver disease. MATERIALS AND METHODS: From September 2009 to September 2010, patients over 2 years old who visited our outpatient clinic for follow-up to manage their chronic liver disease after Kasai portoenterostomy for biliary atresia, were included in this study. Volunteers were assigned to the study or control groups, according to their preference. A COX-2i was given to only the study group after obtaining consent. The degree of hepatic fibrosis (liver stiffness score, LSS) was prospectively measured using FibroScan, and liver function was examined using serum analysis before and after treatment. After 1 year, changes in LSSs and liver function were compared between the two groups. RESULTS: Twenty-five patients (18 females and 7 males) were enrolled in the study group. The control group included 44 patients (26 females and 18 males). After 1 year, the least square mean values for the LSSs were significantly decreased by 3.91±0.98 kPa (p=0.004) only in the study group. Serum total bilirubin did not decrease significantly in either group. CONCLUSION: COX-2i treatment improved the LSS in patients with chronic liver disease after Kasai portoenterostomy for biliary atresia.
Biliary Atresia/complications/enzymology/*surgery ; Child ; Child, Preschool ; Chronic Disease ; Cyclooxygenase 2 Inhibitors/*therapeutic use ; Female ; Humans ; Liver Cirrhosis/etiology/pathology/*prevention & control ; Male ; *Portoenterostomy, Hepatic ; Thiazines/*therapeutic use ; Thiazoles/*therapeutic use

OBJECTIVETo study the effect of perioperative immunomodulatory therapy on postoperative recurrence of rectal cancer.

METHODSThis prospective study was conducted among 238 rectal/anal cancer patients undergoing intersphincteric resection at our center between January, 2010 and January, 2011, among whom 150 were eligible to be included and completed the study. The 150 patients were randomized in a double-blinded fashion into 3 equal groups to receive immunomodulatory therapy with 8 mg/kg celecoxib (group A), 0.4 mg/kg Sou-Medrol (group B), or placebo (group C), given daily from 5 days before surgery to 5 days after surgery, and the postoperative cancer recurrence were compared.

RESULTSAt 3 days after the operation, the 3 groups showed significantly different C-reactive protein (CRP) levels, which decreased obviously in all the 3 groups compared with those at 1 day following the operation (P=0.022), especially in group B. The levels of interleukin-6 (IL-6) at 3 days after the operation also differed significantly between the 3 groups but were lower in all the 3 groups than those at 1 day after the operation (P=0.046), and this reduction was the most obvious in group A. COX-2 expression differed significantly between the 3 groups (P=0.017), among which group A showed the most obvious suppression of COX-2 expression. During the follow-up for a mean of 45 months, no significant difference in the recurrence rate was found between the 3 groups (P=0.549).

CONCLUSIONWith a lower efficacy than Sou-Medrol in decreasing postoperative inflammation, celecoxib produces a better effect in inhibiting COX-2 expression, but it does not lower postoperative recurrence rate of rectal cancer.

C-Reactive Protein ; metabolism ; Celecoxib ; Cyclooxygenase 2 Inhibitors ; therapeutic use ; Humans ; Immunomodulation ; Inflammation ; Interleukin-6 ; blood ; Neoplasm Recurrence, Local ; prevention & control ; Postoperative Period ; Prospective Studies ; Pyrazoles ; therapeutic use ; Rectal Neoplasms ; surgery ; therapy ; Sulfonamides ; therapeutic use

OBJECTIVETo systematically evaluate the efficacy and safety of preoperative administration of cyclooxygenase-2 (COX-2) inhibitor on pain occurring with total knee arthroplasty (TKA).

METHODSWe electronically searched PubMed, Cochrane Library, EMBASE, CNKI, CBM, Wanfang data from inception to March 15, 2014 and manual searched journal of library collection to identify randomized controlled trials (RCTs) about preoperative administration of COX-2 inhibitor on pain occurring with TKA. The methodological quality of the included RCTs was assessed and the data were extracted according to the Cochrane Handbook 5.1.0. Meta-analysis was performed by using RevMan 5.2 software.

RESULTSA total of 6 RCTs involving 228 patients were included. The results of meta-analyses showed that: (1) Efficacy: The visual analog scale (VAS) of post-operation at 12-hour (WMD = -0.60, 95% CI -0.83 to -0.37, P < 0.000 01) and 24-hour (WMD = -0.74, 95% CI -1.29 to - 0.19, P = 0.008) was decreased when COX-2 inhibitor was used before operation. And compared with control group, experimental group decreased the modified numerical pain rating scale (MNPRS) at 24-hour (WMD = -0.50, 95% CI -0.70 to -0.30, P < 0.000 01), 48-hour (WMD = -0.55,95% CI -0.65 to -0.45,P < 0.000 01) under quiescent conditions, and the same result at 24-hour (WMD = -0.82, 95% CI -1.26 to -0.38, P <0.000 01), 48-hour (WMD = -0.71, 95% CI -0.82 to -0.60, P < 0.000 01) under active conditions. The morphine consumption postoperatively were fewer in experimental group at the first day (WMD = - 1.35, 95% CI -1.92 to -0.79, P < 0.000 01) and the second day (WMD = -1.60, 95% CI -2.68 to -0.52, P = 0.004). (2) Safety: COX-2 inhibitor could lessen the incidence of postoperative pruritus (RR = 0.35, 95% CI 0.15 to 0.84, P = 0.02), but not statistically decrease of nausea and vomiting (RR = 0.83, 95% CI 0.54 to 1.28, P = 0.40) and exhaustion (RR = 0.63, 95% CI 0.05 to 7.67, P = 0.72).

CONCLUSIONThe current evidence indicated that preoperative administration of COX-2inhibitor can effectively improve the effect of postoperative analgesia, reduce the consumption of morphine and lessen the incidence of pruritus. Due to the limited quantity of the included studies and the evidence with limited strength,further high-quality RCTs are needed to verify the aforementioned conclusion.

Arthroplasty, Replacement, Knee ; Cyclooxygenase 2 Inhibitors ; therapeutic use ; Humans ; Pain, Postoperative ; drug therapy ; Postoperative Complications ; prevention & control ; Pruritus ; prevention & control

OBJECTIVETo evaluate the clinical efficiency of selective cyclo-oxygenase-2 (COX-2) inhibitor compared to traditional nonselective NSAIDs for the prevention of heterotopic ossification (HO) after total hip arthroplasty (THA).

METHODSBy searching Medline, Embase, CENTRAL (Cochrane Central Register of Controlled Trials) and Science Citation Index et al, only randomised controlled studies of selective COX-2 inhibitors VS nonselective COX-1 and COX-2 inhibitors for the prevention of HO after THA were included. The quality assessment of included studies was evaluated according to the standard of the Cochrane Collaboration, and the data were analysised by statistic software Stata 10.0. The HO incidence of both groups in different degrees was compared.

RESULTSFour eligible randomised controlled trials of totally 808 patients were included. Meta-analysis results showed that no statistically significant difference was found in overall incidence of HO (RR = 1.08, 95% CI: 0.71-1.64,P = 0.73), incidence of moderate severe HO (Brooker II and III) (RR = 0.83, 95% CI: 0.48-1.42, P = 0.49) and any grade of Brooker classification between two groups. In all included studies, 16 patients receiving nonselective COX inhibitor (4.4%) discontinued treatment because of gastrointestinal toxicity,whereas 10 patients in the selective COX-2 inhibitor group (2.7%) discontinued for gastrointestinal side effects.

CONCLUSIONThe selective COX-2 inhibitors are as equally effective as nonselective NSAIDs for the prevention of HO after THA. Considering the side effects of nonselective NSAIDs, selective COX-2 inhibitors were recommend for the prevention of HO after THA.

Anti-Inflammatory Agents, Non-Steroidal ; adverse effects ; therapeutic use ; Arthroplasty, Replacement, Hip ; adverse effects ; Cyclooxygenase 2 Inhibitors ; adverse effects ; therapeutic use ; Cyclooxygenase Inhibitors ; adverse effects ; therapeutic use ; Humans ; Ossification, Heterotopic ; prevention & control ; Randomized Controlled Trials as Topic

The new generation cyclooxygenase (COX-2) inhibitor could reduce the gastrointestinal side effect of NSAID drugs, but eventually increase the cardiovascular risk, because its selective inhibition of COX-2 induces the imbalance between PGI2 and TXA2 and the reduction of vasodilatory NO. Under pathological conditions, active oxygen species (O2-*2, etc) were used to induce endo- thelial dysfunction, activate NF-κB to induce expressions of pro-inflammatory cytokines IL-1β and TNF-α, increase ET-1, TXA2 with vasoconstrictor effect, reduce PGI2 and NO with vasodilatory effect, generate further oxidative damage together with NO, and reduce the bioavailability of NO. NO-NSAIDs and NO-Coxibs drugs raised the level of NO by introducing NO-donor (ONO2). NSAIDs drugs enhanced the anti-inflammatory activity of COX-2 and reduced gastrointestinal side effects by inhibiting selectively COX-2. If antioxidant structures with active ingredients of traditional Chinese medicines were introduced to improve the antioxidant activity of NSAIDs, they could scavenge the active oxygen species to protect the normal function of vascular endothelia and enhance the bioavailability of NO, which is conducive to enhance the cardiovascular safety of cyclooxygenase (COX-2) inhibitor.
Anti-Inflammatory Agents ; therapeutic use ; Biomarkers, Pharmacological ; Cardiovascular Diseases ; drug therapy ; enzymology ; immunology ; Cyclooxygenase 2 ; immunology ; Cyclooxygenase 2 Inhibitors ; adverse effects ; therapeutic use ; Drugs, Chinese Herbal ; therapeutic use ; Humans ; NF-kappa B ; immunology ; Reactive Oxygen Species ; immunology ; Tumor Necrosis Factor-alpha ; immunology

AIM: In the present study, the anti-inflammatory and antioxidant activities of the methanol extract of Ruta graveolens leaves (RG-M) were evaluated using various in vivo and in vitro models. METHOD: For anti-inflammatory activity, RG-M was administered by the oral route (p.o.) in a carrageenan-induced paw edema model, and by the intraperitoneal route (i.p.) in an exudative inflammation model. In vitro inhibition of cyclooxygenase and lipoxygenase enzymes was evaluated. In vitro antioxidant activity was also examined. Endogenous antioxidant status was further evaluated by ferric reducing ability of plasma model. RESULTS: RG-M showed maximum inhibition of carrageenan-induced edema (100 mg·kg⁻¹ - 33.36%; 200 mg·kg⁻¹ - 45.32% and 400 mg·kg⁻¹ - 56.28%). In the exudative inflammation model, a significant reduction in leukocyte migration (200 mg·kg⁻¹ - 54.75% and 400 mg·kg⁻¹ - 77.97%) and protein exudation (200 mg·kg⁻¹ - 31.14% and 400 mg·kg⁻¹ - 49.91%) were observed. RG-M also exhibited inhibition of COX-1 (IC50 182.27 μg·mL⁻¹) and COX-2 (IC50 190.16 μg·mL⁻¹) as well as 5-LOX (IC50 215.71 μg·mL⁻¹). Antioxidant activity was significant with improved endogenous antioxidant status. CONCLUSION The results demonstrated the anti-inflammatory and antioxidant activity of RG-M with potent inhibitory effects on the arachidonic acid pathways.
Animals ; Anti-Inflammatory Agents ; pharmacology ; therapeutic use ; Antioxidants ; pharmacology ; therapeutic use ; Arachidonic Acid ; metabolism ; Carrageenan ; Cyclooxygenase 1 ; metabolism ; Cyclooxygenase 2 ; metabolism ; Cyclooxygenase Inhibitors ; pharmacology ; therapeutic use ; Disease Models, Animal ; Edema ; drug therapy ; Exudates and Transudates ; Ferric Compounds ; metabolism ; Inflammation ; drug therapy ; metabolism ; Leukocytes ; metabolism ; Lipoxygenase Inhibitors ; pharmacology ; therapeutic use ; Lipoxygenases ; metabolism ; Male ; Phytotherapy ; Plant Extracts ; pharmacology ; therapeutic use ; Plant Leaves ; Rats, Wistar ; Ruta

Many studies have shown that chronic inflammation occurs in the brain of patients with Alzheimer's disease (AD). It is well known that long-term administration of non-steroidal anti-inflammatory drugs (NSAIDs) can alleviate the cognitive decline of AD patient and elderly. Several inflammatory cytokines produced in the metabolism of arachidonic acid (AA) are closely related to inflammatory diseases. Lipoxygenases (LOXs) and cyclooxygenases (COXs) play a crucial role in the AA network, the products eicosanoids have an important impact on the progression of AD. Although there are many arguments and conflicting evidence, currently LOXs and COXs are still the hot topics in the research on AD pathogenesis and drug development. Here, we review the progress in research on COXs and LOXs, including their actions on CNS and their association with AD, and explore the feasibility of LOXs and COXs as targets for the drugs to prevent and/or treat AD.
Alzheimer Disease ; drug therapy ; enzymology ; prevention & control ; Amyloid beta-Peptides ; metabolism ; Animals ; Anti-Inflammatory Agents, Non-Steroidal ; pharmacology ; therapeutic use ; Arachidonic Acid ; metabolism ; Brain ; metabolism ; Cyclooxygenase 1 ; metabolism ; Cyclooxygenase 2 ; metabolism ; Cyclooxygenase Inhibitors ; therapeutic use ; Humans ; Lipoxygenase Inhibitors ; therapeutic use ; Lipoxygenases ; metabolism ; Prostaglandin H2 ; metabolism ; Prostaglandin-Endoperoxide Synthases ; metabolism