Anticonvulsant property of celecoxib in maximal electroshock seizure: Correlating the role of inflammation in pathophysiology of epileptic seizures

Background: Epilepsy is an abnormal excessive electric neuronal activity and always represents by recurrent seizures. There is positive feedback cycle between epileptogenesis and brain inflammation. It has been proved that an inflammatory enzyme, cyclooxygenase (COX) (especially isoform-2, a constitutive enzyme), expressed in some important parts of the central nervous system and is responsible to induced inflammation locally and having seizurogenic property. Aim and Objective: The goal of this study was to see if celecoxib (a selective COX-2 inhibitor) could reduce the maximal electroshock seizure (MES)-induced seizures in mice. Materials and Methods: Celecoxib injected intraperitoneally in two different doses 5 mg/kgb/w and 10 mg/kg b/w, in albino Swiss mice and in two different phases. MES was elicited and length of different phases was noted. Length of tonic hindlimb extension was considered as indicator of anti-epileptic activity. Results: Celecoxib, when given intraperitoneally, exert significant reduction in the duration of THLE. This action of celecoxib strongly suggests the involvement of inflammation in the pathophysiology of epilepsy. Conclusion: The findings are suggestive of the therapeutic significance of celecoxib, as a future antiepileptic agent for seizure management.

Effects of preoperative administration of parecoxib sodium on stress reaction and postoperative nausea and vomiting score in patients undergoing laparoscopic cholecystectomy / 中国基层医药

Objective:To investigate the effects of preoperative administration of parecoxib sodium on stress reaction and postoperative nausea and vomiting score in patients undergoing laparoscopic cholecystectomy.Methods:A total of 112 patients undergoing laparoscopic cholecystectomy in Lishui City People's Hospital from January 2020 to January 2021 were included in this study. They were randomly divided into observation group and control group, with 56 patients per group. The observation group was intravenously administered 40 mg parecoxib sodium 30 minutes before surgery, and the control group was identically administered equal amount of 0.9% sodium chloride injection. At 1, 6, 12 and 24 hours after surgery, Visual Analogue Scale (VAS) score, cortisol and adrenocorticotropic hormone levels and postoperative nausea and vomiting score were compared between the two groups.Results:At 1, 6 and 12 hours after surgery, VAS score in the observation group was (3.23 ± 0.85) points, (2.44 ± 0.76) points, (2.37 ± 0.69) points, respectively, which were significantly lower than (4.06 ± 1.12) points, (3.24 ± 0.95) points, (3.10 ± 1.07) points in the control group ( t = 4.41, 4.92, 4.29, all P < 0.001). At 1, 6, 12 and 24 hours after surgery, cortisol level in the observation group was (287.79 ± 35.46) ng/L, (303.55 ± 34.77) ng/L, (368.58 ± 31.22) ng/L, (397.16 ± 32.60) ng/L, respectively, which were significantly lower than (337.64 ± 39.52) ng/L, (364.18 ± 36.90) ng/L, (405.56 ± 37.29) ng/L, (455.51 ± 37.81) ng/L in the control group ( t = 7.02, 8.94, 5.69, 8.74, all P < 0.05). At 1, 6, 12 and 24 hours after surgery, adrenocorticotropic hormone level in the observation group was (59.25 ± 7.63) ng/L, (65.27 ± 8.23) ng/L, (72.29 ± 7.49) ng/L, (83.63 ± 8.57) ng/L, which were significantly lower than (64.48 ± 8.06) ng/L, (71.44 ± 8.59) ng/L, (79.79 ± 8.15) ng/L, (90.08 ± 8.26) ng/L in the control group ( t = 3.52, 3.88, 5.07, 4.05, all P < 0.05). Within 24 hours after surgery, the incidence of postoperative nausea and vomiting in the observation group was significantly lower than that in the control group [12.50% (7/56) vs. 28.57% (16/56), χ2 = 4.43, P < 0.05). Within 2 hours, 2-6 hours, and > 6-24 hours, postoperative nausea and vomiting score in the observation group was (1.31 ± 0.26) points, (1.43 ± 0.32) points, and (1.46 ± 0.41) points, respectively, which was significantly lower than (1.67 ± 0.41) points, (1.83 ± 0.39) points, (1.88 ± 0.44) points in the control group ( t = 2.12, 2.37, 2.14, all P < 0.05). Conclusion:Preoperative administration of parecoxib sodium exhibits a good postoperative analgesic effect in patients undergoing laparoscopic cholecystectomy. It can effectively reduce postoperative stress reactions, decrease the incidence of postoperative nausea and vomiting, and lower the severity of postoperative nausea and vomiting, and thereby can be widely used in clinical practice.

Factores asociados con el uso de inhibidores del factor de necrosis tumoral alfa en una población de pacientes colombianos con espondiloartritis / Factors associated with the use of tumor necrosis factor alpha inhibitors in a population of Colombian patients with spondyloarthritis

RESUMEN Introducción: El uso de TNFi es cada vez más frecuente en los pacientes con espondiloartritis. Identificar tempranamente aquellos que los requerirán o poder predecir su uso puede ayudar a hacer un tratamiento más efectivo y oportuno racionalizando su uso. Objetivo: Determinar los factores qué mejor explican la indicación de TNFi en la población en estudio. Material y métodos: La asociación entre el uso de medicamentos anti-TNFα y las variables categóricas demográficas, clínicas, de laboratorio, radiológicas y de tratamiento se exploró por prueba exacta de Fisher. La asociación con las variables cuantitativas fue evaluada con t de Student o U de Mann Withney, de acuerdo con su distribución. Aquellas variables con p < 0,25 fueron ingresadas a modelos univariante de regresión logística explicativa para construir los OR crudos; aquellas con p < 0,25 se incluyeron en el modelo multivariante para construir OR ajustados. Resultados y discusión: La población está constituida por 181 pacientes. Modelo univariante: la artritis reactiva, uretritis y compromiso periférico fueron factores protectores para el uso de TNFi. Espondiloartritis axial, lumbalgia inflamatoria, dolor glúteo alternante, rigidez matinal sacroilitis demostrada por cualquier método, tratamiento con inhibidores COX-2, tiempo de evolución de tres arios o más y los puntajes de BASDAI y BASFI se asociaron con el uso de TNFi. Modelo multivariante: artritis reactiva (OR 0,1, IC 95% 0,012-0,86, p = 0,036), lumbalgia inflamatoria (OR 13,63, IC 95% 1,36-136, p = 0,026), sacroilitis (OR 7,71, IC 95% 1,04-57, p = 0,045, uso de coxib (OR 10,1, IC 95% 2,71-37,62, p = 0,001) y el puntaje máximo de BASDAI (4-6: OR 6,1, IC 95% 1,3-28,7, p = 0,022, mayor de 6: OR 15,8, IC 95% 2,2-113, p = 0,006) se asociaron independientemente con el uso de TNFi. El uso de coxib se asoció con la indicación de usar TNFi tanto en los pacientes con espondiloartritis axial (OR 4,2, IC 95% 1,74-10,11, p = 0,001) como periférica (OR 4, IC 95% 1,85-8,62, p < 0,001). Conclusiones: El inicio de la enfermedad en la forma de artritis reactiva se comportó como un factor protector para la necesidad posterior de usar TNFi, mientras que presentar lumbalgia inflamatoria, sacroilitis demostrada por cualquier método, el tratamiento con coxib y el puntaje máximo de BASDAI mayor de 4 se asociaron con el uso de estos medicamentos.

ABSTRACT Introduction: The use of tumor necrosis factor (TNF) alpha inhibitors is increasing in patients with spondyloarthritis. Early identification of those that would require them, or the ability to predict their use, could lead to a more effective and timely treatment by rationalizing their use. Objective: To determine factors that better explain the indication of TNFi in the study population. Material and methods: The association between anti-TNFα use and categorical demographic, clinical, laboratory, radiological and treatment variables was explored using Pearson's Chi2 or Fisher's exact test. The association with the quantitative variables was evaluated using Student's t test or Mann Whitney U test, depending on their distribution. Those variables with P < 0.25 were entered into univariate models of explanatory logistic regression to cons truct crude ORs, and those with P < 0.25 were included in the multivariate model to construct adjusted ORs. Results and discussion: The study population includes 181 patients. In the univariate model: reactive arthritis, urethritis, and peripheral involvement were protective factors for the use of TNFi. Axial spondyloarthritis, inflammatory lumbalgia, alternating gluteal pain, morning stiffness, sacroiliitis demonstrated by any method, treatment with COX-2 inhibitors, evolu tion time of three years or more, and BASDAI and BASFI scores were associated with the use of TNFi. Multivariate model: reactive arthritis (P = 0.036), inflammatory back pain (P = 0.026), sacroiliitis (P = 0.045), use of coxibs (P = 0.001) and the maximum score of BASDAI (P = 0.022, P = 0.006) were independently associated with the use of TNFi. The use of coxibs was associa ted with the indication of using TNFi in both patients with axial spondyloarthritis (P = 0.001) and peripheral (P < 0.001). Conclusions: The onset of the disease in the form of reactive arthritis behaved as a protective factor for the subsequent need to use TNFi, while presenting with inflammatory back pain, sacroiliitis, demonstrated by any method, treatment with coxibs, and the maximum score of BASDAI greater than 4 associated with the use of these medications.

Riesgo cardiovascular de los antiinflamatorios no esteroideos / Cardiovascular risk of non-steroidal anti-inflammatory drug

Los antiinflamatorios no esteroideos (AINEs) se encuentran entre los fármacos más utilizados en la práctica clínica. Actúan mediante el bloqueo de las enzimas ciclooxigenasas (COX), pero el grado de inhibición de COX-1 y COX-2 varía entre ellos. Se ha generalizado la clasificación entre COX-2 selectivos o coxibs, y los no selectivos o AINEs tradicionales. Tanto los efectos analgésico y antiinflamatorio como los efectos adversos cardiovasculares dependen de la inhibición de COX-2. Este trabajo revisa las evidencias disponibles del aumento del riesgo de eventos trombóticos tanto para los coxibs como para los AINEs tradicionales. El efecto protrombótico podría deberse a la inhibición de la COX-2 endotelial, con disminución de la prostaciclina y un incremento relativo de los niveles del tromboxano plaquetario. Los coxibs y el diclofenac, 150 mg/día, aumentarían el riesgo de eventos vasculares mayores en más de un tercio. El ibuprofeno 2400 mg/día aumentaría levemente el riesgo de eventos coronarios. El naproxeno 1000 mg/día no incrementaría el riesgo de eventos vasculares. Además, el ibuprofeno y el naproxeno tienen el potencial del disminuir el efecto cardioprotector de bajas dosis de aspirina. El naproxeno (≤ 1000 mg/día) y el ibuprofeno a bajas dosis (≤ 1200 mg/día) deberían considerarse los AINEs con el mejor perfil de seguridad cardiovascular. Las decisiones terapéuticas deben basarse en una adecuada evaluación del riesgo del paciente, utilizando los AINEs más seguros, a las menores dosis efectivas, por el menor tiempo posible que permita el control de los síntomas, restringiendo su utilización en enfermos con aumento del riesgo cardiovascular.

Non-steroidal anti-inflammatories (NSAIDs) are among the most commonly used drugs in clinical practice. They block cyclooxygenases (COX) enzymes, but the degree of inhibition of COX-1 and COX-2 varies between them. In general, NSAIDs are classified in selective COX-2 or coxibs and non-selective or traditional NSAIDs. Both the analgesic and anti-inflammatory effects, as well as the cardiovascular adverse effects, depend on the COX-2 inhibition. This paper reviews the available evidence of the increased risk of thrombotic events for both coxibs and traditional NSAID. The prothrombotic effect could be due to the inhibition of endothelial COX-2, with a decrease in production of prostacyclin and a relative increase in platelet thromboxane levels. Coxibs and diclofenac 150 mg/day seem to increase the risk of major vascular events by more than a third. Ibuprofen 2400 mg/day could slightly increase the risk of coronary events. Naproxen 1000 mg/day apparently does not increase the risk of vascular events. Besides ibuprofen and naproxen have the potential to decrease the cardioprotective effect of low doses of aspirin. Naproxen (≤ 1000 mg/day) and low doses of ibuprofen (≤ 1200 mg/day) are considered to have the most favorable thrombotic cardiovascular safety profiles of all NSAIDs. Therapeutic decisions should be based on an assessment of a person´s individual risk factors, using the safest NSAIDs, at the lowest effective doses, for the shortest duration necessary to control symptoms, restricting their use in patients with increased cardiovascular risk.

Serum sclerostin and Dickkopf-related protein 1 levels of axial spondyloa rthritis can be raised by selective cyclo-oxygenase 2 inhibitor / 中华风湿病学杂志

Objective To investigate the serum levels of dickkopf-related protein 1 (DKK1) and sclerostin (SOST) in patients with axial spondyloarthritis treated with selective cyclo-oxygenase 2 inhibitor and its relation to clinical efficacy.Methods A randomized double-blind controlled trial with axial spondyloarthritis (ax-SpA) was carried out in our hospital.The data from patients in a single center was collected and analyzed.Serum DKK1 and SOST levels were measured by enzyme-linked immuno sorbent assay (ELISA)method before and after 12 weeks treatment,then correlation analysis were conducted for DKK1 and SOST levels with erythrocyte sedimentation rate (ESR),C reactive protein (CRP),Bath ankylosing spondylitis disease activity index (BASDAI),Bath ankylosing spondylitis functional index (BASFI) and SPARCC of the sacroiliac joint inflammation score.Chi-square tests were used for analyzing of categorical data.Fisher exact tests were performed when the expected frequencies were less than 5.Two independent samples t-test was used to compare the difference between groups.Single sample t-test was used to ompare the differences between data before and after treatment.Pearson or Spearman correlation was used for correlation analysis.Results After 12 weeks of treatment,a total of 116 patients completed the follow-up,including 57 cases of imrecoxib group and 59 cases of the celecoxib group.There were no statistically significant difference between the two groups (P＞0.05).The level of serum DKK1 was significantly increased after treatment [(393±137) pg/ml,vs (542±274)pg/ml,P＜0.05].The serum level of SOST increased significantly [(39±19) pg/ml vs (57±36) pg/ml,t=5.814,P＞0.05],too.The difference between the two groups was not statistically significant (P＞0.05).Spearman correlation analysis showed that serum DKK1 was positively correlated with serum SOST (r=0.226,P=0.015).A significantcorrelation was found between SOST level and ESR,CRP,finger to floor distance,left and fight lumbar side flexion and Schober's test (ESR:r=-0.379,P＜0.01;r=-0.309,P=0.001;r=-0.225,P=0.015;r=0.185,P=0.047;r=0.247,P=0.008;r=0.214,P=0.021).Conclusion Imrecoxib and celecoxib have similar efficacy on relieving the signs and symptoms of patients with ax-SpA.Short-term application of selective COX-2 inhibitors can increase DKK1 and SOST and possibly delay radiographic progression.

Study on application effect of cyclooxygenase-2 inhibitor in perioperative pain management in patients with laparoscopic cholecystectomy / 重庆医学

Objective To investigate the application effect of selective cyclooxygenase-2 (COX-2) inhibitor in perioperative preemptive on-demand analgesia of the patients with laparoscopic cholecystectomy under enhanced recovery after surgery(ERAS).Methods The clinical data in 206 cases of gallstones undergoing selective COX-2 inhibitor for preemptive analgesia (new type analgesic group) from June to December 2015 and 198 cases of gallstones undergoing tramadol postoperative analgesia (traditional analgesia group) in the biliary surgery department of West China Hospital of Sichuan University were retrospectively analyzed.The intraoperative anesthesia schemes in the two groups were consistent.The same pain resolution scheme was adopted after operation.Then the VAS pain score,pain relief drug use rate,adverse reactions,analgesic satisfaction and hospitalization time were compared between the two groups.Results The VAS scores at postoperative 2,6,12,24 h in the new type analgesia group were lower than those in the traditional analgesia group,the difference was statistically significant (P＜0.05);the analgesic drug use rate in the new type analgesia group was lower than that in the traditional analgesia group (14.56％ vs.44.95％,P＜0.05),and the use rate of tramadol hydrochloride and pethidine hydrochloride was lower than that in the traditional analgesia group (P＜0.05).The incidence rate of adverse reactions in the new type analgesia group was lower (2.43％ vs.36.36％,P＜0.05).The incidence rate of nausea and vomiting in the new type analgesia group was lower than that in the traditional analgesia group (P＜0.05),and the incidence rate of other complications had no statistically signifiwas higher than that in the traditional analgesia group (P＜0.05);the average hospital stay and postoperative hospital stay had no statistical difference between the two groups (P＞0.05).Conclusion COX-2 inhibitors can effectively reduce perioperative pain degree in the patients with laparoscopic cholecystectomy,reduces the use frequency of analgesic drugs,shortens the hospital stay time and increases the patient satisfaction.cant difference (P＞0.05).The perioperative patient analgesia satisfaction the in the new type analgesia group

Effect of parecoxib combined with ropivacaine for incision infiltration on agitation during recovery from anesthesia in patients undergoing abdominal hepatectomy / 中华麻醉学杂志

Objective To evaluate the effect of parecoxib combined with ropivacaine for incision infiltration on agitation during recovery from anesthesia in patients undergoing abdominal hepatectomy. Methods Forty patients of both sexes, aged 35-64 yr, with body mass index of 18-24 kg∕m2 , of Ameri-can Society of Anesthesiologists physical statusⅠ or Ⅱ, undergoing elective partial hepatectomy, were di-vided into parecoxib sodium group ( group P ) and parecoxib sodium plus ropivacaine group ( group RP ) with 20 cases in each group. Parecoxib sodium 40 mg was intravenously injected at 30 min before operation in group P. Parecoxib sodium 40 mg was intravenously injected at 30 min before operation, and incision in-filtration was performed with 0. 5％ ropivacaine 20 ml at the end of surgery in group RP. Patient-controlled intravenous analgesia was performed at the end of surgery in both groups. The development of agitation, re-spiratory depression and nausea and vomiting was recorded within 30 min after operation. Blood samples were collected from the radial artery immediately before induction ( T0 ) , at the end of surgery ( T1 ) and at removal of extubation ( T2 ) for determination of plasma cortisone ( Cor) concentrations ( by radio-immunity method), plasma epinephrine (E) and norepinephrine (NE) concentrations (by enzyme-linked immu-nosorbent assay) and blood glucose ( using a blood gas analyzer) . Results Compared with the baseline at T0 , the plasma concentrations of Cor, Glu, E and NE were significantly increased at T1,2 in two groups ( P>0. 05) . The incidence of agitation and plasma concentrations of Cor, Glu, E and NE were significantly low-er at T1,2 in group RP than in group P ( P<0. 05) . No patients developed nausea and vomiting and respira-tory depression in two groups. Conclusion Parecoxib combined with ropivacaine for incision infiltration can decrease the occurrence of agitation during recovery from anesthesia, which is related to inhibiting stress responses of patients undergoing abdominal hepatectomy.

Effect of cyclooxygenase-2 antisense RNA combined with celecoxib on the proliferation and apoptosis of hepatoma cells / 临床肝胆病杂志

ObjectiveTo investigate the antitumor effect of cyclooxygenase-2 (COX-2) antisense RNA combined with celecoxib on hepatoma CBRH7919 cells. MethodsThe effect of celecoxib on in vitro proliferative activity, cell cycle, and apoptosis of hepatoma cell lines CBRH7919, CBRH7919-E, and CBRH7919-A (transfected with COX-2 antisense gene segment) were observed. MTT assay, cell cycle analysis, and RT-PCR were used to evaluate the change in in vitro proliferation of hepatoma cell lines. A multivariate analysis of variance was used for comparison of continuous data between groups, and the SNK-q test was used for further comparison between two groups. ResultsAfter the treatment with celecoxib, CBRH7919-A cells had a significant reduction in growth rate compared with CBRH7919 and CBRH7919-E cells (F=38.303, P＜0.01), in a time- and dose-dependent manner (F=162.638 and 22.666, both P＜0.01). Celecoxib significantly increased the proportion of cells in G0/G1 phase and had a marked inhibitory effect on cells in S phase in a dose-dependent manner (F=32.515, P＜0.01), while there was no significant change in the proportion of cells in G2/M phase. Compared with CBRH7919 and CBRH7919-E cells, CBRH7919-A cells were more sensitive to celecoxib (F=1219.506, P＜0.01). After the treatment with celecoxib at different concentrations (40 and 80 μmol/L), all three groups had a significant increase in cell apoptosis (all P＜001), and there was no significant difference in apoptosis between the three groups (P＞0.05). ConclusionCOX-2 antisense RNA combined with celecoxib can inhibit the in vitro growth and proliferation and cell cycle of hepatoma CBRH7919 cells, promote apoptosis, and thus exert a potential therapeutic effect on hepatoma cells.

Perfil dos pacientes com urticária e angioedema por anti-inflamatórios não esteroidais do Serviço de Alergia e Imunologia do Hospital do Servidor Público do Estado de São Paulo / Profile of patients with urticaria and angioedema caused by nonsteroidal anti-inflammatory drugs in the Allergy and Immunology Division of Hospital do Servidor Público Estadual de São Paulo

Objetivos: Identificar pacientes com história de urticária e angioedema desencadeados por anti-inflamatórios não esteroidais (AINEs), no Serviço de Alergia e Imunologia do Hospital do Servidor Público Estadual de São Paulo, classificá-los como seletivos e não seletivos e avaliar a tolerabilidade ao inibidor de COX-2 (etoricoxib 90 mg). Métodos: Os indivíduos com múltiplas reações desencadeadas por AINE, de grupos diferentes, foram submetidos a teste de provocação oral com Etoricoxib 90 mg. Pacientes com história de urticária e/ou angioedema a um único grupo de AINE, ou com primeiro episódio, realizaram testes de provocação oral com outro grupo de AINE, para classificá-los em seletivo ou não. Resultados: Estudou-se 43 pacientes, com idade entre 18 e 71 anos, predomínio do sexo feminino (77%). A maioria dos pacientes apresentavam reações a múltiplos AINE (não seletivos) e 2 (5%) a um único AINEs (seletivos). Observou-se sintomas alérgicos em 53%, com predomínio da rinite (61%). Os fármacos mais implicados foram: dipirona (39%), diclofenaco (18%) e AAS (14%). Todos os pacientes apresentaram teste com etoricoxib 90 mg negativo. Conclusão: A maioria dos pacientes apresentou reação não seletiva, e todos os pacientes apresentaram teste com etoricoxib 90 mg negativo, demonstrando segurança e ser uma boa opção terapêutica.

Objectives: To identify patients with a history of urticaria and angioedema caused by nonsteroidal anti-inflammatory drugs (NSAIDs) at the Allergy and Immunology Division of Hospital do Servidor Público Estadual de São Paulo, to classify them as selective or nonselective, and to evaluate their tolerability to cyclooxygenase-2 inhibitors (etoricoxib 90 mg). Methods: Patients with multiple reactions induced by NSAIDs, from different groups, were subjected to oral provocation test with etoricoxib 90 mg. Patients with a history of urticaria and/or angioedema induced by only one group of NSAIDs, or experiencing their first episode, were subjected to oral provocation test with another NSAID group to classify them as selective or non-selective. Results: A total of 43 patients aged 18-71 years, predominantly female (77%), were studied. The majority of patients showed reactions to multiple NSAIDs (non-selective); only 2 (4.6%) reacted to only one NSAID (selective). Allergic symptoms were observed in 53% of the patients, mainly rhinitis (61%). The drugs most frequently involved were dipyrone (39%), diclofenac (18%) and acetylsalicylic acid (14%). The etoricoxib 90 mg test resulted negative for all patients. Conclusion: The majority of patients showed nonselective reactions, and all of them showed negative etoricoxib 90 mg tests, demonstrating the safety and appropriateness of this treatment option.

Improvement effects of parecoxib on ventricular remodeling after acutemyocardial infarction in rats and its influence in PI3K/Akt signaling pathway / 中国药理学通报

Aim To observe the improvement effects of parecoxib on ventricular remodeling after acute myocardial infarction in rats and its influence on PI3K/Akt signaling pathway.Methods Forty male Sprague-Dawley rats were randomly divided into five groups(n=8):sham operation group (group S), ventricular remodeling model group(group R), low dose of parecoxib group(group P1), middle dose of parecoxib group(group P2), and high dose of parecoxib group(group P3).A myocardial infarction model was established by ligating the left anterior descending branch(LAD) of coronary artery in group R, group P1, group P2 and group P3.One day after the operation,the rats were given intraperitoneal injection of 4,8,12 mg·kg-1 parecoxibin Group P1, group P2 and group P3,respectively, for two weeks.The same volume saline was given in group S and group R.Four weeks later, LVSP, LVEDP,+dp/dtmax,-dp/dtmax were monitored.The hearts were harvested to calculate left ventricular hypertrophy index.The pathological change of heart was examined with an optical microscope.The expressions of atrial natriuretic peptide(ANP) mRNA and brain natriuretic peptide(BNP) mRNA were detected by RT-PCR.The expression of PI3K,Akt,P-Akt and caspase-3 was detected by Western blot.Results Compared with group S, the cardiac function was decreased, the left ventricular hypertrophy index, the expression levels of ANP,BNP mRNA, caspase-3 were increased, and the expression levels of PI3K, P-Akt were reduced in group R(all P<0.05).Compared with group R, the cardiac function was ameliorated, the left ventricular hypertrophy index were reduced in group P2 and group P3(all P<0.05).The expression levels of ANP,BNP mRNA, Caspase-3 were decreased, and the expression levels of PI3K and P-Akt were increased in group P1,group P2 and group P3(all P<0.05).Conclusions Middle and high doses of parecoxib can mitigate the process of ventricular remodeling after myocardial infarctionand improve the myocardial function, and its underlying mechanism may be related to activating PI3K/Akt signaling pathway.

Impact of parecoxib on hospital discharge: retrospective analysis of Brazilian health insurance / Impacto de parecoxibe na desospitalização: análise retrospectiva da saúde suplementar no Brasil

ABSTRACT BACKGROUND AND OBJECTIVES: Adequate postoperative pain and renal colic control is critical for patients' recovery and to decrease hospitalization costs and the use of resources. So, this study aimed at evaluating hospitalization time of patients treated with parecoxib sodium versus other non-steroid anti-inflammatory drugs to manage postoperative pain of appendectomy or fractures and renal colic. METHODS: This is a retrospective data analysis of Brazilian private hospitals medical bills, including patients treated with non-steroid anti-inflammatory drugs to decrease post-appendectomy pain (n=1618), post orthopedic fracture pain (n=2858 and renal colic (n=6555), between January and June 2014. Mean hospitalization time was evaluated according to each group of drugs. Mean difference among groups was calculated by the Kruskal-Wallis method. RESULTS: Mean hospitalization time for patients submitted to appendectomy was 1.95 days with parecoxib versus 2.20 with other non-steroid anti-inflammatory drugs (p= 0.006). For patients submitted to orthopedic fracture surgery, mean time was 1.75 days with parecoxib versus 1.93 days with other anti-inflammatory drugs (p=0.008). Parecoxib has also significantly decreased hospitalization time for renal colic as compared to other drugs (25.2h versus 32.9h; p<0.001). CONCLUSION: Parecoxib sodium has provided shorter hospitalization time with possible decrease in use of resources and costs and should be considered a choice for such painful conditions.

RESUMO JUSTIFICATIVA E OBJETIVOS: O controle adequado da dor pós-operatória e cólica renal é fundamental para a recuperação do paciente e redução de custos relacionados à hospitalização e utilização de recursos. Assim, o objetivo deste estudo foi avaliar o tempo de hospitalização entre pacientes tratados com parecoxibe sódico versus outros fármacos anti-inflamatórios não esteroides, no manuseio da dor pós-operatória associada à apendicectomia ou fraturas e cólica renal. MÉTODOS: Uma análise retrospectiva de dados de contas médicas de hospitais privados no Brasil foi realizada, incluindo pacientes tratados com anti-inflamatório não esteroide para redução da dor pós-apendicectomia (n=1.618), dor pós-fratura ortopédica (n=2.858) e cólica renal (n=6.555), entre janeiro e junho de 2014. O período médio de internação foi avaliado de acordo com cada grupo de fármacos. A diferença média entre os grupos foi avaliada utilizando o método de Kruskal-Wallis. RESULTADOS: O tempo médio de permanência hospitalar para pacientes submetidos à apendicectomia foi de 1,95 dias com parecoxibe versus 2,20 com outros anti-inflamatórios não esteroides (p = 0,006). Para pacientes submetidos a cirurgias de fraturas ortopédicas, o tempo médio foi de 1,75 dias com parecoxibe versus 1,93 dias para outros anti-inflamatórios (p=0,008). Parecoxibe também apresentou redução significativa no tempo de internação hospitalar para cólica renal em comparação com outros fármacos (25,2h versus 32,9h; p<0,001). CONCLUSÃO: Parecoxibe sódico demonstrou menor tempo de permanência hospitalar com possível redução na utilização de recursos e custos, devendo ser considerado como uma escolha para estas condições dolorosas.

Cyclooxygenase-2 Inhibitor Reduces Hepatic Stiffness in Pediatric Chronic Liver Disease Patients Following Kasai Portoenterostomy

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.

Protective effects of the specific cyclooxygenase-2 inhibitor on microglia activation-mediated neuronal damage / 中华行为医学与脑科学杂志

Objective To investigate the protective effect of NS398,a specific cyclooxygenase-2 inhibitor,on microglial activation-mediated neuronal damage.Methods The microglia of neonatal SD rat were isolated and cultured in the medium containing 1 μg/ml of LPS.The morphological changes of microglial were observed.The IL-1β and TNF-α levels were detected by Western blot in LPS group (group L) and control group (group C).The hippocampal neurons of neonatal SD rats were cultured in the control medium (group C),LPS-activated microglial conditioned medium (group L) and LPS-activated microglial conditioned medium with NS398 (group N),respectively.The survival rate of neurons were detected by MTT.The respiration of hippocampus neurons was determined by detecting the ratio of lactic acid/pyruvic acid.Results LPS-induced microglial activation was characterized by the morphological change and increased secretion of IL-1β and TNF-α.The survival rate of neurons cultured by microglia activated conditioned medium was 64.37％,while the group N was 80.25％ (P＜0.01).In group L,the ratio of lactic acid/pyruvic acid (27.34±8.53) was significantly higher than that of group N (20.32±6.05,P＜0.01) and group C (14.95±4.72,P＜0.01).Conclusion NS398,a specific cyclooxygenase-2 inhibitor,has a protective effect on rat hippocampus neuron damaged by activated microglia.

Preventive effect of low-dose sufentanil combined with parecoxib sodium for hyperalgesia of remifentanil anesthesia after postoperative / 中国医师杂志

Objective To explore preventive effect of low-dose sufentanil combined with parecoxib sodium for hyperalgesia of remifentanil anesthesia after postoperative.Methods A total of 120 patients undergoing elective abdominal surgery under general anesthesia was randomly divided into three groups that were given intraoperative remifentanil infusion.At the 30 minutes before surgery,group A were given intravenous sufentanil 0.1 μg/kg combined with 40 mg parecoxib sodium,group B were given intravenous sufentanil 0.2 μg/kg combined with 40 mg parecoxib sodium,and group C were given normal saline 5 ml.Postoperative recovery time,extubation time,postoperative 1,2,6,12,and 24 h visual analog scale (Visual Analogue Scale/Score,VAS) score,and after 24 h additional analgesia number of cases and the restless occurrence of three groups were compared.Results Awakening time and extubation time of group B was significantly longer than groups A and C [(10.9 ± 1.3) min vs (8.6 ± 0.6) min,(8.2 ± 0.7) min;(14.0 ± 2.1) min vs (10.7 ± 2.2) min,(10.8 ± 1.2) min,all P ＜ 0.01].Each point VAS scores of groups A and B were significantly lower than group C (P ＜0.01).After 24 h,the number of cases additional analgesic medication,and restlessness occurrence of group C were significantly more than the number of cases of groups A and B (P ＜ 0.01),the number of cases and the restless occurrence after 24 h additional analgesic drugs of group A were more than group B,but there was no significant difference between two groups (P ＞ 0.05).Conclusions Low dose sufentanil together with parecoxib sodium can inhibit after-remifentanil-induced hyperalgesia,and will not appear awakening time and extubation time delays and safe.

COX-2 and its inhibitors in lung cancer drug resistance / 国际肿瘤学杂志

COX-2 is the inducible form of cyclooxygenase,which is overexpressed in non-small cell lung cancer,especially in the adenocarcinoma,and is involved in the production of lung cancer drug resistance, reducing the sensitivities of tumor cells to chemotherapy drugs. COX-2 inhibitors have the effects of antitumor and prevention of tumor formation. Therefore,in order to reverse the drug resistance of tumor cells,improve the sur-vival rate and the prognosis of patients with tumor,the application of COX-2 inhibitors as adjuvant chemotherapy and combined with chemotherapy drugs has become a new direction in the treatment of lung cancer.

Evaluación clínica, epidemiológica y terapéutica en 14 casos de carcinoma inflamatorio mamario canino / Clinical, Epidemiological and Therapeutic Evaluation in 14 Cases of Inflammatory Breast Cancer in Canines / Avaliação clínica, epidemiológica e terapêutica em 14 casos de carcinoma inflamatório mamário canino

Con el objetivo de evaluar los aspectos clínicos, edad, raza, presencia de metástasis, protocolo quimioterapéutico, utilización de inhibidores de COX-2 y sobrevida en caninas diagnosticadas con carcinoma inflamatorio, en el Hospital Veterinario de Uberaba (HVU), se realizó un análisis retrospectivo de las historias clínicas de 14 hembras caninas atendidas en el HVU entre julio de 2011 y julio de 2012, con diagnóstico de carcinoma inflamatorio mamario. Las razas acometidas fueron mestizo, poodle, terrier brasilero, teckel y pastor belga. Edad media: 11,1 años. En 7 animales fueron detectados focos de metástasis a distancia. De ellos 5 pacientes recibieron como único tratamiento inhibidores de COX-2 y apenas 4 recibieron tratamiento quimioterapéutico. El protocolo, constituido por piroxicam, ciclofosfamida, carboplatina y doxorrubicina, presentó el mayor tiempo de sobrevida (210 días). En conclusión, el carcinoma inflamatorio es una enfermedad de mal pronóstico, poco tiempo de sobrevida, y ocasiona alteraciones sistémicas que disminuyen la respuesta terapéutica. Aparentemente la modalidad terapéutica más indicada es la asociación de inhibidores de COX-2 y quimioterapéuticos; sin embargo, son necesarios estudios clínicos controlados para evaluar estas sugestiones.

With the aim of evaluating clinical aspects, age, breed, presence of metastasis, chemotherapeutical protocol, use of COX-2 inhibitors and survival rate in female dogs diagnosed with inflammatory carcinoma at the Hospital Veterinario de Uberaba (HVU), a retrospective analysis was performed on the medical records of 14 female dogs seen at HVU between July, 2011 and July, 2012 and diagnosed with inflammatory breast cancer. The breeds included were crossbred, poodle, Brazilian terrier, teckel and Belgian shepherd. Average age: 11.1 years. Outbreaks of distant metastasis were detected in 7 animals, out of which 5 patients received COX-2 inhibitors as sole treatment and only 4 received chemotherapeutical treatment. The protocol, constituted by piroxicam, cyclophosphamide, carboplatin and doxorubicin showed the highest survival time (210 days). In conclusion, inflammatory carcinoma is a disease of bad prognosis, short survival time and produces systemic alterations that reduce therapeutic response. Apparently, the most accurate therapeutic form is the association of COX-2 inhibitors and chemotherapeutics; however, controlled clinical studies are needed in order to evaluate these suggestions.

Com o objetivo de avaliar os aspectos clínicos, idade, raça, presença de metástase, protocolo químico-terapêutico, utilização de inibidores de COX-2 e sobrevida em caninas diagnosticadas com carcinoma inflamatório, no Hospital Veterinário de Uberaba (HVU), se realizou uma análise retrospectiva das histórias clínicas de 14 fêmeas caninas atendidas no HVU entre julho de 2011 e julho de 2012, com diagnóstico de carcinoma inflamatório mamário. As raças acometidas foram SRD, poodle, terrier brasileiro, teckel e pastor belga. Idade média: 11,1 anos. Em 7 animais foram detectados focos de metástase a distância. Deles, 5 pacientes receberam como único tratamento inibidores de COX-2 e apenas 4 receberam tratamento químico-terapêutico. O protocolo, constituído por piroxicam, ciclofosfamida, carboplatina e doxorrubicina, apresentou o maior tempo de sobrevida (210 dias). Em conclusão, o carcinoma inflamatório é uma doença de mal prognóstico, pouco tempo de sobrevida, e ocasiona alterações sistêmicas que diminuem a resposta terapêutica. Aparentemente a modalidade terapêutica mais indicada é a associação de inibidores de COX-2 e químico-terapêuticos; contudo, estudos clínicos controlados são necessários para avaliar estas sugestões.

Effects of parecoxib on cellular immune function during patient-controlled intravenous analgesia with butorphanol after modified radical mastectomy / 中华麻醉学杂志

Objective To evaluate the effects of parecoxib on cellular immune function during patientcontrolled intravenous analgesia (PCIA) with butorphanol after modified radical mastectomy in patients.Methods Sixty ASA physical status Ⅰ or Ⅱ patients,aged 36-60 yr,weighing 48-82 kg,scheduled for elective modified radical mastectomy,were randomly divided into 2 groupe (n =30 each):control group (group C) and parecoxib group (group P).PCIA with butorphanol 10μg/kg was used at the end of operation.The PCIA pump was set up to deliver a 0.5 ml bolus dose with a 15-min lockout interval and background infusion at 2 ml/h.In group P,parecoxib 40 mg was injected intravenously at the end of operation and 12,24 and 36 h after surgery,while in group C,the equal volume of normal saline was injected.VAS score was maintained at ≤4.When VAS score≥5,butorphanol was injected intravenously as a rescue analgesic.Blood samples were obtained from the right internal jugular vein at 5 min before induction of anesthesia,2 h after skin incision,and 6 h and 1,3,7 days after surgery for determination of the levels of T lymphocyte subsets (CD3+,CD4+,CD8+,CD4+/CD8+) and natural killer (NK) cells (by flow cytometry).CD4+/CD8+ was calculated.The number of attempts,the number of successfully delivered doses and requirement for rescue analgesics were recorded at 2,6,12,24 and 48 h after surgery.Adverse effects were also recorded after surgery.Results Compared with group C,the number of attempts and requirement for rescue analgesics were significantly decreased,the number of successfully delivered doses was increased,and the levels of CD3+,CD4+,CD4+/CD8+ and NK cells were decreased at 1 day after surgery (P ＜ 0.05).There was no significant difference in adverse effects between the two groups (P ＞ 0.05).Conclusion Parecoxib can enhance the efficacy of postoperative PCIA with butorphanol and reduce the consumption of butorphanol thus improving cellular immune function after modified radical mastectomy in the patients.

Inhibitory effects of cyclooxygenase-2 inhibitor and α-interferon on growth of human liver cancer xenografts and tumor angiogenesis in nude mice / 中华普通外科杂志

Objective To investigate α-interferon (α-IFN) and cyclooxygenase-2 (COX-2)inhibitor celecoxib synergistically inhibit the growth of human liver cancer SMMC-7721 cells xenografts and tumor angiogenesis in a nude mouse model.Methods The effects of celecoxib and α-interferon on tumor volumes and weight were observed.The expressions of VEGF and Cox-2 were determined by immunohistochemistry and RT-PCR,and the effect of α-interferon on MVD also was observed by immunohisto chemistry.Results During the period of observation tumor volume increased progressively in control group,while it was suppressed obviously in other drug treatment groups.The average tumor volume was significantly smaller in celecoxib + α-IFN group than that in IFN group,celecoxib group and control group (P ＜ 0.01,respectively),its inhibitory rate was 61.84％.Immunohistochemistry showes that the VEGF and MVD was significantly smaller in celecoxib + IFN group than that in α-IFN group,celecoxib group and control group (P ＜ 0.01,respectively).RT-PCR shows that the COX-2mRNA and VEGF mRNA pression was lower in the celecoxib + α-IFN group than in α-IFN group,celecoxib group and control group (P ＜ 0.01).Conclusions The COX-2 inhibitor celecoxib and α-interferon synergistically reduces xenografts growth of human liver cancer SMMC-7721 cells effectively via suppressing tumor growth and angiogenesis.

The effects of cyclooxygenase-2 inhibitors on peritoneal lymphangiogenesis and peritoneal function in uremic rats / 中华内科杂志

Objective To investigate the effects of cyclooxygenase-2 (COX-2) inhibitor on peritoneal lymphangiogenesis and peritoneum function in uremic rat.Methods Uremic rats treated by peritoneal dialysis were intragastric administration celecoxib.Structures of peritoneum,peritoneal function,peritoneal lymphatic vessel density (LVD) were detected in every group.The mRNA of vascular endothelial growth factor-C (VEGF-C),lymphatic vessel endothelial hyluronan receptor-1 (LYVE-1) and COX-2 were tested by RT-PCR.The protein expressions of LYVE-1,VEGF-C,COX-2 were tested by western blot.Results With the extension of the duration of dialysis,the peritoneum thickness was increasing,inflammatory cell infiltrated obviously,uhrafiltration volume decreased significantly.But the celecoxib could increase uhrafiltration volume and reduce the glucose transport rate(P ＜0.05).Compared with the normal group,the levels of LVD,COX-2,VEGF-C,and LYVE-1 mRNA and protein were significantly up-regulated in uremic and dialysis groups (P ＜0.05).Compared with the uremic dialysis group,the levels of LVD,COX-2,VEGFC and LYVE-1 mRNA and protein were significantly down-regulated in the celecoxib group.There was a positive correlation between COX-2 and VEGF-C,LVD in protein levels,as well as VEGF-C and LVD (all P values ＜ 0.05).Conclusions Hyper glucose dialysis solution and uremic condition could up-regulate the expression of COX-2,VEGF-C,LYVE-1 in gene and protein level and stimulate lymphangiogenesis.COX-2 inhibitor could delay the change of peritoneal structures and function.COX-2 inhibitor could prevem the lymphangiogenesis in uremic rat treated by peritoneal dialysis,which might down-regulate the expression of VEGF-C by COX-2 depended manner.

Effects of cyclooxygenase-2 inhibitor on peritoneal function and angiogenesis in uremic peritoneal dialysis rats / 中华肾脏病杂志

Objective To investigate the effects of the cyclooxygenase-2 (COX-2) inhibitor (celecoxib) on angiogenesis and peritoneal function of uremic peritoneal dialysis rats.Methods Forty-eight male SD rats were selected,and they were randomly divided into five groups:normal control group(n =8),sham operation group(n =8),uremia group(5/6 nephrectomy,n =8),PD group [4.25％ PD solution,2 weeks PD model(n =8) and 4 weeks PD model(n =8)],PD + celecoxib intervention group[treated by celecoxib(20 mg/kg) via oral gavage,n =8].The peritoneum of uremic peritoneal dialysis rats was observed in different dialysis time from peritoneal structures,functions,peritoneal tissue capillary density (microvessel density,MVD) and COX-2,vascular endothelial growth factor (VEGF) expression level,and the impacts of celecoxib on uremic peritoneal dialysis rats peritoneal angiogenesis and peritoneal function were study.Results With the conduct of the peritoneal dialysis,peritoneal thickness increased,the inflammatory cells infiltrated,peritoneal equilibration test (PET) showed that ultrafiltration volume decreased significantly (P ＜ 0.05),the amount of glucose transport rate rised significantly (P ＜ 0.05),but the celecoxib could improve net ultrafiltration volume (P ＜ 0.05),and reduce the glucose transport rate (P ＜ 0.05).The peritoneal tissue MVD and COX-2,VEGF expression were significantly increased in uremia group and PD group compared with that in the normal control group (all P ＜ 0.05),were significantly lower in PD + Celecoxib intervention group than that in uremia group (P ＜ 0.05).The correlation analysis showed that the level of COX-2 protein expression with MVD,VEGF protein expression was positively correlated (both P ＜ 0.05),the level of VEGF protein expression and MVD was positively correlated (P ＜ 0.05).Conclusions In vivo high glucose dialysate and uremia environmental can stimulate the COX-2 and VEGF expression raised,and the capillaries production increased in peritoneal tissue.Celecoxib can alleviate the change of peritoneal tissue morphology and function in long-term peritoneal dialysis rats.Celecoxib inhibits the peritoneal neovascularization of uremic peritoneal dialysis rats,possibly through inhibition of COX-2 expression to reduce the production of VEGF.