Effects of selective versus non-selective cox-2 inhibition on experimental periodontitis

Abstract In the present study we compared the effects of the selective COX-2 inhibitor etoricoxib with those of the classical non-selective NSAID diclofenac on the inflammatory process and alveolar bone loss in an experimental model of periodontitis in rats. Ninety male Holtzman rats (250 g) were randomly sorted into four experimental groups: Sham+CMC and Ligature+CMC (control) groups which received 0.5% carboxymethylcellulose sodium (CMC) solution; Ligature+Diclofenac and Ligature+Etoricoxib groups which received Potassium Diclofenac and Etoricoxib, respectively, suspended in 0.5% CMC (10 mg/kg/day). At 7, 14 and 21 days after placing ligatures in the cervical region of both the lower right and left first molars, the animals were euthanized. At the end of each period, the mandibles were collected for radiographic examination of alveolar bone loss. In addition, alveolar bone and periodontal ligament tissue samples were collected for COX-2 expression analysis and gingival tissues were collected for measurement of PGE2 contents. Animals with ligature-induced periodontal disease showed significant increased COX-2 gene expression at days 7, 14 and 21 (p<0.05) on alveolar bone and periodontal ligament. However, both treatments resulted in significantly reduced alveolar bone loss when compared to the untreated Ligature group (p<0.05), with no statistical difference between Etoricoxib and Diclofenac Potassium groups. This study shows that both drugs were able to reduce alveolar bone loss after periodontal disease induction.

Resumo No presente estudo nós comparamos os efeitos de um inibidor seletivo da COX-2 (etoricoxibe) com um anti-inflamatório não esteroidal não seletivo (AINE) (diclofenaco de potássio) no processo inflamatório e perda óssea alveolar em modelo de periodontite experimental. Noventa ratos Holtzman machos (250 g) foram randomizados em quatro grupos experimentais: Sham+CMC e Ligadura+CMC (controle) que receberam solução de carboximetilcelulose de sódio (CMC) a 0,5%; Ligadura+Diclofenaco e Ligadura+Etoricoxibe que receberam diclofenaco de potássio e etoricoxibe, respectivamente, suspensos em CMC 0,5% (10 mg/kg/dia). 7, 14 e 21 dias após colocação de ligadura bilateral na região cevical dos primeiros molares inferiores, os animais foram submetidos à eutanásia. No fim de cada período, as mandíbulas foram coletadas para exame radiográfico de perda óssea alveolar. Em adição, osso alveolar e ligamento periodontal foram coletados para determinar a expressão da enzima COX-2, e o tecido gengival foi coletado para determinar a expressão de PGE2. Animais submetidos à indução da doença periodontal pela ligadura (Grupo Ligadura) apresentaram um aumento significativo da expressão gênica de COX-2 nos dias 7, 14 e 21 (p<0,05). Todavia, ambos os tratamentos resultaram em uma significativa redução da perda óssea alveolar em comparação ao grupo Ligadura (p<0,05). Esse estudo mostrou que ambos os fármacos foram capazes de reduzir a perda óssea alveolar após indução da doença periodontal.

Effect of flurbiprofen axetil combined with lung-protective ventilation on postoperative cellular immune function in patients undergoing thoracoscopic radical resection of lung cancer / 中华麻醉学杂志

Objective To investigate the effect of flurbiprofcn axetil combined with lung-protective ventilation on postoperative cellular immune function in the patients undergoing thoracoscopic radical resection of lung cancer.Methods Eighty American Society of Anesthesiologists physical status Ⅰ or Ⅱ patients of both sexes,with no abnormal lung function during the preoperative examination,aged 35-64 yr,with body mass index of 18-28 kg/m2,scheduled for elective thoracoscopic radical resection of lung cancer under general anesthesia,were divided into 4 groups (n =20 each) using a random number table method:conventional mechanical ventilation group (group C),flurbiprofen axetil combined with conventional mechanical ventilation group (group F+C),lung-protective ventilation group (group P) and flurbiprofen axetil combined with lung-protective ventilation group (group F+P).Flurbiprofen axetil 2 mg/kg was intravenously injected at 5 min before induction of anaesthesia in F+C and F+P groups.Patients were mechanically ventilated in volume-controlled mode in four groups.Conventional ventilator settings were adjusted with tidal volume (VT) 10 ml/kg and respiratory rate 10-20 breaths/min during two-lung ventilation and with VT 8 ml/kg and respiratory rate 13-16 breaths/min during one-lung ventilation.Lung-protective ventilator settings were adjusted with VT 8 ml/kg and respiratory rate 12-14 breaths/min during two-lung ventilation and with positive end-expiratory pressure 5 cmH2O,VT 6 ml/kg and respiratory rate 14-16 breaths/min during onelung ventilation.All patients received patient-controlled intravenous analgesia (PCIA) at the end of surgery until 24 h after surgery.PCIA solution contained sufentanil 100 μg and ondansetron 16 mg in 100 ml of normal saline in group C and group P.PCIA solution contained sufentanil 100 μg,flurbiprofen axetil 2 mg/kg and ondansetron 16 mg in 100 ml of normal saline in group F+C and group F+P.The PCIA pump was set up with a 0.5 ml bolus dose,a 15-min lockout interval and background infusion at a rate of 2 ml/h.Visual analog scale score was maintained ≤3.When visual analog scale score ＞3,tramadol 2 mg/kg was intravenously injected.Before induction of anesthesia (T0),at the end of surgery (T1),at 24 and 72 h after surgery (T2,3) and at 1 week after surgery (T4),blood samples were collected from the central vein for measurement of the levels of T lymphocyte subsets CD3+,CD4+,CD8+ and NK cells.The CD4+/CD8+ ratio was calculated.Results Compared with the baseline at T0,the levels of CD3+,CD4+ and NK cells and CD4+/CD8+ratio were significantly decreased at T1-3 in C,F+C and P groups and at T1,2 in group F+P (P＜0.05).Compared with group C,the levels of CD3+,CD4+ and NK cells and CD4+/CD8+ratio were significantly increased at T1-3 in the other three groups (P＜0.05).Compared with group F+C or group P,the levels of CD3+,CD4+ and NK cells and CD4+/CD8+ratio were significantly increased at T1-3 in group F+ P (P＜0.05).Conclusion Flurbiprofen axetil combined with lung-protective ventilation improves postoperative cellular immune function and provides better efficacy than either alone in the patients undergoing thoracoscopic radical resection of lung cancer.

Effect of parecoxib sodium combined with dexmedetomidine on postoperative levels of plasma excita-tory aminoacid and beta-amyloid protein in jugular bulb venous of elderly patients / 中华麻醉学杂志

Objective To investigate the effect of parecoxib sodium combined with dexmedetomi-dine on postoperative levels of plasma excitatory aminoacid and beta-amyloid protein(β-AP)in jugular bulb venous of elderly patients. Methods A total of 135 patients of either sex, aged 65-79 yr, weighing 47-76 kg, of American Society of Anesthesiologists physical status Ⅱ or Ⅲ, undergoing elective open reduc-tion and internal fixation after tibial fracture and hip replacement, were divided into 3 groups(n=45 each) using a random number table: parecoxib sodium group(group P), dexmedetomidine group(group D)and parecoxib sodium combined with dexmedetomidine group(group PD). In group P, parecoxib sodium 40 mg (diluted to 5 ml in normal saline)was injected intravenously at 15 min before induction of anesthesia. In group D, dexmedetomidine was intravenously infused at a loading dose of 05 μg∕kg over 15 min starting from 15 min before induction of anesthesia, followed by an infusion of 05 μg·kg-1·h-1until the end of surgery. In group PD, parecoxib sodium 40 mg(diluted to 5 ml in normal saline)was intravenously injec-ted at 15 min before induction of anesthesia, and dexmedetomidine was intravenously infused at a loading dose of 05 μg∕kg over 15 min followed by an infusion of 05 μg·kg-1·h-1until the end of surgery at the same time. At 15 min before induction of anesthesia(T0), at the end of surgery(T1)and at 24, 48 and 72 h after surgery(T2-4), jugular bulb venous blood samples were taken for determination of concentrations of glutamate and aspartate in plasma(by reversed phase high-performance liquid chromatography)and β-AP(by enzyme-linked immunosorbent assay). Cognitive function was assessed at 1 day before surgery and 7 days after surgery using a battery of neuropsychologic tests including Wechsler Memory Scale, Digit Span (Forward and Backward), visual recognition and associative learning, Wechsler Adult Intelligence Scale and Trail Making Test Part A. The occurrence of postoperative cognitive dysfunction was recorded at 7 days after surgery. Results Compared with P and D groups, the concentrations of plasma glutamate at T2-3, plasma aspartate at T2and β-AP at T1and incidence of postoperative cognitive dysfunction were significantly decreased in group PD(P< 005). Conclusion The mechanism by which parecoxib sodium combined with dexmedetomidine decreases the occurrence of POCD may be related to inhibiting the levels of excitatory aminoacid and β-AP in brain tissues of elderly patients.

Study on the Diastolic Effect and Mechanism of Hui Medicine Hexin Oil Solution on Isolated Thoracic Aor-tic Vascular Rings of Rats / 中国药房

OBJECTIVE:To study the diastolic effect and mechanism of Hui medicine Hexin oil solution on isolated thoracic aortic vascular rings of rats,and provide reference for its treatment for cardiovascular diseases. METHODS:Thoracic aortic vascu-lar rings of rats were taken and then soaked in Kelvin's nutrient solution(K-H). Using 1×10-6 mol/L norepinephrine(PE)or 60 mmol/L potassium chloride (KCl) for inducing the contraction of vascular rings,biological signal acquisition and analysis system was used to determine the diastolic effect and mechanism of Hexin oil solution with concentrations of 0.0204,0.0408,0.0612, 0.0816,0.1020 mg/mL on vascular rings,and diastolic rate was calculated. After culturing vascular rings by 0.1 mmol/L nitric ox-ide synthase inhibitor L-nitro-arginine methyl ester (L-NAME),cyclooxygenase inhibitor indomethacin (INDO),and potassium ion channel blocker glibenclamide(Gli)for 20 min,the diastolic effects of above-mentioned 5 mass concentrations of Hexin oil so-lution on the contraction of vascular rings pre-contracted by PE were determined,and diastolic rate was calculated. The test was based on K-H solution as blank control. RESULTS:Compared with blank control,Hexin oil solution with concentration of 0.0204-0.1020 mg/mL had obvious diastolic effect on the contraction of vascular rings induced by PE and KCl (P<0.05 or P<0.01), showing concentration-dependent relationship. INDO pre-treatment can relieve the diastolic effect of Hexin oil solution on vascular rings pre-contracted by PE;and compared with blank control group,the diastolic rate had no statistical significance (P>0.05). While the pre-treatment of Gli,L-NAME did not affect the diastolic effect of Hexin oil solution on vascular rings pre-contracted by PE;and compared with blank control group,diastolic rate was obviously increased(P<0.05 or P<0.01). CONCLUSIONS:Hex-in oil solution can concentration-dependently conduct the relaxation of thoracic aortic vascular rings pre-contracted by PE,KCl. The mechanism may be associated with activation of cyclooxygenase pathway.

Study on the Diastolic Effect and Mechanism of Hui Medicine Hexin Oil Solution on Isolated Thoracic Aor-tic Vascular Rings of Rats / 中国药房

OBJECTIVE:To study the diastolic effect and mechanism of Hui medicine Hexin oil solution on isolated thoracic aortic vascular rings of rats,and provide reference for its treatment for cardiovascular diseases. METHODS:Thoracic aortic vascu-lar rings of rats were taken and then soaked in Kelvin's nutrient solution(K-H). Using 1×10-6 mol/L norepinephrine(PE)or 60 mmol/L potassium chloride (KCl) for inducing the contraction of vascular rings,biological signal acquisition and analysis system was used to determine the diastolic effect and mechanism of Hexin oil solution with concentrations of 0.0204,0.0408,0.0612, 0.0816,0.1020 mg/mL on vascular rings,and diastolic rate was calculated. After culturing vascular rings by 0.1 mmol/L nitric ox-ide synthase inhibitor L-nitro-arginine methyl ester (L-NAME),cyclooxygenase inhibitor indomethacin (INDO),and potassium ion channel blocker glibenclamide(Gli)for 20 min,the diastolic effects of above-mentioned 5 mass concentrations of Hexin oil so-lution on the contraction of vascular rings pre-contracted by PE were determined,and diastolic rate was calculated. The test was based on K-H solution as blank control. RESULTS:Compared with blank control,Hexin oil solution with concentration of 0.0204-0.1020 mg/mL had obvious diastolic effect on the contraction of vascular rings induced by PE and KCl (P<0.05 or P<0.01), showing concentration-dependent relationship. INDO pre-treatment can relieve the diastolic effect of Hexin oil solution on vascular rings pre-contracted by PE;and compared with blank control group,the diastolic rate had no statistical significance (P>0.05). While the pre-treatment of Gli,L-NAME did not affect the diastolic effect of Hexin oil solution on vascular rings pre-contracted by PE;and compared with blank control group,diastolic rate was obviously increased(P<0.05 or P<0.01). CONCLUSIONS:Hex-in oil solution can concentration-dependently conduct the relaxation of thoracic aortic vascular rings pre-contracted by PE,KCl. The mechanism may be associated with activation of cyclooxygenase pathway.

Efeito antimicrobiano da indometacina no biofilme periodontal: estudo em ratos / Antimicrobial effect of indomethacin on periodontal biofilm: study in rats

Introdução: A doença periodontal é uma doença de caráter multifatorial que se desenvolve em decorrência da interação do biofilme bacteriano com a resposta imuno-inflamatória do hospedeiro que pode ser modulada por fatores sistêmicos e ambientais. Objetivo: o presente estudo teve como objetivo avaliar a ação antimicrobiana do anti-inflamatório não esteroidal indometacina sobre o biofilme retido em ligaduras inseridas subgengivalmente para indução de periodontite experimental em ratos. Método: assim, 20 animais foram divididos aleatoriamente em um dos grupos: grupo Indometacina (n=10); grupo água destilada (n=10). Os animais receberam gavagem diária da medicação (5 mg/kg indometacina) ou de água destilada (2 ml), durante 7 dias. As ligaduras ao redor dos dentes foram coletadas e o biofilme foi dispersado, diluído em 10-1, 10-2 e 10-3, semeado em ágar sangue e as placas foram cultivadas em anaerobiose durante 4 dias. As quantificações foram realizadas a partir da contagem das unidades formadoras de colônias (UFC) totais pelo programa Colony counter aplicativo para androide, caracterizadas pela presença de bactérias aeróbias e aeróbias facultativas relacionadas ao processo de saúde, e pela contagem manual de UFC grandes, que melhor caracterizam as bactérias anaeróbias relacionadas ao processo de doença. Resultado: constatou-se um número significativamente maior de UFC grandes no grupo indometacina quando comparado ao grupo água (p=0,004) e um número significativamente menor de UFC totais no grupo indometacina quando comparado ao grupo água (p=0,0013). Conclusão: dentro dos limites do presente estudo pôde-se concluir que a indometaciana agrava o processo infeccioso periodontal devido ao crescimento de UFC anaeróbias e redução de UFC facultativas.

Introduction: Periodontal disease is a multifactorial disease the develop as a result of the interaction of the bacterial biofilm and the immune-inflammatory response of the individual, which, in its turn, is modulate by systemic and environmental factors. Objective: This study aimed to evaluate the antimicrobial effect of indomethacin, a non-steroidal anti-inflammatory, on the biofilm retained in ligatures inserted in the subgingival region to induce experimental periodontitis in rats. Method: 20 animals were randomly assigned to one of the groups: Indomethacin (n = 10); distilled water (n = 10). The animals received daily gavage of drugs (5 mg / kg indomethacin) or distilled water (2 ml) for 7 days. The ligatures around the teeth were collected and the biofilm was dispersed, diluted 10-1, 10-2 and 10-3, seeded in blood agar and the plates were grown anaerobically for 4 days. The measurements were carried out from the counting of total colony forming units (CFU) by Colony counter application program for android, characterized by the presence of facultative aerobic and aerobic bacteria related health process, and the manual counting of large CFU, which better characterized the anaerobic bacteria-related disease process. Result: it was found a significantly higher number of large CFU in indomethacin group compared to the water group (p = 0.004) and a significantly lower number of total CFU in the indomethacin group compared to the water group (p = 0.0 013). Conclusion: within the limits of this study it was concluded that the indomethacin worsens periodontal infectious process due to the growth of anaerobic CFU and the reduction of facultative CFU.

Beneficial effects of methanolic extract of Indigofera linnaei Ali. on the inflammatory and nociceptive responses in rodent models

ABSTRACT Indigofera linnaei Ali. (Tamil Name: Cheppu Nerinjil) belongs to the family Fabaceae, used for the treatment of various ailments in the traditional system of medicine. In the present study, the beneficial effects of methanol extract of whole plant of I. linnaei (MEIL) were evaluated on inflammation and nociception responses in rodent models. In vitro nitric oxide (NO), lipoxygenase (LOX) and cyclooxygense (COX) inhibitory activities were also performed to understand the mode of action. MEIL at the dose of 200 & 400 mg/kg, p.o. significantly inhibited carrageenan induced rat paw volume and reduced the weight of granuloma in cotton pellet granuloma model. The results obtained were comparable with the standard drug aceclofenac. The anti-nociceptive effect of MEIL in mice was evaluated in hot plate and acetic acid induced writhing model. The plant extract significantly reduced the number of writhes and the analgesic effect was higher than that of the standard drug aspirin. However, the extract fails to increase the latency period in hot plate method suggesting that the extract produce nociception by peripheral activity. The extract produced inhibitory effect on NO, LOX and COX in concentration dependent manner. The extract exhibited pronounced and selective COX-2 inhibition. Altogether, these results suggested that the methanol extract of Indigofera linnaei could be considered as a potential anti-inflammatory and analgesic agent.

RESUMO Indigofera linnaei Ali pertence à família Leguminosae e é utilizada para o tratamento de várias doenças na medicina tradicional. No presente estudo, os efeitos benéficos do extrato metanólico da planta inteira de I. linnaei (MEIL) foram avaliados em respostas inflamatórias e nocicepção em modelos de roedores. Testes in vitro de atividade inibitória do óxido nítrico (NO), lipoxigenase (LOX) e ciclooxigenase (COX) também foram realizados para compreender o modo de ação. MEIL nas doses de 200 e 400 mg/kg, p.o. inibiu significativamente o volume da pata de rato induzido por carragenana e reduziu o peso do granuloma no modelo de pélete de algodão. Os resultados obtidos foram comparáveis ao do fármaco padrão, aceclofenaco. O efeito anti-nociceptivo de MEIL foi avaliado em camundongos no modelo de placa quente e de contorção induzida por ácido acético. O extrato da planta reduziu significativamente o número de contorções e o efeito analgésico foi maior do que o do fármaco padrão, ácido acetilsalicílico. Porém, o extrato não conseguiu aumentar o período de latência no método da placa quente, sugerindo que este produz nocicepção por atividade periférica. O extrato produziu efeito inibitório sobre o NO, LOX e COX dependente da concentração. O extrato exibiu inibição acentuada e seletiva da COX-2. No seu conjunto, estes resultados sugerem que o extrato metanólico de Indigofera linnaei poderia ser considerado como agente anti-inflamatório e analgésico potencial.

Lung protection of flurbiprofen axetil combined with protective mechanical ventilation in patients undergoing thoracic surgery / 中华麻醉学杂志

Objective To evaluate the lung protection of flurbiprofen axetil combined with protective mechanical ventilation in the patients undergoing thoracic surgery.Methods Sixty patients of both sexes,aged 25-64 yr,with body mass index of 18-29 kg/m2,of American Society of Anesthesiologists physical status Ⅰ or Ⅱ,scheduled for elective radical resection of esophageal cancer under general anesthesia,were randomly divided into 4 groups (n =15 each) using a random number table:conventional mechanical ventilation (group CMV),flurbiprofen axetil combined with conventional mechanical ventilation group (group F+CMV),protective mechanical ventilation group (group PMV),and flurbiprofen axetil combined with protective mechanical ventilation group (group F+PMV).Volume-controlled ventilation was performed in the 4 groups.Conventional mechanical ventilation mode was as follows:tidal volume (VT) 10 ml/kg and respiratory rate (RR) 10-12 breaths/min during two-lung ventilation (TLV);VT 8 ml/kg and RR 15-18 breaths/min during one-lung ventilation (OLV).Protective mechanical ventilation mode was as follows:VT 6 ml/kg,positive end-expiratory pressure 5 cmH2O,RR 15-18 breaths/min (during OLV) or 10-12 breaths/min (during TLV),inspiratory/expiratory ratio 1:2,fraction of inspired oxygen 100％,oxygen flow rate 1-2 L/min.The end-tidal pressure of carbon dioxide was maintained at 3545 mmHg in the 4 groups.Flurbiprofen axetil 2 mg/kg was injected intravenously at 15 min before skin incision,and the patient-controlled intravenous analgesia (PCIA) was used after surgery.PCIA solution contained sufentanil 100 μg and flurbiprofen axetil 2 mg/kg in 100 ml of normal saline.The PCIA pump was set up with a 0.5 ml bolus dose,a 15 min lockout interval and background infusion at a rate of 2 ml/h,and visual analogue scale score was maintained ≤ 3.Before induction of anesthesia (T0),at 15 min of TLV (T1),at 1 and 2 h of OLV (T2),at 2 h after OLV (T3),at the end of surgery (T4),and at 24hafter surgery (T5),blood samples were taken from the radial artery for determination of arterial oxygen partial pressure,and oxygenation index was calculated.The occurrence of abnormal pulmonary function was recorded during and after surgery.The parameters of pneumodynamics were recorded at T1-4.Central venous blood samples were taken at T0,4,5 to measure the concentrations of tumor necrosis factor-alpha,interleukin6 (IL-6),and IL-8 in serum.Results Compared with group CMV,arterial oxygen partial pressure,oxygenation index,and dynamic lung compliance were significantly increased,the peak airway pressure,airway plateau pressure and concentrations of tumor necrosis factor-alpha,IL-6,and IL-8 in serum were significantly decreased,and the incidence of abnormal pulmonary function after surgery was significantly decreased in the other 3 groups,especially in group F+PMV (P＜0.05).Conclusion Flurbiprofen axetil used before and after surgery has lung protection,and it produces better efficacy when combined with protective mechanical ventilation in the patients undergoing thoracic surgery.

New COX-2 Inhibitors / 대한내과학회지

Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used to treat pain and inflammation. There are two kinds of NSAID classified according to the selectivity of COX-2 inhibition: non-selective NSAIDs and cyclooxygenase (COX)-2 inhibitors. Non-selective NSAIDs have a high incidence of gastrointestinal and bleeding-associated adverse events, while COX-2 inhibitors are safer in terms of these events. However, COX-2 inhibitors are thought to cause increased cardiovascular events. The COX-2 inhibitors rofecoxib and valdecoxib were withdrawn from the market over safety concerns. Three COX-2 inhibitors are now available in South Korea after the recent approval of etoricoxib and polmacoxib for osteoarthritis patients. After reviewing the history of and recent studies about the safety of COX-2 inhibitors, physicians should find new uses for old drugs.

Effects of different concentrations of parecoxib sodium on rat sperm motility, capacitation and acrosome reaction in vitro / 中华麻醉学杂志

Objective To evaluate the effects of different concentrations of parecoxib sodium on the rat sperm motility,capacitation and acrosome reaction in vitro.Methods The sperm samples from Sprague-Dawley rat epididymis were collected by Klinefelter diffusion method and randomly divided into 4 groups (n =18 each) using a random number table:control group (group C),and parecoxib sodium 100,500,1 000 μmol/L groups (P1-3 groups).Parecoxib sodium with the final concentrations of 100,500 and 1 000 μmol/L was added to the culture medium.The samples were then incubated for 5 h in an airtight container filled with 5 ％ CO2 at 37 ℃.Then sperm motility was examined in vitro at 37 ℃ and analyzed by the computer-assisted sperm analysis,including the sperm motility ((a + b)％),average path velocity (VAP),straight line velocity (VSL),curvilinear velocity (VCL) and amplitude of lateral head displacement (ALH).The capacitation effect was assessed by using the chlortetracycline staining and phase-contract microscopy.The acrosome reaction was evaluated by coomassie brilliant blue staining.Results The VAP,VSL,VCL and capacitation ability of the sperm were gradually decreased in C and P1-3 groups (P ＜ 0.05).Compared with group C,(a + b)％ in P2,3 groups and ALH in P2 group were significantly decreased (P ＜ 0.05).There was no significant difference in the acrosome reaction between groups (P ＞ 0.05).Conclusion Parecoxib sodium has significant inhibitory effects on the rat sperm motility and capacitation in a dose-dependent manner,while has no effect on the acrosome reaction in vitro.

Late administration of a specific COX-2 inhibitor does not treat and/or prevent progression of gastric tumors in rats submitted to duodenogastric reflux procedure

PURPOSE:To assess whether late introduction of a specific COX-2 inhibitor (Meloxicam) can treat and/or prevent the progression of tumors in the stomach of rats submitted to duodenogastric reflux. METHODS: Seventy five male Wistar rats, weighing 150 grams, were submitted to the induction of duodenogastric reflux through the pylorus. At 36 weeks of follow-up were established three experimental groups: DGR36 sacrificed immediately, DGR54 and DGR54MLX both sacrificed at 54th week of follow-up . The animals of the latter group were fed with a rat chow premixed with Meloxicam (2.0 mg/ kg feed; 0.3 mg / kg bw / day) and the other two with standard rat chow. The lesions found in the pyloric mucosa and gastrojejunal anastomosis were analyzed macroscopically and histologically. For statistical analysis was adjusted a generalized linear model assuming a binomial distribution with LOGIT link function. RESULTS: No significant differences were found when comparing the incidences of benign tumor lesions (Adenomatous Hyperplasia), p=0.4915, or malignant (Mucinous Adenocarcinoma), p=0.2731, among groups. CONCLUSION: Late introduction of specific COX-2 inhibitor (Meloxicam) did not treat and was not able to prevent the progression of tumoral lesions induced by duodenogastric reflux in the rat stomachs.

Efficacy of parecoxib sodium for prevention of post-thoracotomy pain syndrome / 中华麻醉学杂志

Objective To evaluate the efficacy of parecoxib sodium for prevention of post-thoracotomy pain syndrome.Methods Ninety ASA physical status Ⅰ or Ⅱ patients,aged 40-64 yr,weighing 50-80 kg,scheduled for elective thoracotomy,were equally and randomly divided into 3 groups using a random number table:control group (group C) and two different treatments with parecoxib sodium groups (P1 and P2 groups).At 20 min before skin incison,parecoxib sodium 40 mg was injected intravenously in P1 and P2 groups,while the equal volume of normal saline was given in group C.An increment of parecoxib sodium 40 mg was given every 12 h for 6 times after surgery in group P2.General anesthesia combined with epidural anesthesia was used during surgery and patient-controlled epidural analgesia was used for postoperative analgesia in the three groups.Morphine was used as rescue analgesic to maintain VAS score ≤ 3.The consumption of morphine within 72 h after operation,development of adverse effects and development and duration of pain (VAS score ＞ 3) within 6 months after operation were recorded.The blood coagulation was measured at 72 h after operation.Results Morphine was not used within 72 h after operation in P2 group.The abnormality of blood coagulation at 72 h after operation was not observed in the three groups.Compared with group C,no significant changes were found in the incidence and duration of pain within 6 months after operation in P1 group (P ＞ 0.05),the incidence of pain was significantly decreased and duration of pain was shortened within 6 months after operation in P2 group,and the incidence of nausea,vomiting and pruritus was decreased in P1 and P2 groups (P ＜ 0.05 or 0.01).The incidence of nausea,vomiting and pruritus was significantly lower in P2 group than in P1 group (P ＜ 0.01).Conclusion Continuous application of parecoxib sodium for 72 h can decrease the development of post-thoracotomy pain syndrome without increasing the incidence of adverse effects.

Effect of parecoxib pretreatment on expression of aquaporin-4 during focal cerebral ischemia-reperfusion in rats / 中华麻醉学杂志

Objective To investigate the effect of parecoxib pretreatment on the expression of aquaporin-4 (AQP4) during focal cerebral ischemia-reperfusion (I/R) in rats.Methods One hundred and twenty-eight adult male Sprague-Dawley rats,aged 6-8 weeks,weighing 230-280 g,were randomly divided into 4 groups (n =32 each):sham operation group (S group),I/R group,parecoxib 5 mg/kg group (group P5) and parecoxib 10 mg/kg group (group P10).The rats were anesthetized with 10％ chloral hydrate 3.5 ml/kg.Focal cerebral I/R was induced by 2 h middle cerebral artery occlusion followed by reperfusion.Parecoxib 5 and 10 mg/kg were injected via the right internal jugular vein at 30 min before middle cerebral artery occlusion in groups P5 and P10,respectively.The equal volume of normal saline was injected instead of parecoxib in groups S and I/R.Neurological deficit score (NDS) was assessed at 2 and 24 h of reperfusion.The rats were then sacrificed and brains were removed for determination of infract volume (by TTC staining).Brain water content was measured by wet/dry brain weight ratio.Their brains were cut into sections which were stained with haematoxylin and eosin and examined under microscope.The expression of AQP4 in brain tissues was measured.Results Compared with S group,NDS and brain water content were significandy increased,the infarct volume was enlarged,and the expression of AQP4 in brain tissues was up-regulated in I/R group (P ＜ 0.05 or 0.01).NDS and brain water content were significantly lower,the infarct volume was smaller,and the expression of AQP4 in brain tissues was lower in groups P5 and P10 than in I/R group (P ＜ 0.05 or 0.01).Microscopic examination showed that brain injury was significantly attenuated in groups P5 and P10 as compared with I/R group.Conclusion The mechanism by which parecoxib pretreatment alleviates the focal cerebral I/R injury in rats is related to down-regulation of the expression of AQP4.

Efficacy of parecoxib sodium for preemptive analgesia: a meta-analysis / 中华麻醉学杂志

Objective To evaluate the efficacy of parecoxib sodium for preemptive analgesia.Methods PubMed,EMBASE,Cochrane Library,and CNKI database were searched for randomized placebo-controlled trials involving the efficacy of parecoxib sodium for preemptive analgesia.The modified Jadad scale was used for quality assessment.Evaluation indexes included VAS scores at 1,6,12 and 24 h after operation,consumption of morphine within 24 h after operation,and incidences of nausea and vomiting after operation.Meta-analysis was conducted using the Cochrane Collaboration's RevMan 5.0.2 software.Results Fourteen randomized placebo-controlled trials involving 1086 patients were included in our meta-analysis.The modified Jadad scale scores for the 14 studies were ≥ 4.The patients were divided into 2 groups:placebo group and parecoxib sodium 40 mg injected before operation group.The results of meta-analysis showed that VAS scores at 1,6,12 and 24 h after operation were significantly decreased,the consumption of morphine within 24 h after operation was reduced,and the incidences of nausea and vomiting after operation were decreased in parecoxib sodium 40 mg injected before operation group as compared with placebo group (P ＜ 0.05).Conclusion Intravenous injection of parecoxib sodium 40 mg before operation can produce significant preemptive analgesic efficacy and is helpful in decreasing the adverse effect of postoperative analgesia.

Cyclooxygenase-2 inhibitors modulate skin aging in a catalytic activity-independent manner

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.

Efficacy of intramuscular parecoxib for postoperative analgesia in patients undergoing total knee arthroplasty / 中华麻醉学杂志

Objective To evaluate the efficacy of intramuscular parecoxib for postoperative analgesia in patients undergoing total knee arthroplasty.Methods Fifty-four ASA Ⅰ-Ⅲ patients,aged 65-75 yr,scheduled for unilateral total knee arthroplasty,were randomly divided into 2 groups (n =27 each)∶ tramadol group (group T) and parecoxib group (group P).Total intravenous anesthesia was used in both groups.Group P received intramuscular injection of parecoxib 40 mg at 12 h before operation and 12,24,36,48,60 and 72 h after operation,and group T received tramadol 100 mg at the same time points.When VAS score was more than 3 after operation,intramuscular parecoxib 50 mg was given as rescue analgesic.The ineffective analgesia at rest and during activity was recorded.The time for knee range of motion to reach 90° and cardiovascular events were recorded.The ultrasonic inspection was performed on veins of the bilateral lower extremities at 7 and 14 days after operation for detection of vein thrombosis.Results Compared with T group,the rate of ineffective analgesia at rest and during activity was significantly decreased,the time for knee range of motion to reach 90° was shortened,and the incidence of deep vein thrombosis was significantly decreased (P ＜ 0.05 or 0.01),and no significant change was found in the incidences of cardiovascular events and intramuscular venous thrombosis in group P (P ＞ 0.05).Conclusion Parecoxib 40 mg injected intramuscularly before and after operation can significantly relieve postoperative pain,is helpful for the hip function rehabilitation and can reduce the occurrence of deep vein thrombosis in patients undergoing total knee arthroplasty.

Effects of different concentrations of parecoxib on proliferation and apoptosis of colon cancer LoVo cells / 中华麻醉学杂志

Objective To investigate the effects of different concentrations of parecoxib on proliferation and apoptosis of colon cancer LoVo cells.Methods The colon cancer LoVo cells were inoculated in cuhure plate and cultured for 24 h.The cells were randomly divided into 4 groups (n =6 each):control group (C group) and different concentrations of parecoxib groups (P1-3 groups).The cells were incubated with parecoxib 10,40 and 160μmol/L for 24 h in P1-3 groups respectively.The rates of proliferation inhibition were measured by MTT assay.The colony formation rates were measured by colony formation assay.The apoptotic rate was determined by flow cytometry.The Survivin and caspase-3 mRNA expression in the cells was detected by RT-PCR.Results Compared with C group,the rates of proliferation inhibition and apoptotic rate were significantly increased,the colony formation rates were significantly decreased,the expression of Survivin mRNA was down-regulated,and the expression of caspase-3 mRNA was up-regulated in a concentration-dependent manner in P1-3 groups (P ＜ 0.05).Conclusion Parecoxib can inhibit the proliferation of LoVo cells and induce the apoptosis in LoVo cells in a concentration-dependent manner through down-regulating the expression of Survivin mRNA and up-regulating the expression of caspase-3 mRNA.

The Effect of a Topical Selective Cyclooxygenase-2 Inhibitor on Skin-Wound Scarring of the Rabbit Ear

PURPOSE: The inflammatory phase is considered an integral part of adult wound healing, but fetal wound healing studies have shown scarless healing results in the absence of the inflammation process. The COX-2 pathway is an essential component of inflammation. The purpose of this study is to identify the effect of a topical selective COX-2 inhibitor on inflammation in rabbit skin wound healing and scarring. METHODS: Full-thickness wounds were made on 6 New Zealand rabbits' ears. Topical 5% celecoxib + vehicle (experimental tissue) and vehicle only (controlled tissue) were applied daily for 14d on each side of the ears. Scar samples were harvested at 2 wks, 4 wks, and 8 wks after the wounding. Each sample was stained with hematoxylin and eosin and the Masson's trichrome stain to evaluate inflammation and scar formation. RESULTS: Histological analysis demonstrated a significant reduction of inflammation, neovascularization, and scar elevation in the experimental tissue as compared to the control. Additionally, experimental tissue exhibited faster improvement of collagen organization similar to that of normal tissue. CONCLUSION: This study suggests that the topical application of a selective COX-2 inhibitor on a rabbit ear wound resulted in decreased inflammation and had a positive effect on the reduction of scar formation.

Observation of postoperative analgesic effects of intravenous parecoxib in gerontal patients undergoing laparoscopic cholecystectomy / 中华老年医学杂志

Objective To observe the postoperative analgesic effects of perioperative intravenous parecoxib in gerontal patients undergoing laparoscopic cholecystectomy. Methods A prospective,randomized, double-blind, placebo-controlled, parallel group study was performed. The 40 American Society of Anesthesiologists (ASA) Ⅰ or Ⅱ patients (aged 60-80 years) undergoing elective laparoscopic cholecystectomy under general anesthesia were randomly allocated to 2 groups (n = 20,each): the parecoxib group received intravenous parecoxib 40 mg at 10 minutes before incision and 12 hours and 24 hours after incision; however, the placebo group received 5 ml normal saline instead of parecoxib at the same time. The intensity of algesia was measured using visual analogue scale (VAS)scores (1-10, 0 = no pain, 10 = worst pain), and was recorded at 2, 4, 6, 12, 24 hours after operation. The patients' global evaluation of postoperative analgesia was recorded and compared between the two groups. Results The VAS scores at the different time points were significantly less in parecoxib group than in placebo group (all P＜ 0.05). The patients' global evaluation of postoperative analgesia was higher in parecoxib group than in placebo group [(8. 1 ± 1.2) scores vs.(5.2± 0. 9 ) scores, t = 7. 402, P ＜ 0. 05]. Conclusions Intravenous parecoxib can effectively relieve postoperative algesia and improve postoperative analgesia after laparoscopic cholecystectomy.

Effect of expression of P-glycoprotein in tumor tissue on analgesic efficacy of fentanyl and lornoxicam in patients with cancer pain / 中华麻醉学杂志

Objective To evaluate the effect of the expression of P-glycoprotein (P-gp) in the tumor tissue on the analgesic efficacy of fentanyl and lornoxicam in patients with cancer pain. Methods One hundred advanced cancer patients with pain aged 49-64 yr weighing $$-65 kg were included in this study. The expression of Pgp was positive in the tumor tissue in 50 patients (groups F1 and L1, n = 25 each) and negative in 50 patients (groups F2 and L2, n = 25 each). The patients in 4 groups received 48 h of pstient-controlled intravenous analgesia (PCIA). A loading dose of fentanyl 0.05 mg was administered before PCIA was started in groups F1 and F2 .The PCIA solution contained fentanyl 1 mg and droperidol 5 mg in 100 ml of normal saline in groups Ft and F2, or lomoxicam 64 mg and droperidol 5 mg in 100 ml of normal saline in groups L1 and L2. The PCA pump was set to deliver a background infusion of 2 ml/h and a bolus dose of 0.5 ml at 15 min lockout interval. Pain was assessed with VAS scores (0 = no pain, 10 = worst pain), and VAS score was maintained at ≤3 during PCIA. Flurbiprofen 50 mg was injected intravenously when VAS score≥4 and the consumption of flurbiprofen was recorded. The consumption of fentanyl and lornoxicam during PCIA was recorded. Blood samples from the internal jugular vein were taken at the beginning of PCIA (T0), and at 4, 12, 24, 48 h of PCIA (T1-4) for determination of blood fentanyl and lornoxicam concentrations. Results Flurbiprofen was not used in groups F2, L1 and L2. The consumption of flurbiprofen was ( 184 ± 41 ) mg in group F1 . There was no significant difference in the consumption of fentanyl during PCIA between groups F1 and F2 ( P ＞ 0.05). Blood fentanyl concentrations were not detected at all the time points in groups F1 and F2 . The VAS score during PCIA ≤ 3 in groups L1 and L2, and there was no significant difference in blood concentrations of lornoxicam at each time point and the consumption of lornoxicam during PCIA between groups L1 and L2 ( P ＞ 0.05). Conclusion Positive P-gp expression in the tunor tissue can decrease the analgesic efficacy of fentanyl, but exerts no effect on the analgesic efficacy of lornoxicam in patients with cancer pain.