Celecoxib: Antiangiogenic and Antitumoral Action / Celecoxib: Acción Antiangiogénica y Antitumoral

SUMMARY: Angiogenesis, a process by which new blood vessels are generated from pre-existing ones, is significantly compromised in tumor development, given that due to the nutritional need of tumor cells, pro-angiogenic signals will be generated to promote this process and thus receive the oxygen and nutrients necessary for its development, in addition to being a key escape route for tumor spread. Although there is currently an increase in the number of studies of various anti-angiogenic therapies that help reduce tumor progression, it is necessary to conduct a review of existing studies of therapeutic alternatives to demonstrate their importance.

La angiogénesis, proceso por el cual se generan nuevos vasos sanguíneos a partir de otros preexistentes, se encuentra comprometida de forma importante en el desarrollo tumoral, dado que por necesidad nutritiva de las células tumorales se generarán señales pro angiogénicas para promover este proceso y así recibir el oxígeno y los nutrientes necesarios para su desarrollo, además de ser una ruta de escape clave para la diseminación tumoral. Si bien, actualmente existe un aumento en la cantidad de estudios de diversas terapias anti angiogénicas que ayudan a reducir el avance tumoral, es necesario realizar una revisión de los estudios existentes de alternativas terapéuticas para demostrar su importancia.

Comparison between 200 mg generic celecoxib hard capsules and Celebra®: bioequivalence study in healthy male and female subjects under fasting conditions after a single dose / Comparação entre celecoxibe genérico de 200 mg em cápsulas duras e Celebra®: estudo de bioequivalência em indivíduos saudáveis do sexo masculino e feminino, em jejum, após uma dose única

ABSTRACT BACKGROUND AND OBJECTIVES: The objective of this study was to assess the bioequivalence between two 200 mg celecoxib hard capsule formulations administered to healthy male and female participants under fasting conditions with the aim of providing an alternative pharmaceutical product to the reference drug, Celebra®. METHODS: A randomized, open label, single dose, 2x2 crossover trial was conducted with 60 adult healthy subjects under fasting conditions comparing single doses of two celecoxib hard capsules formulation. Pharmacokinetic parameters were calculated following the determination of drugs concentrations in human plasma using a validated liquid chromatography with a tandem mass spectrometer detector method (LC-MS/MS). RESULTS: Statistical analysis provided geometric mean of test/reference ratio, confidence intervals, intra-subject variation coefficient and power of the test to the pharmacokinetic parameters Cmax, AUC0-t, and AUC0-∞. Confidence intervals for the geometric mean (90% CI) of the test/reference drugs for celecoxib were 98.26 to 122.75% for Cmax, 100.27% to 110.78% for AUC0-t, and 96.87% to 110.29% for AUC0-∞. The power of the test found was 95.09% for Cmax, 100.00% for AUC0-t, and 99.99% for AUC0-∞. CONCLUSION: The formulations met the Brazilian standards for interchangeability, as the confidence intervals for Cmax and AUC0-t ratios are within the range of 80% to 125%, thus meeting the requirements of the legislation during market registration. The researched product was approved by the regulatory authorities and became a commercially competitive option to the reference product for the Brazilian population.

RESUMO JUSTIFICATIVA E OBJETIVOS: O objetivo deste estudo foi avaliar a bioequivalência entre duas formulações de cápsulas duras de celecoxibe de 200 mg administradas a participantes saudáveis do sexo masculino e feminino em condições de jejum com o objetivo de fornecer um produto farmacêutico alternativo ao fármaco de referência, Celebra®. MÉTODOS: Estudo randomizado, aberto, de dose única e cruzado 2x2. Foi conduzido com 60 indivíduos adultos saudáveis em condições de jejum, comparando doses únicas de duas formulações de cápsulas duras de celecoxibe. Os parâmetros farmacocinéticos foram calculados após a determinação das concentrações dos fármacos no plasma humano usando uma cromatografia líquida validada com um método detector de espectrômetro de massa em tandem (LC-MS/MS). RESULTADOS: A análise estatística forneceu a média geométrica da razão teste/referência, os intervalos de confiança, o coeficiente de variação intra-sujeito e o poder do teste para os parâmetros farmacocinéticos Cmáx, AUC0-t e AUC0-∞. Os intervalos de confiança para a média geométrica (IC 90%) dos fármacos teste/referência para o celecoxibe foram 98,26 a 122,75% para Cmáx, 100,27% a 110,78% para AUC0-t e 96,87% a 110,29% para AUC0-∞. O poder do teste encontrado foi de 95,09% para Cmáx, 100,00% para AUC0-t e 99,99% para AUC0-∞. CONCLUSÃO: As formulações atenderam aos padrões brasileiros de intercambialidade, pois os intervalos de confiança para as razões Cmáx e AUC0-t estão dentro da faixa de 80% a 125%, atendendo, assim, às exigências da legislação para o registro no mercado. O produto pesquisado foi aprovado pelas autoridades regulatórias e tornou-se uma opção comercialmente competitiva ao produto de referência para a população brasileira.

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.

Efecto angiogénico comparado del celecoxib microencapsulado en PLGA v/s no encapsulado en un ensayo in vivo de angiogénesis / Comparative angiogenic effect of microencapsulated celecoxib in PLGA v/s non-encapsulated in an in vivo angiogenesis assay

RESUMEN: La angiogénesis es el proceso de formación de vasos sanguíneos a partir de otros formados previamente. Existen varios factores que están involucrados en el proceso, así como agentes capaces de modular distintas etapas de esta. Si bien, se ha observado que Celecoxib es capaz de inhibir la angiogénesis en distintos modelos, aún no se ha observado la potencial capacidad antiangiogénica de este agente cuando es microencapsulado en PLGA. Se incubaron huevos fertilizados y a las 48 horas se dividieron en 4 grupos para ser instilados con PBS (control), PLGA, Celecoxib 1000 ppm o Celecoxib 1000 ppm + PLGA. Se realizó un conteo de los vasos sanguíneos a las 48, 72 y 96 horas post aplicación de la solución a estudiar. Los resultados muestran que tanto Celecoxib como Celecoxib+PLGA reducen los vasos sanguíneos, manteniendo el mismo efecto a las 48, 72 y 96 horas y no existen diferencias significativas entre los dos tratamientos. Esto podría ser explicado por la concentración de Celecoxib usada o el margen de tiempo analizado, pudiendo encontrarse diferencias posteriores a este rango de tiempo o con concentraciones distintas.

SUMMARY: Angiogenesis is the process of blood vessel formation from previously formed ones. There are several factors involved in the process, as well as agents capable of modulating different stages of it. Although, it has been observed that Celecoxib is capable of inhibiting angiogenesis in different models, the potential antiangiogenic capacity of this agent has not yet been observed when it is microencapsulated in PLGA. Fertilized eggs were incubated and at 48 hours they were divided into 4 groups to be instilled with PBS (control), PLGA, Celecoxib 1000ppm or Celecoxib 1000 ppm + PLGA. A blood vessel count was performed at 48, 72 and 96 hours after application of the solution to be studied. The results show that both Celecoxib and Celecoxib + PLGA reduce blood vessels, maintaining the same effect at 48, 72 and 96 hours and there are no significant differences between the two treatments. This could be explained by the concentration of Celecoxib used or the time frame analyzed, being able to find differences after this time range or with different concentrations.

Clinical efficacy of controlled-release morphine tablets combined with celecoxib in pain management and the effects on WNK1 expression

OBJECTIVES: This study was designed to evaluate the clinical efficacy of controlled-release morphine tablets combined with celecoxib in relieving osteocarcinoma-related pain and the effects of the combination on WNK1 expression. METHODS: A total of 110 patients with osteocarcinoma-related pain were selected and divided into two groups based on the treatment administered, including the control group (treated with controlled-release morphine tablets alone) and the study group (treated with a combination of controlled-release morphine tablets and celecoxib). We compared the treatment efficacy, pain level (visual analog scale (VAS)), time of onset of breakthrough pain (BTP), dose of morphine, incidence of adverse events, quality of life (QOL) score, and With-no-lysine 1 (WNK1) expression in the peripheral blood (PB) as determined with qRT-PCR before and after treatment, of the two groups. RESULTS: The total effective rate of the study group was higher than that of the control group, while the VAS score, time of onset of BTP, dose of morphine, incidence of adverse events, QOL score, and relative WNK1 expression in the PB were lower than those of the control group (p<0.05). CONCLUSION: Combination treatment with controlled-release morphine tablets and celecoxib can be extensively used in the clinical setting because it effectively improves the symptoms, QOL score, and adverse effects in patients with osteocarcinoma-related pain.

Therapeutic effect of celecoxib-loaded microspheres on rheumatoid arthritis in rats after intra-articular injection / 中国药科大学学报

@#This study sought to assess the therapeutic effect of celecoxib (CEL)-loaded polylactic acid-glycolic acid copolymer (PLGA) microspheres on rheumatoid arthritis in rats after intra-articular injection.The celecoxib-loaded microspheres (CEL-MS) were prepared by the O/W solvent volatilization method with PLGA as carrier.In order to investigate the therapeutic effect of CEL-MS on rheumatoid arthritis in rats after intra-articular injection, a rat model of adjuvant arthritis (AA) was constructed by complete Freund''s adjuvant, and the evaluation indicators of the therapeutic effect were rat paw swelling, arthritis index,spleen index and joint synovial histopathological examination. The results showed that the microspheres had a smooth spherical morphology with a particle size of (2.1 ± 0.3) μm and a drug loading efficiency of (20.8 ± 0.6)%.The results of the in vivo efficacy test showed that intra-articular injection of CEL-MS compared to the CEL suspension oral and the celecoxib suspension intra-articular injection in adjuvant arthritis rat model can significantly reduce joint swelling and arthritis index, thus effectively inhibiting synovial inflammation.The above results indicate that intra-articular injection of CEL-MS has a good therapeutic effect on rheumatoid arthritis in rats.

The mechanism of RCE-4, an active ingredient of Reineckia carnea, in combination with celecoxib on the anti-proliferation of cervical cancer Ca Ski cells / 药学学报

This research explored the synergistic effects and the potential mechanisms of RCE-4 and various nonsteroidal anti-inflammatory drugs (NSAIDs) on the proliferation of cervical cancer Ca Ski cells. The MTT assay and CalcuSyn V2.0 software were used to detect cell proliferation and calculate the combination index (CI); the expression levels of various proteins were analyzed using Western blot assay; mitochondrial membrane potential (MMP) was assessed using JC-1 staining; acridine orange/ethidium bromide (AO/EB) double-fluorescence staining was used to detect the apoptosis of Ca Ski cells; a co-immunoprecipitation (Co-IP) assay was used to analyze the relative content of Bcl-2-Beclin 1 complex in Ca Ski cells. The results demonstrate that the combination of RCE-4 and NSAIDs increases the inhibition of Ca Ski cells compared to the single-RCE-4 group, and celecoxib provided the best synergistic effect among the four NSAIDs tested, with a CI of 0.32. The combination of RCE-4 and celecoxib significantly down-regulated the expression of cyclooxygenase-2 (COX-2) and nuclear transcription factor-κB (NF-κB), and promoted the expression of non-steroidal anti-inflammatory drugs activity gene-1 (NAG-1). In addition, autophagy induced by RCE-4 was markedly inhibited in combination with celecoxib, which was associated with down-regulation of the expression of microtubule-associated protein 3 (LC3)-II, Beclin 1, p62 and autophagy-related gene (ATG) 3/4B/5/7/14. RCE-4-induced apoptosis was significantly enhanced by altering the depolarization of mitochondrial membrane potential and the expression of B cell lymphoma-2 (Bcl-2), B cell lymphoma-xl (Bcl-xl), Bcl-2 associated X protein (Bax), Bcl-2/Bcl-xl-associated death promoter (Bad) and cleaved cysteinyl aspartate specific proteinase (cleaved-caspase) 3/7/9. Furthermore, the formation of the Bcl-2-Beclin 1 complex was significantly inhibited in Ca Ski cells treated with RCE-4 in combination with celecoxib. Taken together, this research shows that the combination of RCE-4 and celecoxib has a significant synergistic effect on the proliferation of Ca Ski cells by promoting apoptosis, inhibiting autophagy and disturbing the formation of the Bcl-2-Beclin 1 complex, which may be a novel strategy to increase the sensitivity of anti-cervical cancer drugs.

Metronomic palliative chemotherapy in locally advanced, recurrent and metastatic head-and-neck cancer: A single-arm, retrospective study of a regional cancer center of North India (Asia)

Background: Head-and-neck cancer is the most common cancer in developing countries of Southeast Asia. Most of the patients present to the hospital in advanced stage and have a poor prognosis. This study aims to evaluate the efficacy and toxicity profile of oral metronomic chemotherapy (MCT) in the form of methotrexate and celecoxib in locally advanced, recurrent and metastatic head-and-neck cancers. Materials and Methods: This was a single-arm retrospective observational study that included posttreatment patients with locally advanced, recurrent and metastatic disease in the year 2016 (January 1, to December 31, 2016). A total of 84 patients warranting palliative chemotherapy but not willing to take intravenous chemotherapy were included in the study. The oral MCT schedule consisted of oral celecoxib (200 mg twice daily) and oral methotrexate (15 mg/m2/week). Response evaluation was done using the Response Evaluation Criteria in Solid Tumors criteria version 1.1, and toxicity profile was assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03. Descriptive statistics and Kaplan–Meier analysis were performed. Results: Eighty-four patients, 68 males and 16 females, with a median age of 62 years (range: 35–80 years), were enrolled in the study to receive oral MCT. The Eastern Cooperative Oncology Group performance status was 0–1 in 62 patients and 2–3 in 22 patients. The primary sites of disease were buccal mucosa (18), tongue (22), tonsil (24), lower alveolus (7), hypopharynx (10), and soft palate (3). The best clinical response rate in post oral MCT was seen in the first 4 months (120 days). Objective response was observed in 67% of patients in the form of stable disease (56%) and partial response (11%). Disease progression was observed in 27% of patients. The median follow-up was 192 (6.4 months) days. The median estimated overall survival was 195 (6.5 months) days. The median estimated progression-free survival was 110 (3.6 months) days. Symptomatic relief with respect to pain was reported in about 75% of patients. Eighteen (21%) patients had Grade I–II mucosal reactions. Grade III–IV mucosal reactions were observed in five (6%) patients. Seventy-eight (93%) patients died at the end of the study at 1 year. Dose reduction was required in 15 (18%) patients. Conclusion: Oral MCT using celecoxib and methotrexate is an effective, economical, and well-tolerated regimen with good pain control and low toxicity profile in patients with locally advanced, recurrent and metastatic head-and-neck cancer.

Clinical Efficacy of Flavored Sanxitang Combined with Celecoxib in Treatment of Gonarthromeningitis Cased by Dampness and Cold / 中国实验方剂学杂志

Objective::To observe the clinical efficacy of flavored Sanxitang combined with celecoxib in treating gonarthromeningitis caused by dampness and cold. Method::Totally 120 case were randomly divided into the control group and the treatment group, with 60 cases in each group. The control group was given celecoxib, and the treatment group was treated with flavored sanxitang combined with celecoxib for 30 d. The visual analogue scale (VAS), American knee association knee function scale (AKS), arthritis impact scale (AIMS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) were observed before and after treatment. The circumferential diameter, articular cavity effusion and synovial hyperplasia thickness were measured. The serum tumor necrosis factor-α(TNF-α), matrix metalloproteinase (MMP)-3, serum interleukin-1 (IL-1) and erythrocyte sedimentation rate (ESR) were detected. The effective rate and adverse reactions were observed in two groups. Result::The total effective rate in treatment group was 94.8% (55/58), which was higher than 80.7% (46/57) in control group (P<0.05). Compared with before treatment, VAS, AIMS, WOMAC, knee circumference, articular cavity effusion and synovial hyperplasia thickness were significantly reduced in two groups (P<0.05), while the AKS score was significantly increased (P<0.05). Compared with after treatment, VAS, AIMS, WOMAC, knee circumference, articular cavity effusion and synovial hyperplasia thickness were significantly reduced in observation group (P<0.05), whereas the AKS score was significantly increased (P<0.05). TNF-α, MMP-3, IL-1 and ESR in two groups were significantly lower than those group before treatment (P<0.05). After treatment, TNF-α, MMP-3, IL-1 and ESR levels in observation group were significantly reduced compared with those in control group (P<0.05). The incidence rate of adverse reactions in treatment group was 5.89% (4/58), which was lower than 22.81% (13/57) in control group (P<0.05). Conclusion::Flavored Sanxitang combined with celecoxib could alleviate the clinical symptoms of gonarthromeningitis caused by dampness and cold, with a low incidence of adverse reactions.

Efficacy and characteristics of parecoxib and celecoxib in the treatment of pain after orthopedic surgery: A meta-analysis / 中国组织工程研究

BACKGROUND: Improper management of postoperative pain will seriously affect the recovery of patients, leading to a high disability rate. Celecoxib and parecoxib are selective cyclooxygenase 2 inhibitors, and have good analgesic effects. However, there is no comparison between the two in the treatment of postoperative pain in orthopedics department. OBJECTIVE: To systematically evaluate the efficacy of parecoxib and celecoxib in the treatment of postoperative pain in orthopedic surgery. METHODS: Databases including CNKI, CBM, Wanfang Data, PubMed and the Cochrane Library were searched from inception to June 2019. The randomized controlled trials regarding the efficacy of parecoxib versus celecoxib in the treatment of pain after orthopedic surgery were collected. Data were extracted and the quality of the study was evaluated. RevMan 5.3 software and Stata 12.0 software were used for result analysis. RESULTS AND CONCLUSION: (1) Seven randomized controlled trials were involved, containing 524 patients undergoing orthopedic surgery. The experimental group was treated with parecoxib and the control group with celecoxib. (2) Meta-analysis results showed that at 24, 48 and 72 hours after surgery, compared with celecoxib, parecoxib significantly reduced visual analogue scale scores [MD=-0.86, 95%C/=(-1.30, -0.42), P=0.000 1; MD=-0.81, 95%C/=(-1.43, -0.20), P=0.009; MD=-0.32, 95%C/=(-0.48, -0.17), P < 0.000 1], and decreased the dosage of central analgesics [SMD=-2.12, 95%C/=(-2.90, -1.34), P < 0.000 01]. (3) Results suggested that compared with celecoxib, parecoxib significantly reduced postoperative pain and the dose of central analgesics after orthopedic surgery.

Clinical effect of knee arthroscopy combined with celecoxib in the treatment of elderly patients with knee osteoarthritis / 中国基层医药

Objective@#To investigate the clinical effect of knee arthroscopy combined with celecoxib in the treatment of elderly patients with knee osteoarthritis.@*Methods@#According to the random table method, 62 elderly patients with knee osteoarthritis admitted to the Third People's Hospital of Zhuji from October 2016 to October 2018 were divided into control group (31 cases) and observation group (31 cases) according to the digital table.The control group was treated with knee arthroscopic debridement, while the observation group was orally given celecoxib on the basis of the control group.Both two groups were treated for 12 weeks.The curative effect of the two groups was compared, and the changes of WOMAC scale score, knee joint active flexion and extension and inflammatory factors before and after treatment were compared.@*Results@#The excellent and good rate of the observation group (83.88%) was higher than that of the control group (51.62%) (χ2=7.381, P<0.05). After treatment, the scores of stiffness[(3.56±0.38)points], difficulty in daily activities[(27.38±7.19)points]and pain[(7.94±2.45)points] in the observation group were lower than those in the control group[(5.81±0.76)points, (38.98±5.42)points and (11.36±1.87)points](t=10.182, 14.743, 6.178, all P<0.05). After treatment, the knee joint active flexion and extension in the observation group[(91.24±7.86)°] was higher than that in the control group[(83.42±7.39)°](t=4.036, P<0.05). After treatment, the serum levels of IL-1beta[(16.58±4.25)ng/L], TNF-α[(183.25±24.15)ng/L]and IL-6[(9.98±2.43) ng/L] in the observation group were lower than those in the control group[(26.31±5.47)ng/L, (219.82±29.96)ng/L and (14.52±4.35)ng/L](t=7.821, 5.291, 5.073, all P<0.05).@*Conclusion@#Knee arthroscopy combined with celecoxib has good clinical effect on elderly patients with knee osteoarthritis.It can improve knee function, alleviate inflammation and improve active knee flexion and extension.

Inhibitory effect of celecoxib on Cal-27 tongue squamous cell carcinoma cell proliferation / 口腔疾病防治

Objective@# To explore the inhibitory effect of celecoxib (CELE) on the proliferation of tongue squamous cell carcinoma Cal-27 cells and its mechanism.@*Methods@# A CCK-8 assay was used to investigate the cytotoxicity of different concentrations CELE(10, 20, 40, 60, 80, and 100 mol/L) at 24 and 48 h in Cal-27 cells. According to the concentration of CELE, samples were divided into a control group (0 μmol/L) and experimental groups (10, 20, and 40 μmol/L), and cell invasiveness was detected by the Transwell method. The expression levels of c-Myc and Cyclin D1 mRNA were detected with qPCR, and western blots were used to detect the expression of phosphate and tension homologue deleted on chromosome ten (PTEN), phospho-protein kinase B (p-AKT) (Thr308), c-Myc, cyclin D1 and other proteins in Cal-27 cells after 24 h of treatment with different doses of CELE (10, 20, and 40 μ mol/L) and after 6, 12, and 24 h of treatment with 40 μmol/L CELE.@*Results @# The different concentrations of CELE were able to inhibit the proliferation of Cal-27 cells, and the higher the concentration of CELE was, the more significant the inhibition of the proliferation of Cal-27 cells was. The cell survival rates of cells exposed to 40 μmol/L CELE were 80% and 75% after 24 and 48 h, respectively. In the four groups of patients, the number of invasive cells was compared, and the results in decreasing order were the control group, 10 μmol/L CELE, 20 μmol/L CELE, and 40 μmol/L CELE. The expression level of c-Myc, cyclin D1 mRNA and the protein in P-AKT (Thr308), c-Myc, and cyclin D1 significantly decreased and the expression of PTEN protein increased in the Cal-27 cells after administration of CELE at different concentrations. @*Conclusion@# CELE can inhibit the proliferation of Cal-27 cells, possibly through inhibition of the expression of proliferation signal factors, such as c-Myc and cyclin D1, by activating the PTEN signaling pathway.

Clinical effect of knee arthroscopy combined with celecoxib in the treatment of elderly patients with knee osteoarthritis / 中国基层医药

Objective To investigate the clinical effect of knee arthroscopy combined with celecoxib in the treatment of elderly patients with knee osteoarthritis.Methods According to the random table method,62 elderly patients with knee osteoarthritis admitted to the Third People's Hospital of Zhuji from October 2016 to October 2018 were divided into control group (31 cases) and observation group (31 cases) according to the digital table.The control group was treated with knee arthroscopic debridement ,while the observation group was orally given celecoxib on the basis of the control group.Both two groups were treated for 12 weeks.The curative effect of the two groups was compared,and the changes of WOMAC scale score,knee joint active flexion and extension and inflammatory factors before and after treatment were compared.Results The excellent and good rate of the observation group (83.88％) was higher than that of the control group (51.62％) (χ2 =7.381,P<0.05).After treatment,the scores of stiffness[(3.56 ±0.38)points], difficulty in daily activities[(27.38 ±7.19)points]and pain[(7.94 ±2.45)points] in the observation group were lower than those in the control group [(5.81 ±0.76)points,(38.98 ±5.42)points and (11.36 ±1.87)points](t=10.182,14.743,6.178,all P<0.05).After treatment,the knee joint active flexion and extension in the observation group[(91.24 ±7.86)°] was higher than that in the control group [(83.42 ±7.39)°](t=4.036,P<0.05).After treatment,the serum levels of IL -1beta[(16.58 ±4.25) ng/L],TNF-α[(183.25 ±24.15) ng/L] and IL -6 [(9.98 ±2.43) ng/L] in the observation group were lower than those in the control group [(26.31 ±5.47)ng/L, (219.82 ±29.96)ng/L and (14.52 ±4.35)ng/L](t =7.821,5.291,5.073,all P <0.05).Conclusion Knee arthroscopy combined with celecoxib has good clinical effect on elderly patients with knee osteoarthritis .It can improve knee function,alleviate inflammation and improve active knee flexion and extension .

Thermodynamic analysis of celecoxib in amphiprotic and amphiprotic-aprotic solvent mixtures at several temperatures / Análisis termodinámico del celecoxib en mezclas disolventes anfipróticas y anfipróticas-apróticas a varias temperaturas

SUMMARY The solubilities of celecoxib (CLX), a COX-2 selective nonsteroidal anti-inflammatory drug, were determined in water-ethanol and ethanol-ethyl acetate mixtures at several temperatures (288.15-308.15 K). The solubility curves as a function of ethanol ratio were studied at five temperatures, they showed a single maximum located at 50% ethanol-ethyl acetate (δ1 = 22.50 MPa1/2). The measurements of the variation of inherent drug solubility with temperature were used to estimate different thermodynamic parameters, enthalpy, entropy and Gibbs free energy of solution (ΔH S , ΔS S and ΔG S hm , respectively). The apparent enthalpies of the solution were a nonlinear function of the ethanol ratio in aqueous mixture. Non-linear enthalpy-entropy compensation analysis was observed indicating different dissolution mechanism with the variation in mixtures composition. The solubility enhancement is entropy driven at water-rich region (0-40% v/v ethanol) and enthalpy controlled at ethanol-rich region (40-100% v/v ethanol), likely due to water-structure loss around nonpolar moieties of the drug and for the ethanol-rich mixtures it is the enthalpy, probably due to the drug better solvation.

RESUMEN Se determinó la solubilidad del celecoxib (CLX), un fármaco antiinflamatorio no esteroide selectivo de COX-2, en agua-etanol y etanol-acetato de etilo a varias temperaturas (288,15-308,15 K). Los perfiles de solubilidad obtenidos fueron estudiados en función de la proporción de etanol en las cinco temperaturas de estudio. Los resultados muestran solamente un máximo en el 50% de etanol-acetato de etilo (δ1 = 22,50 MPa1/2). La variación de la solubilidad con la temperatura se utilizó para calcular diferentes parámetros termodinámicos, entalpia, entropía y energía de disolución libre de Gibbs (ΔH3, ΔS S y ΔGS hm, respectivamente). Las entalpias aparentes de disolución fueron no lineales en la mezcla acuosa. Además, se observó un análisis de compensación de entalpía-entropía no lineal, lo que indica un mecanismo de disolución que varía con la composición de cada mezcla. El aumento de la solubilidad es impulsado por la entropía en la región rica en agua (0-40% v/v de etanol) y la entalpía en la región rica en etanol (40-100% v/v de etanol), probablemente debido a la pérdida de la estructura del agua alrededor de los residuos no polares del fármaco y para las mezclas ricas en etanol es la entalpía, probablemente debido a la mejor solvatación del fármaco.

The use of cyclooxygenase-2 inhibitors in depression: a narrative review of the state of evidence

Multiple lines of evidence suggest that inflammation contribute to the pathophysiology of depression. Various studies have found that patients with major depression have higher levels of pro-inflammatory cytokines like interleukin-1, interleukin-6, tumor necrosis factor-alpha and C-reactive protein. As a consequence of above findings this narrative literature review was done to look for the role of cyclooxygenase (COX)-2 inhibitors in the patients of depression. A web based search was done using the keywords like antidepressants, anti-inflammatory treatment, celecoxib, depression, neuro inflammation in well recognized databases like PubMed, Google scholar from the year 2006 to 2019 to come out with data that matches our inclusion criteria that have been pooled and critically analyzed. Although the exact mechanism remains to become elucidated the results suggest that COX-2 have beneficial role in treatment of depression and it may be used as an adjunct to the anti-depressant treatment as it may hasten the response to current treatment without any serious side effects.

PEGylated Lipova E120 liposomes loaded with celecoxib: in-vitro characterization and enhanced in-vivo anti-inflammatory effects in rat models

Brown adipose tissue (BAT) is responsible for adaptive thermogenesis. We previously showed that genetic deficiency ofreceptor for advanced glycation end products (RAGE) prevented the effects of high-fat diet (HFD). This study was tocompare BAT activity in RAGE knock out (Ager-/-, RKO) and wild-type (WT) mice after treated with HFD or LFD.[18F]FDG PET-CT imaging under identical cold-stimulated conditions and mean standard uptake values (SUVmean), ratio ofSUViBAT/SUVmuscle (SUVR, muscle as the reference region) and %ID/g were used for BAT quantification. The resultsshowed that [18F]FDG uptake (e.g., SUVR) in WT-HFD mice was significantly reduced (three-fold) as compared to that inWT-LFD (1.40 ± 0.07 and 4.03 ± 0.38; P = 0.004). In contrast, BAT activity in RKO mice was not significantly affectedby HFD, with SUVRRKO-LFD: 2.14 ± 0.10 and SUVRRKO-LFD: 1.52 ± 0.13 (P = 0.3). The uptake in WT-LFD was almostdouble of that in RKO-LFD (P = 0.004); however, there was no significant difference between RKO-HFD and WT-HFDmice (P = 0.3). These results, corroborating our previous findings on the measurement of mRNA transcripts for UCP1 inthe BAT, suggest that RAGE may contribute to altered energy expenditure and provide a protective effect against HFD byAger deletion (Ager -/-).

Periapical bone response to bacterial lipopolysaccharide is shifted upon cyclooxygenase blockage

Abstract Objectives: Infection, inflammation and bone resorption are closely related events in apical periodontitis development. Therefore, we sought to investigate the role of cyclooxygenase (COX) in osteoclastogenesis and bone metabolism signaling in periapical bone tissue after bacterial lipopolysaccharide (LPS) inoculation into root canals. Methodology: Seventy two C57BL/6 mice had the root canals of the first molars inoculated with a solution containing LPS from E. coli (1.0 mg/mL) and received selective (celecoxib) or non-selective (indomethacin) COX-2 inhibitor. After 7, 14, 21 and 28 days the animals were euthanized and the tissues removed for total RNA extraction. Evaluation of gene expression was performed by qRT-PCR. Statistical analysis was performed using analysis of variance (ANOVA) followed by post-tests (α=0.05). Results: LPS induced expression of mRNA for COX-2 (Ptgs2) and PGE2 receptors (Ptger1, Ptger3 and Ptger4), indicating that cyclooxygenase is involved in periapical response to LPS. A signaling that favours bone resorption was observed because Tnfsf11 (RANKL), Vegfa, Ctsk, Mmp9, Cd36, Icam, Vcam1, Nfkb1 and Sox9 were upregulated in response to LPS. Indomethacin and celecoxib differentially modulated expression of osteoclastogenic and other bone metabolism genes: celecoxib downregulated Igf1r, Ctsk, Mmp9, Cd36, Icam1, Nfkb1, Smad3, Sox9, Csf3, Vcam1 and Itga3 whereas indomethacin inhibited Tgfbr1, Igf1r, Ctsk, Mmp9, Sox9, Cd36 and Icam1. Conclusions: We demonstrated that gene expression for COX-2 and PGE2 receptors was upregulated after LPS inoculation into the root canals. Additionally, early administration of indomethacin and celecoxib (NSAIDs) inhibited osteoclastogenic signaling. The relevance of the cyclooxygenase pathway in apical periodontitis was shown by a wide modulation in the expression of genes involved in both bone catabolism and anabolism.

Clinical study of Simiao pill combined with celecoxib in the treatment of acute gouty arthritis / 中国基层医药

Objective To observe the efficacy of Simiao pill combined with celecoxib in the treatment of acute gouty arthritis(AGA). Methods From January 2015 to January 2017,70 patients with AGA in the Central Hospital of Luohe were selected and randomly divided into two groups,with 35 cases in each group. The control group received celecoxib treatment,while the treatment group received Simiao pill combined with celecoxib. The treatment course was 7 days in each group. The clinical efficacy and the blood uric acid ( UA) changes were observed and compared before and after treatment. Results The total effective rate of the treatment group was 91. 4% (32/35), which was remarkably higher than 77. 1% (27/35) of the control group,the difference between the two groups was statistically significant(χ2=4. 381,P ＜0. 05). Before treatment,there was no significant difference in UA level between the treatment group and control group(P＞0. 05). After treatment,the level of UA in the treatment group was (402. 17 ± 18. 43) μmol/L,which was lower than (475. 29 ± 37. 82) μmol/L in the control group,the difference between the two groups was statistically significant (t= －11. 051,P＜0. 05). Conclusion The clinical efficacy of Simiao pill combined with celecoxib in the treatment of AGA is effective,and is worthy of clinical promotion.

Augmented cytotoxic, mutagenic and genotoxic response triggered by carvedilol and celecoxib combinations

It is understood that drugs regardless of their order of administration can exhibit drug interactions. Established on the fact that treatment of hypertension may last for decades and prolong usage of multiple drug regimen may induce substantial pathophysiological changes. Hence, This study was designed to evaluate the possible synergistic toxic effects of anti-hypertensive (carvedilol), and anti-inflammatory drug (celecoxib) alone and in combinations. Well-established MTT assay, Single Cell Gel Electrophoresis (SCGE) and Ames assay were employed to evaluate the toxicity at cellular level. Results from MTT assay on Vero cell line revealed that drug combinations have more pronounced anti-proliferative activity with combine IC50 value of 13.7:47.8 µg/mL. Likewise, exposure of peripheral blood mononuclear cells with drug combinations revealed significant (P<0.05) DNA damage (Class 3) in a dose dependent manner at concentrations ≥ 0.78: 2.34 µg/mL. However, carvedilol and celecoxib were non mutagenic against either mutant strain (TA 100 and TA 98) and combinations have also shown mild to moderate mutagenic potential. Nevertheless, upon addition of metabolic activation enzyme, concentration <12.5:37.5 µg/plate exhibited significant (P<0.05) mutagenicity against both tester strains. In conclusion, this study provides additional genotoxicity and mutagenicity data that could be used in considering options for formulating regimens with reduced mutagenic potential

Research of Feiliuping Gao and its combination with different types of drugs intervention on expression of PI3K/AKT/NF-κB in lung metastatic microenvironment / 中国中药杂志

The aim of this paper was to observe the effect of Feiliuping Gao and its combination with different types of drugs intervention on the expression of PI3K/AKT/NF-κB in lung metastatic microenvironment, and to reveal the advantage of Chinese medicine intervention time on the key molecule in lung metastatic microenvironment. The mouse model of Lewis lung carcinoma was established, and lung tissues were collected at 14 days, 21 days and 28 days after the intervention of Feiliuping Gao, and the expressions of PI3K, AKT and NF-κB were detected by immunohistochemistry and Western blot. At 14 days, there was no significant difference in PI3K expression between each group and the control group. The expression of AKT protein was significantly inhibited in the celecoxib (CLB) group, the Feiliuping Gao (FLP) combination with cyclophosphamide (FLP+CTX) group, and the Feiliuping Gao combination with celecoxib (FLP+CLB) group (<0.05). The inhibition of AKT protein expression in FLP+CLB group was superior. The FLP+CLB group can inhibit the expression of NF-κB protein (<0.05). At 21 days, compared with the control group, the expression of PI3K was inhibited in FLP group and the FLP+CTX group (<0.05), while the expression of PI3K was best inhibited in the FLP+CLB group (<0.001). Only the FLP+CLB group could significantly inhibit the expression of AKT protein (<0.01). The FLP+CTX group had the best effect in inhibiting the expression of NF-κB protein (<0.001). At 28 days, compared with the control group, the expression of PI3K and AKT was inhibited in the FLP+CLB group (<0.001). Feiliuping ointment combination with celecoxib has an advantage in regulating the expression of PI3K/AKT/NF-κB molecules in lung metastatic microenvironment.