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.

Chemoprevention of colorectal cancer in general population and high-risk population: a systematic review and network meta-analysis / 中华医学杂志(英文版)

BACKGROUND@#Many nutritional supplements and pharmacological agents have been reported to show preventive effects on colorectal adenoma and colorectal cancer (CRC). We performed a network meta-analysis to summarize such evidence and assess the efficacy and safety of these agents.@*METHODS@#We searched PubMed, Embase, and the Cochrane Library for studies published in English until October 31, 2021 that fit our inclusion criteria. We performed a systematic review and network meta-analysis to assess the comparative efficacy and safety of candidate agents (low-dose aspirin [Asp], high-dose Asp, cyclooxygenase-2 inhibitors [coxibs], calcium, vitamin D, folic acid, ursodeoxycholic acid [UDCA], estrogen, and progesterone, alone or in combination) for preventing colorectal adenoma and CRC. Cochrane risk-of-bias assessment tool was employed to evaluate the quality of each included study.@*RESULTS@#Thirty-two randomized controlled trials (278,694 participants) comparing 13 different interventions were included. Coxibs significantly reduced the risk of colorectal adenoma (risk ratio [RR]: 0.59, 95% confidence interval [CI]: 0.44-0.79, six trials involving 5486 participants), advanced adenoma (RR: 0.63, 95% CI: 0.43-0.92, four trials involving 4723 participants), and metachronous adenoma (RR: 0.58, 95% CI: 0.43-0.79, five trials involving 5258 participants) compared with placebo. Coxibs also significantly increased the risk of severe adverse events (RR: 1.29, 95% CI: 1.13-1.47, six trials involving 7109 participants). Other interventions, including Asp, folic acid, UDCA, vitamin D, and calcium, did not reduce the risk of colorectal adenoma in the general and high-risk populations compared with placebo.@*CONCLUSIONS@#Considering the balance between benefits and harms, regular use of coxibs for prevention of colorectal adenoma was not supported by the current evidence. Benefit of low-dose Asp for chemoprevention of colorectal adenoma still requires further evidence.@*REGISTRATION@#PROSPERO, No. CRD42022296376.

Mecanismo de los AINES y antiinflamatorios derivados para el control del dolor y la inflamación. Uso de antiinflamatorios en odontología / Mechanism of NSAIDs and derived drugs for pain and inflammation control. Use of anti-inflammatories in odontology

Las urgencias odontológicas son, quizá, las razones principales de atención en el consultorio, muchas veces el significado de dolor se encuentra acompañado por inflamación; el uso de antiinflamatorios no esteroideos (AINES) es común en el ejercicio de la odontología por la excelente respuesta analgésica y antiinflamatoria que tiene, por lo que es importante conocer la fisiopatología de la inflamación y el dolor y cómo actúan los AINES, ya que algunos de estos fármacos tienen respuestas adversas y sitios de acción importantes. Los factores de riesgo por inflamación y dolor nos obligan a conocer la variedad de fármacos que no entran en la clasificación de AINES y que tenemos a disposición, hay más opciones para la elección ante la presencia de inflamación por un factor en particular, cada uno de éstos tienen indicaciones y contraindicaciones que conoceremos, lo cual nos ampliará el conocimiento para dar una prescripción ante la presencia de eventos inflamatorios. Se realizó un estudio detallado de artículos bibliográficos de cada tema, los fármacos más usados en odontología son los AINES, hay poco uso y conocimiento de antiinflamatorios que podemos usar en urgencias, el porcentaje de uso de los AINES derivados del ácido propiónico es alto por la excelente respuesta en pacientes y otras veces por el desconocimiento de más opciones (AU)

Dental emergencies are perhaps the main reasons for care in the office, many times the meaning of pain is accompanied by inflammation, the use of non-steroidal anti-inflammatory drugs is common in the practice of dentistry due to the excellent analgesic and anti-inflammatory response it has, important is knowing the pathophysiology of inflammation and pain, how NSAIDs act, some of these drugs have adverse responses and important sites of action, risk factors for inflammation and pain require us to know the variety of drugs that do not enter the classification of NSAIDs and we have at our disposal, there are more options for choosing in the presence of inflammation due to a particular factor, each of these have indications and contraindications that we will know, it expands our knowledge to give a prescription in the presence of inflammatory events. A detailed study of bibliographic articles on each topic was carried out, the drugs most used in dentistry are NSAIDs, there is little use and knowledge of anti-inflammatories that we can use in the emergency room, the percentage of use of NSAIDs derived from propionic acid is high, due to the excellent response in patients and others due to lack of knowledge of more options (AU)

Immunohistochemical Study and Clinicopathologic Correlation of Cox-2 and Her-2 Expression in Colorectal Carcinoma: A 5-Year Retrospective Study

BACKGROUND: Colorectal cancer (CRC) is the fourth most common cancer in Nigeria, and it affects mostly persons in their middle age. In a bid to gain some insight into the molecular characteristics of CRC in our environment, we set out to investigate the expression of COX-2 and HER-2 among Nigerian subjects. OBJECTIVES: To evaluate the expression of COX-2 and HER2 and determine their correlation with clinicopathologic parameters in surgically resected histologically diagnosed cases of colorectal cancer. METHODS: Fifty-three paraffin-embedded tissue blocks of colorectal resections and corresponding patient information were retrieved from the archives of the Anatomic and Molecular Pathology Department of Lagos University Teaching Hospital.A 4-micron slide section was obtained from each specimen and immunohistochemistry for COX-2 and HER-2 expression was performed. RESULTS: Mean age of cases was 53.9years with an almost equal M:F ratio of 1.12:1. Half of the cases were moderately differentiated adenocarcinoma and 17% were high grade tumors.Eighty three percent of the tumours showed positive cytoplasmic COX-2 expression and extremely low membranous HER-2 positivity was observed in 2%. There was no significant correlation between COX-2 expression and age, gender, tumour location, tumour size, depth of invasion or lymph node status.However, COX-2 expression revealed a significant correlation with tumour grade (p= 0.013). CONCLUSION: This study detects a high COX-2 and low HER2 expression in colorectal cancer using immunohistochemistry,suggesting a possible role for COX-2 in CRC pathogenesis.This report should trigger further investigations of both markers vis-à-vis the management of CRC in our environment. WAJM 2022; 39(11): 1134­1140.

Mechanism study of the protective effects of selective cyclooxygenase-2 enzyme inhibitors on the liver of rats with type 2 diabetes mellitus combined with nonalcoholic steatohepatitis via Rho/ROCK pathway / 中华肝脏病杂志

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

Lack of dystrophin influences muscle inflammation but not myogenic regulatory factors after eccentric exercise in mdx mice

Abstract Aim: To investigate the consequences of chronic eccentric exercise in histopathology, inflammatory, and myogenic regulatory factors response in gastrocnemius muscle of X-chromosome-linked muscular dystrophy (mdx) mice. Method: Male mdx and control mice (C57BL/10 lineage) were distributed in the following groups: Sedentary Control (SC), Trained Control (TC), Sedentary Mdx (S-Mdx), and Trained Mdx (T-Mdx). Trained animals were subjected to downhill running for 7 weeks. Gastrocnemius was submitted to histopathological analysis and immunoexpression of Cyclooxygenase-2 (COX-2) and myogenic regulatory factors (myoD and myogenin). Results: The exercise influenced inflammation response as demonstrated by the increased COX-2 immunoexpression in T-Mdx. Interestingly, Myogenic regulatory factors revealed that the lack of dystrophin has not been influenced myoD and the increase of myogenin occurred due to exercise and was not aggravated by the absence of dystrophin. Conclusion: In conclusion, an eccentric exercise in gastrocnemius of mdx mice was characterized by an intense inflammatory process without myogenic response. These findings suggest that special attention should be given to inflammatory aspects related to COX-2 associated with a decrease of myoD expression, as biomarkers in motor rehabilitation programs.

Comparison of safety and analgesic efficacy of diclofenac sodium with etodolac after surgical extraction of third molars: a randomized, double-blind, double-dummy, parallel-group study

BACKGROUND: Surgical extraction of third molars is associated with postoperative pain and swelling at the extraction site. Pain is commonly managed using non-steroidal anti-inflammatory drugs (NSAIDs). Postoperative pain is usually moderate to severe in the first 12 h postoperatively and lasts for 3–5 days. However, with NSAIDs, these symptoms usually subside within 24 h. Diclofenac sodium and etodolac are NSAIDs, more selectively cyclooxygenase-2 inhibitors, with good analgesic efficacies.METHODS: We compared the safety and analgesic efficacy of diclofenac sodium with etodolac peroral after surgical extraction of third molars in a double-blind, double-dummy, parallel-group study. The subjective pain improvement and pain relief after 2, 6, 24, 48, and 72 h using the visual analogue scale were measured as the study outcome.RESULTS: Etodolac was equivalent to diclofenac sodium in pain alleviation at all postoperative time periods. No significant differences were found between diclofenac sodium and etodolac groups (P > 0.05). Both study medications were well tolerated and safe with mild adverse effects in only a few participants.CONCLUSION: Diclofenac sodium and etodolac are comparable in terms of analgesic efficacy and safety after surgical removal of third molars.

Effects of ranibizumab and amfenac on the functional abilities and radiosensitivity of uveal melanoma cells / Efeitos do ranibizumabe e do amfenac nas habilidades funcionais e na radiossensibilidade de células de melanoma uveal

ABSTRACT Purpose: To evaluate the effects of ranibizumab and amfenac in human uveal melanoma cell lines and to explore the ability of these compounds to sensitize uveal melanoma cells to radiation therapy. Methods: The 92.1 human uveal melanoma cell line was cultured and subjected to the proposed treatment (ranibizumab, amfenac, and a combination of both). Proliferation, migration, and invasion assays of the 92.1 uveal melanoma cell line were assessed after pretreatment with ranibizumab (125 mg/mL), amfenac (150 nM), or a combination of both. In addition, proliferation rates were assessed after treatment with ranibizumab and amfenac, and the cells were subsequently exposed to various radiation doses (0, 4, and 8 Gy). Results: Proliferation assay: cells treated with a combination of ranibizumab and amfenac had lower proliferation rates than controls (p=0.016) and than those treated with only ranibizumab (p=0.033). Migration assay: a significantly lower migration rate was observed in cells treated with amfenac than the control (p=0.014) and than those treated with ranibizumab (p=0.044). Invasion assay: there were no significant differences among the studied groups. Irradiation exposure: in the 4 Gy dose group, there were no significant differences among any groups. In the 8 Gy dose group, treatment with ranibizumab, amfenac, and their combination prior to application of the 8 Gy radiation led to a marked reduction in proliferation rates (p=0.009, p=0.01, and p=0.034, respectively) compared with controls. Conclusion: Combination of ranibizumab and amfenac reduced the proliferation rate of uveal melanoma cells; however, only amfenac monotherapy significantly decreased cell migration. The radiosensitivity of the 92.1 uveal melanoma cell line increased following the administration of ranibizumab, amfenac, and their combination. Further investigation is warranted to determine if this is a viable pretreatment strategy to render large tumors amenable to radiotherapy.

RESUMO Objetivo: Avaliar os efeitos do ranibizumabe em associação com o amfenac nas células de melanoma uveal humano e explorar a capacidade desses compostos em sensibilizar as células de melanoma uveal à radioterapia. Métodos: Células de melanoma uveal humano do tipo 92.1 foram cultivadas e submetidas ao tratamento proposto (ranibizumabe, amfenac e a combinação de ambos). Ensaios de proliferação, migração e invasão com as células de melanoma uveal do tipo 92.1 foram avaliados após tratamento com ranibizumabe (125 mg/ml), amfenac (150 nM) e a combinação de ambos. Além disso, as taxas de proliferação foram avaliadas após tratamento com ranibizumabe e amfenac com subsequente exposição das células a diferentes doses de radiação (0 Gy, 4 Gy e 8 Gy). Resultados: Ensaio de proliferação: células tratadas com ranibizumabe e amfenac combinados apresentaram taxas de proliferação inferiores em comparação ao grupo controle (p=0,016), do que as tratadas apenas com ranibizumabe (p=0,033). Ensaio de migração: foi observada uma taxa de migração significativamente mais baixa nas células tratadas com amfenac do que no grupo controle (p=0,014) e do que nas tratadas com ranibizumabe (p=0,044). Ensaio de invasão: não houve diferenças significativas entre os grupos estudados. Exposição à irradiação: no grupo da dose de 4 Gy, não houve diferença significante entre os grupos. No grupo da dose de 8 Gy, o tratamento com ranibizumabe, afenac e sua combinação antes da aplicação da radiação de 8 Gy levou a uma redução acentuada nas taxas de proliferação (p=0,009, p=0,01 e p=0,034, respectivamente) em comparação aos grupos controle. Conclusão: A combinação de ranibizumabe e amfenac reduziu a taxa de proliferação das células de melanoma uveal; no entanto, apenas o amfenac diminuiu significativamente a migração celular. A radiossensibilidade das células de melanoma uveal do tipo 92.1 aumentou após a administração de ranibizumabe, amfenac e sua combinação. Mais investigações são necessárias para determinar se esta é uma estratégia de pré-tratamento viável para tornar grandes tumores passíveis de radioterapia.

Protective efficacy of combined use of parecoxib and dexmedetomidine on postoperative hyperalgesia and early cognitive dysfunction after laparoscopic cholecystectomy for elderly patients

Abstract Purpose: To investigate efficacy of combined use of parecoxib and dexmedetomidine on postoperative pain and early cognitive dysfunction after laparoscopic cholecystectomy for elderly patients. Methods: The present prospective randomized controlled study included a total of 80 patients who underwent laparoscopic cholecystectomy surgery during January 2016 to November 2017 in our hospital. All patients were randomly divided into 4 groups, the parecoxib group, the dexmedetomidine group, the parecoxib and dexmedetomidine combined group, and the control group. Demographic data and clinical data were collected. Indexes of heart rate (HR), mean arterial pressure (MAP), levels of jugular venous oxygen saturation (SjvO2) and jugular venous oxygen pressure (PjvO2) were recorded at different time points before and during the surgery. The mini-mental state examination (MMSE) score, Ramsay score and Visual Analogue Score (VAS) were measured. Results: Levels of both SjvO2 and PjvO2 were significantly higher in parecoxib group, dexmedetomidine group and the combined group than the control group. Meanwhile, levels of both SjvO2 and PjvO2 in the combined group were the highest. VAS scores were significantly lower in the combined group than all other groups, and total patient controlled intravenous analgesia (PCIA) pressing times within 48 h after surgery were the lowest in the combined group. Both Ramsay and MMSE scores were the highest in the combined group compared with other groups, while were the lowest in the control group. Conclusion: The combined use of parecoxib and dexmedetomidine could reduce the postoperative pain and improve the postoperative sedation and cognitive conditions of patients after laparoscopic cholecystectomy.

Phenotypes of Severe Cutaneous Adverse Reactions Caused by Nonsteroidal Anti-inflammatory Drugs

PURPOSE: Nonsteroidal anti-inflammatory drugs (NSAIDs) are common cause of severe cutaneous adverse reactions (SCARs). The present study aimed to investigate the characteristics of SCARs induced by NSAIDs in the Korean SCAR registry. METHODS: A retrospective survey of NSAID-induced SCARs recorded between 2010 and 2015 at 27 university hospitals in Korea was conducted. Clinical phenotypes of SCARs were classified into Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), SJS-TEN overlap syndrome and drug reaction with eosinophilia and systemic symptoms (DRESS). Causative NSAIDs were classified into 7 groups according to their chemical properties: acetaminophen, and propionic, acetic, salicylic, fenamic and enolic acids. RESULTS: A total of 170 SCARs, consisting of 85 SJS, 32 TEN, 17 SJS-TEN overlap syndrome and 36 DRESS reactions, were induced by NSAIDs: propionic acids (n=68), acetaminophen (n=38), acetic acids (n=23), salicylic acids (n=16), coxibs (n=8), fenamic acids (n=7), enolic acids (n=5) and unclassified (n=5). Acetic acids (22%) and coxibs (14%) accounted for higher portions of DRESS than other SCARs. The phenotypes of SCARs induced by both propionic and salicylic acids were similar (SJS, TEN and DRESS, in order). Acetaminophen was primarily associated with SJS (27%) and was less involved in TEN (10%). DRESS occurred more readily among subjects experiencing coxib-induced SCARs than other NSAID-induced SCARs (62.5% vs. 19.7%, P = 0.013). The mean time to symptom onset was longer in DRESS than in SJS or TEN (19.1 ± 4.1 vs. 6.8 ±1.5 vs. 12.1 ± 3.8 days). SCARs caused by propionic salicylic acids showed longer latency, whereas acetaminophen- and acetic acid-induced SCARs appeared within shorter intervals. CONCLUSIONS: The present study indicates that the phenotypes of SCARs may differ according to the chemical classifications of NSAIDs. To establish the mechanisms and incidences of NSAID-induced SCARs, further prospective studies are needed.

COX-2 Inhibitors in Dental Pain Management / Inhibidores de la COX-2 en el Tratamiento del Dolor Dental

ABSTRACT: Pain is a major symptom in many dental procedures. Studies show consistently that pain, including dental pain, is not effectively treated; management of pain is a critical and challenging component in dentistry. Improvement and efficacy on the treatment depends on knowing which treatments are the most effective. Knowing how well an analgesic works and its associated adverse effects is fundamental to clinical decision. The aim of this review is to provide information to the dentistry field on the treatment of dental pain specifically with COX-2 inhibitors providing a useful guide to dentist on controlling pain. Therefore, nonsteroidal anti-inflammatory drugs (NSAIDs) are the most commonly prescribed analgesic agents in surgical outpatients. Major limitations of NSAIDs are their gastrointestinal (GI) adverse events (perforation, ulceration, and bleeding), impairment of hemostatic function, and renal failure (with long-term therapy). A new class of NSAIDs, COX2 selective inhibitors (Coxibs), have been developed with the aim of reducing the GI adverse events of traditional NSAIDs while maintaining their effective anti-inflammatory and analgesic properties.

RESUMEN: El dolor es un síntoma principal en muchos procedimientos dentales. Los estudios demuestran consistentemente que el dolor, incluido el dolor dental, no se trata de manera efectiva; el manejo del dolor es un componente crítico y desafiante en odontología. La mejora y la eficacia en el tratamiento depende de saber qué tratamientos son los más efectivos. Saber qué tan bien funciona un analgésico y sus efectos adversos asociados es fundamental para la decisión clínica. El objetivo de esta revisión es proporcionar información al campo de la odontología sobre el tratamiento del dolor dental específicamente con los inhibidores de la COX-2, proporcionando una guía útil para el control del dolor por parte del dentista. Por lo tanto, los fármacos antiinflamatorios no esteroideos (AINE) son los agentes analgésicos más comúnmente prescritos en pacientes ambulatorios quirúrgicos. Las principales limitaciones de los AINE son los eventos adversos gastrointestinales (perforación, ulceración y hemorragia), deterioro de la función hemostática e insuficiencia renal (con terapia a largo plazo). Una nueva clase de AINE, los inhibidores selectivos de la COX-2 (Coxibs), se han desarrollado con el objetivo de reducir los eventos adversos gastrointestinales de los AINE tradicionales mientras se mantienen sus propiedades antiinflamatorias y analgésicas efectivas.

Quantitative analysis of COX-2 promoter methylation in gastric carcinoma

PURPOSE: To determine the occurrence of COX-2 methylation in gastric carcinoma (GC), the status and level of CpG methylation in the promoter region of cyclooxygenase-2 (COX-2) were analyzed in early and advanced GCs, as well as in normal gastric tissues. METHODS: The extent of promoter methylation of the COX-2 gene was assessed quantitatively using pyrosequencing in 60 early and 60 advanced GCs samples harvested upon gastrectomy, and 40 normal gastric mucosa samples from patients with benign gastric diseases as controls. RESULTS: The methylation frequency for the COX-2 gene was significantly higher in early than in advanced GCs (40.0% vs. 20.0%, P < 0.05). A significant difference was found in COX-2 methylation between GCs and normal gastric tissues (30.0% vs. 10.0%, by PS; P < 0.05). COX-2 gene methylation was significantly associated with the depth of invasion (P = 0.003), lymph node metastasis (P = 0.009), distant metastasis (P = 0.036), and TNM staging (P = 0.007). The overall survival of patients with COX-2 methylation was significantly lower than that of patients without COX-2 methylation (P = 0.005). CONCLUSION: These results demonstrated that COX-2 promoter methylation was significantly higher in tumor tissues, and was an early event for GC, thus, COX-2 gene methylation may be important in the initial development of gastric carcinogenesis. Thus, GCs with methylation in COX-2 may not be good candidates for treatment with COX-2 inhibitors. Furthermore, COX-2 methylation could be a significant prognostic factor predicting a favorable effect on GC patient outcome when downregulated.

Preemptive use of etodolac on tooth sensitivity after in-office bleaching: a randomized clinical trial

Abstract Purpose: This study determined the effectiveness of the preemptive administration of etodolac on risk and intensity of tooth sensitivity and the bleaching effect caused by in-office bleaching using 35% hydrogen peroxide. Material and methods: Fifty patients were selected for this tripleblind, randomized, crossover, and placebo-controlled clinical trial. Etodolac (400 mg) or placebo was administrated in a single-dose 1 hour prior to the bleaching procedure. The whitening treatment with 35% hydrogen peroxide was carried out in two sessions with a 7-day interval. Tooth sensitivity was assessed before, during, and 24 hours after the procedure using the analog visual scale and the verbal rating scale. Color alteration was assessed by a bleach guide scale, 7 days after each session. Relative risk of sensitivity was calculated and adjusted by session, while overall risk was compared by the McNemar's test. Data on the sensitivity level of both scales and color shade were subjected to Friedman, Wilcoxon, and Mann-Whitney tests, respectively (α=0.05). Results: The preemptive administration of etodolac did not affect the risk of tooth sensitivity and the level of sensitivity reported, regardless of the time of evaluation and scale used. The sequence of treatment allocation did not affect bleaching effectiveness, while the second session resulted in additional color modification. The preemptive administration of etodolac in a single dose 1 hour prior to in-office tooth bleaching did not alter tooth color, and the risk and intensity of tooth sensitivity reported by patients. Conclusion: A single-dose preemptive administration of 400 mg of etodolac did not affect either risk of tooth sensitivity or level of sensitivity reported by patients, during or after the in-office tooth bleaching procedure.

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.

Selective COX-2 Inhibitor (Meloxicam) and Tooth-Supporting Bone Quality. A Histomorphometric Study in Rats

Abstract The effects of the non-steroidal anti-inflammatory drugs (NSAIDs) on bone quantity and quality were investigated for years. However, there is lack of information on the impact of NSAIDs on the quality of tooth-supporting alveolar bone in absence of periodontal inflammation. Thus, the aim of this study was to evaluate histometrically the influence of a selective COX-2 NSAID (Meloxicam) on the inter-radicular bone mineral density in rats. Forty-nine adult male Wistar rats were randomly divided into four experimental groups: Subcutaneous injection of 0.9% sterile saline for 15 days (G1; n=12) and 45 days (G2; n=11); and subcutaneous injection of Meloxicam for 15 days (G3; n=13) and 45 days (G4; n=13). Mineral density was histometrically determined in the inter-radicular area of the 1st mandibular molars and data analysis performed by two-way ANOVA (a=5%). Results showed no interaction between time and treatment (p>0.05) and that meloxicam did not affect the alveolar bone density. In contrast, it was found that inter-radicular alveolar bone density increased with time (91.88±3.08% and 92.86±2.38% for groups 15 and 45 days, respectively) (p<0.05). Within the limits of this study, daily administration of a selective COX-2 inhibitor (Meloxicam) did not affect the quality of the inter-radicular alveolar bone in absence of periodontal infection.

Resumo Os efeitos dos fármacos anti-inflamatórios não esteroidais (AINEs) sobre a quantidade e qualidade óssea tem sido investigados ao longo dos anos.Entretanto, há falta de informação sobre o impacto dos AINEs na qualidade do osso alveolar de suporte na ausência de inflamação periodontal. Assim, o objetivo deste estudo foi avaliar, histometricamente, a influência de um AINE seletivo para COX-2 (Meloxicam) na densidade mineral óssea inter-radicular em ratos. Quarenta e nove ratos Wistar, machos e adultos foram divididos aleatoriamente em quatro grupos experimentais: injeções subcutâneas de 0,9% de solução salina estéril por 15 dias (G1, n=12) e 45 dias (G2, n=11); e injeções subcutâneas de Meloxicam por 15 (G3, n=13) e 45 dias (G4, n=13). A densidade mineral foi determinada histometricamente na área inter-radicular dos primeiros molares mandibulares e a análise dos dados realizada por meio de ANOVA (a=5%). Os resultados mostraram nenhuma interação entre tempo e tratamento (p>0,05) e que o meloxicam não afetou a densidade óssea alveolar. Em contraste, foi encontrado que a densidade óssea alveolar inter-radicular aumentou ao longo do tempo (91,88±3,08% e 92,86±2,38% para os grupos 15 e 45 dias, respectivamente) (p<0,05). Dentro dos limites deste estudo, a administração diária de um inibidor seletivo para COX-2 (Meloxicam) não afetou a qualidade do osso alveolar inter-radicular na ausência de infecção periodontal.

Editor's Introduction to This Issue (G&I 15:2, 2017)

No abstract available.

Fixed drug eruption by etoricoxib confirmed by patch test

Abstract: Non-steroidal, anti-inflammatory drugs, followed by antibiotics, are the main causes of fixed drug eruption. They provoke one or several round erythematous or bullous lesions that recur in the same place after taking the causative medication. A positive patch test on residual, lesional skin can replace satisfactorily oral reintroduction. We describe the case of a 74-year-old woman with numerous, rounded, erythematous lesions on the trunk and recurrent blistering on the fifth right-hand finger, which developed a few hours after taking etoricoxib. Lesional patch testing with etoricoxib was positive and reproduced the typical pattern of a fixed drug eruption upon histopathology. We emphasize the specific reactivity of the etoricoxib patch test, and the capacity to reproduce the histologic pattern of the reaction.

Design, synthesis and biological evaluation of4-[imidazolylmethyl]-2-[4-methylsulfonyl phenyl]-quinoline derivatives as selective COX-2 inhibitors and in-vitro anti-breast cancer agents

A new group of 4-[Imidazolylmethyl] quinoline derivatives possessing a methylsulfonyl COX-2 pharmacophore at the para position of the C-2 phenyl ring were designed and synthesized as selective COX-2 inhibitors and in-vitro anti breast cancer agents. In-vitro COX-1 and COX-2 inhibition studies showed that all the compounds were potent and selective inhibitors of the COX-2 isozyme with IC[50] values in the potent range 0.063-0.090 microM, and COX-2 selectivity indexes in the 179.9 to 547.6 range. Molecular modeling studies indicated that the methylsulfonyl substituent can be inserted into the secondary pocket of COX-2 active site for interactions with Arg[513]. Cytotoxicity of quinolines 9a-e against human breast cancer MCF-7 and T47D cell lines were also evaluated. All the compounds 9a-e were more cytotoxic against MCF-7 cells in comparison with those of T47D which express aromatase mRNA less than MCF-7 cells. The data showed that the increase of lipophilic properties of substituents on the C-7 and C-8 quinoline ring increased their cytotoxicity on MCF-7cells and COX-2 inhibitory activity. Among the quinolines 9a-e, 4-[[1H-Imidazol-1-yl]methyl] 7,8,9,10-tetrahydro-2-[4-methylsulfonylphenyl]-benzo[h]quinoline [9d]was identified as the most potent and selective COX-2 inhibitor as well as the most cytotoxic agent against MCF-7 cells

Gastric and renal effects of COX-2 selective and non-selective NSAIDs in rats receiving low-dose aspirin therapy

Abstract The consumption of low-dose aspirin (LDA) to prevent cardiovascular disease continues to increase worldwide. Consequently, the number of chronic LDA users seeking dental procedures that require complementary acute anti-inflammatory medication has also grown. Considering the lack of literature evaluating this interaction, we analyzed the gastric and renal effects caused by a selective COX-2 inhibitor (etoricoxib) and a non-selective COX-2 inhibitor (ibuprofen) nonsteroidal anti-inflammatory drug (NSAID) in rats receiving chronic LDA therapy. Male Wistar rats were divided into six experimental groups (carboxymethylcellulose (CMC) - vehicle; LDA; LDA + ibuprofen; ibuprofen; LDA + etoricoxib; and etoricoxib) and submitted to long-term LDA therapy with a subsequent NSAID administration for three days by gavage. After the experimental period, we analyzed gastric and renal tissues and quantified serum creatinine levels. The concomitant use of LDA with either NSAID induced the highest levels of gastric damage when compared to the CMC group (F = 20.26, p < 0.05). Treatment with either LDA or etoricoxib alone was not associated with gastric damage. No significant damage was observed on kidney morphology and function (F = 0.5418, p > 0.05). These results suggest that even the acute use of an NSAID (regardless of COX-2 selectivity) can induce gastric damage when combined with the long-term use of low-dose aspirin in an animal model. Additional studies, including clinical assessments, are thus needed to clarify this interaction, and clinicians should be careful of prescribing NSAIDs to patients using LDA.