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1.
J Oral Maxillofac Surg ; 74(8): 1524-30, 2016 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-27160363

RESUMEN

PURPOSE: To compare the efficacy of ibuprofen (IBU) and etodolac (ETO) for controlling pain, edema, and trismus after extraction of lower third molars. MATERIALS AND METHODS: Twenty adolescents and adults with 2 impacted mandibular-third molars (in similar positions) were selected for the study. Patients were randomly assigned either to the IBU group (600 mg of IBU 3 times a day for 3 days) or to the ETO group (300 mg of ETO 3 times a day for 3 days). Drugs were administered immediately after dental extraction. RESULTS: During the first 2 days after extraction, swelling was more pronounced in the IBU group than in the ETO group (P = .033). Seven days after surgery, there was no difference in the degree of edema between the groups. At the 2- and 7-day evaluation points, mouth opening was significantly more reduced in the IBU group than in the ETO group (P < .05). After the first 6 hours, the ETO group had more effective pain relief (P < .05), but after this time point, both groups reported similar degrees of relief. Compared with the IBU group, the ETO group had a lower need for administration of additional rescue analgesics. CONCLUSIONS: After extraction of impacted lower third molars, we found that swelling, trismus, and pain were more effectively controlled with ETO than with IBU.


Asunto(s)
Inhibidores de la Ciclooxigenasa 2/uso terapéutico , Edema/tratamiento farmacológico , Etodolaco/uso terapéutico , Ibuprofeno/uso terapéutico , Tercer Molar/cirugía , Dolor Postoperatorio/tratamiento farmacológico , Diente Impactado/cirugía , Trismo/tratamiento farmacológico , Adolescente , Femenino , Humanos , Masculino , Mandíbula/cirugía , Manejo del Dolor , Dimensión del Dolor , Extracción Dental , Resultado del Tratamiento , Adulto Joven
2.
Hepatogastroenterology ; 62(140): 787-9, 2015 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-26902001

RESUMEN

BACKGROUND/AIMS: To identify predictive factors for NSAIDs-related GI toxicity and to clarify whether cox-2 selective inhibitors can prevent it or not. METHODOLOGY: We have surveyed all patients received esophagogastroduodenoscopy examined at our hospital between January 2008 and September 2011. We performed the following retrospective analyses of the clinical records of the 253 patients prescribed NSAIDs. The severity of gastro duodenal mucosal lesions was evaluated using the modified gastro duodenal LANZA score. The following scores for response were used: 0 = no lesions (LANZA score 0); 1 = erosion and redness (LANZA score 1-3); 2 = ulcer (LANZA score 4). Predictors evaluated were factors potentially related to pathogenesis of NSAIDs related GI toxicity. Ordered logistic regression analysis was performed to identify predictive factors for NSAIDs related. ulcer. RESULTS: A multivariate logistic regression identified number of risk factors (odds ratio (OR) = 6.82, confidence interval (CI) = 5.31-8.76; P = 0.01), concomitant use of anti- cancer drugs (OR = 2.17, Cl = 1.02-4.62; P = 0.04) were found to be significant factors. CONCLUSIONS: Number of risk factors and concomitant use of anticancer drugs were shown to be predictive factors for NSAID-related GI toxicity. Use of celecoxib or proton pump inhibitor was not identified as a protective factor.


Asunto(s)
Corticoesteroides/uso terapéutico , Antiinflamatorios no Esteroideos/uso terapéutico , Anticoagulantes/uso terapéutico , Antineoplásicos/uso terapéutico , Inhibidores de la Ciclooxigenasa 2/uso terapéutico , Úlcera Duodenal/epidemiología , Inhibidores de la Bomba de Protones/uso terapéutico , Úlcera Gástrica/epidemiología , Anciano , Aspirina/uso terapéutico , Celecoxib/uso terapéutico , Estudios de Cohortes , Diclofenaco/uso terapéutico , Enfermedades Duodenales/epidemiología , Enfermedades Duodenales/patología , Úlcera Duodenal/patología , Endoscopía del Sistema Digestivo , Etodolaco/uso terapéutico , Femenino , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Fenilpropionatos/uso terapéutico , Factores Protectores , Estudios Retrospectivos , Factores de Riesgo , Gastropatías/epidemiología , Gastropatías/patología , Úlcera Gástrica/patología
3.
Med Oral Patol Oral Cir Bucal ; 19(2): e149-56, 2014 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-24316711

RESUMEN

OBJECTIVE: To compare the three non-steroidal anti-inflammatory agents (NSAIDs) Diclofenac potassium, Etodolac and Naproxen sodium in relation to pain, swelling and trismus following impacted third molar surgery. STUDY DESIGN: The study was a randomized and a double-blinded study which included 42 healthy young individuals with impacted third molars and bone retention. Patients were randomly assigned to 3 groups (n: 14) to which Diclofenac potassium, Naproxen sodium and Etodolac were administered orally an hour before the operation. Impacted third molars were surgically extracted with local anaesthesia. Visual analog scales (VAS) were used to assess the pain in the 6th, 12th hours and on the 1st, 2nd, 3rd, 5th, and 7th days postoperatively. Swelling was evaluated using ultrasound (US) and mouth opening (trismus) was measured with a composing stick pre and post operatively on the 2nd and 7th days respectively. RESULTS: Regarding pain alleviation, Diclofenac potassium was better than Naproxen sodium and Naproxen sodium was better than Etodolac but these differences were not statistically significant. US measurements showed that the swelling on postoperative 2nd day was significantly lowest with Diclofenac potassium as compared to others (p= 0.027) while Naproxen sodium and Etodolac acted similarly (p=0.747). No difference was noted regarding trismus in any of the groups. CONCLUSION: NSAIDs (Diclofenac, Naproxen and Etodolac) are somehow similarly effective for controlling pain and trismus following extraction of mandibular third molars but Diclofenac potassium surpasses others in reduction of swelling.


Asunto(s)
Antiinflamatorios no Esteroideos/uso terapéutico , Diclofenaco/uso terapéutico , Edema/prevención & control , Etodolaco/uso terapéutico , Tercer Molar/cirugía , Naproxeno/uso terapéutico , Dolor Postoperatorio/prevención & control , Extracción Dental , Diente Impactado/cirugía , Trismo/prevención & control , Adolescente , Adulto , Estudios Cruzados , Método Doble Ciego , Femenino , Humanos , Masculino , Adulto Joven
4.
J Orthop Sci ; 18(2): 208-15, 2013 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-23203845

RESUMEN

BACKGROUND: Quality of life (QOL) is a concern for patients with lumbar spinal stenosis (LSS). In this study, QOL was examined using the 5-item EuroQol (EQ-5D). METHODS: QOL and activities of daily living (ADL) were surveyed for 91 patients who visited 18 medical institutions in our prefecture and were diagnosed with LSS-associated intermittent claudication. A second survey was performed after ≥6 weeks for 79 of the subjects to evaluate therapy with limaprost (an oral prostaglandin E1 derivative) or etodolac (an NSAID). Symptoms, maximum walking time, QOL, ADL items, and relationships among these variables were investigated for all 91 patients. Leg pain, leg numbness, and low back pain while walking were surveyed by use of VAS scores (0-100). RESULTS: Leg pain, leg numbness, and low back pain while walking (VAS ≥25) were present in 83.5, 62.6, and 54.9 % of the patients in the first survey, and approximately half of the patients had a maximum walking time <15 min. The mean EQ-5D utility value for QOL was 0.59 ± 0.12. This value was significantly associated with maximum walking time (p = 0.030) based on classification of patients into groups with walking times <7.5, 7.5-15, 15-30, and >30 min, showing that maximum walking time affected health-related QOL. Of the 79 patients who completed the second survey, 56 had taken limaprost and 23 (control group) had received etodolac. Limaprost improved possible walking time, reduced ADL interference, and significantly increased the EQ-5D utility score, whereas no significant changes occurred in the control group. Maximum walking time was prolonged by ≥10 min and the EQ-5D utility value was improved by ≥0.1 points in significantly more patients in the limaprost group than in the control group. CONCLUSION: According to the findings of this survey, at an average of 8 weeks after administration limaprost improved symptoms, QOL, and ADL in LSS patients whereas treatment with an NSAID reduced pain but did not have any other effects.


Asunto(s)
Alprostadil/análogos & derivados , Inhibidores de la Ciclooxigenasa 2/uso terapéutico , Etodolaco/uso terapéutico , Dolor de la Región Lumbar/tratamiento farmacológico , Calidad de Vida , Estenosis Espinal/tratamiento farmacológico , Vasodilatadores/uso terapéutico , Actividades Cotidianas , Anciano , Alprostadil/uso terapéutico , Distribución de Chi-Cuadrado , Evaluación de la Discapacidad , Femenino , Humanos , Claudicación Intermitente/tratamiento farmacológico , Vértebras Lumbares , Masculino , Dimensión del Dolor , Estadísticas no Paramétricas , Resultado del Tratamiento , Caminata
5.
Clin Exp Nephrol ; 16(2): 221-30, 2012 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-22147282

RESUMEN

BACKGROUND AND METHODS: There is increasing evidence that a change in glomerular hemodynamics may promote the development of glomerulosclerosis. In this study, we focused on the pharmacological effects of 2 contrasting agents, etodolac, a preferential cyclooxygenase-2 inhibitor, and beraprost sodium (BPS), a prostaglandin I(2) analog, delivered renally, on the disease course of progressive anti-Thy-1 (ATS) glomerulonephritis. RESULTS: Intravital microscopic analysis showed that the diameters of glomerular capillaries and glomerular blood flow in unilaterally nephrectomized (Nx) rats treated locally with BPS were significantly increased, as compared to those of Nx rats treated locally with normal saline (NS) or etodolac. We then examined the effects of BPS and etodolac on the course of progressive glomerulosclerosis. Mesangial cell proliferation, adhesion of glomerular capillary tufts and crescent formation in the BPS-treated group appeared to be more severe compared to the ATS + NS and the ATS + etodolac groups. Scoring of mesangial proliferation and glomerulosclerosis revealed that local BPS treatment significantly worsened glomerular pathology. At day 28, there were significant differences in blood flow between the ATS + etodolac group and both the ATS + NS and ATS + BPS groups, indicating that local treatment with etodolac enhanced the recovery of glomerular circulation. CONCLUSION: This study provides hemodynamic-based evidence showing that disturbance of intraglomerular microcirculation is a critical marker for progressive glomerulonephritis.


Asunto(s)
Inhibidores de la Ciclooxigenasa 2/farmacología , Epoprostenol/análogos & derivados , Etodolaco/uso terapéutico , Mesangio Glomerular/efectos de los fármacos , Glomerulonefritis/tratamiento farmacológico , Glomérulos Renales/patología , Animales , Progresión de la Enfermedad , Epoprostenol/farmacología , Epoprostenol/uso terapéutico , Etodolaco/farmacología , Mesangio Glomerular/patología , Glomerulonefritis/patología , Isoanticuerpos , Glomérulos Renales/irrigación sanguínea , Glomérulos Renales/efectos de los fármacos , Ratas , Ratas Wistar
6.
Pharmacology ; 90(1-2): 47-54, 2012.
Artículo en Inglés | MEDLINE | ID: mdl-22739568

RESUMEN

BACKGROUND AND PURPOSE: The excitability of nociceptors is modulated by the transient receptor potential cation channel, ankyrin subfamily, member 1 (TRPA1). We have previously reported that etodolac, a nonsteroidal anti-inflammatory drug, attenuates mechanical allodynia in a mouse model of neuropathic pain by a mechanism that is independent of cyclooxygenase inhibition. Here, we investigate the role of TRPA1 in the mechanism of the antinociceptive action of etodolac in vitro and in vivo. EXPERIMENTAL APPROACH: Ca(2+) influx was measured in HEK-293 cells expressing mouse TRPA1 and in mouse dorsal root ganglion (DRG) neurons. The effect of etodolac on the nociceptive behavior induced in mice by the TRPA1 agonist allyl isothiocyanate (AITC) was also measured. RESULTS: Etodolac induced Ca(2+) influx in HEK-293 cells expressing mouse TRPA1 and in mouse DRG neurons. The Ca(2+) influx induced by etodolac was inhibited by pretreatment with the TRPA1-specific antagonist HC-030031. In contrast, etodolac did not induce Ca(2+) influx in cells expressing TRPV1, TRPV2 or TRPM8. In addition, pretreatment with etodolac inhibited the Ca(2+) influx induced by AITC. CONCLUSION AND IMPLICATION: Etodolac showed a selective TRPA1 agonist action, providing evidence that etodolac desensitizes nociceptors by the selective activation of TRPA1. Etodolac may be clinically useful in the treatment of neuropathic pain.


Asunto(s)
Analgésicos no Narcóticos/farmacología , Inhibidores de la Ciclooxigenasa 2/farmacología , Etodolaco/farmacología , Dolor/fisiopatología , Células Receptoras Sensoriales/efectos de los fármacos , Canales de Potencial de Receptor Transitorio/fisiología , Analgésicos no Narcóticos/uso terapéutico , Animales , Conducta Animal/efectos de los fármacos , Células CHO , Calcio/fisiología , Células Cultivadas , Cricetinae , Cricetulus , Inhibidores de la Ciclooxigenasa 2/uso terapéutico , Etodolaco/uso terapéutico , Ganglios Espinales/citología , Células HEK293 , Humanos , Isotiocianatos , Masculino , Ratones , Dolor/tratamiento farmacológico , Células Receptoras Sensoriales/fisiología , Canal Catiónico TRPA1
7.
Acta Cytol ; 56(4): 394-400, 2012.
Artículo en Inglés | MEDLINE | ID: mdl-22846758

RESUMEN

OBJECTIVE: We previously reported that oral administration of the selective cyclooxygenase-2 (COX-2) inhibitor etodolac results in antitumor effects in endometrial cancer tissue. Herein, we investigated whether these antitumor effects could be assessed using endometrial cytological findings. STUDY DESIGN: Etodolac (400 mg b.i.d. for 2 weeks) was administered preoperatively to 21 endometrial cancer patients: 16 had COX-2-positive disease and 5 had COX-2-negative disease. Twenty-one pairs of pre- and post-etodolac-treatment endometrial cytological samples were collected to review changes in the cytological features. RESULTS: In the COX-2-positive patients, nuclear atypia was slightly decreased in 3 of the 16 cases, while the mitotic index was decreased in all cases. Cellular overlapping and tumor cell cluster outlines were somewhat affected in 6 and 8 cases, respectively. Nuclear/cytoplasmic ratio, anisokaryosis and hyperchromasia were also reduced in 6, 4, and 2 cases, respectively; however, tumor diathesis and nucleoli features were unchanged. In contrast, endometrial cytological features did not appear to be affected in the 5 COX-2-negative patients. CONCLUSIONS: We conclude that the antitumor effects observed in endometrial cancer tissues following oral administration of etodolac are reflected in and can be easily assessed by evaluating endometrial cytological features.


Asunto(s)
Antineoplásicos/uso terapéutico , Inhibidores de la Ciclooxigenasa 2/uso terapéutico , Neoplasias Endometriales/tratamiento farmacológico , Endometrio/efectos de los fármacos , Etodolaco/uso terapéutico , Anciano , Neoplasias Endometriales/patología , Endometrio/patología , Femenino , Humanos , Persona de Mediana Edad , Terapia Neoadyuvante
8.
Curr Radiopharm ; 15(3): 242-248, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35319403

RESUMEN

BACKGROUND: Radioresistance is found to be the main therapeutic restriction in colorectal radiation therapy. The aim of this study was to investigate the synergistic effect of Etodolac (ET) and ionizing radiation on human colorectal cancer cells. METHODS: Pretreated HT-29 cells with ET were exposed to ionizing radiation. The radiosensitizing effect of ET was evaluated using MTT, flow cytometry, and clonogenic assay. The amount of nitrite oxide (NO) in irradiated cells was also measured with the Griess reagent. RESULTS: The present study found that pretreatment of HT-29 cells with ET decreases their survival and colony formation. Higher concentrations of ET cause total apoptosis and an increase in NO levels in irradiated cells. CONCLUSION: Applying ET in a concentration-dependent manner had an incremental effect on the amount of apoptosis and cell death induced by radiation.


Asunto(s)
Neoplasias Colorrectales , Fármacos Sensibilizantes a Radiaciones , Apoptosis/efectos de la radiación , Línea Celular Tumoral , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/metabolismo , Neoplasias Colorrectales/radioterapia , Etodolaco/farmacología , Etodolaco/uso terapéutico , Células HT29 , Humanos , Tolerancia a Radiación/efectos de la radiación , Fármacos Sensibilizantes a Radiaciones/farmacología , Radiofármacos/farmacología
9.
Sci Rep ; 11(1): 24445, 2021 12 27.
Artículo en Inglés | MEDLINE | ID: mdl-34961782

RESUMEN

The aim of this study is to evaluate the preemptive analgesic effects of dexamethasone (DEX) alone or combined with non-steroidal anti-inflammatory drugs (NSAIDs) in third molar surgeries. The subjects were divided into five groups (n = 20 teeth/group); subjects received only 8 mg of dexamethasone 1 h before the surgical procedure (DEX group), or in combination with etodolac (DEX + ETO), ketorolac (DEX + KET), ibuprofen (DEX + IBU), loxoprofen (DEX + LOX). Paracetamol 750 mg was provided as the number of rescue analgesics (NRA). Salivary PGE2 expression was measured preoperatively and at 48 h. Edema and Maximum mouth opening (MMO) were measured postoperatively at 48 h and 7 days. A visual analog scale (VAS) was performed postoperatively at 6, 12, 24, 48, 72 h, and 7 days. Salivary expression of PGE2 showed a decrease only for the DEX group. Edema and MMO and NRA consumption showed no significant differences among the groups (P > 0.05). The VAS showed a significantly lower pain perception at 6 h after the surgery for the DEX + ETO and DEX + KET groups (P < 0.05). The combination of DEX and NSAIDS should be considered for preemptive acute postsurgical pain management in third molar surgery. In some drug associations such as dexamethasone 8 mg + NSAIDS (ETO and KET) in the pre-operative time, only a few rescue analgesics are necessary.


Asunto(s)
Analgésicos/uso terapéutico , Antiinflamatorios no Esteroideos/uso terapéutico , Dexametasona/uso terapéutico , Tercer Molar/cirugía , Extracción Dental , Adolescente , Adulto , Quimioterapia Combinada , Etodolaco/uso terapéutico , Femenino , Glucocorticoides/uso terapéutico , Humanos , Ibuprofeno/uso terapéutico , Ketorolaco/uso terapéutico , Masculino , Fenilpropionatos/uso terapéutico , Estudios Prospectivos , Extracción Dental/métodos , Adulto Joven
10.
Int J Cancer ; 126(6): 1467-73, 2010 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-19711347

RESUMEN

The present study investigated the preventive effects of etodolac, a selective cyclo-oxygenase (COX)-2 inhibitor, on metachronous cancer development after endoscopic resection of early gastric cancer. Among 267 early gastric cancer patients who underwent endoscopic resection, 47 patients with extensive metaplastic gastritis were selected based on endoscopic findings and our previously described criteria of serum pepsinogen (PG) test-positive and Helicobacter pylori antibody-negative conditions. Nonrandomized etodolac treatment (300 mg/day) was administered to 26 patients (Group A), while the remaining 21 patients were untreated (Group B). No significant differences in age, sex distribution, lifestyle factors or extent of metaplastic gastritis at baseline were identified between groups. Patients were followed for metachronous cancer development with endoscopy every 6-12 months for up to 5 years. Mean (standard deviation) follow-up period was 4.2 (0.9) years. In Group B, 5 cancers developed (incidence rate = 6,266/100,000 person-years), significantly more than the 1 cancer in Group A (incidence rate = 898/100,000 person-years; p < 0.05). Long-term etodolac treatment did not influence the extent of metaplastic gastritis as revealed by endoscopic findings or by serum PG levels, but effectively reduced metachronous cancer development in patients with extensive metaplastic gastritis. These results strongly suggest that chemoprevention of cancer in the metaplastic stomach is possible by controlling COX-2 expression.


Asunto(s)
Inhibidores de la Ciclooxigenasa 2/uso terapéutico , Etodolaco/uso terapéutico , Gastritis/prevención & control , Neoplasias Gástricas/prevención & control , Anciano , Femenino , Estudios de Seguimiento , Gastritis/complicaciones , Gastritis/diagnóstico , Helicobacter pylori/efectos de los fármacos , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Lesiones Precancerosas/complicaciones , Lesiones Precancerosas/microbiología , Lesiones Precancerosas/prevención & control , Estómago/efectos de los fármacos , Estómago/patología , Estómago/cirugía , Neoplasias Gástricas/complicaciones , Neoplasias Gástricas/cirugía , Resultado del Tratamiento
11.
Int J Clin Pharmacol Ther ; 48(7): 429-34, 2010 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-20557835

RESUMEN

OBJECTIVE: To compare the efficacy and safety of S-etodolac with etodolac in the treatment of osteoarthritis in Indian patients. MATERIALS AND METHODS: This was a double-blind, multicentric, comparative clinical trial conducted in 108 Indian patients with osteoarthritis. All patients received either S-etodolac ER 300 mg or etodolac ER 600 mg tablets once daily. Assessment was done on the basis of WOMAC score and VAS pain score, patient's and physician's global assessment of the arthritic condition. All patients were evaluated after every 2 weeks for 4 weeks for efficacy and safety variables. RESULTS AND DISCUSSION: Total 49 patients in the test group and 52 patients in the reference group completed the study. There was significant improvement (p < 0.0001) in all WOMAC subscales (pain, stiffness and physical function), WOMAC total score and VAS pain score in both the groups. Patient's and physician's global assessment of the arthritic condition also improved significantly (p < 0.0001). All patients showed improvement in WOMAC and VAS pain score by (3) 20%. There was no significant difference between the groups for the efficacy parameters. The adverse events reported were few and no serious adverse events were reported. Total 5 patients in S-etodolac group and 2 patients in etodolac group dropped out of the study. Only 1 patient dropped out because of the side effects of burning sensation, palpitations and anxiety in the test group. CONCLUSION: The present study has established the efficacy, tolerability and safety of S-etodolac extended release tablets in the treatment of osteoarthritis in Indian patients.


Asunto(s)
Antiinflamatorios no Esteroideos/uso terapéutico , Etodolaco/uso terapéutico , Osteoartritis/tratamiento farmacológico , Adulto , Anciano , Método Doble Ciego , Etodolaco/efectos adversos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Dimensión del Dolor
12.
Rheumatol Int ; 30(7): 985-6, 2010 May.
Artículo en Inglés | MEDLINE | ID: mdl-19533139

RESUMEN

We report a case of acute sacroiliitis with severe disability after only 3 weeks of isotretinoin therapy with graduate reduction of pain, limitation and muscle incompetence after discontinuation of the drug and ACTH-depo injection and Ethodolac therapy. Naranjo probability scale indicated a probable relationship between isotretinoin therapy and bilateral sacroiliitis. We discussed possible mechanisms of sacroiliitis and disability due to isotretinoin treatment.


Asunto(s)
Artralgia/inducido químicamente , Artritis/inducido químicamente , Fármacos Dermatológicos/efectos adversos , Isotretinoína/efectos adversos , Articulación Sacroiliaca/efectos de los fármacos , Acné Vulgar/tratamiento farmacológico , Hormona Adrenocorticotrópica/uso terapéutico , Adulto , Antiinflamatorios no Esteroideos/uso terapéutico , Artralgia/patología , Artralgia/fisiopatología , Artritis/patología , Artritis/fisiopatología , Evaluación de la Discapacidad , Edema/inducido químicamente , Edema/patología , Etodolaco/uso terapéutico , Humanos , Enfermedad Iatrogénica/prevención & control , Dolor de la Región Lumbar/inducido químicamente , Dolor de la Región Lumbar/patología , Dolor de la Región Lumbar/fisiopatología , Imagen por Resonancia Magnética , Masculino , Debilidad Muscular/etiología , Debilidad Muscular/fisiopatología , Radiografía , Articulación Sacroiliaca/diagnóstico por imagen , Articulación Sacroiliaca/patología , Resultado del Tratamiento , Imagen de Cuerpo Entero/métodos
13.
BMJ Open ; 10(9): e040406, 2020 09 30.
Artículo en Inglés | MEDLINE | ID: mdl-32998931

RESUMEN

INTRODUCTION: Pancreatic cancer is the fourth-leading cause of cancer-related death in developed countries. Despite advances in systemic chemotherapy, the mainstay of curative therapy for non-metastatic disease is surgical resection. However, the perioperative period is characterised by stress and inflammatory reactions that can contribute to metastatic spread and disease recurrence. Catecholamines and prostaglandins play a crucial role in these reactions. Therefore, a drug repurposing of betablockers and cyclooxygenase inhibitors seems reasonable to attenuate tumour-associated inflammation by inhibiting psychological, surgical and inflammatory stress responses. This may cause a relevant antitumourigenic and antimetastatic effect during the perioperative period, a window for cancer-directed therapy that is currently largely unexploited. METHODS AND ANALYSIS: This is a prospective, single-centre, two-arm randomised, patient and observer blinded, placebo-controlled, phase-II trial evaluating safety and feasibility of combined perioperative treatment with propranolol and etodolac in adult patients with non-metastatic cancer of the pancreatic head undergoing elective pancreatoduodenectomy. 100 patients fulfilling the eligibility criteria will be randomised to perioperative treatment for 25 days perioperatively with a combination of propranolol and etodolac or placebo. Primary outcome of interest will be safety in terms of serious adverse events and reactions within 3 months. Furthermore, adherence to trial medication will be assessed as feasibility outcomes. Preliminary efficacy data will be evaluated for the purpose of power calculation for a potential subsequent phase-III trial. The clinical trial is accompanied by a translational study investigating the mechanisms of action of the combined therapy on a molecular basis. ETHICS AND DISSEMINATION: The PROSPER-trial has been approved by the German Federal Institute for Drugs and Medical Devices (reference number 4042875) and the Ethics Committee of the Medical Faculty of the University of Heidelberg (reference number AFmo-385/2018). The final trial results will be published in a peer-reviewed journal and will be presented at appropriate national and international conferences. TRIAL REGISTRATION NUMBERS: DRKS00014054; EudraCT number: 2018-000415-25.


Asunto(s)
Etodolaco , Propranolol , Adulto , Ensayos Clínicos Fase II como Asunto , Reposicionamiento de Medicamentos , Etodolaco/uso terapéutico , Humanos , Pancreatectomía , Propranolol/uso terapéutico , Estudios Prospectivos , Ensayos Clínicos Controlados Aleatorios como Asunto
14.
Artículo en Inglés | MEDLINE | ID: mdl-19862936

RESUMEN

BACKGROUND AND OBJECTIVE: Cyclooxygenase (COX) is an enzyme that converts arachidonic acid to prostanoids. There are two isoforms of COX, namely COX-1 and COX-2. COX-2 is highly inducible by several stimuli and is associated with inflammation. Recent studies have shown that COX-2 is upregulated in the airway epithelium of patients with asthma but little is known about the role it plays in cough, a common symptom of bronchial asthma. This study was designed to investigate the role of COX-2 in cough reflex sensitivity in patients with asthma. PATIENTS AND METHODS: The effect of etodolac, a potent COX-2 inhibitor, on cough response to inhaled capsaicin was examined in 17 patients with stable asthma in a randomized, placebo-controlled crossover study. Capsaicin cough threshold, defined as the lowest concentration of capsaicin eliciting 5 or more coughs, was measured as an index of airway cough reflex sensitivity. RESULTS: The geometric mean (geometric SEM) cough threshold was significantly increased after a 2-week treatment program with oral etodolac (200 mg twice a day) compared with placebo (36.7 [1.2] vs 21.6 [1.2] gM, P<.02). CONCLUSIONS: These findings indicate that COX-2 may be a possible modulator augmenting airway cough reflex sensitivity in asthmatic airways.


Asunto(s)
Asma/enzimología , Tos/enzimología , Ciclooxigenasa 2/inmunología , Inhibidores de la Ciclooxigenasa/farmacología , Etodolaco/farmacología , Adulto , Anciano , Anciano de 80 o más Años , Asma/tratamiento farmacológico , Asma/inmunología , Capsaicina/inmunología , Tos/tratamiento farmacológico , Tos/inmunología , Estudios Cruzados , Inhibidores de la Ciclooxigenasa/uso terapéutico , Interacciones Farmacológicas , Etodolaco/uso terapéutico , Femenino , Volumen Espiratorio Forzado , Humanos , Masculino , Persona de Mediana Edad , Estadísticas no Paramétricas , Capacidad Vital
15.
J Headache Pain ; 10(4): 295-8, 2009 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-19370308

RESUMEN

A 28-year-old woman had thunderclap headache (TCH), after 7 days she had left hemiparesis. She had a history of oral contraceptive and citalopram medications. Brain magnetic resonance (MR) angiography demonstrated multiple stenotic segments. Digital subtraction angiography (DSA) showed multiple segments of narrowing in vessel calibre. Two probable diagnoses performed; primary angiitis of the central nervous system and reversible cerebral vasoconstriction syndrome (RCVS). Because of clinical characteristics and normal cerebrospinal fluid findings she was set on medication for probable RCVS. Follow-up MR angiography after 4 weeks and DSA after 7 weeks demonstrated improvement in vessel calibre. Thus, diagnosis RCVS was established. Diagnosis and management of TCH contain many potential difficulties. Clinicians should consider the imaging of cerebral arteries, even if computed tomography scan and lumbar puncture are normal in TCH. Potential precipitating factors and triggers should also be known and avoided.


Asunto(s)
Arterias Cerebrales/fisiopatología , Trastornos Cerebrovasculares/complicaciones , Trastornos Cerebrovasculares/fisiopatología , Cefaleas Primarias/etiología , Cefaleas Primarias/fisiopatología , Vasoconstricción/fisiología , Adulto , Angiografía de Substracción Digital , Antiinflamatorios no Esteroideos/uso terapéutico , Infarto Encefálico/etiología , Infarto Encefálico/patología , Infarto Encefálico/fisiopatología , Bloqueadores de los Canales de Calcio/uso terapéutico , Arterias Cerebrales/diagnóstico por imagen , Arterias Cerebrales/patología , Trastornos Cerebrovasculares/diagnóstico por imagen , Citalopram/efectos adversos , Anticonceptivos Orales/uso terapéutico , Etodolaco/uso terapéutico , Femenino , Humanos , Angiografía por Resonancia Magnética , Arteria Cerebral Media/diagnóstico por imagen , Arteria Cerebral Media/patología , Arteria Cerebral Media/fisiopatología , Paresia/etiología , Paresia/patología , Paresia/fisiopatología , Inhibidores de Agregación Plaquetaria/uso terapéutico , Inhibidores Selectivos de la Recaptación de Serotonina/efectos adversos , Resultado del Tratamiento , Vasoconstricción/efectos de los fármacos , Vasodilatación/efectos de los fármacos , Vasodilatación/fisiología
16.
Int J Nanomedicine ; 14: 7561-7581, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31571864

RESUMEN

INTRODUCTION: This study was conducted to elucidate the chemopreventive potential, cytotoxic, and suppression of cellular metastatic activity of etodolac (ETD)-loaded nanocarriers. METHODS: To esteem the effect of charge and composition of the nanovectors on their performance, four types of vectors namely, negative lipid nanovesicles; phosalosomes (N-Phsoms), positive phosalosomes (P-Phsoms), nanostructured lipid carriers (NLCs) and polymeric alginate polymer (AlgNPs) were prepared and compared. ETD was used as a model cyclo-oxygenase-2 (COX-2) inhibitor to evaluate the potency of these nanovectors to increase ETD permeation and retention through human skin and cytotoxicity against squamous cell carcinoma cell line (SCC). Moreover, the chemopreventive activity of ETD nanovector on mice skin cancer model was evaluated. RESULTS: Among the utilized nanovectors, ETD-loaded N-Phsoms depicted spherical vesicles with the smallest particle size (202.96±2.37 nm) and a high zeta potential of -24.8±4.16 mV. N-Phsoms exhibited 1.5, and 3.6 folds increase in the ETD amount deposited in stratum corneum, epidermis and dermis. Moreover, cytotoxicity studies revealed a significant cytotoxic potential of such nanovector with IC50=181.76 compared to free ETD (IC50=982.75), correlated to enhanced cellular internalization. Its efficacy extended to a reduction in the relative tumor weight with 1.70 and 1.51-fold compared to positive control and free ETD, that manifested by a 1.72-fold reduction in both COX-2 and proliferating cell nuclear antigen mRNA (PCNA-mRNA) levels and 2.63-fold elevation in caspase-3 level in skin tumors relative to the positive control group with no hepato-and nephrotoxicity. CONCLUSION: Encapsulation of ETD in nanovector enhances its in-vitro and in-vivo anti-tumor activity and opens the door for encapsulation of more relevant drugs.


Asunto(s)
Quimioprevención , Inhibidores de la Ciclooxigenasa 2/uso terapéutico , Ciclooxigenasa 2/metabolismo , Nanoestructuras/química , Neoplasias Cutáneas/tratamiento farmacológico , Neoplasias Cutáneas/enzimología , Animales , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Inhibidores de la Ciclooxigenasa 2/farmacología , Inhibidores de la Ciclooxigenasa 2/toxicidad , Portadores de Fármacos/química , Liberación de Fármacos , Etodolaco/farmacología , Etodolaco/uso terapéutico , Femenino , Humanos , Concentración 50 Inhibidora , Lípidos/química , Ratones , Nanoestructuras/ultraestructura , Tamaño de la Partícula , Estudios Prospectivos , Absorción Cutánea/efectos de los fármacos , Neoplasias Cutáneas/patología , Electricidad Estática , Resultado del Tratamiento
17.
Carcinogenesis ; 29(4): 830-3, 2008 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-18296437

RESUMEN

The present study was designed to determine whether etodolac, a selective cyclooxygenase-2 inhibitor, prevents chemically induced intraductal papillary carcinoma (IPC) in the main pancreatic duct of hamsters. Hamsters were subjected to cholecystoduodenostomy with dissection of the distal end of the common duct. Four weeks after surgery, the surviving hamsters received subcutaneous injections of N-nitrosobis(2-oxopropyl)amine four times at a dose of 10 mg/kg body wt, every 2 weeks. The animals were divided into three groups according to the simultaneous oral intake of a standard pelleted diet containing etodolac at 0% (group CE, n = 30), 0.01% (group ET, n = 21) and 0.04% (group ET4, n = 25), respectively. Hamsters were killed for pathological examination at 36 weeks after the operation. The incidence of induced pancreatic carcinoma was 93, 81 and 72% in groups CE, ET and ET4, respectively. The pancreatic carcinomas were histologically classified into four types, i.e. tubular, papillary, cyst adenocarcinoma and IPC. The incidence of IPC and the number of IPCs per animal were significantly lower in groups ET4 (36% and 0.48) and ET (48% and 0.62) when compared with group CE (67% and 1.30). The proliferating cell nuclear antigen labeling indices in the non-cancerous epithelial cells of the main pancreatic duct were 2.8 and 6.8% in groups ET4 and ET, respectively, and were significantly lower than that in group CE (10.8%). In conclusion, etodolac inhibited N-nitrosobis(2-oxopropyl)amine-induced IPC in hamsters. Suppression of epithelial cell proliferation of the main pancreatic duct was considered as a possible mechanism of cancer prevention in this hamster model.


Asunto(s)
Adenocarcinoma Papilar/tratamiento farmacológico , Anticarcinógenos/uso terapéutico , Carcinoma Ductal Pancreático/tratamiento farmacológico , Inhibidores de la Ciclooxigenasa 2/uso terapéutico , Ciclooxigenasa 2/metabolismo , Etodolaco/uso terapéutico , Adenocarcinoma Papilar/enzimología , Adenocarcinoma Papilar/patología , Animales , Antiinflamatorios no Esteroideos/uso terapéutico , Carcinoma Ductal Pancreático/enzimología , Carcinoma Ductal Pancreático/patología , Cricetinae , Modelos Animales de Enfermedad , Femenino , Cinética , Mesocricetus
18.
Neuroscience ; 152(2): 477-86, 2008 Mar 18.
Artículo en Inglés | MEDLINE | ID: mdl-18262365

RESUMEN

The present study investigated whether the endogenous pro-inflammatory cytokines [interleukin (IL)-1beta and tumor necrosis factor-alpha (TNF-alpha)]-dependent expression of cyclooxygenase-2 (COX-2) mRNA within the spinal cord could be involved in the development of chronic inflammatory pain-like behaviors in mice. We demonstrated that the expression of COX-2 mRNA on the ipsilateral side of the spinal cord was significantly increased 6 h and 3 days after intraplantar injection of complete Freund's adjuvant (CFA), compared with the expression in saline-treated mice. In addition, the chronic pain-like behaviors following CFA injection were markedly suppressed by repeated intrathecal (i.t.) pre-treatment with the COX-2 inhibitor etodolac, but not with the COX-1 inhibitor mofezolac. The cytosolic level of the activated form of nuclear factor-kappa B (NF-kappaB), which is a major contributor to the induction of COX-2, on the ipsilateral side of the mouse spinal cord was also increased compared with that in the saline-treated mice. The key finding in the present study was that a single i.t. injection with either IL-1beta or TNF-alpha induced a marked increase in spinal COX-2 mRNA and persistent thermal hyperalgesia in mice. Furthermore, CFA-induced hypersensitivity to inflammatory pain was significantly reduced by repeated i.t. pre-injection of the recombinant Fc chimera of IL-1 receptor I or soluble TNF receptor I, which sequesters endogenous IL-1beta or TNF-alpha, respectively. In contrast, the expression of spinal COX-2 mRNA in CFA-treated mice was similar to that in saline-treated mice at 7 days after CFA injection. The present findings strongly indicate the early intrathecal use of the COX-2 inhibitor for the relief of chronic inflammatory pain. Furthermore, together with the result in a previous study that pro-inflammatory cytokines lead to stimulation of a NF-kappaB-dependent transcriptional pathway, these findings suggest that a spinal cytokine/NF-kappaB/COX-2 pathway may play an important role in the development, but not maintenance, of chronic pain following peripheral tissue inflammation.


Asunto(s)
Ciclooxigenasa 2/genética , Regulación Enzimológica de la Expresión Génica/fisiología , Hiperalgesia/enzimología , Interleucina-1beta/fisiología , ARN Mensajero/metabolismo , Factor de Necrosis Tumoral alfa/fisiología , Animales , Ciclooxigenasa 2/metabolismo , Inhibidores de la Ciclooxigenasa/uso terapéutico , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Interacciones Farmacológicas , Etodolaco/uso terapéutico , Adyuvante de Freund , Lateralidad Funcional , Regulación Enzimológica de la Expresión Génica/efectos de los fármacos , Hiperalgesia/etiología , Hiperalgesia/patología , Hiperalgesia/prevención & control , Inflamación/inducido químicamente , Inflamación/complicaciones , Inflamación/tratamiento farmacológico , Interleucina-1beta/administración & dosificación , Masculino , Ratones , Ratones Endogámicos ICR , Dimensión del Dolor , Tiempo de Reacción/efectos de los fármacos , Médula Espinal/enzimología , Factores de Tiempo , Factor de Necrosis Tumoral alfa/administración & dosificación
19.
Oncol Rep ; 19(2): 393-9, 2008 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-18202786

RESUMEN

Non-steroidal anti-inflammatory drugs (NSAIDs) and cyclooxygenase-2 (COX-2) inhibitors are representative agents for the chemoprevention of sporadic colorectal neoplasia. However, few reports have described the chemopreventive effects of such agents on colitis-associated tumorigenesis. To clarify whether treatment with the COX-2 inhibitor may reduce the risk of colitis-associated neoplasia, we investigated the effect of one such agent, etodolac, on tumorigenesis in the colitis-associated neoplasia model using p53-deficient mice treated with dextran sulfate sodium (DSS). The p53-/- mice were divided into four groups: i) treatment with DSS + etodolac, then after two cycles of DSS, the mice were given distilled water for 84 days. In addition, etodolac was administered three times a week at a dose of 10 mg/kg body weight throughout the experiment. ii) Treatment with two cycles of DSS only, followed by distilled water for 84 days. iii) Treatment with etodolac alone. iv) Distilled water alone was administered to the control group. The incidence of mice with neoplasia was 82.4% in the DSS + etodolac group and 100% in the DSS-alone group. No neoplasia was observed in the etodolac-alone and control groups. The mean (+/- SEM) number of total neoplasias per mouse was 1.29+/-0.2 in the DSS + etodolac group and 3.0+/-0.52 in the DSS-alone group, the inter-group difference being significant (p<0.01). There was no significant difference in the inflammation score between these two groups. These results showed that treatment with etodolac significantly reduced the occurrence of neoplasia, suggesting that this COX-2 inhibitor has chemopreventive activity against colitis-associated tumorigenesis.


Asunto(s)
Transformación Celular Neoplásica/efectos de los fármacos , Colitis/complicaciones , Neoplasias del Colon/etiología , Neoplasias del Colon/prevención & control , Inhibidores de la Ciclooxigenasa 2/uso terapéutico , Etodolaco/uso terapéutico , Animales , Transformación Celular Neoplásica/inducido químicamente , Transformación Celular Neoplásica/patología , Quimioprevención , Colitis/inducido químicamente , Colitis/patología , Neoplasias del Colon/patología , Inhibidores de la Ciclooxigenasa 2/farmacología , Sulfato de Dextran/toxicidad , Modelos Animales de Enfermedad , Etodolaco/farmacología , Ratones , Ratones Mutantes
20.
J Appl Oral Sci ; 26: e20160473, 2018 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-29412363

RESUMEN

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. 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). 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. 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.


Asunto(s)
Desensibilizantes Dentinarios/uso terapéutico , Sensibilidad de la Dentina/inducido químicamente , Sensibilidad de la Dentina/prevención & control , Etodolaco/uso terapéutico , Peróxido de Hidrógeno/efectos adversos , Blanqueadores Dentales/efectos adversos , Blanqueamiento de Dientes/efectos adversos , Adolescente , Adulto , Color , Inhibidores de la Ciclooxigenasa 2/uso terapéutico , Femenino , Humanos , Masculino , Dimensión del Dolor , Reproducibilidad de los Resultados , Medición de Riesgo , Índice de Severidad de la Enfermedad , Estadísticas no Paramétricas , Factores de Tiempo , Resultado del Tratamiento , Adulto Joven
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