Evaluation of peritoneal endometriosis treatment using intralesional acetylsalicylic acid injection in rabbits

PURPOSE: To investigate the efficacy of intralesional 20% aspirin injection for treatment of experimental peritoneal endometriosis. Methods: Peritoneal endometriosis was experimentally induced in forty adult nulligravid female rabbits. On day 30 post-endometriosis induction, rabbits were randomly divided to assess early (10 days) and late (20 days) effects of intralesional injection of physiological saline solution (control groups) in comparison to intralesional injection of 20% bicarbonate aspirin solution (experimental groups) as follows: control group 1 (10 days, n=10); control group 2 (20 days, n=10); experimental group 3 (10 days, n=10); experimental group 4 (20 days, n=10). Resected tissues, including endometriosis foci, were qualitatively (general morphology and signs of inflammatory cells infiltrate, necrosis and apoptosis) and quantitatively (remaining endometriosis area) assessed by histopathological analysis. Results: Extensive necrosis, hemorrhage, apoptosis, and fibrosis were observed in the experimental groups 3 and 4. Groups 1 and 2 presented typical endometrial tissue cysts, respectively. Groups 3 and 4 showed sparse endometrial tissue foci and no endometrial tissue, respectively. Quantitative analysis revealed that aspirin-treated groups 3 and 4 had significantly (p<0.05) smaller remaining endometriosis area, compared to control groups 1 and 2. Conclusion: Intralesional 20% aspirin injection caused total destruction of peritoneal endometriosis foci in rabbits.

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

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

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

La combinación de atorvastatina y meloxicam inhibe la neuroinflamación y atenúa el daño celular en la isquemia cerebral experimental por embolia arterial / Atorvastatin-meloxicam association inhibits neuroinflammation and attenuates the cellular damage in cerebral ischemia by arterial embolism.

Introducción. El accidente cerebrovascular es la segunda causa de muerte y la primera de discapacidad en el mundo, y más de 85 % es de origen isquémico. Objetivo. Evaluar en un modelo de infarto cerebral por embolia arterial el efecto de la atorvastatina y el meloxicam, administrados por separado y de forma conjunta, sobre la respuesta neuronal, los astrocitos y la microglia. Materiales y métodos. Se sometieron ratas Wistar a embolia de la arteria carótida y a tratamiento con meloxicam y atorvastatina, administrados por separado y conjuntamente, a las 6, 24, 48 y 72 horas. Se evaluó la reacción de las proteínas COX-2, GFAP y OX-42 en las neuronas, los astrocitos y la microglia mediante inmunohistoquímica y estudios morfológicos y de densitometría. Los datos obtenidos se evaluaron por medio de un análisis de varianza y de pruebas no paramétricas de comparación múltiple. Resultados. La isquemia cerebral por embolia arterial incrementó significativamente (p<0,001) la reacción de los astrocitos y la microglia, en tanto que la atorvastatina y el meloxicam, administrados por separado y de forma conjunta, la redujeron. La isquemia produjo acortamiento de las proyecciones de los astrocitos, engrosamiento celular, ruptura de las expansiones protoplásmicas (clasmatodendrosis) y cambios morfológicos en la microglia propios de diversas etapas de actividad. En las zonas circundantes del foco se incrementó la reacción inmunológica de la COX-2 y se redujo en el foco isquémico, en tanto que el meloxicam y la atorvastatina redujeron significativamente (p<0,001) la reacción inmunológica en la zona circundante del foco, restableciendo la marcación de la ciclooxigenasa en el foco isquémico. Conclusión. La combinación de meloxicam y atorvastatina atenúa la respuesta de los astrocitos y la microglia en el proceso inflamatorio posterior a la isquemia cerebral por embolia arterial, reduciendo la degeneración neuronal y restableciendo el equilibrio morfológico y funcional del tejido nervioso.

Introduction: Stroke is the second leading cause of death and the first cause of disability in the world, with more than 85% of the cases having ischemic origin. Objective: To evaluate in an embolism model of stroke the effect of atorvastatin and meloxicam on neurons, astrocytes and microglia. This evaluation was done administering each medication individually and in association. Materials and methods: Wistar rats were subjected to carotid arterial embolism and treatment with meloxicam and atorvastatin at 6, 24, 48 and 72 hours. Using immunohistochemistry, we evaluated the immunoreactivity of COX-2 protein, GFAP and OX-42 in neurons, astrocytes and microglia by densitometric and morphological studies. Data were evaluated by variance analysis and non-parametric multiple comparison. Results: Cerebral ischemia by arterial embolism increased significantly the reactivity of microglia and astrocytes (p<0.001), whereas it was reduced by atorvastatin, meloxicam and their association. Ischemia produced astrocytic shortening, cellular thickening, protoplasmic rupture expansions (clasmatodendrosis) and microglial morphological changes characteristic of various activity stages. In perifocal areas, immunoreactivity of COX-2 was increased and in the ischemic focus it was reduced, while meloxicam and atorvastatin significantly reduced (p<0.001) perifocal immunoreactivity, restoring the marking of cyclooxygenase in the ischemic focus. Conclusion: These results suggest that the meloxicam-atorvastatin association attenuates astrocytic and microglial response in the inflammatory process after cerebral ischemia by arterial embolism, reducing neurodegeneration and restoring the morphological and functional balance of nervous tissue .

Comparação de ibuprofeno via oral e indometacina intravenosa no tratamento da persistência do canal arterial em neonatos com extremo baixo peso ao nascer / Comparison of oral ibuprofen and intravenous indomethacin for the treatment of patent ductus arteriosus in extremely low birth weight infants

OBJETIVO: Existem poucos relatórios publicados com relação à eficácia do ibuprofeno via oral no tratamento da persistência do canal arterial (PCA) em neonatos com extremo baixo peso ao nascer (EBPN). Comparamos o ibuprofeno via oral à indometacina intravenosa no que diz respeito à eficácia e segurança no tratamento de PCA em neonatos com peso inferior a 1.000 g ao nascer. MÉTODO: Este foi um estudo retrospectivo em um único centro. Coletamos dados de neonatos com EBPN que tiveram PCA ecocardiograficamente confirmada. Os neonatos foram tratados tanto com indometacina intravenosa quanto com ibuprofeno via oral. A taxa de fechamento do canal, a necessidade de tratamentos adicionais, os efeitos colaterais ou as complicações relacionadas ao medicamento e a mortalidade foram comparados entre os dois grupos de tratamento. RESULTADO: Examinamos 26 neonatos que receberam indometacina e 22 que receberam ibuprofeno. A taxa geral de fechamento do canal foi semelhante nos dois tratamentos: o fechamento do canal ocorreu em 23 dos 26 neonatos (88,5%) no grupo indometacina, e em 18 dos 22 neonatos (81,8%) no grupo ibuprofeno (p = 0,40). A taxa de ligadura cirúrgica (11,5% em comparação a 18,2%; p = 0,40) não diferiu de forma significativa entre os dois grupos de tratamento. Após o tratamento, não foi encontrada nenhuma diferença significativa nas concentrações de creatinina sérica entre os dois grupos. Não houve diferenças significativas com relação a efeitos colaterais ou complicações adicionais. CONCLUSÃO: Em neonatos com EBPN, o ibuprofeno via oral é tão eficaz quanto a indometacina intravenosa no tratamento da PCA. Não há diferenças entre os medicamentos no que diz respeito à segurança. O ibuprofeno via oral poderia ser usado como um agente alternativo no tratamento da PCA em neonatos com EBPN.

OBJECTIVE: There are few published reports concerning the efficacy of oral ibuprofen for the treatment of patent ductus arteriosus (PDA) in extremely low birth weight (ELBW) infants. Oral ibuprofen was compared to intravenous indomethacin regarding efficacy and safety in the treatment of PDA in infants weighting less than 1,000 g at birth. METHOD: This was a retrospective study in a single center. Data on ELBW infants who had an echocardiographically confirmed PDA were collected. The infants were treated with either intravenous indomethacin or oral ibuprofen. Rate of ductal closure, need for additional treatment, drug-related side effects or complications, and mortality were compared between the two treatment groups. RESULT: 26 infants who received indomethacin and 22 infants who received ibuprofen were studied. The overall rate of ductal closure was similar between the two treatments: it occurred in 23 of 26 infants (88.5%) treated with indomethacin, and in 18 of 22 infants (81.8%) treated with ibuprofen (p = 0.40). The rate of surgical ligation (11.5% versus 18.2%; p = 0.40) did not differ significantly between the two treatment groups. No significant difference was found in post-treatment serum creatinine concentrations between the two groups. There were no significant differences regarding additional side effects or complications. CONCLUSION: In ELBW infants, oral ibuprofen is as efficacious as intravenous indomethacin for the treatment of PDA. There were no differences between the two drugs with respect to safety. Oral ibuprofen could be used as an alternative agent for the treatment of PDA in ELBW infants.

Aspirin intake suppresses MMC-induced genotoxicity in mice.

The genotoxicity induced by mitomycin C (MMC) was found to be decreased by aspirin on alkaline single cell gel electrophoresis (SCG) assay in multiple organs of mice. Aspirin at doses of 0.5, 5 and 50 mg/kg and MMC at 2 mg/kg were administered and then liver, lung, kidney, spleen, colon and bone marrow were sampled after 3 h. Significant protective effects of aspirin against MMC-induced genotoxicity was observed in all but the bone marrow, where no change was evident. The results suggest that the radical scavenging ability of aspirin prevents danage by MMC-induced reactive oxygen species (ROS) in multiple organs.

Comparison of Parecoxib and Proparacetamol in Endoscopic Nasal Surgery Patients

PURPOSE: The aim of the study was to compare the efficacy of parecoxib for postoperative analgesia after endoscopic turbinate and sinus surgery with the prodrug of acetaminophen, proparacetamol. MATERIALS AND METHODS: Fifty American Society of Anesthesiology (ASA) physical status I-II patients, receiving functional endoscopic sinus surgery (FESS) and endoscopic turbinectomy, were investigated in a prospective, randomized, double-blind manner. After local infiltration with 1% mepivacaine, patients were randomly allocated to receive intravenous (IV) administration of either 40mg of parecoxib (n=25) or 2g of proparacetamol (n=25) 15 min before discontinuation of total IV anaesthesia with propofol and remifentanil. A blinded observer recorded the incidence and severity of pain at admission to the post anaesthesia care unit (PACU) at 10, 20, and 30 min after PACU admission, and every 1 h thereafter for the first 6 postoperative h. RESULTS: The area under the curve of VAS (AUC(VAS)) calculated during the study period was 669 (28-1901) cm·min in the proparacetamol group and 635 (26-1413) cm·min in the parecoxib group (p=0.34). Rescue morphine analgesia was required by 14 patients (56%) in the proparacetamol group and 12 patients (48%) in the parecoxib (p> or=0.05), while mean morphine consumption was 5-3.5mg and 5-2.0mg in the proparacetamol groups and parecoxib, respectively (p> or=0.05). No differences in the incidence of side effects were recorded between the 2 groups. Patient satisfaction was similarly high in both groups, and all patients were uneventfully discharged 24h after surgery. CONCLUSION: In patients undergoing endoscopic nasal surgery, prior infiltration with local anaesthetics, parecoxib administered before discontinuing general anaesthetic, is not superior to proparacetamol in treating early postoperative pain.

Flowcytometric evidence of platelet activation in patients on aspirin following myocardial infarction.

BACKGROUND: Following a myocardial infarction, patients are usually started on long term antiplatelet therapy with aspirin in a dose of 80-150 mg/day. However, there are no quick and easy methods to assess the efficacy of the antiplatelet activity of aspirin. METHODS: We studied 60 consecutive patients (men, < 40 years of age) 8-10 weeks after they had had acute myocardial infarction. These patients were receiving 100 mg aspirin daily orally with or without b-blockers. We measured P-selectin expression and fibrinogen binding by flowcytometry at least 3 times over a period of 2 years in all the patients. We also studied 100 age- and sex-matched controls. RESULTS: Of the 60 patients, 30 (50%) showed both increased P-selectin and fibrinogen binding by platelets, suggesting platelet activation. Fourteen other patients had increased fibrinogen binding but normal P-selectin expression. Sixteen patients and all the controls had normal results of both tests. CONCLUSION: Our data show evidence of platelet activation in at least 50% of patients receiving 100 mg of aspirin daily. Flowcytometry for P-selectin expression and fibrinogen binding to platelets can be used to monitor antiplatelet therapy with aspirin following acute myocardial infarction.

Clinical pharmacokinetic of celecoxib in healthy Thai volunteers.

BACKGROUND: Celecoxib, a nonsteroidal antiinflammatory drug exhibits its antiinflammatory effect by selective inhibition of cyclooxygenase-2 (COX-2) enzyme. Its efficacy has been accepted for the treatment of arthritic pain with superior gastrointestinal side effect profile compared with other conventional NSAIDs. OBJECTIVE: To elucidate clinical pharmacokinetic of celecoxib following an oral dose administration. MATERIAL AND METHOD: Eighteen healthy Thai male volunteers were enrolled in the present study. Their mean age was 20.94 +/- 1.21 years and their mean weight was 63 +/- 5.17 kg. They were orally administered 200 mg celecoxib after an over night fasting, serial blood samples were drawn before and at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24 and 48 hours after dosing. Plasma celecoxib was analysed by reversed-phase HPLC. RESULTS: Following a 200 mg celecoxib oral administration, the drug was absorbed into the systemic circulation and reach maximum concentration (Tmax) within 2.50 +/- 1.22 hrs by average with the mean peak concentration (Cmax) of 686.83 +/- 211.35 ng/ml. The extent of absorption (area under the curve, AUC) was approximately 5157.12 +/- 1499.46 and 5911.48 +/- 1363.51 ng hr/ml for AUC(0-->t) and AUC(0-->infinity) respectively. The apparent volume of distribution (Vd) was found to be 458.93 +/- 323.28 L/hr. Celecoxib was eliminated after biotransformation and the metabolites were excreted in both urine and feces. The elimination half-life (t(1/2)) of celecoxib appeared to be 8.79 +/- 5.49 hrs with the apparent clearance (CL) of 35.91 +/- 9.85 L. The elimination rate constant for celecoxib obtained from this present study was about 0.11 +/- 0.05 hr(-1). CONCLUSION: Pharmacokinetic parameters following an oral dose of 200 mg celecoxib administration were characterized, including Cmax, Tmax, Vd, kel, CL, AUC. These parameters reflected absorption, distribution, biotransformation and excretion of celecoxib in healthy Thai volunteers.

The preemptive analgesic effect of celecoxib for day-case diagnostic laparoscopy.

In a randomized trial, the preemptive analgesic effect of celecoxib in 110 infertile women undergoing day-case diagnostic laparoscopy was studied at King Chulalongkorn Memorial Hospital, Bangkok, Thailand. The patients randomly received either 200 mg celecoxib or placebo orally 2 hours before diagnostic laparoscopy. The post-operative shoulder pain and wound pain were self assessed and recorded, using Visual Analogue Scores (VAS) at 1, 2, 4, 12, and 24 hours. Total post-operative analgesic requirements were recorded at 24 hours. The mean Visual Analogue Scores (VAS) of shoulder pain in celecoxib group was statistically lower than those of the placebo group (p = 0.04). Nevertheless, the mean VAS of wound pain and the total post-operative analgesic requirements were not significantly different. It was concluded that the preemptive celecoxib in day-case diagnostic laparoscopy might have the advantage of decreasing post laparoscopic shoulder pain.

Efecto de diferentes dosis de asoirina sobre el precondocionamiento contra el atontamiento en ovejas / Effect of different doses of aspirin on preconditioning against stunning in conscious sheep

Se ha postulado que los antiinflamatorios no esteroides que actuan inhibiendo la ciclooxigenasa (COX) podrían tener efectos nocivos sobre el corazón. Recientemente se ha demostrado que los inhibidores de la COX-2 bloquean la protección por precondicionamiento tardío (PT). Se desconoce sin embargo, el efecto que pudiera tener la aspirina, el antiinflamatorio no esteroide más ampliamente utilizado en la clínica, sobre el PT en mamíferos grandes. La aspirina actúa inhibiendo las dos isoenzimas de la ciclooxigenasa (COX-1 y COX-2), siendo empleada en dosis altas como droga antiinflamatoria y en dosis bajas como agente antitrombótico.El propósito de este estudio fue analizar qué efecto tienen distintas dosis de aspirina sobre la protección delPT contra el atontamiento y las arritmias en ovejas conscientes. Se consideraron 5 grupos; control (C): 12 minde isquemia (I) y 2 hr de reperfusión (R); PT: 6 períodos de 5 min I-5 min R, 24 hr antes de la I de 12 min, ytres grupos igual que PT, pero con 1.5 (PTA1.5), 8 (PTA8) y 20 (PTA20) mg/kg de aspirina respectivamente, administrados 10 min antes de la primera I de precondicionamiento. Los resultados demostraron que la dosis antiinflamatoria de aspirina (20 mg/kg) fue capaz de inhibir el PT contra el atontamiento (C vs PTA20, NS),mientras que las dosis bajas (1.5 mg/kg) e intermedia (8 mg/kg) no afectaron la protección (C vs PT, PT1.5 yPT8, p<0.01). Asimismo, ninguna de las tres dosis alteró la protección contra las arritmias. Conclusión: Lasdosis antiagregantes plaquetarias de aspirina no producirían riesgo de inhibir la protección contra el atontamiento por PT, mientras que dosis antiinflamatorias elevadas serían perjudiciales. Como la aspirina se administró antes de los períodos precondicionantes, la inhibición de la cardioprotección sugiere que la COX actúacomo mecanismo gatillador del PT contra el atontamiento.

Evaluation of the efficacy, safety and tolerability of valdecoxib gel (1%) in adult patients with painful inflammatory joint disease.

Valdecoxib, a COX-2 inhibitor, has recently been introduced as a gel formulation. The present study was conducted to evaluate the efficacy, safety and tolerability of valdecoxib gel in adult patients with painful inflammatory joint conditions. The present study was a 10-day prospective, open, multicentric (6 centres) trial. Patients with clinical and radiological diagnosis of painful inflammatory joint conditions were treated with valdecoxib gel (1%). Efficacy was assessed by visual analogue scale (VAS), patient's and physician's global assessment of pain relief. Grading of associated clinical manifestations such as stiffness, swelling, tenderness and restriction of mobility was done. Tolerability and safety was assessed by physical examination, laboratory parameters and evaluation of adverse events. There was a statistically significant decrease in the mean pain visual analogue score (p<0.05). Onset of pain relief was within 15 minutes. There was a reduction of 58.8%, 57.2%, 65.4% and 60.2% in mean scores of stiffness, swelling, tenderness and mobility respectively from the baseline which was statistically significant. The laboratory values were within normal limits. The drug was well tolerated. There was no report of any hypersensitivity reaction. This study confirms that valdecoxib gel (1%) is an effective and safe option for the management of painful inflammatory joint conditions.

A comparison of oral ibuprofen and intravenous indomethacin for closure of patent ductus arteriosus in preterm infants.

BACKGROUND: Indomethacin is widely accepted as the treatment for patent ductus arteriosus (PDA) in preterm infants but it has various side effects. Ibuprofen is the alternative treatment and believed to be less likely to induce side effects. OBJECTIVE: To compare efficacy and side effects of ibuprofen versus indomethacin treatment for symptomatic patent ductus arteriosus (PDA) in preterm infants. METHOD: The authors studied 30 infants (gestational age < or = 35 weeks, aged < or = 10 days) who were diagnosed as having symptomatic PDA confirmed by echocardiogram. The infants were randomly assigned to receive three intravenous doses of indomethacin given at 12-hour intervals or three doses of ibuprofen given at 24-hour intervals, starting within ten days of life. The demographic data, rate of clinical closure, need for additional treatment, side effects, complications and the infants' clinical course were recorded within 28 days. RESULTS: The rate of ductal closure was similar with the two treatment regimes. Ductal closure occurred in 7 of 15 infants given ibuprofen (46.67%) and 10 of 15 infants given indomethacin (66.67%). (Relative risk 0.669; 95% confidence interval, 0.328 to 1.364; p = 0.462) The number of infants who needed a second pharmacologic treatment was not significantly different between the two groups, (6 cases in the ibuprofen group, 5 cases in the indomethacin group) but surgical ligation was performed in two cases in the indomethacin group. There was a significant difference in using the diuretic drug (furosemide) in the indomethacin group (11 cases), compared to the ibuprofen group (3 cases), (p = 0.009). More cases of necrotizing enterocolitis were seen in the indomethacin group (66.67% compared to 40% in the ibuprofen group) but there was no statistically significant difference. CONCLUSION: Ibuprofen has the same efficiency as indomethacin for the treatment of symptomatic patent ductus arteriosus in preterm infants and less likely to induce necrotizing enterocolitis and renal toxicity than indomethacin.

Formulation, evaluation and comparison of gels containing different COX-2 inhibitors.

PG synthesis plays major role in inflammation. The enzymes responsible for PG synthesis are cox-1 and cox-2. Cox-1 regulates physiological functions in gut and kidney while cox-2 induces inflammation. Selective cox-2 inhibitors have little effect on cox-1 and thus showed better GI tolerability. The efficacy of new drugs is not greater than that of NSAID's by oral route of administration. In the present study new selective cox-2 inhibitors also showed less efficacy than NSAID'S by topical route of administration. However if current studies confirm the reduced GI toxicity this can be the only advantage of these drugs because these drugs showed less efficacy than NSAID'S by oral and topical routes of administration.