Silicon containing ibuprofen derivatives with antioxidant and anti-inflammatory activities: An in vivo and in silico study.

There are many chronic diseases related with inflammation. The chronic inflammation can produce other problems as cancer. Therefore, it is necessary to design drugs with better anti-inflammatory activity than those in the clinic. Likewise, these could be used in chronic treatments with minimum adverse effects. The amide or ester functionality in combination with the insertion of a silyl alkyl moiety is able to improve some drug properties. In this context, the evaluation of a group of silicon containing ibuprofen derivatives (SCIDs) as antioxidants and anti-inflammatory agents is reported. Antioxidant activity was evaluated by the 2,2-Diphenyl-1-picrylhydrazyl (DPPH⨪), 2,2'-Azino-bis(3-ethylbenzothiazoline-6-sulfonic) acid (ABTS•+) and the Fe(II) chelating ability methods. The anti-inflammatory activity was determined by using the carrageenan induced rat paw edema. The gastrotoxic profile of the SCIDs that displayed significant anti-inflammatory activity was determined by the indomethacin induced ulceration method. The SCIDs performed better than ibuprofen as chelating agents for Fe(II) and as scavengers for the free radicals DPPH• and ABTS•+. On the anti-inflammatory test, compound 4a inhibited the edema up to 87%, while 4d &10b achieved significant inflammation inhibition at a lower effective dose 50 (ED50) than ibuprofen´s. None of the SCIDs endowed with anti-inflammatory activity, showed significant gastrotoxic effects with respect to those displayed by ibuprofen. Based on the experimental results and aided by the theoretical docking approach, it was possible to rationalize how the SCIDs may bind to cyclooxygenase isoforms and helped to explain their reduced gastrotoxicity. The evaluated effects were improved in SCIDs with respect to ibuprofen.

TRREMS procedure (transanal repair of rectocele and rectal mucosectomy with one circular stapler): a prospective multicenter trial.

CONTEXT: Since anorectocele is usually associated with mucosa prolapse and/or rectal intussusceptions, it was developed a stapled surgical technique using one circular stapler. OBJECTIVE: To report the results of Transanal Repair of Rectocele and Rectal Mucosectomy with one Circular Stapler (TRREMS procedure) in the treatment of anorectocele with mucosa prolapse in a prospective multicenter trial. METHODS: It was conducted by 14 surgeons and included 75 female patients, mean aged 49.6 years, with symptoms of obstructed defecation due to grade 2 (26.7%) and grade 3 (73.3%) anorectocele associated with mucosa prolapse and/or rectal intussusception (52.0%) and an average validated Wexner constipation score of 16. All patients were evaluated by a proctological examination, cinedefecography, anal manometry and colonic transit time. The TRREMS procedure consists of the manual removal of the rectocele wall with circumferential rectal mucosectomy performed with a circular stapler. The mean follow-up time was 21 months. RESULTS: All patients presented obstructed defecation and they persisted with symptoms despite conservative treatment. The mean operative time was 42 minutes. In 13 (17.3%) patients, bleeding from the stapled line required hemostatic suture. Stapling was incomplete in 2 (2.6%). Forty-nine patients (65.3%) required 1 hospitalization day, the remainder (34.7%) 2 days. Postoperatively, 3 (4.0%) patients complained of persistent rectal pain and 7 (9.3%) developed stricture on the stapled suture subsequently treated by stricturectomy under anesthesia (n = 1), endoscopic stricturectomy with hot biopsy forceps (n = 3) and digital dilatation (n = 3). Postoperative cinedefecography showed residual grade I anorectoceles in 8 (10.6%). The mean Wexner constipation score decreased significantly from 16 to 4 (0-4: n = 68) (6: n = 6) (7: n = 1) (P<0.0001). CONCLUSION: Current trial results suggest that TRREMS procedure is a safe and effective technique for the treatment of anorectocele associated with mucosa prolapse. The stapling technique is low-cost as requires the use of a single circular stapler.

TRREMS procedure (transanal repair of rectocele and rectal mucosectomy with one circular stapler): a prospective multicenter trial / Procedimento TRREMS (reparo transanal de retocele e mucosectomia retal com um grampeador circular): estudo multicêntrico prospectivo

CONTEXT: Since anorectocele is usually associated with mucosa prolapse and/or rectal intussusceptions, it was developed a stapled surgical technique using one circular stapler. OBJECTIVE: To report the results of Transanal Repair of Rectocele and Rectal Mucosectomy with one Circular Stapler (TRREMS procedure) in the treatment of anorectocele with mucosa prolapse in a prospective multicenter trial. METHODS: It was conducted by 14 surgeons and included 75 female patients, mean aged 49.6 years, with symptoms of obstructed defecation due to grade 2 (26.7 percent) and grade 3 (73.3 percent) anorectocele associated with mucosa prolapse and/or rectal intussusception (52.0 percent) and an average validated Wexner constipation score of 16. All patients were evaluated by a proctological examination, cinedefecography, anal manometry and colonic transit time. The TRREMS procedure consists of the manual removal of the rectocele wall with circumferential rectal mucosectomy performed with a circular stapler. The mean follow-up time was 21 months. RESULTS: All patients presented obstructed defecation and they persisted with symptoms despite conservative treatment. The mean operative time was 42 minutes. In 13 (17.3 percent) patients, bleeding from the stapled line required hemostatic suture. Stapling was incomplete in 2 (2.6 percent). Forty-nine patients (65.3 percent) required 1 hospitalization day, the remainder (34.7 percent) 2 days. Postoperatively, 3 (4.0 percent) patients complained of persistent rectal pain and 7 (9.3 percent) developed stricture on the stapled suture subsequently treated by stricturectomy under anesthesia (n = 1), endoscopic stricturectomy with hot biopsy forceps (n = 3) and digital dilatation (n = 3). Postoperative cinedefecography showed residual grade I anorectoceles in 8 (10.6 percent). The mean Wexner constipation score decreased significantly from 16 to 4 (0-4: n = 68) (6: n = 6) (7: n = 1) (P<0.0001). CONCLUSION: Current trial results suggest that TRREMS procedure is a safe and effective technique for the treatment of anorectocele associated with mucosa prolapse. The stapling technique is low-cost as requires the use of a single circular stapler.

CONTEXTO: Como a anoretocele está sempre associada a prolapso mucoso e/ou intussuscepção retal, foi desenvolvida uma técnica cirúrgica grampeada, utilizando somente um grampeador mecânico. OBJETIVO: Demonstrar os resultados do estudo multicêntrico que realizou o tratamento cirúrgico de pacientes com anorretocele associado a prolapso mucoso, utilizando o reparo transanal da retocele e mucosectomia com grampeador circular mecânico. MÉTODO: Foram incluídos 75 pacientes, média de idade 49,6 anos, com sintomas de evacuação obstruída, apresentando escore médio de constipação de Wexner de 16 e diagnóstico de anorretocele grau II (26.7 por cento), grau III (73,3 por cento) associado a prolapso mucoso e intussuscepção (52 por cento). Todos foram avaliados com exame proctológico, defecografia, manometria anorretal e tempo de trânsito colônico. O procedimento cirúrgico foi realizado por 14 cirurgiões e consiste na remoção manual da parede do reto no local da retocele e mucosectomia circunferencial com um grampeador circular mecânico. O seguimento médio foi de 21 meses. RESULTADOS: Os pacientes apresentavam sintomas de evacuação obstruída, mesmo após tratamento clinico. O tempo operatório médio foi de 42 minutos. Houve sangramento transanal na linha de sutura em 13 (17,3 por cento) pacientes, sutura grampeada incompleta em 2 (2,6 por cento) e dor retal persistente em 3 (4,0 por cento). O tempo médio de internação hospitalar foi de 1 dia em 49 (65,3 por cento) e 2 dias em 34,7 por cento. Ocorreu redução na linha de sutura em 7 (9,3 por cento), sendo necessário estricturotomia cirúrgica sob anestesia (n = 1), utilizando "hot biopsy" (n = 3) e dilatação anal (3). Defecografia no pós-operatório demonstrou anorretocele residual grau I em 8 (10.6 por cento). O escore de constipação de Wexner reduziu 16 para 4 (0-4: n = 68) (6: n = 6) (7: n = 1) (P<0.0001). CONCLUSÃO: O resultado do estudo multicêntrico demonstrou que a técnica cirúrgica apresentada é segura e efetiva para tratamento da anorretocele associada a prolapso mucoso. Apresenta baixo custo pois utiliza um grampeador circular mecânico.

Stapled hemorrhoidectomy: initial experience of a Latin American group.

The purpose of the present study was to determine the value of circular hemorrhoidectomy (procedure for prolapse and hemorrhoids [PPH]) on the basis of data collected prospectively during the initial experience of a group of Latin American surgeons. Between 2000 and 2001, PPH was performed using a circular stapler in 177 patients who had third- and fourth-degree hemorrhoidal disease. The average age of the patients was 47.7 years (range 26 to 85 years). Anal bleeding was the most common preoperative complaint (93.2%) followed by anal pain (60.2%), anal itching (43%), and constipation (41%). Hemorrhoids were classified as third degree in 132 patients (74%) and fourth degree in 45 patients (25.4%). Skin tags were detected in 86 patients (48.8%) and rectocele in 14 patients (7.9%). Data collected included patient demographics, type of anesthesia, and specific details of the surgery such as duration of the operation, distance from the staple line to the dentate line, need for complementary hemostasis, and any unexpected occurrences. Postoperative data collected included the degree of pain, which was evaluated on the basis of the type and dosage of analgesics required, laxative consumption, and the presence of bleeding, fever, urinary retention, or hematomas. Each patient completed a written questionnaire addressing these events. Patients returned for follow-up visits on days 7, 15, 30, and 90. Responses to pain, bleeding, fever, anal continence, recurrence of hemorrhoids, and level of satisfaction were compiled. The duration of the procedure ranged from 6 minutes to 2 hours (average 23 minutes), and most operations lasted no more than 20 minutes, with the exception of one that lasted 2 hours because of intraoperative bleeding. Intraoperative problems were minor. An additional one or a few sutures were required in 58.7% of patients to achieve perfect hemostasis. In 128 patients (72.3%) the hospital stay was less than 24 hours. Same-day surgery was chosen for 37 patients (20.9%). Pain was controlled with analgesia only using one to six doses of oral dipirona in 126 patients. Five patients were readmitted to the hospital: four for control of bleeding and one for conventional hemorrhoidectomy due to an acute episode of external hemorrhoidal thrombosis. At day 30, patients rated the efficacy of the procedure in alleviating preoperative symptoms as follows: 77.5% excellent; 16% good; 5.3% average, and 1.2% poor. At 3 months postoperatively no patient had had a recurrence of hemorrhoidal prolapse, and there were no instances of stenosis or anal incontinence. Surgeons also rated the efficacy of the procedure as excellent in 75%, good in 19.8%, average in 4.7%, and poor in 0.6%. With proper selection of patients and adequate stapling technique, stapled hemorrhoidectomy may be considered safe; it is easily learned, has a satisfactory degree of pain, and is well accepted by both patients and surgeons.