RESUMEN
BACKGROUND: One of the most prevalent postoperative complications is believed to be intra-abdominal peritoneal adhesions, which is followed by several complications. Several adhesion prevention products have been examined, yet none of them were found to be completely effective. The current research is conducted to evaluate the beneficial effects of Salvia miltiorrhiza hydroalcoholic extract in inhibiting postoperative peritoneal adhesions in rats. METHODS: Forty rats were randomly classified into five equal groups (n = 8): 1) the normal group did not undergo surgical operations, 2) the control group in which the adhesion was induced, and which did not receive any treatment, 3) distilled water group that received distilled water, and 4,5) treatment groups treated with 1 and 5% of Salvia miltiorrhiza hydroalcoholic extract. The rats were euthanized 14 days following the surgery and the macroscopic score, the microscopic score of granulomatous inflammation and granulation tissue formation, IHC markers (vimentin, CD31, IL-1ß, COX-2, and iNOS), and oxidative stress biomarkers (MDA, GPx, CAT, and TAC) were assessed in the experimental groups of the study. RESULTS: The difference between the control group and other groups for the adhesions macroscopic score, microscopic score, IHC markers, and oxidative stress biomarkers was significant (p < 0.05). Distilled water had no protective effect on the formation of peritoneal adhesions. Salvia miltiorrhiza treatment in two different doses significantly reduced macroscopic and microscopic scores, MDA concentration, Vimentin, IL-1ß, COX-2, and iNOS compared to the control group (p < 0.05). The levels of GPx, CAT, and TAC in the treatment groups increased significantly compared with the control group (p < 0.05). Our findings revealed that a higher dose of Salvia miltiorrhiza was more effective in reducing peritoneal adhesions, proinflammatory and mesenchymal cell markers, and oxidative stress. CONCLUSIONS: Salvia miltiorrhiza extract, owing to its strong antioxidant and anti-inflammatory properties, could effectively reduce peritoneal adhesions. Therefore, Salvia miltiorrhiza is recommended to be used as an effective anti-peritoneal post-operative adhesive agent.
Asunto(s)
Medicamentos Herbarios Chinos/farmacología , Enfermedades Peritoneales/prevención & control , Salvia miltiorrhiza , Animales , Modelos Animales de Enfermedad , Medicamentos Herbarios Chinos/uso terapéutico , Femenino , Fitoterapia , Complicaciones Posoperatorias/prevención & control , Ratas , Ratas Wistar , Adherencias Tisulares/prevención & controlRESUMEN
Postoperative peritoneal adhesion (PPA) is a serious clinical condition that affects the high percentage of patients after abdominal surgery. In this review, we have tried to focus on pathophysiology and different underlying signal pathways of adhesion formation based on recent progress in the molecular and cellular mechanisms. Also, the strategies, developed based on traditional herbal and modern medicines, to prevent and treat the PPA via regulation of the molecular mechanisms were investigated. The search engines such as Google Scholar, PubMed, Scopus, and Science Direct have been used to evaluate the current literature related to the pathogenesis of adhesion formation and novel products. Recently, different mechanisms have been defined for adhesion formation, mainly categorized in fibrin formation and adhesion fibroblast function, inflammation, and angiogenesis. Therefore, the suppression of these mechanisms via traditional and modern medicine has been suggested in several studies. While different strategies with encouraging findings have been developed, most of the studies showed contradictory results and were performed on animals. The herbal products have been introduced as safe and effective agent which can be considered in future preclinical and clinical studies. Although a wide range of therapeutics based on traditional and modern medicines have been suggested, there is no agreement in the efficacy of these methods to prevent or treat adhesion formation after surgeries. Further basic and clinical researches are still needed to propose the efficiency of recommended strategies for prevention and treatment of PPA.
Asunto(s)
Enfermedades Peritoneales , Complicaciones Posoperatorias , Animales , Humanos , Medicina Tradicional , Enfermedades Peritoneales/tratamiento farmacológico , Enfermedades Peritoneales/etiología , Enfermedades Peritoneales/prevención & control , Peritoneo/patología , Fitoterapia , Complicaciones Posoperatorias/tratamiento farmacológico , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/prevención & control , Adherencias Tisulares/tratamiento farmacológico , Adherencias Tisulares/etiología , Adherencias Tisulares/prevención & controlRESUMEN
BACKGROUND: Although mechanical barriers and modern surgical techniques have been developed to prevent postoperative adhesion formation, high incidence of adhesions still represents an important challenge in abdominal surgery. So far, there has been no available therapeutic drug in clinical practice. PURPOSE: In this study, we explored the efficacy of sodium aescinate (AESS) treatment against postoperative peritoneal adhesions, the potential molecular mechanism was also investigated. STUDY DESIGN AND METHODS: Sixty male Sprague-Dawley rats were randomly divided into 6 groups for the study: the blank, vehicle, positive control and three AESS administration groups (0.5, 1 and 2 mg/kg/d, intravenous administration for 7 days). Adhesions were induced by discretely ligating peritoneal sidewall. An IL-1ß-induced HMrSV5 cell model was also performed to explore possible functional mechanism. RESULTS: The results indicated that the incidence and severity of peritoneal adhesions were significantly lower in the AESS-treated groups than that in the vehicle and positive control group. AESS-treated groups showed that the secretion, activity, and expression of tPA in rat peritoneum were notably increased. The FIB levels in rat plasma were decreased. The immunohistochemical staining analysis demonstrated that collagen I and α-SMA deposition were significantly attenuated in AESS-treated peritoneal tissues. Besides, we found that AESS treatment reduced the protein levels of p-MYPT1. To further explore the mechanisms of AESS, both activator and inhibitors of RhoA/ROCK pathway were employed in this study. It was found that AESS-induced up-regulation of tPA was reversed by activator of ROCK, but the effects of ROCK inhibitors were consistent with AESS. CONCLUSION: Taken together, the findings of in vivo and in vitro experiments proved that AESS could significantly suppress postoperative peritoneal adhesion formation through inhibiting the RhoA/ROCK signaling pathway. Our researches provide important pharmacological basis for AESS development as a potential therapeutic agent on peritoneal adhesions.
Asunto(s)
Enfermedades Peritoneales/tratamiento farmacológico , Complicaciones Posoperatorias/tratamiento farmacológico , Saponinas/farmacología , Triterpenos/farmacología , Proteínas de Unión al GTP rho/metabolismo , Quinasas Asociadas a rho/metabolismo , Animales , Línea Celular , Colágeno Tipo I/metabolismo , Fibrinógeno/metabolismo , Humanos , Interleucina-1beta/metabolismo , Interleucina-1beta/farmacología , Masculino , Enfermedades Peritoneales/patología , Enfermedades Peritoneales/prevención & control , Peritoneo/citología , Peritoneo/cirugía , Complicaciones Posoperatorias/patología , Complicaciones Posoperatorias/prevención & control , Ratas Sprague-Dawley , Transducción de Señal/efectos de los fármacos , Adherencias TisularesRESUMEN
OBJECTIVE: Peritoneal adhesions may develop after every abdominopelvic surgery. Many agents and technical modifications have been investigated to minimize adhesions. Punica granatum (pomegranate) flower has some anti-inflammatory and antioxidative effects that would reduce the formation of peritoneal adhesions. In the present study, the effects of different doses of oral Punica granatum flower extract on postoperative peritoneal adhesions were evaluated in a rat model. STUDY DESIGN: Thirty-two female Wistar rats were divided into four groups: one control group (CG) and three experimental groups, treated with 100 (EG100), 200 (EG200), and 400 (EG400) mg/kg/day Punica granatum extract orally for eight days. Induction of peritoneal adhesions was done in all groups using the same method. Two weeks after the first surgery, all rats re-operated and adhesions were evaluated via both macroscopic and microscopic changes. RESULTS: We observed that rats in the control group had statistically higher adhesion area and more severe adhesions when compared to all experimental groups. Besides, those in the EG-400 group had a significantly lower rate of foreign body reaction in serosal layer when compared to the other three study groups. Other microscopic findings were comparable between the four groups. CONCLUSION: Administration of the oral Punica granatum flower extract was associated with a decreased quantity and quality of the adhesions in the animal model of rat in this study. This therapy might be an effective and safe strategy to reduce intraperitoneal adhesion after abdominal surgeries in animal models.
Asunto(s)
Flores , Enfermedades Peritoneales/prevención & control , Peritoneo/efectos de los fármacos , Fitoterapia , Extractos Vegetales/farmacología , Granada (Fruta) , Adherencias Tisulares/prevención & control , Administración Oral , Animales , Femenino , Fibrosis , Reacción a Cuerpo Extraño/patología , Linfocitos/patología , Macrófagos/patología , Neutrófilos/patología , Enfermedades Peritoneales/patología , Peritoneo/patología , Peritoneo/cirugía , Células Plasmáticas/patología , Ratas , Adherencias Tisulares/patologíaRESUMEN
PURPOSE: To evaluate the effect of garlic on formation of postoperative adhesions in rats. METHODS: Twenty-four Sprague dawley rats were divided into three groups. In Group 1 (sham), laparotomy was performed and stitched up. In Group 2 (control), after laparotomy was performed, punctate hemorrhage was induced by cecal abrasion in the cecum and 2 cc of saline was intraperitoneally administered to each rat. In Group 3 (experimental), after laparotomy was performed, punctate hemorrhage was induced by cecal abrasion in the cecum and each rat was intraperitoneally administered a sterile Allium sativum derivative. The rats in all groups were re-laparotomized on postoperative day 7; samples were obtained from the peritoneal tissue surrounding the cecum. RESULTS: In Group 3, there was a statistically significant difference in terms of inflammation, lymph node size, and free oxygen radicals; these parameters tended to increase. In terms of fibrosis evaluated using H&E and MT, there was no significant difference between groups 2 and 3. CONCLUSIONS: No positive outcomes indicating that Allium sativum reduces intra-abdominal adhesions were obtained. However, it caused severe inflammation in the tissue. Additionally, in immunohistochemical analyses conducted to detect oxidative stress, allium sativum increased the production of free oxygen radicals in the tissue.
Asunto(s)
Ajo/química , Enfermedades Peritoneales/prevención & control , Animales , Fibrosis , Radicales Libres/análisis , Inmunohistoquímica , Laparotomía , Ganglios Linfáticos/efectos de los fármacos , Ganglios Linfáticos/patología , Estrés Oxidativo/efectos de los fármacos , Enfermedades Peritoneales/patología , Complicaciones Posoperatorias/patología , Complicaciones Posoperatorias/prevención & control , Ratas Sprague-Dawley , Reproducibilidad de los Resultados , Adherencias Tisulares/patología , Adherencias Tisulares/prevención & controlRESUMEN
Abstract Purpose: To evaluate the effect of garlic on formation of postoperative adhesions in rats. Methods: Twenty-four Sprague dawley rats were divided into three groups. In Group 1 (sham), laparotomy was performed and stitched up. In Group 2 (control), after laparotomy was performed, punctate hemorrhage was induced by cecal abrasion in the cecum and 2 cc of saline was intraperitoneally administered to each rat. In Group 3 (experimental), after laparotomy was performed, punctate hemorrhage was induced by cecal abrasion in the cecum and each rat was intraperitoneally administered a sterile Allium sativum derivative. The rats in all groups were re-laparotomized on postoperative day 7; samples were obtained from the peritoneal tissue surrounding the cecum Results: In Group 3, there was a statistically significant difference in terms of inflammation, lymph node size, and free oxygen radicals; these parameters tended to increase. In terms of fibrosis evaluated using H&E and MT, there was no significant difference between groups 2 and 3. Conclusions: No positive outcomes indicating that Allium sativum reduces intra-abdominal adhesions were obtained. However, it caused severe inflammation in the tissue. Additionally, in immunohistochemical analyses conducted to detect oxidative stress, allium sativum increased the production of free oxygen radicals in the tissue.
Asunto(s)
Animales , Enfermedades Peritoneales/prevención & control , Ajo/química , Enfermedades Peritoneales/patología , Complicaciones Posoperatorias/patología , Complicaciones Posoperatorias/prevención & control , Fibrosis , Inmunohistoquímica , Adherencias Tisulares/patología , Adherencias Tisulares/prevención & control , Reproducibilidad de los Resultados , Ratas Sprague-Dawley , Estrés Oxidativo/efectos de los fármacos , Radicales Libres/análisis , Laparotomía , Ganglios Linfáticos/efectos de los fármacos , Ganglios Linfáticos/patologíaRESUMEN
BACKGROUND: EW-7197 is an oral transforming growth factor ß type I receptor kinase inhibitor currently undergoing phase I clinical trials for cancer treatment in the United States. This study evaluates whether EW-7197 prevents peritoneal adhesion formation in a rat model. METHODS: Forty-eight female Wistar rats underwent peritoneal adhesion induction by the creation of peritoneal ischemic buttons and were randomly divided into 4 groups of 12 each. The control group received 0.3 mL vehicle by oral gavage once daily for 7 days after adhesion induction. The 10 mg and 20 mg groups received 10 or 20 mg/kg EW-7197 phosphate dissolved in 0.3 mL vehicle by oral gavage once daily for 7 days after adhesion induction. The rebound group received 20 mg/kg EW-7197 phosphate dissolved in 0.3 mL vehicle by oral gavage once daily for 7 days after adhesion induction followed by 0.3 mL vehicle only by gavage once daily for an additional 21 days. After the respective treatments were completed, the animals were euthanized. RESULTS: All rats survived until the end of the study without complications. EW-7197 reduced the incidence, quality, and tenacity of peritoneal adhesions in a dose-dependent manner. Fibrosis and collagen production were reduced in EW-7197-treated peritoneal ischemic buttons. Transforming growth factor ß/Smad2/3 signaling and mesothelial-to-mesenchymal transition were inhibited in EW-7197-treated peritoneal ischemic buttons. Discontinuation of EW-7197 was not associated with rebound effects. CONCLUSION: EW-7197 prevented peritoneal adhesion formation potentially via inhibition of transforming growth factor ß1/Smad2/3-induced mesothelial-to-mesenchymal transition in a rat model.
Asunto(s)
Compuestos de Anilina/farmacología , Enfermedades Peritoneales/prevención & control , Complicaciones Posoperatorias/prevención & control , Inhibidores de Proteínas Quinasas/farmacología , Adherencias Tisulares/prevención & control , Triazoles/farmacología , Administración Oral , Compuestos de Anilina/uso terapéutico , Animales , Modelos Animales de Enfermedad , Evaluación Preclínica de Medicamentos , Transición Epitelial-Mesenquimal/efectos de los fármacos , Femenino , Fibrosis , Humanos , Enfermedades Peritoneales/etiología , Enfermedades Peritoneales/patología , Peritoneo/efectos de los fármacos , Peritoneo/patología , Peritoneo/cirugía , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/patología , Inhibidores de Proteínas Quinasas/uso terapéutico , Ratas , Ratas Wistar , Receptor Tipo I de Factor de Crecimiento Transformador beta/antagonistas & inhibidores , Transducción de Señal/efectos de los fármacos , Procedimientos Quirúrgicos Operativos/efectos adversos , Adherencias Tisulares/etiología , Adherencias Tisulares/patología , Resultado del Tratamiento , Triazoles/uso terapéuticoRESUMEN
Postoperative peritoneal adhesions, fibrous bands formed in the peritoneal cavity following surgery, represent a common, challenging and costly problem faced by surgeons and patients, for which effective therapeutic options are lacking. Since aberrant inflammation is one of the key mechanisms underlying peritoneal adhesion formation, here we set out to study the role of developmental endothelial locus-1 (Del-1), which has been recently identified as an endogenous inhibitor of inflammation, in the formation of postoperative peritoneal adhesions using a mouse model of peritoneal adhesions induced by ischemic buttons. Del-1-deficient mice had a higher incidence of adhesions, and their adhesions had higher quality and tenacity scores. Del-1 deficiency also led to enhanced inflammation mediators and collagen production. Finally, Del-1 supplementation decreased the incidence and severity of postoperative peritoneal adhesions. Taken together, these results indicate a protective role for Del-1 in postoperative peritoneal adhesion formation.
Asunto(s)
Proteínas Portadoras/metabolismo , Enfermedades Peritoneales/metabolismo , Enfermedades Peritoneales/prevención & control , Peritoneo/patología , Adherencias Tisulares/metabolismo , Adherencias Tisulares/prevención & control , Animales , Proteínas de Unión al Calcio , Moléculas de Adhesión Celular , Matriz Extracelular/metabolismo , Proteínas de la Matriz Extracelular/metabolismo , Inflamación/patología , Péptidos y Proteínas de Señalización Intercelular , Masculino , Ratones Endogámicos C57BL , Inhibidor 1 de Activador Plasminogénico/metabolismo , Complicaciones Posoperatorias/etiología , Receptores Fc/metabolismo , Índice de Severidad de la Enfermedad , Adherencias Tisulares/etiologíaRESUMEN
PURPOSE: To investigate the effects of pycnogenol on peritoneal adhesions and additionally to investigate the immunohistochemical effects of free oxygen radicals and reactive lymph nodes detected in the adhesive tissue that was sampled surrounding the cecum on intra-abdominal adhesions. METHODS: Twenty-seven Wistar Albino rats were divided into three groups. In group 1 (sham), laparotomy was performed and stitched up. In group 2 (control), after laparotomy was performed, punctate hemorrhage was induced by cecal abrasion in the cecum and each rat was intraperitoneally administered 2 cc of saline. In group 3 (experimental), after laparotomy was performed, punctate hemorrhage was induced by cecal abrasion in the cecum and each rat was intraperitoneally administered a sterile Pycnogenol derivative. The rats in all groups were re-laparotomized on postoperative day 7; samples were obtained from the peritoneal tissue surrounding the cecum, and the rats were sacrificed. RESULTS: In group 3, there was a statistically significant difference in terms of inflammation, lymph node size, and free oxygen radicals; these parameters tended to increase. In terms of fibrosis evaluated using H&E and MT, there was no significant difference between groups 2 and 3. CONCLUSIONS: No positive outcomes indicating that pycnogenol reduces intra-abdominal adhesions were obtained. However, it caused severe inflammation in the tissue. Moreover, a significant increase in lymph node size was detected secondary to inflammation. Additionally, in immunohistochemical analyses conducted to detect oxidative stress, pycnogenol increased the production of free oxygen radicals in the tissue.
Asunto(s)
Flavonoides/uso terapéutico , Ganglios Linfáticos/efectos de los fármacos , Enfermedades Peritoneales/prevención & control , Peritoneo/cirugía , Adherencias Tisulares/prevención & control , Animales , Antiinflamatorios/uso terapéutico , Antioxidantes/uso terapéutico , Modelos Animales de Enfermedad , Flavonoides/efectos adversos , Radicales Libres/análisis , Inmunohistoquímica , Inflamación/inducido químicamente , Inflamación/patología , Laparotomía , Ganglios Linfáticos/patología , Estrés Oxidativo/efectos de los fármacos , Enfermedades Peritoneales/etiología , Peritoneo/patología , Extractos Vegetales , Complicaciones Posoperatorias , Ratas , Ratas Wistar , Especies Reactivas de Oxígeno/metabolismo , Adherencias Tisulares/etiología , Adherencias Tisulares/patologíaRESUMEN
Abstract Purpose: To investigate the effects of pycnogenol on peritoneal adhesions and additionally to investigate the immunohistochemical effects of free oxygen radicals and reactive lymph nodes detected in the adhesive tissue that was sampled surrounding the cecum on intra-abdominal adhesions. Methods: Twenty-seven Wistar Albino rats were divided into three groups. In group 1 (sham), laparotomy was performed and stitched up. In group 2 (control), after laparotomy was performed, punctate hemorrhage was induced by cecal abrasion in the cecum and each rat was intraperitoneally administered 2 cc of saline. In group 3 (experimental), after laparotomy was performed, punctate hemorrhage was induced by cecal abrasion in the cecum and each rat was intraperitoneally administered a sterile Pycnogenol derivative. The rats in all groups were re-laparotomized on postoperative day 7; samples were obtained from the peritoneal tissue surrounding the cecum, and the rats were sacrificed. Results: In group 3, there was a statistically significant difference in terms of inflammation, lymph node size, and free oxygen radicals; these parameters tended to increase. In terms of fibrosis evaluated using H&E and MT, there was no significant difference between groups 2 and 3. Conclusions: No positive outcomes indicating that pycnogenol reduces intra-abdominal adhesions were obtained. However, it caused severe inflammation in the tissue. Moreover, a significant increase in lymph node size was detected secondary to inflammation. Additionally, in immunohistochemical analyses conducted to detect oxidative stress, pycnogenol increased the production of free oxygen radicals in the tissue.
Asunto(s)
Animales , Ratas , Enfermedades Peritoneales/prevención & control , Peritoneo/cirugía , Flavonoides/uso terapéutico , Adherencias Tisulares/prevención & control , Enfermedades Peritoneales/etiología , Peritoneo/patología , Complicaciones Posoperatorias , Flavonoides/efectos adversos , Inmunohistoquímica , Extractos Vegetales , Adherencias Tisulares/etiología , Adherencias Tisulares/patología , Especies Reactivas de Oxígeno/metabolismo , Ratas Wistar , Estrés Oxidativo/efectos de los fármacos , Modelos Animales de Enfermedad , Radicales Libres/análisis , Inflamación/inducido químicamente , Inflamación/patología , Laparotomía , Ganglios Linfáticos/efectos de los fármacos , Ganglios Linfáticos/patología , Antiinflamatorios/uso terapéutico , Antioxidantes/uso terapéuticoRESUMEN
AIM: In this study, we researched the effect of local administration of N-acetylcysteine (NAC) on postoperative intraabdominal adhesion formation in the rat models. METHODS: 20 female Wistar Albino rats which were 5-7 months old are used for the study. The rats were divided into two equal groups. Group one was administered saline solution (n=10) while group two was administered NAC (n=10) after caecal abrasion. They were dissected on postoperative tenth day and were examined macroscopically and microscopically for the adhesion formation. Intraperitoneal adhesion formation was scored blinded with Evans model. The most adherent bowel section was excised for histopathologic examination. Mann Whitney U test were used for statistical analysis. RESULTS: In Group one, all rats have had adhesions. None of the rats in Group two had either severe inflammatory cell reaction or dense interstitial fibrosis. Macroscopic adhesion formation and microscopic inflammatory cell reaction and interstitial fibrosis formation after surgery were less at the group two (NAC applied) (p<0.05, p<0.05, p<0.05). CONCLUSION: We believe that the intraperitoneal single dose usage of NAC may be promising for decreasing the postoperative intraabdominal adhesions. KEY WORDS: N-acetylcysteine, Postoperative adhesion, Rat, Fibrosis.
Asunto(s)
Acetilcisteína/uso terapéutico , Antioxidantes/uso terapéutico , Enfermedades Peritoneales/prevención & control , Adherencias Tisulares/prevención & control , Acetilcisteína/administración & dosificación , Animales , Antioxidantes/administración & dosificación , Apoptosis/efectos de los fármacos , Ciego/lesiones , Ciego/cirugía , Evaluación Preclínica de Medicamentos , Femenino , Fibrosis , Instilación de Medicamentos , Cavidad Peritoneal , Ratas , Ratas Wistar , Método Simple CiegoRESUMEN
BACKGROUND: Oxaliplatin-based hyperthermic intraperitoneal chemotherapy (HIPEC-ox) induces specific morbidity with hemorrhagic complications (HC). The aim of this study was to identify preoperative, intraoperative and postoperative HC predictive factors after HIPEC-ox. METHODS: A prospective single center study that included all consecutive patients treated with curative-intent HIPEC-ox, whatever the origin of peritoneal disease, was conducted. All patients underwent systematic blood tests exploring primary hemostasis and endothelial activation before surgical incision (D0) and on postoperative days 2 (POD2) and 5 (POD5). RESULTS: Between May 2012 and August 2015, 47 patients were enrolled in the study. The overall HC rate was 38%. Major morbidity was significantly higher in patients with HC. Patients presenting HC were significantly more often affected with pseudomyxoma peritonei and had less preoperative chemotherapy. Multivariate analysis showed that a higher plasmatic level of Von Willebrand factor antigen at D0 (D0 VWF:Ag) was a protective predictive factor for HC (p = 0.049, HR: 0.97 CI 95% [0.94-1.00]). A D0 VWF:Ag level below 138% had a sensitivity of 87.5%, a specificity of 67% and an area under the curve of 80.3% (CI 95% [66.5-94], p < 0.01) for predicting HC. CONCLUSIONS: Through the identification of prognostic factors, this study highlighted a subgroup of patients with low risk of HC after HIPEC-ox. Based on these results, we propose a routine preoperative dosage of VWF that would help the surgeon to select the most suitable patients for HIPEC-ox.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Procedimientos Quirúrgicos de Citorreducción , Hipertermia Inducida/métodos , Compuestos Organoplatinos/administración & dosificación , Neoplasias Peritoneales/terapia , Hemorragia Posoperatoria/epidemiología , Factor de von Willebrand/metabolismo , Adulto , Anciano , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/terapia , Epistaxis/epidemiología , Epistaxis/metabolismo , Epistaxis/prevención & control , Femenino , Hemorragia Gastrointestinal/epidemiología , Hemorragia Gastrointestinal/metabolismo , Hemorragia Gastrointestinal/prevención & control , Humanos , Infusiones Parenterales , Neoplasias Intestinales/patología , Neoplasias Intestinales/terapia , Masculino , Persona de Mediana Edad , Análisis Multivariante , Oxaliplatino , Enfermedades Peritoneales/epidemiología , Enfermedades Peritoneales/metabolismo , Enfermedades Peritoneales/prevención & control , Neoplasias Peritoneales/secundario , Hemorragia Posoperatoria/metabolismo , Hemorragia Posoperatoria/prevención & control , Pronóstico , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Neoplasias Uterinas/patología , Neoplasias Uterinas/terapia , Factor de von Willebrand/uso terapéuticoRESUMEN
BACKGROUND: Adhesions commonly occur after abdominal surgery and can cause bowel obstruction, chronic abdominal pain, and infertility. Their prevention remains a challenge. OBJECTIVES: To evaluate the effects of the application of low-level lasers on the prevention of adhesions and scarring of the skin after peritoniectomia. METHOD: Twenty-four New Zealand breed male rabbits, approximately 2 months of age, were randomly divided into 3 groups (n = 8): GC-control group not subjected to laser, GL1-group with laser application at a dose of 0.2 J, and GL2-group with laser application at a dose of 3.6 J. All animals received a longitudinal midline incision and a bilateral resection of the peritoneal fragment, measuring 3 × 1 cm(2) . The animals received a laser treatment of one application every 24 hours, beginning at the time of surgery and lasting for a period of 4 days. After 14 days post-surgery, the animals were killed and adhesion formation was evaluated qualitatively and quantitatively by means of a laparotomy shaped inverted "U", which allowed for the verification of the broad wall of the abdominal cavity and organs. Differences were considered significant at P < 0.05. RESULTS: The adhesion formation was observed in 100% of the rabbits from groups GC and GL1, as compared to 37.5% of the rabbits from group GL2 (P < 0.01). The evaluation of the vascularization and tenacity of adhesions among the groups showed no significant difference. In groups CG and GL1, 72% and 83% of adhesions were verified between visceras, respectively whereas in GL2 occurred among abdominal wall. The tensile strength of the skin between the groups was not significant (P = 0.3106). The resistance of abdominal wall segments without skin he resistance of skin segments between groups GL2 and GC were higher than in GL1 (P = 0.01). CONCLUSION: Low-level LASER is effective in preventing intra-abdominal adhesions in rabbits without compromising strength and healing of the abdominal wall.
Asunto(s)
Pared Abdominal/cirugía , Cicatriz/prevención & control , Terapia por Luz de Baja Intensidad , Enfermedades Peritoneales/prevención & control , Peritoneo/cirugía , Complicaciones Posoperatorias/prevención & control , Adherencias Tisulares/prevención & control , Animales , Cicatriz/etiología , Masculino , Enfermedades Peritoneales/etiología , Conejos , Distribución Aleatoria , Adherencias Tisulares/etiología , Cicatrización de HeridasRESUMEN
PURPOSE: This study tested the ability of pycnogenol, an extract from the bark of the French maritime pine (Pinus pinaster), to prevent intra-abdominal adhesions. METHODS: Thirty female Wistar albino rats were separated randomly into three equal groups: Group (1) the control group, which underwent surgery, but was given no drug; Group (2) given 10 mg/kg of pycnogenol dissolved in normal saline intraperitoneally for 10 days after surgery; and Group (3) given 0.1 mL of normal saline for 10 days intraperitoneally after surgery. On post-operative day 10, all of the animals were killed and any adhesions were evaluated macroscopically and histopathologically. RESULTS: The macroscopic adhesion scores (mean ± SD) for Groups 1, 2, and 3 were 2.5 ± 0.53, 0.60 ± 0.70, and 2.0 ± 0.82, respectively. The macroscopic adhesion score was significantly lower in Group 2 than in Groups 1 and 3 (p < 0.001). All three components of the histopathological evaluation (inflammation, fibrosis, and neovascularization) were significantly lower in Group 2 than in Groups 1 or 3 (p < 0.001, p < 0.001, and p = 0.004, respectively). CONCLUSIONS: Pycnogenol was found to be effective at preventing surgery-related adhesions in an animal model.
Asunto(s)
Flavonoides/farmacología , Enfermedades Peritoneales/prevención & control , Fitoterapia , Extractos Vegetales/uso terapéutico , Animales , Modelos Animales de Enfermedad , Femenino , Fibrosis , Flavonoides/uso terapéutico , Inflamación/patología , Inflamación/prevención & control , Enfermedades Peritoneales/patología , Pinus/química , Complicaciones Posoperatorias/prevención & control , Ratas , Ratas Wistar , Adherencias Tisulares/patología , Adherencias Tisulares/prevención & control , Cicatrización de Heridas/efectos de los fármacosRESUMEN
Postsurgical peritoneal adhesion bands are the most important causes of intestinal obstruction, pelvic pain, and female infertility. In this study, we used a mouse model of adhesion and compared the protective effect of activated protein C (APC) to that of the Food and Drug Administration-approved antiadhesion agent, sodium hyaluronate/carboxymethylcellulose (Seprafilm) by intraperitoneal administration of either APC or Seprafilm to experimental animals. Pathological adhesion bands were graded on day 7, and peritoneal fluid concentrations of tissue plasminogen activator (tPA), d-dimer, thrombin-antithrombin complex, and cytokines (IL-1ß, IL-6, interferon-γ, tumor necrosis factor-α, transforming growth factor-ß1) were evaluated. Inflammation scores were also measured based on histologic data obtained from peritoneal tissues. Relative to Seprafilm, intraperitoneal administration of human APC led to significantly higher reduction of postsurgical adhesion bands. Moreover, a markedly lower inflammation score was obtained in the adhesive tissues of the APC-treated group, which correlated with significantly reduced peritoneal concentrations of proinflammatory cytokines and an elevated tPA level. Further studies using variants of human APC with or without protease-activated receptor 1 (PAR1) signaling function and mutant mice deficient for either endothelial protein C receptor (EPCR) or PAR1 revealed that the EPCR-dependent signaling activity of APC is primarily responsible for its protective activity in this model. These results suggest APC has therapeutic potential for preventing postsurgical adhesion bands.
Asunto(s)
Enfermedades Peritoneales/prevención & control , Complicaciones Posoperatorias/prevención & control , Proteína C/administración & dosificación , Adherencias Tisulares/prevención & control , Animales , Citocinas/genética , Citocinas/metabolismo , Evaluación Preclínica de Medicamentos , Inflamación/tratamiento farmacológico , Inflamación/genética , Inflamación/metabolismo , Mediadores de Inflamación/metabolismo , Infusiones Parenterales , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Enfermedades Peritoneales/genética , Enfermedades Peritoneales/metabolismo , Peritonitis/tratamiento farmacológico , Peritonitis/genética , Peritonitis/metabolismo , Complicaciones Posoperatorias/genética , Complicaciones Posoperatorias/metabolismo , Adherencias Tisulares/genética , Adherencias Tisulares/metabolismoRESUMEN
INTRODUCTION: Peritoneal adhesions are pathological fibrous connections between peritoneal surfaces resulting from incomplete peritoneal repair. Adhesions cause various health problems ranging from pelvic pain and bowel obstruction to infertility. To date, no effective agent exists for intra-abdominal adhesion prevention. Bromelain is the crude extract of the pineapple and it has fibrinolytic, antithrombotic, and anti-inflammatory properties. Bromelain has been shown to be effective for removing necrotic tissues and has been found to be effective for treating various wounds, inflammatory conditions, and thrombotic pathologies. In the present study, we evaluated bromelain as a novel agent for preventing intra-abdominal adhesions. METHODS: Group 1 (control group): Adhesions were produced by cecal abrasion method, and no treatment was applied. Group 2 (i.p. bromelain-treated group): After adhesion formation, 10 mg/kg/BW of bromelain dissolved in 1 mL saline solution was applied intraperitoneally for 10 days. Group 3 (i.p. saline-treated group): After adhesion formation, 1 mL saline solution was applied intraperitoneally for 10 days. On postoperative day 10, all animals were sacrificed. RESULTS: All 30 rats survived surgery. Throughout the follow-up period, no complications were observed. Statistically significant differences were found between the groups with regards to macroscopic adhesion scores, inflammation, fibrosis and neo-vascularization (p < 0.001, <0.001, p = 0.001, p = 0.002, respectively). Macroscopic and histopathologic (inflammation, fibrosis, neo-vascularization) adhesion scores were lowest in the bromelain-treated group. CONCLUSION: Bromelain, acting through its barrier, anti-inflammatory, antioxidant, and proteolytic effects and without increasing bleeding tendency or having any adverse effects on wound healing, may be a suitable agent for intra-abdominal adhesion prevention.
Asunto(s)
Bromelaínas/uso terapéutico , Enfermedades Peritoneales/prevención & control , Fitoterapia , Extractos Vegetales/uso terapéutico , Animales , Bromelaínas/administración & dosificación , Femenino , Complicaciones Posoperatorias/prevención & control , Ratas Wistar , Adherencias Tisulares/prevención & control , Cicatrización de Heridas/efectos de los fármacosRESUMEN
OBJECTIVE(S): Peritoneal adhesion is a serious problem that develops after most abdominopelvic surgeries. Allium sativum (garlic) has been used for centuries as both a nutrient and a traditional medicine. The anti-inflammatory, antibacterial, fibrinolytic, and wound-healing properties of garlic are well-recognized. We evaluated the effect of garlic on formation of postoperative adhesions in rats. STUDY DESIGN: Thirty Wistar-Albino female rats weighing 200-250 g were randomly divided into three groups (10 rats/group). Group 1 rats received 5 ml/kg garlic oil intraperitoneally and no surgery was performed. The ceca of Group 2 rats (controls) were scraped, to trigger adhesion formation, and no treatment was given. In Group 3 rats, 5 ml/kg garlic oil was added to the peritoneal cavity immediately after the cecum was scraped. All animals were sacrificed 10 d after surgery and adhesions graded in terms of severity and histopathologic characteristics. RESULTS: All animals tolerated the operations well. No adhesions were evident upon laparotomy of Group 1 animals. In Group 2 three rats had an adhesion grade 2 and seven rats had an adhesion of grade 3, whereas in Group 3 no adhesions were found in four rats, five rats had an adhesion grade of 1. Only one rat had a grade 2 adhesion. Macroscopic adhesions and mean adhesion scores of Group 3 were significantly lower than Group 2 (p<0.001). Histopathologic evaluation of the specimens also revealed a statistically significant differences in inflammation, fibrosis, and neovascularization scores between Group 2 and 3 (p=0.001, p=0.001, and p=0.011, respectively). Inflammation, fibrosis and vascularization scores in Group 3 were found significantly lower than Group 2. CONCLUSION: The anti-inflammatory, antibacterial, fibrinolytic, antithrombotic, and wound-healing effects of garlic likely prevent formation of peritoneal adhesions in a rat model, and garlic may be effective and cheap when used to prevent such adhesions in humans.
Asunto(s)
Compuestos Alílicos/administración & dosificación , Fibrinolíticos/administración & dosificación , Enfermedades Peritoneales/prevención & control , Peritoneo/patología , Complicaciones Posoperatorias/prevención & control , Sulfuros/administración & dosificación , Animales , Ciego/cirugía , Femenino , Fibrosis/patología , Fibrosis/prevención & control , Inflamación/patología , Inflamación/prevención & control , Inyecciones Intraperitoneales , Neovascularización Patológica/patología , Neovascularización Patológica/prevención & control , Enfermedades Peritoneales/patología , Peritoneo/cirugía , Complicaciones Posoperatorias/patología , Ratas , Ratas Wistar , Adherencias Tisulares/patología , Adherencias Tisulares/prevención & controlRESUMEN
Post-operative peritoneal adhesions are serious consequences of abdominal or pelvic surgery and cause severe bowel obstruction, chronic pelvic pain and infertility. In this study, a novel nano-hydrogel system based on a monomethoxy poly(ethylene glycol)-poly(lactic acid) (MPEG-PLA) di-block copolymer was studied for its ability to prevent abdominal adhesion in rats. The MPEG-PLA hydrogel at a concentration of 40% (w/v) was injected and was able to adhere to defect sites at body temperature. The ability of the hydrogel to inhibit adhesion of post-operative tissues was evaluated by utilizing a rat model of abdominal sidewall-cecum abrasion. It was possible to heal wounded tissue through regeneration of neo-peritoneal tissues ten days after surgery. Our data showed that this hydrogel system is equally as effective as current commercialized anti-adhesive products.
Asunto(s)
Abdomen/cirugía , Implantes Absorbibles , Hidrogeles/uso terapéutico , Polietilenglicoles/uso terapéutico , Adherencias Tisulares/prevención & control , Técnicas de Cierre de Herida Abdominal/efectos adversos , Animales , Enfermedades del Ciego/prevención & control , Ciego , Evaluación Preclínica de Medicamentos , Femenino , Hidrogeles/química , Hidrogeles/farmacocinética , Enfermedades Peritoneales/prevención & control , Polietilenglicoles/química , Polietilenglicoles/farmacocinética , Complicaciones Posoperatorias/prevención & control , Ratas , Ratas Wistar , TemperaturaRESUMEN
AIM: We aim to evaluate the effect of Nigella sativa oil (NSO) on postoperative peritoneal adhesion formation in female rats. This experimental study is the first on the prevention of postoperative adhesion formation by NSO. METHODS: Twenty-four Wistar albino female rats were randomly assigned to three groups of eight rats each. Rats in group 1 were each injected i.p. with 1 mL of NSO. In group 2, an adhesion model was created with no injection of NSO. In group 3, an adhesion model was created and the area was covered with 1 mL of NSO. The rats were killed on postoperative day 8, and the severity of adhesions was evaluated macroscopically and histopathologically. RESULTS: There was a statistically significant difference in adhesion scores between group 2 (control) and group 3 (NSO-treated) (P = 0.003). Statistically significant differences in angiogenesis, fibrosis and inflammation were observed between the control and Nigella sativa groups (P = 0.002, P = 0.001 and P = 0.004, respectively). CONCLUSION: Covering peritoneal surfaces with NSO after peritoneal trauma is effective in decreasing peritoneal adhesion formation.
Asunto(s)
Enfermedades Peritoneales/prevención & control , Aceites de Plantas/uso terapéutico , Complicaciones Posoperatorias/prevención & control , Animales , Femenino , Peritoneo/cirugía , Distribución Aleatoria , Ratas , Ratas Wistar , Índice de Severidad de la Enfermedad , Adherencias Tisulares/prevención & controlRESUMEN
OBJECTIVE: Postsurgical abdominal adhesions are common, serious postoperative complications. The present study compared the usefulness of 4% icodextrin and canola oil in preventing postoperative peritoneal adhesions. METHODS: Twenty-four Wistar albino rats were divided into three groups. Following a laparotomy, a serosal abrasion was made by brushing the cecum, and 3 mL of 0.9% NaCl, 4% icodextrin, or 3 mL of canola oil were intraperitoneally administered for the control, icodextrin, and canola oil groups, respectively. The abdomen was then closed. All of the rats were sacrificed at day 10. Macroscopic, histopathological, and biochemical evaluations were performed. The results were statistically analyzed using Kruskal-Wallis and ANOVA tests. RESULTS: Macroscopic analyses revealed that both canola oil and 4% icodextrin reduced adhesion formation, but the difference was not statistically significant (p = 0.17). The histopathological examinations revealed no significant differences in terms of giant cell, lymphocyte/plasmocyte, neutrophil, ICAM1, or PECAM1 scores. However, both canola oil and 4% icodextrin significantly reduced fibrosis (p = 0.025). In the canola oil group, the histiocytic reactions were significantly increased (p = 0.001), and the hydroxyproline levels were significantly lower than those in the other groups (p = 0.034). CONCLUSIONS: In the present study, canola oil was determined to be superior to 4% icodextrin in lowering hydroxyproline levels and increasing histiocytic reactions. Considering these results, we believe that canola oil is a promising agent for preventing adhesion formation.