Adrenomedulline improves ischemic left colonic anastomotic healing in an experimental rodent model

BACKGROUND: Leakage from colonic anastomosis is a major complication causing increased mortality and morbidity. Ischemia is a well-known cause of this event. This study was designed to investigate the effects of adrenomedullin on the healing of ischemic colon anastomosis in a rat model. METHODS: Standardized left colon resection 3 cm above the peritoneal reflection and colonic anastomosis were performed in 40 Wistar rats that were divided into four groups. To mimic ischemia, the mesocolon was ligated 2 cm from either side of the anastomosis in all of the groups. The control groups (1 and 2) received no further treatment. The experimental groups (3 and 4) received adrenomedullin treatment. Adrenomedullin therapy was started in the perioperative period in group 3 and 4 rats (the therapeutic groups). Group 1 and group 3 rats were sacrificed on postoperative day 3. Group 2 and group 4 rats were sacrificed on postoperative day 7. After careful relaparotomy, bursting pressure, hydroxyproline, malondialdehyde, interleukin 6, nitric oxide, vascular endothelial growth factor, and tumor necrosis factor alpha levels were measured. Histopathological characteristics of the anastomosis were analyzed. RESULTS: The group 3 animals had a significantly higher bursting pressure than group 1 (p<0.05). Hydroxyproline levels in group 1 were significantly lower than in group 3 (p<0.05). The mean bursting pressure was significantly different between group 2 and group 4 (p<0.05). Hydroxyproline levels in groups 3 and 4 were significantly increased by adrenomedullin therapy relative to the control groups (p<0.05). When all groups were compared, malondialdehyde and nitric oxide were significantly lower in the control groups (p<0.05). When vascular endothelial growth factor levels were compared, no statistically significant difference between groups was observed. Interleukin 6 and tumor necrosis factor alpha were significantly decreased by adrenomedullin therapy (p<0.05). The healing parameters and inflammatory changes (e.g., granulocytic cell infiltration, necrosis, and exudate) were significantly different among all groups (p<0.05). CONCLUSION: Adrenomedullin had positive effects on histopathologic anastomotic healing in this experimental model of ischemic colon anastomosis

Surgical Treatment Of Posttraumatic Ankylosis Of The Tmj With Different Pathogenic Mechanisms

Objective: Posttraumatic ankylosis of the TMJ can be caused by many different pathogenic mechanisms. Prosthetic alloplastic grafts and autogenous grafts are the options for surgical treatment. Methods: Seven patients were examined clinically and radiologically. Autogenous interpositioners were used for treatment of TMJ ankylosis. Results: No major complications were seen after surgery. Interincisal distances have significantly widened following mouth opening exercises for one year. Conclusions: Human skulls have many structure and shape differences, so it is difficult to replace a jaw joint successfully with an artificial one. Using autogenous tissues seems an appropriate choice for treatment.PubMe

Strangulated inguinal hernia accompanied by paratesticular leiomyosarcoma

Sarcomas that arise from the spermatic cord constitute 2.1% of soft tissue sarcomas and are observed at a rate of 1% to 2% in the genitourinary system. A 74-year-old patient presented at the emergency department with complaints of groin pain and swelling persisting for 3 days. On physical examination, a firm mass that was approximately 5x5 cm in size and could not be reduced was observed at the right inguinal area as well as a right inguinal hernia. Computed tomography revealed a large hernia sac in the right inguinal area and a mass that was 77x55 mm in size within the hernial sac. A radical orchiectomy and hernia repair were performed. A diagnosis of leiomyosarcoma was made based on the pathological evaluation of the mass. At the 7-month postoperative follow-up, no local relapse or distant metastasis was found. To conclude, although paratesticular leiomyosarcoma is rare, it should be kept in mind as one of the possible diagnoses for older patients presenting with an inguinal mass

Trocar-Site Hernia After Diagnostic Laparoscopy

Trocar-site hernias occur due to various reasons and may cause life-threatening complications. Early diagnosis and treatment reduces morbidity and mortality rates. In this paper, we present a 43-year-old patient who presented to our emergency department with the complaints of nausea, vomiting, distention and inability to defecate occurred after a diagnostic laparoscopy for an abdominal stab wound. A computed tomography revealed a trocar-site hernia involving a small bowel segment. Trocar site was evaluated under general anesthesia and, after reduction of the bowel, the defect was closed primarily. On the first postoperative day, he was discharged uneventfully. Immediate mechanical bowel obstruction after laparoscopic surgery should be kept in mind to deal with these complications

Trocar-Site Hernia After Diagnostic Laparoscopy

Trocar-site hernias occur due to various reasons and may cause life-threatening complications. Early diagnosis and treatment reduces morbidity and mortality rates. In this paper, we present a 43-year-old patient who presented to our emergency department with the complaints of nausea, vomiting, distention and inability to defecate occurred after a diagnostic laparoscopy for an abdominal stab wound. A computed tomography revealed a trocar-site hernia involving a small bowel segment. Trocar site was evaluated under general anesthesia and, after reduction of the bowel, the defect was closed primarily. On the first postoperative day, he was discharged uneventfully. Immediate mechanical bowel obstruction after laparoscopic surgery should be kept in mind to deal with these complications

The effect of progesterone in the prevention of the chemically induced experimental colitis in rats Efeito da progesterona na prevenção de colite experimental induzida quimicamente em ratos

PURPOSE: To study the effects of progesterone on an experimental colitis model. METHODS: Wistar albino rats were treated subcutaneously with 2mg/kg once a day during seven days Colitis was induced by intrarectal administration of 5mg trinitrobenzene sulfonic acid (TNBS). Disease activities, macroscopic and microscopic scores were evaluated. To determine the response provoked by progesterone we measured Colonic malondialdehyde (MDA), TNF alfa, IL-6 and Nitric oxide (NO) levels in addition to the MPO (Myeloperoxidase) and caspase-3 activities. RESULTS: Progesterone ameliorated significantly the macroscopic and microscopic scores. TNBS-induced colitis significantly increased the colonic MDA levels and caspase-3 activities in group 2 in comparison to the control group. The results of the study revealed a decline in MDA, NO, IL6 and TNF-&#945; levels in the colon tissue and in blood due to progesterone therapy in group 3 when compared to the group 2, a significant improvement. Progesterone treatment was associated with decreased MDA, MPO, TNF alfa and caspase-3 activity. CONCLUSION: Progesterone therapy decreased oxidative damage in the colonic mucosa.<br>OBJETIVO: Investigar os efeitos da progesterona em um modelo de colite experimental. MÉTODOS: Ratos albinos Wistar foram tratados subcutaneamente com 2mg/kg por dia durante sete dias. A colite foi induzida por administração intrarretal de 5mg ácido sulfônico trinitrobenzeno (TNBS). Foram avaliadas as atividades da doença, escores macroscópicos e microscópicos Para determinar a resposta provocada pela progesterona foi medida no cólon os níveis de malondialdeído (MDA), TNF alfa, IL-6 e óxido nítrico (NO), além da atividade da MPO (Myeloperoxidase) e caspase-3. RESULTADOS: A progesterone melhorou significantemente os escores macroscópicos e microscópicos. A colite induzida pelo TNBS significantemente aumentou os níveis colônicos de MDA e a atividade da caspase-3 no grupo 2 em comparação com o grupo controle. Os resultados do estudo revelaram um declínio nos níveis de MDA, NO, IL6 e TNF-&#945; no tecido colônico e no sangue devido à terapia com a progesterona no grupo 3 quando comparado ao grupo 2. O tratamento com a progesterona foi associado com decréscimo do MDA, MPO, TNF alfa e atividade da caspase-3. CONCLUSÃO: A terapia com progesterona decresce o dano oxidativo na mucosa do cólon

Proposing novel MDM2 inhibitors: Combined physics-driven high-throughput virtual screening and in vitro studies

The mouse double minute 2 (MDM2) protein acts as a negative regulator of the p53 tumor suppressor. It directly binds to the N terminus of p53 and promotes p53 ubiquitination and degradation. Since the most common p53-suppressing mechanisms involve the MDM2, proposing novel inhibitors has been the focus of many in silico and also experimental studies. Thus, here we screened around 500,000 small organic molecules from Enamine database at the binding pocket of this oncogenic target. The screening was achieved systematically with starting from the high-throughput virtual screening method followed by more sophisticated docking approaches. The initial high number of screened molecules was reduced to 100 hits which then were studied extensively for their therapeutic activity and pharmacokinetic properties using binary QSAR models. The structural and dynamical profiles of the selected molecules at the binding pocket of the target were studied thoroughly by all-atom molecular dynamics simulations. The free energy of the binding of the hit molecules was estimated by the MM/GBSA method. Based on docking simulations, binary QSAR model results, and free energy calculations, 11 compounds (E1-E11) were selected for in vitro studies. HUVEC vascular endothelium, colon cancer, and breast cancer cell lines were used for testing the binding affinities of the identified hits and for further cellular effects on human cancer cell. Based on in vitro studies, six compounds (E1,E2,E5,E6,E9, andE11) in breast cancer cell lines and six compounds (E1,E2,E5,E6,E8, andE10) in colon cancer cell lines were found as active. Our results showed that these compounds inhibit proliferation and lead to apoptosis.WOS:0005503426000042-s2.0-85088278516PubMed: 3269196