Glucagon-like peptide-1(7–36) amide is a new incretin/enterogastrone candidate

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72032/1/j.1365-2362.1991.tb01802.x.pd

The desmosomal cadherin desmoglein-3 acts as a keratinocyte anti-stress protein via suppression of p53

Desmoglein-3 (Dsg3), the Pemphigus Vulgaris (PV) antigen (PVA), plays an essential role in keratinocyte cell–cell adhesion and regulates various signaling pathways involved in the progression and metastasis of cancer where it is upregulated. We show here that expression of Dsg3 impacts on the expression and function of p53, a key transcription factor governing the responses to cellular stress. Dsg3 depletion increased p53 expression and activity, an effect enhanced by treating cells with UVB, mechanical stress and genotoxic drugs, whilst increased Dsg3 expression resulted in the opposite effects. Such a pathway in the negative regulation of p53 by Dsg3 was Dsg3 specific since neither E-cadherin nor desmoplakin knockdown caused similar effects. Analysis of Dsg3−/− mouse skin also indicated an increase of p53/p21WAF1/CIP1 and cleaved caspase-3 relative to Dsg3+/− controls. Finally, we evaluated whether this pathway was operational in the autoimmune disease PV in which Dsg3 serves as a major antigen involved in blistering pathogenesis. We uncovered increased p53 with diffuse cytoplasmic and/or nuclear staining in the oral mucosa of patients, including cells surrounding blisters and the pre-lesional regions. This finding was verified by in vitro studies where treatment of keratinocytes with PV sera, as well as a characterized pathogenic antibody specifically targeting Dsg3, evoked pronounced p53 expression and activity accompanied by disruption of cell–cell adhesion. Collectively, our findings suggThe study was supported by the Barts and The London School of Medicine and Dentistry and Guizhou Medical University, China. The animal work was supported by Deutsche Forschungsgemeinschaft (TR-SFB 156). Jutamas Uttagomol was supported by a scholarship from Naresuan University, Thailand

The desmosome and pemphigus

Desmosomes are patch-like intercellular adhering junctions (“maculae adherentes”), which, in concert with the related adherens junctions, provide the mechanical strength to intercellular adhesion. Therefore, it is not surprising that desmosomes are abundant in tissues subjected to significant mechanical stress such as stratified epithelia and myocardium. Desmosomal adhesion is based on the Ca2+-dependent, homo- and heterophilic transinteraction of cadherin-type adhesion molecules. Desmosomal cadherins are anchored to the intermediate filament cytoskeleton by adaptor proteins of the armadillo and plakin families. Desmosomes are dynamic structures subjected to regulation and are therefore targets of signalling pathways, which control their molecular composition and adhesive properties. Moreover, evidence is emerging that desmosomal components themselves take part in outside-in signalling under physiologic and pathologic conditions. Disturbed desmosomal adhesion contributes to the pathogenesis of a number of diseases such as pemphigus, which is caused by autoantibodies against desmosomal cadherins. Beside pemphigus, desmosome-associated diseases are caused by other mechanisms such as genetic defects or bacterial toxins. Because most of these diseases affect the skin, desmosomes are interesting not only for cell biologists who are inspired by their complex structure and molecular composition, but also for clinical physicians who are confronted with patients suffering from severe blistering skin diseases such as pemphigus. To develop disease-specific therapeutic approaches, more insights into the molecular composition and regulation of desmosomes are required

Reconstruction with fascia lata after extensive chest wall resection: results.

Abstract OBJECTIVES: Following extensive chest wall resection, the reconstruction technique should fulfill two opposing functional requirements: adequate rigidity and flexibility of the chest wall during the breathing phases. Reconstruction with fascia lata enables a balance between these two parameters, thus favouring the patients' respiratory dynamics and producing low morbidity and good functional results. METHODS: Sixty patients underwent chest wall reconstruction using fascia lata alone or in combination with titanium plates between 2006 and 2011, due to primary tumours in 28 patients, metastases in 23 and local recurrences in 9. The mean area of resected tissue was 107.7 cm(2), distributed among the anterior, anterolateral, lateral and posterior zones. One-to-eight ribs were resected, and additional sternum resection was performed in 75% of patients. Forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) were evaluated in 33 patients. RESULTS: 46.6% of patients underwent reconstruction with fascia lata alone, 1.6% with fascia lata, DualMesh\uae and titanium plates and 51.6% with fascia lata and titanium plates. There was no 30-day mortality. All patients were extubated after the operation with no need for reintubation. Five patients had postoperative complications: 2 wound dehiscences, 2 haematomas and 1 seroma. There were no significant differences between preoperative and postoperative FEV1 and FVC measurements in patients with or without lobectomy and wedge resections. CONCLUSIONS: Chest wall reconstruction with fascia lata, alone or in combination with titanium plates, allows the surgeon to perform a dynamic reconstruction without flail chest in extensive exeresis. Risks of infection associated with the use of prosthetic materials are also minimized. In addition, the characteristic flexibility of this tissue makes it a precious tool in paediatric chest wall reconstruction, since fascia lata naturally adapts to the physiological growth of younger bodies, thus reducing the risk of scoliosis and local deformities

Reconstruction with fascia lata after extensive chest wall resection: results.

Abstract OBJECTIVES: Following extensive chest wall resection, the reconstruction technique should fulfill two opposing functional requirements: adequate rigidity and flexibility of the chest wall during the breathing phases. Reconstruction with fascia lata enables a balance between these two parameters, thus favouring the patients' respiratory dynamics and producing low morbidity and good functional results. METHODS: Sixty patients underwent chest wall reconstruction using fascia lata alone or in combination with titanium plates between 2006 and 2011, due to primary tumours in 28 patients, metastases in 23 and local recurrences in 9. The mean area of resected tissue was 107.7 cm(2), distributed among the anterior, anterolateral, lateral and posterior zones. One-to-eight ribs were resected, and additional sternum resection was performed in 75% of patients. Forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) were evaluated in 33 patients. RESULTS: 46.6% of patients underwent reconstruction with fascia lata alone, 1.6% with fascia lata, DualMesh\uae and titanium plates and 51.6% with fascia lata and titanium plates. There was no 30-day mortality. All patients were extubated after the operation with no need for reintubation. Five patients had postoperative complications: 2 wound dehiscences, 2 haematomas and 1 seroma. There were no significant differences between preoperative and postoperative FEV1 and FVC measurements in patients with or without lobectomy and wedge resections. CONCLUSIONS: Chest wall reconstruction with fascia lata, alone or in combination with titanium plates, allows the surgeon to perform a dynamic reconstruction without flail chest in extensive exeresis. Risks of infection associated with the use of prosthetic materials are also minimized. In addition, the characteristic flexibility of this tissue makes it a precious tool in paediatric chest wall reconstruction, since fascia lata naturally adapts to the physiological growth of younger bodies, thus reducing the risk of scoliosis and local deformities

Tubercular bowel perforation: What to do?

BACKGROUND The incidence of abdominal tuberculosis (TB) is increasing in western and developed countries. This pathology has several complications, including free intestinal perforation. The aim of this study was to analytically summarize all the pertinent literature discussing the various treatments for TB-related perforations. METHODS We reviewed the patient database of the Emergency Surgery Department of the Bologna University Hospital, checking the last 13 years. A retrospective review was conducted of all reported cases of intestinal perforation due to intestinal TB published through 3 March 2009. RESULTS 119 cases of abdominal TB presenting with intestinal perforation were published. There are no standardized guidelines regarding the surgical treatment. Of the 119 reported cases, 40 (33.6%) were treated with resection and anastomosis, 17 (14.2%) with direct sutures, 4 (3.3%) with a simple drain, and in 57, the treatment was not reported. CONCLUSION No clinical evidence has been available for analysis to discern the optimal surgical strategy for treating intestinal perforations induced by TB. The direct closure of the perforation typically correlates with poor morbidity and mortality results. The better treatment seems to be the surgical resection of the perforated part with anastomosis. However, pharmacological therapy remains the essential pillar of treatment

Xenograft of piscine insular tissue in nude streptozotocin-diabetic mice: a transplantation model.

none6---noneMORSIANI E; CAPPELLARI; FOGLI L; RICCI D; PUVIANI C; G. AZZENAMorsiani, E; Cappellari, Lorenzo; Fogli, L; Ricci, Daniele; Puviani, C; Azzena, Gianfranc

Immediate and long-term results of surgical treatment with extracorporeal circulation in interatrial communication of the ostium secundum type. Clinico-instrumental evaluation with study of the polycardiographic findings

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Liver transplantation in recipients with portal vein thrombosis: experience of a single transplat center.

Although portal vein thrombosis (PVT) is no longer considered a contraindication for liver transplantation (OLT), it is still considered a high risk because of the complexity of the surgical procedure. The aim of this study was to evaluate the impact of PVT in the recipient during OLT on intra- and perioperative management and outcome