https://www.um.es/biomybiotec/web/Seminarios/2010/papers/Cano_2.pdf

Epithelial-Mesenchymal Transitions in Development and Disease

Acute kidney injury (AKI) is a complex disorder for which currently there is no accepted definition. Having a uniform standard for diagnosing and classifying AKI would enhance our ability to manage these patients. Future clinical and translational research in AKI will require collaborative networks of investigators drawn from various disciplines, dissemination of information via multidisciplinary joint conferences and publications, and improved translation of knowledge from pre-clinical research. We describe an initiative to develop uniform standards for defining and classifying AKI and to establish a forum for multidisciplinary interaction to improve care for patients with or at risk for AKI. Members representing key societies in critical care and nephrology along with additional experts in adult and pediatric AKI participated in a two day conference in Amsterdam, The Netherlands, in September 2005 and were assigned to one of three workgroups. Each group's discussions formed the basis for draft recommendations that were later refined and improved during discussion with the larger group. Dissenting opinions were also noted. The final draft recommendations were circulated to all participants and subsequently agreed upon as the consensus recommendations for this report. Participating societies endorsed the recommendations and agreed to help disseminate the results. The term AKI is proposed to represent the entire spectrum of acute renal failure. Diagnostic criteria for AKI are proposed based on acute alterations in serum creatinine or urine output. A staging system for AKI which reflects quantitative changes in serum creatinine and urine output has been developed. We describe the formation of a multidisciplinary collaborative network focused on AKI. We have proposed uniform standards for diagnosing and classifying AKI which will need to be validated in future studies. The Acute Kidney Injury Network offers a mechanism for proceeding with efforts to improve patient outcomes.

Acute Kidney Injury Network: report of an initiative to improve outcomes in acute kidney injury

Bevacizumab plus Irinotecan,Fluorouracil,and Leucovorin for Metastatic Colorectal Cancer

Tumors are cellularly and molecularly heterogeneous, with subsets of undifferentiated cancer cells exhibiting stem cell-like features (CSCs). Epithelial to mesenchymal transitions (EMT) are transdifferentiation programs that are required for tissue morphogenesis during embryonic development. The EMT process can be regulated by a diverse array of cytokines and growth factors, such as transforming growth factor (TGF)-β, whose activities are dysregulated during malignant tumor progression. Thus, EMT induction in cancer cells results in the acquisition of invasive and metastatic properties. Recent reports indicate that the emergence of CSCs occurs in part as a result of EMT, for example, through cues from tumor stromal components. Recent evidence now indicates that EMT of tumor cells not only causes increased metastasis, but also contributes to drug resistance. In this review, we will provide potential mechanistic explanations for the association between EMT induction and the emergence of CSCs. We will also highlight recent studies implicating the function of TGF-β-regulated noncoding RNAs in driving EMT and promoting CSC self-renewal. Finally we will discuss how EMT and CSCs may contribute to drug resistance, as well as therapeutic strategies to overcome this clinically.

/pdf/emt-cancer-stem-cells-and-drug-resistance-an-emerging-axis-3ztp4dopjd.pdf

EMT, cancer stem cells and drug resistance: an emerging axis of evil in the war on cancer

Rapid improvements in sequencing and array-based platforms are resulting in a flood of diverse genome-wide data, including data from exome and whole-genome sequencing, epigenetic surveys, expression profiling of coding and noncoding RNAs, single nucleotide polymorphism (SNP) and copy number profiling, and functional assays. Analysis of these large, diverse data sets holds the promise of a more comprehensive understanding of the genome and its relation to human disease. Experienced and knowledgeable human review is an essential component of this process, complementing computational approaches. This calls for efficient and intuitive visualization tools able to scale to very large data sets and to flexibly integrate multiple data types, including clinical data. However, the sheer volume and scope of data pose a significant challenge to the development of such tools.

Integrative Genomics Viewer

Maximum use of organs from a single donor is mandatory as a result of the current organ shortage. In combined liver and pancreas allograft retrieval, it is vital that one remember the variability in the anatomy of vessels. Based on our experience, we describe a new technique of dividing the celiac trunk horizontally with subsequent arterial reconstruction, depending on the anatomical situation. Vascular division of the grafts can be performed either in situ or in an ex situ fashion in cases where cardiovascular function has deteriorated.

Standardized combined pancreas and liver explantation

OBJECTIVE
Infection of pancreatic necrosis in necrotizing pancreatitis increases the lethality of patients with acute pancreatitis. To examine mechanisms underlying this clinical observation, we developed and tested a model, in which primary infection of necrosis is achieved in taurocholate-induced pancreatitis in mice.

METHODS
Sterile necrosis of acute necrotizing pancreatitis was induced by retrograde injection of 4% taurocholate into the common bile duct of Balb/c mice. Primary infection of pancreatic necrosis was induced by coinjecting 10 colony-forming units of Escherichia coli. Animals were killed after 6, 12, 24, 48, and 120 hours, and pancreatic damage and pancreatitis-associated systemic inflammatory response were assessed.

RESULTS
Mice with pancreatic acinar cell necrosis had an increased bacterial concentration in all tissues and showed sustained bacteremia. Acute pancreatitis was induced only by coinjection of taurocholate and not by bacterial infection alone. Infection of pancreatic necrosis increased pancreatic damage and the pulmonary vascular leak. Serum glucose concentrations serving as a parameter of hepatic function were reduced in mice with infected pancreatic necrosis.

CONCLUSIONS
Primary infection of pancreatic necrosis with E. coli increases both pancreatic damage and pulmonary and hepatic complications in acute necrotizing pancreatitis in mice.

Infected pancreatic necrosis increases the severity of experimental necrotizing pancreatitis in mice.

Purpose: This investigation focuses on the physiological characteristics of gene transcription of intestinal tissue following anastomosis formation. <

Searching for the Molecular Benchmark of Physiological Intestinal Anastomotic Healing in Rats: An Experimental Study

Die dynamische Grazilisplastik (DGP) und der Acticon™Neosphincter („artificial bowel sphincter“, ABS) sind die zwei klinisch am besten etablierten Verfahren, die bei Patienten mit hochgradiger Stuhlinkontinenz am Ende der therapeutischen Moglichkeiten stehen. Neueingefuhrte Systeme wie der Prosthetic Anal Sphincter oder das A.M.I. Softanalband befinden sich noch in der klinischen Evaluierung. In vorliegender Ubersichtsarbeit wurden insgesamt 1510 Patienten aus 52 Studien zur DGP (n=29) und ABS (n=23) analysiert und die Studien nach den Oxford EBM-Kriterien evaluiert. Nur 3 Arbeiten zeigten einen Evidenzgrad von ≤3b auf. Des weiteren wurden die Ergebnisse nach Komplikationsraten analysiert und statistisch ausgewertet. Beide Verfahren zeigen postoperativ signifikante Verbesserungen der Kontinenz-Scores p<0,001, mit einem Vorteil fur den ABS. Dem stehen hohe Infektions- (21,74% ABS vs. 35,1% DGP) und Revisionsraten (37,53% ABS vs. 40,64% DGP) gegenuber, bei einer deutlich hoheren Explantationsrate des ABS (30% ABS vs. 18% DGP). Eine therapeutische Empfehlung kann anhand der wenig evidenten Datenlage nicht ausgesprochen werden. Die Therapie sollte in spezialisierten Zentren durchgefuhrt werden und unterliegt gerade in Anbetracht der Systemkosten einer hohen Patientenselektion.

Schließmuskelprothese vs. Ersatzmuskelplastik bei hochgradiger Stuhlinkontinenz

Background Fecal incontinence (FI) is a major part of illness and physical discomfort in the general population. Since the 1990s, sacral nerve stimulation has been well established in the treatment of neurogenic FI. The precise placement of the electrode is crucial for the success of the procedure. Eighty percent of the patients benefit from permanent treatment, but in 10–20% of the patients tested electrode placement proves impossible due to anatomical variations of the sacral foramina. In this study, we describe the technical requirements and a new method of electrode placement with reference to the anatomical (bone) landmarks in an animal model.



Methods  With a small endoscope (Verres needle), we accessed the perirectal space to identify the nervous structures. A stimulated sphincter EMG was obtained for the experimental animals and muscle action potential (MAP/M-wave), latency time [ms], and the amplitude of the motor response [μV] were recorded. Electrodes were placed, the animals killed and dissected leaving the pelvic cavity untouched. The specimens were examined in a magnetic resonance scanner and in a multi-slice computed tomography scanner to detect the electrode material and possible surgical complications. After that the specimens were dissected.



Key Results  In all eight cases in the four animals tested, we were able to stimulate the sacral nerve as demonstrated by the EMG findings. No major surgical complications were observed for the procedure.



Conclusions & Inferences  Endoscopic sacral nerve root stimulation is a safe and effective method for delivering stimulation material in the pelvis of the sheep. It is a promising procedure to be tested in humans.

Ulrich T. Hopt

Papers

Standardized combined pancreas and liver explantation

Infected pancreatic necrosis increases the severity of experimental necrotizing pancreatitis in mice.

Searching for the Molecular Benchmark of Physiological Intestinal Anastomotic Healing in Rats: An Experimental Study

Schließmuskelprothese vs. Ersatzmuskelplastik bei hochgradiger Stuhlinkontinenz

New selective endoscopic sacral nerve root stimulation – an advance in the treatment of fecal incontinence