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

1029 Mortality After Nonhepatic General Surgery in Patients with Concomitant Liver Cirrhosis: An Analysis of 138 Operations in the 2000s Using Child- and MELD Scores

BACKGROUND: Intra-abdominal hypertension (IAH) has a high prevalence among critically ill patients. It is increasingly recognised as a risk factor for poor outcome. PATIENTS / MATERIAL AND METHODS: A review of the literature including explicit management instructions was performed. We report the standardised techniques for intra-abdominal pressure (IAP) measurement as well as consensus definitions and treatment recommendations ranging from conservative measures to decompression laparotomy. RESULTS: The abdominal compartment syndrome (ACS) is defined as a sustained IAH > 20 mmHg accompanied by new organ dysfunctions. It occurs predominantly in surgical patients and is asso-ciat-ed with a poor outcome. Organ dysfunctions related to IAH mainly concern the kidneys and -respiratory system. The mechanism of action essentially is a perfusion deficit. Clinical judgement alone does not allow a valid estimate of intra-abdominal pressure. CONCLUSION: In patients at risk the IAP should be measured. In case of IAH conservative options for lowering the pressure are mandatory. Decompression laparotomy should be considered if conservative measures fail.

The Abdominal Compartment Syndrome - Relevance and Therapeutic Consequences

Introduction: Microcirculatory derangements caused by ischemia-reperfusion (I/R) injury play a pivotal role in acute pancreatitis and graft pancreatitis. The inducible isoform of heme oxygenase (HO-1) has been shown to decrease I/R injury influencing capillary perfusion in other organs. It was the aim of this study to evaluate the effect of HO-1 on pancreatic tissue after I/R. Methodology: Male Sprague-Dawley-rats (200–300 gms) were randomly assigned to four groups: 1) control group with sham-operation, 2) ischemia group: 1 h ischemia and 2 h reperfusion (I/R), 3) CoPP group: pretreatment with cobalt protoporphyrin (CoPP), an inducer of HO-1 (24 h before ischemia), 1 h ischemia and 2 h reperfusion, 4) SnPP group: pretreatment with CoPP (24 h before ischemia) and tin protoporphyrin (SnPP), an inhibitor of HO activity (5 min before ischemia), 1 h ischemia and 2 h reperfusion. Normothermic ischemia was induced by clipping the pancreas supplying arteries for 1 h. Functional capillary density (FCD) was measured by intravital epifluorescence microscopy after 2 h of reperfusion. Expression of HO-1 mRNA and HO enzyme activity were assessed by northern blot and activity assay. Results: Comparison of FCD showed a significant (p<0.05) decrease in the I/R group after 2 h of reperfusion (173 ± 25 cm/cm2) as compared to control (267 ± 25 cm/cm2). Preinduction with CoPP increased FCD after I/R to control values (257 ± 25cm/cm2). Inhibition of HO of preinduced animals by SnPP decreased FCD after I/R significantly (217 ± 26 cm/cm2) as compared to CoPP (MEAN±SD, ANOVA on ranks and Student-Newman-Keuls). An increase in HO-1 mRNA expression was shown by northern blot for the CoPP pretreated groups. HO activity was increased after preinduction but reduced in the SnPP treated group. Conclusion: We could show that exogenous preinduction of HO-1 plays a beneficial role in pancreatic microcirculatory derangements after normothermic I/R. Given this improvement on postischemic pancreatitis, we hypothesize that HO-1 could be of clinical relevance in pancreas transplantation and other forms of postischemic pancreatitis by decreasing acute I/R injury during the early onset of reperfusion.

Protektion der Mikrozirkulation bei postischämischer Pankreatitis durch die exogene Induktion der Hämoxygenase-1

Aim  The aim of the article is to investigate a new anastomotic technique compared with standardized intestinal anastomotic procedures. Materials and Methods  A total of 32 male Wistar rats were randomized to three groups. In the Experimental Group ( n  = 10), the new double 90 degrees inversely rotated anastomosis was used, in the End Group ( n  = 10) a single-layer end-to-end anastomosis, and in the Side Group ( n  = 12) a single-layer side-to-side anastomosis. All anastomoses were done using interrupted sutures. On postoperative day 4, rats were relaparotomized. Bursting pressure, hydroxyproline concentration, a semiquantitative adhesion score and two histological anastomotic healing scores (mucosal healing according to Chiu and overall anastomotic healing according to Verhofstad) were collected. Most data are presented as median (range). p Results  Anastomotic insufficiency occurred only in one rat of the Side Group. Median bursting pressure in the Experimental Group was 105 mm Hg (range = 72–161 mm Hg), significantly higher in the End Group (164 mm Hg; range = 99–210 mm Hg; p  = 0.021) and lower in the Side Group by trend (81 mm Hg; range = 59–122 mm Hg; p  = 0.093). Hydroxyproline concentration did not differ significantly in between the groups. The adhesion score was 2.5 (range = 1–3) in the Experimental Group, 2 (range = 1–2) in the End Group, but there were significantly more adhesions in the Side Group (range = 3–4); p  = 0.020 versus Experimental Group, p p  = 0.031 and p  = 0.002 in the Experimental Group, compared with the Side Group (mean = 1.729; SD = 0.682) and the End Group (mean = 1.571; SD = 0.612). Conclusion  The new anastomotic technique is feasible and did not show any relevant complication. Even though it was superior to the side-to-side anastomosis by trend with respect to functional stability, mucosal healing surprisingly showed the worst results. Classical end-to-end anastomosis still seems to be the best choice regarding structural and functional anastomotic stability.

Double 90 Degrees Counterrotated End-to-End-Anastomosis: An Experimental Study of an Intestinal Anastomosis Technique.

Exocrine pancreatic secretion is regulated by gastrointestinal hormone and the autonomic nervous system. The interaction of both systems is still unclear. In humans CCK mediated regulation of exocrine pancreatic secretion requires a cholinergic tonus. The CCK receptor is thought to be localized on the acinuscell and modulated by cholinergic neurons. Pancreas transplantation and percutaneous diversion of the pancreatic juice offers the opportunity to investigate pancreatic secretion under the condition of complete extrinsic denervation. In the present study the influence of denervation on exogene CCK stimulation and simultaneous cholinergic stimulation or suppression with atropine, respectively, was investigated. CCK stimulation alone showed a reduced, dose dependent increase in enzyme secretion. Simultaneous stimulation with bethachenol resulted in a 2-fold increased secretion. Atropine suppressed the low dose CCK effect completely. Whereas CCK at high doses caused a 1.5 fold increase despite atropine. After extrinsic denervation the human pancreas remains sensitive to exogene stimulation. The intrinsic system remains also intact and is sensitive to cholinergic stimulation. The extrinsic nervous system seems to be necessary for an adequate CCK response. The results are in line with the hypothesis that CCK receptors are only partly localized on the acinuscell, whereas the majority is localized in extrinsic cholinergic neurons.

Ulrich T. Hopt

Papers

1029 Mortality After Nonhepatic General Surgery in Patients with Concomitant Liver Cirrhosis: An Analysis of 138 Operations in the 2000s Using Child- and MELD Scores

The Abdominal Compartment Syndrome - Relevance and Therapeutic Consequences

Protektion der Mikrozirkulation bei postischämischer Pankreatitis durch die exogene Induktion der Hämoxygenase-1

Double 90 Degrees Counterrotated End-to-End-Anastomosis: An Experimental Study of an Intestinal Anastomosis Technique.

Influence of the extrinsic nervous system on exocrine pancreatic secretion in the human