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- Grinberg, Marianna, et al.
(författare)
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Toxicogenomics directory of chemically exposed human hepatocytes
- 2014
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Ingår i: Archives of Toxicology. - : Springer Science and Business Media LLC. - 1432-0738 .- 0340-5761. ; 88:12, s. 2261-2287
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Tidskriftsartikel (refereegranskat)abstract
- A long-term goal of numerous research projects is to identify biomarkers for in vitro systems predicting toxicity in vivo. Often, transcriptomics data are used to identify candidates for further evaluation. However, a systematic directory summarizing key features of chemically influenced genes in human hepatocytes is not yet available. To bridge this gap, we used the Open TG-GATES database with Affymetrix files of cultivated human hepatocytes incubated with chemicals, further sets of gene array data with hepatocytes from human donors generated in this study, and publicly available genome-wide datasets of human liver tissue from patients with non-alcoholic steatohepatitis (NASH), cirrhosis, and hepatocellular cancer (HCC). After a curation procedure, expression data of 143 chemicals were included into a comprehensive biostatistical analysis. The results are summarized in the publicly available toxicotranscriptomics directory (http://wiki.toxbank.net/toxicogenomics-map/) which provides information for all genes whether they are up- or downregulated by chemicals and, if yes, by which compounds. The directory also informs about the following key features of chemically influenced genes: (1) Stereotypical stress response. When chemicals induce strong expression alterations, this usually includes a complex but highly reproducible pattern named 'stereotypical response.' On the other hand, more specific expression responses exist that are induced only by individual compounds or small numbers of compounds. The directory differentiates if the gene is part of the stereotypical stress response or if it represents a more specific reaction. (2) Liver disease-associated genes. Approximately 20 % of the genes influenced by chemicals are up- or downregulated, also in liver disease. Liver disease genes deregulated in cirrhosis, HCC, and NASH that overlap with genes of the aforementioned stereotypical chemical stress response include CYP3A7, normally expressed in fetal liver; the phase II metabolizing enzyme SULT1C2; ALDH8A1, known to generate the ligand of RXR, one of the master regulators of gene expression in the liver; and several genes involved in normal liver functions: CPS1, PCK1, SLC2A2, CYP8B1, CYP4A11, ABCA8, and ADH4. (3) Unstable baseline genes. The process of isolating and the cultivation of hepatocytes was sufficient to induce some stress leading to alterations in the expression of genes, the so-called unstable baseline genes. (4) Biological function. Although more than 2,000 genes are transcriptionally influenced by chemicals, they can be assigned to a relatively small group of biological functions, including energy and lipid metabolism, inflammation and immune response, protein modification, endogenous and xenobiotic metabolism, cytoskeletal organization, stress response, and DNA repair. In conclusion, the introduced toxicotranscriptomics directory offers a basis for a rationale choice of candidate genes for biomarker evaluation studies and represents an easy to use source of background information on chemically influenced genes.
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- Mantel, H. T. J., et al.
(författare)
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Strict Selection Alone of Patients Undergoing Liver Transplantation for Hilar Cholangiocarcinoma Is Associated with Improved Survival
- 2016
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Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 11:6
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Tidskriftsartikel (refereegranskat)abstract
- Liver transplantation for hilar cholangiocarcinoma (hCCA) has regained attention since the Mayo Clinic reported their favorable results with the use of a neo-adjuvant chemoradiation protocol. However, debate remains whether the success of the protocol should be attributed to the neo-adjuvant therapy or to the strict selection criteria that are being applied. The aim of this study was to investigate the value of patient selection alone on the outcome of liver transplantation for hCCA. In this retrospective study, patients that were transplanted for hCCA between 1990 and 2010 in Europe were identified using the European Liver Transplant Registry (ELTR). Twenty-one centers reported 173 patients (69%) of a total of 249 patients in the ELTR. Twenty-six patients were wrongly coded, resulting in a study group of 147 patients. We identified 28 patients (19%) who met the strict selection criteria of the Mayo Clinic protocol, but had not undergone neo-adjuvant chemoradiation therapy. Five-year survival in this subgroup was 59%, which is comparable to patients with pretreatment pathological confirmed hCCA that were transplanted after completion of the chemoradiation protocol at the Mayo Clinic. In conclusion, although the results should be cautiously interpreted, this study suggests that with strict selection alone, improved survival after transplantation can be achieved, approaching the Mayo Clinic experience.
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- Rayes, N, et al.
(författare)
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Early enteral supply of fiber and Lactobacilli versus conventional nutrition: A controlled trial in patients with major abdominal surgery
- 2002
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Ingår i: Nutrition. - 1873-1244. ; 18:7-8, s. 609-615
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Early enteral nutrition with fiber-containing solutions plus Lactobacillus may reduce bacterial translocation and minimize the incidence of infections after surgery. METHODS: In a prospective, randomized trial in three groups (n = 30/group) of patients after major abdominal surgery, we compared our previous regimen with parenteral nutrition or fiber-free enteral nutrition (group A) with enteral fiber-containing nutrition with living Lactobacillus (group B) and heat-killed Lactobacillus (group C). The main endpoint was the development of bacterial infection. Other analyzed parameters were the durations of antibiotic therapy and hospital stay. non-infectious complications. side effects of the nutrition, and onset of bowel movement. Routine parameters, nutritional parameters, and cellular immune status in the blood were measured preoperatively and on 1, 5, and 10 d postoperatively. RESULTS: The incidence of infections was significantly lower (P = 0.01) in groups B and C with enteral nutrition containing fibers (10% each) than in group A (30%). Patients in group B received antibiotics for a significantly shorter time (P = 0.04) than did the patients in groups A and C. The length of hospital stay and the incidence of non-infectious complications did not differ significantly. Fibers and lactobacilli were well tolerated. There were no general benefits of living Lactobacillus as opposed to heat-killed Lactobacillus in the entire study population, but benefits were observed in the patients with gastric and pancreas resections, although no statistical analysis was done due to their small numbers. CONCLUSIONS: Early enteral nutrition with fiber-containing solutions reduced the rate of postoperative infections in comparison with parenteral nutrition and fiber-free enteral formula. Addition of living Lactobacillus seemed to increase the benefits in patients with gastric and pancreatic resections.
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- Rayes, N, et al.
(författare)
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Early enteral supply of lactobacillus and fiber versus selective bowel decontamination: A controlled trial in liver transplant recipients
- 2002
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Ingår i: Transplantation. - 1534-6080. ; 74:1, s. 123-128
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Tidskriftsartikel (refereegranskat)abstract
- Background. Early enteral nutrition with solutions containing prebiotics (fiber) and probiotics (Lactobacillus) is suggested to reduce bacterial translocation and minimize the incidence of infections after liver transplantation. Methods. In a prospective, randomized placebo-controlled trial consisting of 95 patients, we compared the incidence of postoperative infections and other complications after liver transplantation among three different groups, all supplied with early enteral nutrition: (a) standard formula plus selective bowel decontamination (SBD), (b) fiber-containing formula plus living Lactobacillus plantarum 299, and (c) fiber-containing formula plus heat-killed L plantarum 299. Results. The groups were comparable regarding preoperative American Society of Anesthesiologists classification, Child-Pugh classification of cirrhosis, operative data, and degree of immunosuppression. The patients who received living lactobacilli plus fiber developed significantly fewer bacterial infections (1370) than the patients with SBD (48%). The incidence of infections was 34% in the group with inactivated lactobacilli and fiber. Cholangitis and pneumonia were the leading infections and enterococci the most commonly isolated bacteria. In the living Lactobacillus group, the mean duration of antibiotic therapy, the mean total hospital stay, and the stay on the intensive care unit were also shorter than in the groups with inactivated lactobacilli and fiber as well as with SBD. However, these differences did not reach statistical significance. Conclusions. Early enteral nutrition with fiber-containing solutions and living L plantarum 299 was well tolerated. It decreases markedly the rate of postoperative infections both in comparison with inactivated L plantarum 299 and significantly with SBD and a standard enteral nutrition formula. As it is a cheap and feasible alternative to SBD, further studies should evaluate whether this ecoimmunonutrition should be already started while patients are on the waiting list for transplantation.
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- Rayes, N, et al.
(författare)
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Einfluss von Probiotika und Ballaststoffen auf die Inzidenz bakterieller Infektionen nach viszeralchirurgischen Eingriffen - Ergebnisse einer prospektiven Studie
- 2002
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Ingår i: Zeitschrift für Gastroenterologie. - : Georg Thieme Verlag KG. - 0044-2771 .- 1439-7803. ; 40:10, s. 869-876
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Early enteral nutrition with fibre and probiotics has been effective in preventing bacterial translocation and is therefore expected to reduce the incidence of postoperative bacterial infections. Patients and methods: In a prospective randomized trial including 172 patients following major abdominal surgery or liver transplantation, the incidence of bacterial infections was compared in patients receiving either a) conventional parenteral or enteral nutrition, b) enteral nutrition with fibre and lactobacillus plantarum 299 or c) enteral nutrition with fibre and heat inactivated lactobacilli (placebo). Liver transplant recipients were also treated with selective bowel decontamination (SBD). Routine laboratory parameters, nutritional parameters and the cellular immune status were measured preoperatively and on postoperative days 1, 5 and 10. Results: Patients were comparable regarding preoperative ASA-classification, Child-Pugh classification of cirrhosis, operative data and immunosuppression. The incidence of bacterial infections after liver, gastric oder pancreas resection was 31% in the conventional group a) compared to 4% in the lactobacillus-group b) and 13% in the placebo-group c). In the analysis of 95 liver transplant recipients, 13% group b)-patients developed infections compared to 48% group a)-patients and 34% group c)-patients. The difference between groups a) and b) was statistically significant in both cases. In addition, the duration of antibiotic therapy was significantly shorter in the lactobacillus-group. Cholangitis and pneumonia were the most frequent infections and enterococci the most frequently isolated bacteria. Fibre and lactobacilli were well tolerated in most cases. Conclusion: Fibre and probiotics could lower the incidence of bacterial infections following major abdominal surgery in comparison to conventional nutrition with or without SBD. With this new concept, costs can be reduced by shortening the duration of antibiotic therapy and sparing SBD.
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