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| 1 | Arachidyl amido cholanoic acid improves liver glucose and lipid homeostasis in nonalcoholic steatohepatitis via AMPK and mTOR regulation显示文摘BACKGROUND Arachidyl amido cholanoic acid(Aramchol)is a potent downregulator of hepatic stearoyl-CoA desaturase 1(SCD1)protein expression that reduces liver triglycerides and fibrosis in animal models of steatohepatitis.In a phase IIb clinical trial in patients with nonalcoholic steatohepatitis(NASH),52 wk of treatment with Aramchol reduced blood levels of glycated hemoglobin A1c,an indicator of glycemic control.AIM To assess lipid and glucose metabolism in mouse hepatocytes and in a NASH mouse model[induced with a 0.1%methionine and choline deficient diet(0.1MCD)]after treatment with Aramchol.METHODS Isolated primary mouse hepatocytes were incubated with 20μmol/L Aramchol or vehicle for 48 h.Subsequently,analyses were performed including Western blot,proteomics by mass spectrometry,and fluxomic analysis with 13C-uniformly labeled glucose.For the in vivo part of the study,male C57BL/6J mice were randomly fed a control or 0.1MCD for 4 wk and received 1 or 5 mg/kg/d Aramchol or vehicle by intragastric gavage for the last 2 wk.Liver metabolomics were assessed using ultra-high-performance liquid chromatography-time of flight-MS for the determination of glucose metabolism-related metabolites.RESULTS Combination of proteomics and Western blot analyses showed increased AMPK activity while the activity of nutrient sensor mTORC1 was decreased by Aramchol in hepatocytes.This translated into changes in the content of their downstream targets including proteins involved in fatty acid(FA)synthesis and oxidation[PACCα/β(S79),SCD1,CPT1A/B,HADHA,and HADHB],oxidative phosphorylation(NDUFA9,NDUFB11,NDUFS1,NDUFV1,ETFDH,and UQCRC2),tricarboxylic acid(TCA)cycle(MDH2,SUCLA2,and SUCLG2),and ribosome(P-p70S6K[T389]and P-S6[S235/S236]).Flux experiments with 13Cuniformely labeled glucose showed that TCA cycle cataplerosis was reduced by Aramchol in hepatocytes,as indicated by the increase in the number of rounds that malate remained in the TCA cycle.Finally,liver metabolomic analysis showed that glucose homeostasis was improved by Aramchol in 0.1MCD fed mice in a dose-dependent manner,showing normalization of glucose,G6P,F6P,UDP-glucose,and Rbl5P/Xyl5P.CONCLUSION Aramchol exerts its effect on glucose and lipid metabolism in NASH through activation of AMPK and inhibition of mTORC1,which in turn activate FAβ-oxidation and oxidative phosphorylation. | David Fernández-Ramos Fernando Lopitz-Otsoa Laura Delacruz-Villar Jon Bilbao Martina Pagano Laura Mosca Maider Bizkarguenaga Marina Serrano-Macia Mikel Azkargorta Marta Iruarrizaga-Lejarreta Jesús Sot Darya Tsvirkun Sebastiaan Martijn van Liempd Felix M Goni Cristina Alonso María Luz Martínez-Chantar Felix Elortza Liat Hayardeny Shelly C Lu JoséM Mato | 2020 | World Journal of Gastroenterology2020,26,34: | 5 |
| 2 | Long-term follow-up study of gastroduodenal lesions after radioembolization of hepatic tumors显示文摘AIM:To evaluate the long-term natural history of the gastroduodenal lesions secondary to extrahepatic embolization with Ytrium 90(90 Y) spheres.METHODS:From September 2003 to January 2012,379 procedures of liver radioembolization(RE) using resin microspheres loaded with 90 Y were performed in our center.We have retrospectively compiled the data from 379 RE procedures performed in our center.We report a comprehensive clinical,analytical,endoscopic and histologic long-term follow-up of a series of patients who developed gastroduodenal lesions after the treatment.RESULTS:Six patients(1.5%) developed gastrointestinal symptoms and had gastrointestinal lesions as shown by upper endoscopy in the next 12 wk after RE.The mean time between RE and the appearance of symptoms was 5 wk.Only one patient required endoscopic and surgical treatment.The incidence of gastrointestinal ulcerations was 3.75%(3/80) when only planar images were used for the pre-treatment evaluation.It was reduced to 1%(3/299) when singlephoton emission computed tomography(SPECT) images were also performed.The symptoms that lasted for a longer time were nausea and vomiting,until 25 mo after the treatment.CONCLUSION:All patients were free from severe symptoms at the end of follow-up.The routine use of SPECT has decreased the incidence of gastrointestinal lesions due to unintended deployment of 90 Y particles. | Iago Rodríguez-Lago Cristina Carretero Maite Herráiz José C Subtil Maite Betés Macarena Rodríguez-Fraile Jesús J Sola José I Bilbao Miguel Muoz-Navas Bruno Sangro | 2013 | World Journal of Gastroenterology2013,19,19: | 2 |
| 3 | Drying kinetics of apple cylinders under combined hot air-microwave dehydration显示文摘 | Ana Andres Cristina Bilbao Pedro Fito | 2004 | Journal of Food Engineering2004,63,1: | 1 |
| 4 | Microsatellite instability predicts clinical outcome in radiationtreated endometrioid endometrial cancer 显示文摘 | CRISTINA BILBAO PEDRO CARLOS LARA RAQUEL RAMIREZ | 2010 | Int J Radiat Oncol Biol Phyicss2010,76,1: | 1 |
| 5 | Multiple indications for everolimus after liver transplantation in current clinical practice显示文摘AIM: To assess our experience with the use and management of everolimus-based regimens post-liver transplantation and to redefine the potential role of this drug in current clinical practice.METHODS: From October 1988 to December 2012, 1023 liver transplantations were performed in 955 patients in our Unit. Seventy-four patients(7.74%) received immunosuppression with everolimus at some time post-transplantation. Demographic characteristics, everolimus indication, time elapsed from transplantation to the introduction of everolimus, doses and levels administered, efficacy, side effects, discontinuation andpost-conversion survival were analyzed. RESULTS: Mean age at the time of conversion to everolimus was 57.7 ± 10 years. Indications for conversion were: refractory rejection 31.1%, extended hepatocellular carcinoma in explanted liver 19%, post-transplant hepatocellular carcinoma recurrence 8.1%, de novo tumour 17.6%, renal insufficiency 8.1%, severe neurotoxicity 10.8%, and others 5.4%. Median time from transplantation to introduction of everolimus was 6 mo(range: 0.10-192). Mean follow-up post-conversion was 22 ± 19 mo(range: 0.50-74). The event for which the drug was indicated was resolved in 60.8% of patients, with the best results in cases of refractory rejection, renal insufficiency and neurotoxicity. Results in patients with cancer were similar to those of a historical cohort treated with other immunosuppressants. The main side effects were dyslipidemia and infections. Post-conversion acute rejection occurred in 14.9% of cases. The drug was discontinued in 28.4% of patients.CONCLUSION: Everolimus at low doses in combination with tacrolimus is a safe immunosuppressant with multiple early and late indications post-liver transplantation. | Itxarone Bilbao Cristina Dopazo Jose Lazaro Lluis Castells Mireia Caralt Gonzalo Sapisochin Ramon Charco | 2014 | World Journal of Transplantation2014,4,2: | 1 |
| 6 | Drying kinetics of apple cylinders under combined hot air - microwave dehydration 显示文摘 | Ana Andres Cristina Bilbao Pedro Fito | 2004 | Journal of Food Engineering2004,63,: | 1 |
| 7 | Drying kinetics of apple cylinders under combined hot air-microwave dehydration显示文摘 | Ana Andres Cristina Bilbao Pedro Fito | 2004 | Journal of Food Engineering2004,63,: | 1 |
| 8 | Single HCC in Cirrhotic Patients: Liver Resection or Liver Transplantation? Long-term Outcome According to an Intention-to-treat Basis显示文摘 | Gonzalo Sapisochin Lluis Castells Cristina Dopazo Itxarone Bilbao Beatriz Minguez Jose Luis Lázaro Helena Allende Joaquin Balsells Mireia Caralt Ramón Charco | 2013 | Annals of Surgical Oncology2013,,4: | 1 |
| 9 | Drying kinetics of apple cylinders under combined hot air-microwave dehydration显示文摘 | Ana Andr s Cristina Bilbao Pedro Fito | 2003 | Journal of Food Engineering2003,63,: | 1 |
| 10 | Drying kinetics of apple cylinders under eomhined hot air-microwave dehydration 显示文摘 | Andres Ana Bilbao Cristina Fito Pedro | 2004 | Journal of Food Engineering2004,63,1: | 1 |
| 11 | Isolated bilateral Tapia's syndrome after liver transplantation: A case report and review of the literature显示文摘AIM To describe one case of bilateral Tapia's syndrome in a liver transplanted patient and to review the literature.METHODS We report a case of bilateral Tapia's syndrome in a 50-year-old man with a history of human immunodeficiency virus and hepatitis C virus child. A liver cirrhosis and a bi-nodular hepatocellular carcinoma, who underwent liver transplantation after general anesthesia under orotracheal intubation. Uneventful extubation was performed in the intensive care unit during the following hours. On postoperative day(POD) 3, he required urgent re-laparotomy due to perihepatic hematoma complicated with respiratory gram negative bacilli infection. On POD 13, patient was extubated, but required immediate re-intubation due to severe respiratory failure. At the following day a third weaning failure occurred, requiring the performance of a percutaneous tracheostomy. Five days later, the patient was taken off mechanical ventilation and severe dysphagia, sialorrea and aphonia revealed. A computerized tomography and a magnetic resonance imaging of the head and neck excluded central nervous injury. A stroboscopy showed bilateral paralysis of vocal cords and tongue and a diagnosis of bilateral Tapia's syndrome was performed. With conservative management, including a prompt establishment of a speech and swallowing rehabilitation program, the patient achieved full recovery within four months after liver transplantation. We carried out MEDLINE search for the term Tapia's syndrome. The inclusion criteria had no restriction by language or year but must provide sufficientavailable data to exclude duplicity. We described the clinical evolution of the patients, focusing on author, year of publication, age, sex, preceding problem, history of endotracheal intubation, unilateral or bilateral presentation, diagnostic procedures, type of treatment, follow-up, and outcome.RESULTS Several authors mentioned the existence of around 70 cases, however only 54 fulfilled our inclusion criteria. We found only five published studies of bilateral Tapia's syndrome. However this is the first case reported in the literature in a liver transplanted patient. Most patients were male and young and the majority of cases appeared as a complication of airway manipulation after any type of surgery, closely related to the positioning of the head during the procedure. The diagnosis was founded on a rapid suspicion, a complete head and neck neurological examination and a computed tomography and or a magnetic resonance imaging of the brain and neck to establish the origin of central or peripheral type of Tapia's syndrome and also the nature of the lesion, ischemia, abscess formation, tumor or hemorrhage. Apart from corticosteroids and anti- inflammatory therapy, the key of the treatment was an intensive and multidisciplinary speech and swallowing rehabilitation. Most studies have emphasized that the recovery is usually completed within four to six months. CONCLUSION Tapia's syndrome is almost always a transient complication after airway manipulation. Although bilateral Tapia's syndrome after general anesthesia is exceptionally rare, this complication should be recognized in patients reporting respiratory obstruction with complete dysphagia and dysarthria after prolonged intubation. Both anesthesiologists and surgeons should be aware of the importance of its preventing measurements, prompt diagnosis and intensive speech and swallowing rehabilitation program. | Itxarone Bilbao Cristina Dopazo Mireia Caralt Lluis Castells Elisabeth Pando Amaia Gantxegi Ramón Charco | 2016 | World Journal of Hepatology2016,8,36: | 0 |