A5101487347- Drug Transport and Resistance Mechanisms
- Pediatric Hepatobiliary Diseases and Treatments
- Hepatitis B Virus Studies
- Sarcoma Diagnosis and Treatment
- Liver Diseases and Immunity
- Congenital Heart Disease Studies
- Folate and B Vitamins Research
- Sulfur Compounds in Biology
- Polyamine Metabolism and Applications
- Congenital heart defects research
- Pharmacogenetics and Drug Metabolism
- Endoplasmic Reticulum Stress and Disease
- Cardiovascular Function and Risk Factors
- Amino Acid Enzymes and Metabolism
- Hormonal and reproductive studies
- Cholangiocarcinoma and Gallbladder Cancer Studies
- Skin and Cellular Biology Research
- Cardiomyopathy and Myosin Studies
- Pharmacological Effects and Toxicity Studies
- Metabolism and Genetic Disorders
- Muscle Physiology and Disorders
- Vascular anomalies and interventions
- Liver physiology and pathology
- Forensic Toxicology and Drug Analysis
- Thermoregulation and physiological responses
Hospital La Paz Institute for Health Research
2014-2016
Hospital Universitario La Paz
2003-2015
Tulane University
2013
Universidad de Granada
1985-1999
Consejo Superior de Investigaciones Científicas
1992-1997
Institut d'Investigacions Biomèdiques de Barcelona
1997
Instituto de Investigaciones Biomédicas Sols-Morreale
1994
The University of Texas Southwestern Medical Center
1994
Hospital Universitario Virgen de las Nieves
1993
Universidad Autónoma de Madrid
1992
Sirtuin1 (SIRT1) regulates central metabolic functions such as lipogenesis, protein synthesis, gluconeogenesis, and bile acid (BA) homeostasis through deacetylation. Here we describe that SIRT1 tightly controls the regenerative response of liver. We performed partial hepatectomy (PH) to transgenic mice overexpress (SIRT). SIRT showed increased mortality, impaired hepatocyte proliferation, BA accumulation, profuse liver injury after surgery. The damaging phenotype in correlated with farnesoid...
Severe bile salt export pump (BSEP) deficiency is a hereditary cholestatic condition that starts in infancy and leads to end-stage liver disease. Three children who underwent orthotopic transplantation for severe BSEP had post-transplantation episodes of dysfunction mimicked the original Remission all was achieved by intensifying immunosuppressive regimen. The phenotypic recurrence disease correlated with presence circulating high-titer antibodies against inhibit transport vitro. When...
<h3>Objective</h3> Progressive familial intrahepatic cholestasis type 3 (PFIC3) is a potentially lethal autosomal recessive liver disease associated with mutations in <i>ABCB4</i>, the gene encoding canalicular translocator of phosphatidylcholine MDR3. While some affected children benefit from ursodeoxycholic acid (UDCA) therapy, others evolve to end-stage disease. We aimed evaluate whether these different outcomes are related impact <i>ABCB4</i> mutations. <h3>Design</h3> Six PFIC3 were...
Farnesoid X receptor (FXR) is a transcription factor that controls bile acid homeostasis. The phenotype of Fxr null mice characterized by hypercholanaemia, impaired secretion acids and failure to thrive. Human disorders with these characteristics include FIC1 disease (caused mutations in ATP8B1, which encodes putative aminophospholipid translocase, FIC1, whose function handling unknown) salt export pump (BSEP) mutation ABCB11, BSEP, the primary canalicular pump). We investigated possibility...
Progressive familial intrahepatic cholestasis type 2 (PFIC2) results from recessive mutations in the adenosine triphosphate–binding cassette B11 gene, which encodes for bile salt export pump (BSEP). Liver transplantation (LT) is offered to PFIC2 patients with end-stage liver disease. Reports have described recurrent after transplantation, and this has been associated immunoglobulin G antibodies BSEP. High-titer anti-BSEP appear correlate episodes of cholestatic graft dysfunction. There no...
Prohibitin‐1 (PHB1) is an evolutionarily conserved pleiotropic protein that participates in diverse processes depending on its subcellular localization and interactome. Recent data have indicated a role for PHB1 the pathogenesis of obesity, cancer, inflammatory bowel disease, among others. Data presented here suggest also linked to cholestatic liver disease. Expression markedly reduced patients with primary biliary cirrhosis atresia or Alagille syndrome, two major pediatric conditions. In...
Multidrug resistance protein 3 (MDR3, ABCB4) is a hepatocellular membrane that mediates biliary secretion of phosphatidylcholine. Null mutations in ABCB4 gene give rise to severe early-onset cholestatic liver disease. We have previously shown the disease-associated p.G68R, p.G228R, p.D459H, and p.A934T resulted retention endoplasmic reticulum, thus failing target plasma membrane. In present study, we tested ability two compounds with chaperone-like activity, 4-phenylbutyrate curcumin, rescue...
A 3 kb cDNA coding for rat liver S ‐adenosylmethionine (AdoMet) synthetase has been isolated. The M r of the protein unequivocally determined by sequencing and enzyme purification on a thiopropyl‐Sepharose column. length mRNA 5′ non‐coding region defined primer‐extension analysis. cloned also used to detect in human liver.
The effects of glucocorticoids on the regulation rat liver S-adenosylmethionine synthetase were studied in vivo and two culture systems. Livers from adrenalectomized animals examined for enzyme activity, immunoreactive protein, messenger RNA (mRNA) content. All three parameters showed a similar trend, i.e. they decreased 3-fold after adrenalectomy increased over control values upon triamcinolone replacement. These results suggested that glucocorticoid hepatic was mediated at mRNA level....
Monoallelic defects in ABCB4, which encodes the canalicular floppase for phosphatidylcholine MDR3, have been encountered association with a variety of hepatobiliary disorders, particularly adult subjects. In this study, we examined presence heterozygous ABCB4 variants cohort children chronic cholestasis and assessed pathogenicity missense changes identified.Sixty-seven liver dysfunction were studied by sequencing multiplex ligation-dependent probe amplification analysis. The molecular...
Progressive familial intrahepatic cholestasis type 3 (PFIC-3) is a severe liver disorder associated with inherited dysfunction of multidrug resistance protein (MDR3/ABCB4), which functions as phospholipid floppase, translocating phosphatidylcholine from the inner to outer hemileaflet canalicular membrane hepatocytes. MDR3 deficiency results in disbalanced bile may damage luminal cells hepatobiliary system. We evaluated clinical, biochemical and histological improvement genetically proven...
Farnesoid X receptor (FXR) is a bile acid-sensing nuclear that controls acid homeostasis. It has been suggested downregulation of FXR contributes to the pathogenesis an inherited disorder secretion caused by mutations in ATP8B1. We have investigated relationship between ATP8B1 knockdown and human hepatoblastoma cell line HepG2. Transfection HepG2 cells with small interfering RNA (siRNA) duplexes led 60% reduction endogenous levels mRNA protein concomitant decrease content, as well...
A 26-year-old male presented with three weeks of jaundice after the self-initiation injectable anabolic steroid, Mastabol [Dromastanolone Di-Propionate (17 beta-Hydroxy-2alpha-methyl-5alpha-androstan-3one propionate)].He reported dark urine, light stools, and pruritus.He denied abdominal pain, intravenous drug use, intranasal cocaine, blood transfusions, newly placed tattoos, or sexually transmitted diseases.He used alcohol sparingly.Physical exam revealed deep scleral icterus.The liver was...
Abstract The tetralogy of Fallot was produced experimentally in the chick embryo by altering development conus and delaying disappearance conoventricular groove. experimental procedure used consisted placing a ligature or cerclage around proximal portion for 24 hr embryos Hamburger‐Hamilton stages 17–21, thus cardiac hemodynamics particularly clonal region. At same time prevented from aquiring its normal position owing to persistence As result, most frequently observed abnormality (50%)...
Classical cytotoxic treatment of rhabdomyosarcoma (RMS) is accompanied often by significant morbidity and poor response. The use agents may induce a multidrug resistance phenotype, which plays an important role in the sensitivity tumoral cells to drugs. Using actinomycin D, drug choice RMS, we induced TE.32.7 human RMS cell line. TE.32.7-DAC-resistant line exhibited cross-resistance vincristine doxorubicin showed mdr1/P-glycoprotein over-expression, suggesting that this mechanism was...
Thoracic duct cannulation was performed prior to exploratory laparotomy in 23 patients with obstructive jaundice caused by diverse factors. High flow of hemorrhagic lymph, usually under increased pressure, distinguished hepatic cirrhosis from those extrahepatic biliary obstruction and cholangiolitic hepatitis. Very low flows were observed only widespread malignancy involving the tract. Information concerning flow, composition thoracic lymph is helpful understanding distinguishing whether...