Bile secretory function in the obese Zucker rat: evidence of cholestasis and altered canalicular transport function.

Background: Obese Zucker rats (ZR) have been used as an experimental model for non-alcoholic fatty liver disease and are particularly susceptible to various types of liver injury. Bile secretory function has not been assessed in ZR.

Aim: To study bile secretion and expression of the main hepatobiliary transporters in ZR.

[Outpatient laparoscopic cholecystectomy. Experience in 357 patients].

Background: Laparoscopic cholecystectomy (LC) is a widely used technique in the treatment of gallstone disease. Outpatient laparoscopic cholecystectomy (OLC) is a cost/effective and safe procedure in selected patients.

Aim: A pilot program of OLC was conducted in a Chilean Public Hospital to evaluate the feasibility and results, including and patients' satisfaction using OLC.

From blood to bile: recent advances in hepatobiliary transport.

Transport of endogenous and exogenous substances from blood to bile is an essential function of the liver. In the last decade a still growing number of specific transport proteins present at the sinusoidal and canalicular membrane domains of hepatocytes and cholangiocytes have been cloned and functionally characterized. Studies assessing the molecular expression and function of these hepatobiliary transport proteins under different experimental conditions has helped to define the adaptive responses of hepatocytes to certain physiological states and to cholestatic liver injury and to a better understanding of the physiology of bile formation and of the pathophysiology of certain cholestatic diseases.

Molecular aspects of bile formation and cholestasis.

Recent insights into the cellular and molecular mechanisms that control the function and regulation of hepatobiliary transport have led to a greater understanding of the physiological significance of bile secretion. Individual carriers for bile acids and other organic anions in both liver and intestine have now been cloned from several species. In addition, complex networks of signals that regulate key enzymes and membrane transporters located in cells that participate in the metabolism or transport of biliary constituents are being unraveled.

Hepatic overexpression of caveolins increases bile salt secretion in mice.

Caveolins are cholesterol-binding proteins involved in the regulation of several intracellular processes, including cholesterol transport. Because hepatocytes express caveolin-1 and caveolin-2, these proteins might modulate hepatic lipid metabolism and biliary lipid secretion. Our aim was to investigate the potential physiologic role of caveolins in hepatic cholesterol and bile salt (BS) metabolism and transport using adenoviral gene transfer.

Bile secretory function after warm hepatic ischemia-reperfusion injury in the rat.

Hepatic ischemia-reperfusion (I-R) injury frequently is associated with cholestasis. However, the underlying mechanisms are not fully understood. The aim of the study is to assess bile secretory function in vivo in rats subjected to warm lobar hepatic ischemia at different times during reperfusion.

Down-regulation of the Na+/taurocholate cotransporting polypeptide during pregnancy in the rat.

Background: Experimental studies have shown decreased bile acid (BA) uptake and reduced excretion of cholephilic compounds in pregnant rodents.

Aim: To assess the expression and function of the main BA importer, the Na(+)/taurocholate cotransporting polypeptide (Ntcp) in pregnant rats.

Methods: BA uptake and Ntcp expression were studied in control and timed-pregnant rats in late gestation.

Saccharomyces cerevisiae fungemia after Saccharomyces boulardii treatment in immunocompromised patients.

Saccharomyces cerevisiae is widely used as a probiotic compound. Clinical data suggest that this agent is safe and effective. We report two cases of fungemia caused by S.

[Identification of molecular defects in liver diseases. Recent advances].

Recent molecular studies have resulted in the identification of genetic alterations underlying several hereditary disorders of the liver. Cloning of disease genes are increasing our understanding of the basic defects in liver diseases. This review focuses on selected inherited liver diseases such as hyperbilirubinemic syndromes, hemochromatosis, Wilson disease and genetic cholestatic syndromes and illustrate the knowledge gained on these disorders from molecular studies.

[Molecular medicine: present and future].

The genetic background of individuals is recognized as an important clue in the analysis of classical hereditary and multifactorial acquired diseases. This new concept derives from the development and increasing use of molecular genetics in clinical medicine. The application of molecular biology techniques in biomedical investigation has encompassed the identification of the pathogenesis and etiology of diseases, prenatal diagnosis the production of new therapeutic agents, gene therapy and the development of pharmacogenetics.

The rat liver Na(+)/bile acid cotransporter. Importance of the cytoplasmic tail to function and plasma membrane targeting.

To understand the potential functions of the cytoplasmic tail of Na(+)/taurocholate cotransporter (Ntcp) and to determine the basolateral sorting mechanisms for this transporter, green fluorescent protein-fused wild type and mutant rat Ntcps were constructed and the transport properties and cellular localization were assessed in transfected COS 7 and Madin-Darby canine kidney (MDCK) cells. Truncation of the 56-amino acid cytoplasmic tail demonstrates that the cytoplasmic tail of rat Ntcp is involved membrane delivery of this protein in nonpolarized and polarized cells and removal of the tail does not affect the bile acid transport function of Ntcp. Using site-directed mutagenesis, two tyrosine residues, Tyr-321 and Tyr-307, in the cytoplasmic tail of Ntcp have been identified as important for the basolateral sorting of rat Ntcp in transfected MDCK cells.

Differential expression of canalicular membrane Ca2+/Mg(2+)-ecto-ATPase in estrogen-induced and obstructive cholestasis in the rat.

Extracellular adenosine triphosphate (ATP) may regulate hepatocyte and cholangiocyte functions, and under some conditions it may have deleterious effects on bile secretion and cause cholestasis. The canalicular membrane enzyme Ca2+/Mg2+-ecto-ATPase (ecto-ATPase) hydrolyzes ATP/adenosine diphosphate (ATP/ADP) and regulates hepatic extracellular ATP concentration. Changes in liver ecto-ATPase in estrogen-induced cholestasis were examined in male rats receiving 17alpha-ethinylestradiol (E groups) for 1, 3, or 5 days (5 mg/kg/day, sc) and compared with changes in rats subjected to obstructive cholestasis (O groups) for 1, 3, or 8 days.

[Hepatotoxicity by amoxicillin/clavulanic acid: case report].

We report a 72 years old diabetic male that, after the use of combined amoxicillin-clavulanic acid, developed pruritus and jaundice. Liver function tests showed serum total bilirubin of 4.3 mg/dL aspartate aminotransferase 140 U/l (normal < 35 U/L), alanine aminotransferase 470 U/L (normal < 40) and alkaline phosphatases of 400 U/L (normal < 100).

Ileal bile acid transport regulates bile acid pool, synthesis, and plasma cholesterol levels differently in cholesterol-fed rats and rabbits.

We investigated the effect of ileal bile acid transport on the regulation of classic and alternative bile acid synthesis in cholesterol-fed rats and rabbits. Bile acid pool sizes, fecal bile acid outputs (synthesis rates), and the activities of cholesterol 7alpha-hydroxylase (classic bile acid synthesis) and cholesterol 27-hydroxylase (alternative bile acid synthesis) were related to ileal bile acid transporter expression (ileal apical sodium-dependent bile acid transporter, ASBT). Plasma cholesterol levels rose 2.

[Molecular biology and medicine: basic concepts].

Through the advancements of molecular genetics, physicians and researchers are in an extraordinary period of study concerning the molecular basis of medicine. Molecular biology is making a tremendous impact on both diagnosis and treatment of diseases through the clinical introduction of molecular methods. These techniques, restricted for many years to basic biological research, include the polymerase chain reaction, DNA and protein electrophoresis, cloning of genes into viral or bacterial vectors and methods to rapidly sequence DNA and identify mutations.

Mutational analysis of influenza A virus nucleoprotein: identification of mutations that affect RNA replication.

The influenza A virus nucleoprotein (NP) is a multifunctional polypeptide which plays a pivotal role in virus replication. To get information on the domains and specific residues involved in the different NP activities, we describe here the preparation and characterization of 20 influenza A virus mutant NPs. The mutations, mostly single-amino-acid substitutions, were introduced in a cDNA copy of the A/Victoria/3/75 NP gene and, in most cases, affected residues located in regions that were highly conserved across the NPs of influenza A, B, and C viruses.

Molecular analysis of the adaptive response of intestinal bile acid transport after ileal resection in the rat.

Background & Aims: The apical sodium-dependent bile acid transporter is critical for intestinal reclamation of bile salts. Its expression and activity, along with the ileal lipid-binding protein, were studied before and after intestinal resection in the rat.

Methods: The effects of surgical resection and bile acid feeding on the expression of ileal bile acid transport were assessed by a combination of functional (taurocholate uptake into crude brush border membrane vesicles) and molecular assays (Northern and Western blotting).

Neither intestinal sequestration of bile acids nor common bile duct ligation modulate the expression and function of the rat ileal bile acid transporter.

The regulatory responses of bile acid (BA) transport in the terminal ileum to perturbations in BA homeostasis are complex, and conflicting results have been reported by different investigators. These studies were designed to examine the response of this system to a reduction in ileal bile salt concentrations at both a functional and molecular level. Common bile duct ligation (BDL) or feeding of a novel bile acid-binding compound, GT31-104HB, for 7 days were used to reduce ileal apical membrane bile salt flux.

Maternal cholestasis does not affect the ontogenic pattern of expression of the Na+/taurocholate cotransporting polypeptide (ntcp) in the fetal and neonatal rat liver.

To assess the effects of cholestasis during pregnancy on fetal and neonatal mRNA expression, protein mass, and function of the Na+/taurocholate cotransporting polypeptide (Ntcp), common bile duct ligation (BDL) was performed in pregnant rats on day 14 of pregnancy (maternal cholestasis [MC] group), and livers were harvested at days 20 and 21 of fetal life, as well as at days 4, 7, 14, 21, and 28 after birth. Sham-operated rats and their litters were used as controls. Ntcp steady-state mRNA levels, protein mass, and function were determined by Northern blotting, immunoblotting, and taurocholate (TC) transport studies in isolated short-term cultured hepatocytes, respectively.