[Management of severe ulcerative colitis: An up-to-date].

Ulcerative Colitis (UC) is a chronic inflammatory disease involving the colon, with alternating periods of remission and activity. Exacerbations can be severe and associated with complications and mortality. Diagnosis of severe UC is based on clinical, biochemical and endoscopic variables.

Prevalence of lactose intolerance in Chile: a double-blind placebo study.

Background And Study Aims: Lactase non-persistence (LNP), or primary hypolactasia, is a genetic condition that mediates lactose malabsorption and can cause lactose intolerance. Here we report the prevalence of lactose intolerance in a double-blind placebo study.

Methods: The LCT C>T-13910 variant was genotyped by RT-PCR in 121 volunteers and lactose malabsorption was assessed using the hydrogen breath test (HBT) after consuming 25 g of lactose.

[Phenotype and genotype of thiopurine methyltransferase in Chilean individuals].

Background: Thiopurines (azathioprine and 6-mercaptopurine) are highly effective medications but with potential adverse effects. Thiopurine methyltransferase (TMPT) is the key enzyme in their pharmacokinetics and is genetically regulated. A low activity of TPMT is associated with myelotoxicity.

The European lactase persistence genotype determines the lactase persistence state and correlates with gastrointestinal symptoms in the Hispanic and Amerindian Chilean population: a case-control and population-based study.

Background: The lactase persistent (LP) or lactase non-persistent (LNP) state in European adults is genetically determined by a single nucleotide polymorphism (SNP) located 13.9 kb upstream of the lactase (LCT) gene, known as LCT C>T(-13910) (rs4988235). The LNP condition leads to an inability to digest the milk sugar lactose leading to gastrointestinal symptoms and can affect nutrient and calcium intake in certain populations.

Measuring students' perceptions of the educational climate of the new curriculum at the Pontificia Universidad Católica de Chile: performance of the Spanish translation of the Dundee Ready Education Environment Measure (DREEM).

Context: During the last decade a major curriculum reform was carried out at the Pontificia Universidad Católica de Chile Medical School. The process included changes in curriculum development, staff development and in the infrastructure. However, it is not known how students perceived the climate of their education within the new model.

Bucillamine induces glutathione biosynthesis via activation of the transcription factor Nrf2.

The properties of bucillamine, a synthetic antioxidant, have been attributed mainly to the donation of thiol groups to glutathione (GSH). We recently demonstrated that glutamate-cysteine ligase catalytic subunit (GCLC), the rate-limiting enzyme of GSH biosynthesis, and the multidrug-resistance-associated protein 2 (Mrp2/MRP2) are coordinately induced in response to xenobiotic through the activation of the antioxidant-response element (ARE) by nuclear factor-erythroid 2 p45-related factor (Nrf2). We tested the hypothesis that bucillamine and its oxidized metabolite SA 981 also activate the Nrf2 pathway, thereby increasing glutathione biosynthesis in human HepG2 and murine Hepa 1-6 hepatoma cell lines, through the induction of the GCLC enzyme as well as the Mrp2/MRP2 transporter, which mediates the excretion of glutathione and its conjugates from hepatocytes.

Role of Nrf2 in the regulation of the Mrp2 (ABCC2) gene.

The Nrf2 (nuclear factor-erythroid 2 p45-related factor 2) transcription factor regulates gene expression of the GCLC (glutamate-cysteine ligase catalytic subunit), which is a key enzyme in glutathione synthesis, and GSTs (glutathione S-transferases) via the ARE (antioxidant-response element). The Mrp2 (multidrug-resistance protein 2) pump mediates the excretion of GSH and GSSG excretion as well as endo- and xeno-biotics that are conjugated with GSH, glucuronate or sulphate. Considering that Mrp2 acts synergistically with these enzymes, we hypothesized that the regulation of Mrp2 gene expression is also dependent on Nrf2.

[Polymorphisms of the multiple drug resistance gene (MDR1) in Mapuche, Mestizo and Maori populations in Chile].

Background: There are significant differences in drug responses among different ethnic groups. The multidrug transporter P-gp, encoded by the MDR1 gene, plays a key role in determining drug bioavailability, and an association between a polymorphism in exon 26 (C3435T) and lower P-gp expression has been found. The co-segregation of this polymorphism with the polymorphism in exon 12 (C1236T) and in exon 21 (G2677T/A) determines several MDR1 haplotypes in humans.

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.

Induction of the multispecific organic anion transporter (cMoat/mrp2) gene and biliary glutathione secretion by the herbicide 2,4,5-trichlorophenoxyacetic acid in the mouse liver.

The canalicular multispecific organic anion transporter, cMoat, is an ATP-binding-cassette protein expressed in the canalicular domain of hepatocytes. In addition to the transport of endo- and xenobiotics, cMoat has also been proposed to transport GSH into bile, the major driving force of bile-acid-independent bile flow. We have shown previously that the herbicide 2,4,5-trichlorophenoxyacetic acid (2,4,5-T), a peroxisome-proliferator agent, significantly increases bile-acid-independent bile flow in mice.

Enhanced differentiation of HL-60 leukemia cells to macrophages induced by ciprofibrate.

Ciprofibrate, an hypolipidaemic peroxisome proliferator, induced differentiation of HL-60 cells. The effect was greatly potentiated by phorbol 12-myristate 13-acetate at a concentration where neither phorbol ester nor ciprofibrate alone had any effect on these cells. As occurs for HL-60 cell differentiation induced by high phorbol ester concentration, the ciprofibrate-induced phorbol ester-dependent differentiation of HL-60 cells proceeded through the monocytic/macrophage pathway and induced the phosphorylation of proteins with similar molecular weights suggesting that increased protein kinase C activity may be involved in the effect.

Genetic polymorphisms of CYP2D6, CYP1A1 and CYP2E1 in the South-Amerindian population of Chile.

Polymorphisms of cytochrome P450 genes show pronounced interethnic variation and have not been previously studied in the South-Amerindian population, which probably has an Asian origin. Therefore, a similar distribution of allelic and haplotype frequencies of cytochrome P450 genes to Asian populations might be expected in South-Amerindians. We analysed the allelic frequencies and haplotype distribution for CYP2D6, CYP1A1 and CYP2E1 genes in the South-Amerindian population of Chile (Mapuche, n = 84) by Southern blot or polymerase chain reaction-restriction fragment length polymorphism.

[Intrasphincteric injection of botulinum toxin in patients with esophageal achalasia].

Background: Intrasphincteric injection of botulinum toxin (BoTx) has demonstrated to be effective in the short-term treatment of achalasia.

Aim: To assess the efficacy, safety and long-term outcome of BoTx injection into the lower esophageal sphincter (LES) of patients with achalasia.

Patients And Methods: Eight patients received 80 units of BoTx.

Overexpression of mdr2 gene by peroxisome proliferators in the mouse liver.

Background: In mice, fibrates induce mdr2 gene expression, and its encoded P-glycoprotein in the canalicular domain of hepatocytes, as well as increasing biliary phospholipid output. It is not known whether this effect is restricted to fibrates or is a common property of peroxisome proliferators.

Aims: To test the effect of structurally unrelated peroxisome proliferators on mdr2 gene expression and biliary phospholipid output, and to explore the molecular mechanism(s) of mdr2 gene induction.

[Semiquantitative histopathologic analysis of chronic gastritis: extension and grading score].

Three endoscopic systematic biopsies were obtained from 261 patients showing chronic gastritis. Histopathologic features of chronic gastritis were graded from 0 to 3 points according to the Sydney System. In addition, an extension and grading histopathologic score was applied.

Modulation of hepatic content and biliary excretion of P-glycoproteins in hepatocellular and obstructive cholestasis in the rat.

Background/aims: Release into bile of canalicular membrane enzymes, such as alkaline phosphatase and gamma-glutamyl transpeptidase, is significantly increased in rats subjected to experimental models of hepatocellular or obstructive cholestasis. This effect appears to be related to a greater susceptibility of these membrane intrinsic proteins to the solubilizing effects of secreted bile acids. It is not known whether canalicular membrane transport proteins, such as P-glycoprotein isoforms, involved in ATP-dependent xenobiotic biliary excretion and phospholipid secretion, are excreted into bile and whether this process is modified in cholestasis.

[Frequency and histopathologic features of chronic gastritis in 300 patients without endoscopic lesions].

Three gastric mucosal biopsies were obtained from 300 patients showing a normal upper digestive tract endoscopy. Histologically, in 9% of the patients the biopsies were normal: in 87%, showed a common-type chronic gastritis, and in 4% showed a reactive (chemical or reflux-type) gastritis. Helicobacter pylori was present in 25.

Fibrates induce mdr2 gene expression and biliary phospholipid secretion in the mouse.

Disruption of the murine mdr2 gene leads to the complete absence of biliary phospholipids. We tested the hypothesis that the increase in biliary phospholipid output induced by fibrates is mediated via induction of the hepatic mdr2 gene and its encoded product, the P-glucoprotein canalicular flippase. Increased levels of mdr2 mRNA were observed in the liver of mice treated with different fibrates: ciprofibrate, 660+/-155% (as compared with control group); clofibrate, 611+/-77%; bezafibrate, 410+/-47%; fenofibrate, 310+/-52%; gemfibrozil, 190+/-25% (P <0.

Differences between nuclear run-off and mRNA levels for multidrug resistance gene expression in the cephalocaudal axis of the mouse intestine.

P-glycoprotein is a multidrug transporter encoded by the mdr3 gene in the mouse intestinal epithelium. The aims of this study were to characterize the mdr3 gene expression in the cephalocaudal axis of the intestine in adult animals and during perinatal development, and to define the molecular mechanism responsible for the heterogeneous expression of the gene along the cephalocaudal axis. RNA extracted from stomach, duodenum, jejunum, ileum, cecum and colon was hybridized by slot blot and Northern blot using a mdr3 cDNA probe.

Endoscopic intrasphincteric injection of botulinum toxin for the treatment of achalasia.

Three patients with achalasia were treated with endoscopic injection of botulinum toxin (BoTx). BoTx (80 U) was injected via a sclerotherapy needle into the lower esophageal sphincter (LES). One patient complained of transient heartburn that resolved after omeprazole treatment.

Effect of colchicine and heat shock on multidrug resistance gene and P-glycoprotein expression in rat liver.

The multidrug resistance genes encode plasma membrane glycoproteins named P-glycoproteins, that act as an ATP-dependent drug efflux pump and decrease the cytosolic concentration of chemotherapeutic agents. It has been hypothesized that in rat liver, this protein may have a physiological role as a biliary transporter of xenobiotics and endobiotics. Some human tumor cell lines turn on the human multidrug resistance gene in response to high temperature and after exposure to toxic chemicals.

[Treatment of non-variceal upper digestive hemorrhage with endoscopic thermocoagulation].

Over a year period, 60 of 172 patients presenting with upper gastrointestinal bleeding were treated by endoscopic thermocoagulation. Entry criteria included active bleeding (pulsatile or oozing), a visible vessel, sentinel clot or the presence of a pigmented protuberance at the ulcer crater. Hemostatic therapy was performed using the heat probe.