Browsing by Author "Chianale, Jose"

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    Bucillamine induces glutathione biosynthesis via activation of the transcription factor Nrf2
    (PERGAMON-ELSEVIER SCIENCE LTD, 2006) Wielandt, Ana M.; Vollrath, Valeska; Farias, Marcelo; Chianale, Jose
    The properties of bucillamine, a synthetic antioxidant, have been attributed mainly to the donation of thiol groups to glutathione (GSH). We recently demonstrated that glutamatecysteine 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. Both bucillamine and SA 981 produced a significant dose-dependent increase in the mRNA levels of Mrp2/MRP2 and GCLC after 24 h. The levels of the transcription factor Nrf2 in the nuclei were maximal at 3 h, remained elevated at 6 h, and decreased to control values at 24 h in both cell lines. Moreover, both bucillamine and SA 981 significantly increased the expressions of Mrp2/MRP2 and GCLC proteins in both cell lines. Finally, in both cell lines, bucillamine and SA 981 increased the GSH content two- to three-fold. These results demonstrate that bucillamine and SA 981 activate the ARE-ARE pathway increasing the expression of ARE-driven genes such as those of GCLC and Mrp2/MRP2. The role of bucillamine as a chemopreventive agent against cancer remains to be elucidated. (c) 2006 Elsevier Inc. All rights reserved.
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    Diagnóstico y manejo de colitis ulcerosa grave. Una mirada actualizada
    (2017) Hernandez Rocha, Cristian; Ibanez, Patricio; Elena Molina, Maria; Klaassen, Julieta; Valenzuela, Andrea; Candia, Roberto; Bellolio, Felipe; Zuniga, Alvaro; Miguieles, Rodrigo; Francisco Miquel, Juan; Chianale, Jose; Alvarez Lobos, Manuel
    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. Patients with severe UC must be hospitalized. First line therapy is the use of intravenous corticoids which achieve clinical remission in most patients. However, 25% of patients will be refractory to corticoids, situation that should be evaluated at the third day of therapy. In patients without response, cytomegalovirus infection must be quickly ruled out to escalate to second line therapy with biological drugs or cyclosporine. Total colectomy must not be delayed if there is no response to second line therapy, if there is a contraindication for second line therapies or there are complications such as: megacolon, perforation or massive bleeding. An active management with quick escalation on therapy allows to decrease the prolonged exposure to corticoids, reduce colectomy rates and its perioperative complications.
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    Phenotype and genotype of thiopurine methyltransferase in Chilean individuals
    (SOC MEDICA SANTIAGO, 2012) Jorquera, Andres; Solari, Sandra; Vollrath, Valeska; Guerra, Irene; Chianale, Jose; Cofre, Colomba; Kalergis, Alexis; Ibanez, Patricio; Bueno, Susan; Alvarez Lobos, Manuel
    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 genotype and enzyme activity can vary by ethnicity. Aim: To study the activity and genotype of TPMT in a group of Chilean subjects. Material and Methods: In 200 healthy adult blood donors, TPMT activity was determined by high performance liquid chromatography (HPLC). Deficient, low, normal or high levels were defined when enzymatic activity was <= 5, 6-24, 25-55 and >= 56 nmol/grHb/h, respectively. Genotyping of TPMT ((star)1, (star)2, (star)3A, (star)3B, (star)3C) was performed by PCR. Results: Seventy seven women (38.5%) and 123 men (61.5%), with an average age of 34.9 years were studied. Eighteen subjects (9%) had a low enzymatic activity, 178 (89%) had normal activity, 4 (2%) had high activity and no genotype deficient subjects were identified. The wild type genotype ((star)1) was found in 184 (92%) individuals and 16 (8%) were heterozygous for the variants: (star)2 (n = 2), (star)3A (n = 13) and (star)3C (n = 1). No homozygous subjects for these variants were identified. Wild type genotype had an increased enzymatic activity (40.8 +/- 7.2 nmol/gHb/h) compared to heterozygous group (21.2 +/- 3 nmol/gHb/h; p < 0.001). Conclusions: Less than 10% of a Chilean population sample has a low enzymatic activity or allelic variants in the TPMT gene, supporting the use of thiopurines according to international recommendations. (Rev Med Chile 2012; 140: 889-895).
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    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
    (BMJ PUBLISHING GROUP, 2011) Morales, Eugenia; Azocar, Lorena; Maul, Ximena; Perez, Claudio; Chianale, Jose; Francisco Miquel, Juan
    Background: The lactase persistent (LP) or lactase nonpersistent (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.