Kolageni elastin u jetri štakora otrovanih živinim kloridom

Intoxication of rats with mercuric chloride (0.5 mg Hg/kg of body weight, daily for 10 weeks) increased the hepatic contents of soluble and insoluble collagen and elastin. The increase was associated with elevated serum aminotransferase and alkaline phosphatase activities, and decreased total protein level in serum. Inflammatory changes were found in the liver. An increase in the fibrous protein content suggests that inflammatory reaction to mercuric chloride can result in hepatic fibrosis.Trovanje štakora živinim kloridom (0,5 mg Hg/kg tjelesne težine na dan tijekom deset tjedana) imalo je za rezultat povećan sadržaj topljivog i netopljivog kolagena i elastina u jetri. Povećanje je dovedeno u vezu s povišenim aktivnostima aminotransferaze i alkalne fosfataze u serumu, i sa smanjenim nivoom ukupnog proteina u serumu. U jetri su zamijećene upalne promjene. Povišen sadržaj vlaknastog proteina upućuje na to da upalna reakcija na živin klorid može dovesti do fibroze jetre

Production of benzylisoquinoline alkaloids in Saccharomyces cerevisiae

The benzylisoquinoline alkaloids (BIAs) are a diverse class of metabolites that exhibit a broad range of pharmacological activities and are synthesized through plant biosynthetic pathways comprised of complex enzyme activities and regulatory strategies. We have engineered yeast to produce the key intermediate reticuline and downstream BIA metabolites from a commercially available substrate. An enzyme tuning strategy was implemented that identified activity differences between variants from different plants and determined optimal expression levels. By synthesizing both stereoisomer forms of reticuline and integrating enzyme activities from three plant sources and humans, we demonstrated the synthesis of metabolites in the sanguinarine/berberine and morphinan branches. We also demonstrated that a human P450 enzyme exhibits a novel activity in the conversion of (R)-reticuline to the morphinan alkaloid salutaridine. Our engineered microbial hosts offer access to a rich group of BIA molecules and associated activities that will be further expanded through synthetic chemistry and biology approaches

Helicobacter pylori Perturbs Iron Trafficking in the Epithelium to Grow on the Cell Surface

Helicobacter pylori (Hp) injects the CagA effector protein into host epithelial cells and induces growth factor-like signaling, perturbs cell-cell junctions, and alters host cell polarity. This enables Hp to grow as microcolonies adhered to the host cell surface even in conditions that do not support growth of free-swimming bacteria. We hypothesized that CagA alters host cell physiology to allow Hp to obtain specific nutrients from or across the epithelial barrier. Using a polarized epithelium model system, we find that isogenic ΔcagA mutants are defective in cell surface microcolony formation, but exogenous addition of iron to the apical medium partially rescues this defect, suggesting that one of CagA's effects on host cells is to facilitate iron acquisition from the host. Hp adhered to the apical epithelial surface increase basolateral uptake of transferrin and induce its transcytosis in a CagA-dependent manner. Both CagA and VacA contribute to the perturbation of transferrin recycling, since VacA is involved in apical mislocalization of the transferrin receptor to sites of bacterial attachment. To determine if the transferrin recycling pathway is involved in Hp colonization of the cell surface, we silenced transferrin receptor expression during infection. This resulted in a reduced ability of Hp to colonize the polarized epithelium. To test whether CagA is important in promoting iron acquisition in vivo, we compared colonization of Hp in iron-replete vs. iron-deficient Mongolian gerbils. While wild type Hp and ΔcagA mutants colonized iron-replete gerbils at similar levels, ΔcagA mutants are markedly impaired in colonizing iron-deficient gerbils. Our study indicates that CagA and VacA act in concert to usurp the polarized process of host cell iron uptake, allowing Hp to use the cell surface as a replicative niche

Kolageni elastin u jetri štakora otrovanih živinim kloridom

Intoxication of rats with mercuric chloride (0.5 mg Hg/kg of body weight, daily for 10 weeks) increased the hepatic contents of soluble and insoluble collagen and elastin. The increase was associated with elevated serum aminotransferase and alkaline phosphatase activities, and decreased total protein level in serum. Inflammatory changes were found in the liver. An increase in the fibrous protein content suggests that inflammatory reaction to mercuric chloride can result in hepatic fibrosis.Trovanje štakora živinim kloridom (0,5 mg Hg/kg tjelesne težine na dan tijekom deset tjedana) imalo je za rezultat povećan sadržaj topljivog i netopljivog kolagena i elastina u jetri. Povećanje je dovedeno u vezu s povišenim aktivnostima aminotransferaze i alkalne fosfataze u serumu, i sa smanjenim nivoom ukupnog proteina u serumu. U jetri su zamijećene upalne promjene. Povišen sadržaj vlaknastog proteina upućuje na to da upalna reakcija na živin klorid može dovesti do fibroze jetre