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David Kershenobich

Publications and source records attributed to David Kershenobich.

8 recordsLinked to original sources
PubMed2003

Interleukin 8 response and oxidative stress in HepG2 cells treated with ethanol, acetaldehyde or lipopolysaccharide.

The aim of this work was to study the induction and secretion of interleukin 8 (IL-8) and some oxidative stress parameters after ethanol (EtOH), acetaldehyde (Ac) or lipopolysaccharide (LPS) treatment on HepG2 cells. Cells were treated with 50 mM EtOH, 175 &mgr;M Ac or 1 &mgr;g/ml of LPS. IL-8 induction and secretion were determined in the presence of the toxics, and the effect of antioxidants N-acetyl-L-cysteine and 1,1,3,3-tetramethyl-2-thiourea was evaluated. Further, the effect of adding polyclonal anti-human tumor necrosis factor alpha (TNF-alpha) and H(2)O(2) was studied, and catalase, superoxide dismutase and glutathione peroxidase activities were determined. Lipid peroxidation increased significantly only in Ac-treated cells. All toxics failed to decrease significantly the intracellular levels of reduced GSH. Catalase activity was diminished in all treatments, while other enzyme activities did not present changes. No change in peroxide production was found with any treatment. IL-8 secretion increased in Ac (41%) and in LPS (38%)-treated cells. Antioxidant and anti-TNF-alpha treatments decreased IL-8 secretion. H(2)O(2) (0.25 mM)-treated cells increased IL-8 secretion. IL-8 reverse transcriptase-polymerase chain reaction results correlated with secretion values. Our results show that Ac and LPS treatment produced an increased IL-8 induction and secretion. Oxidative stress and TNF-alpha are mediators in IL-8 response. This observation suggests that in the in vivo liver, the mechanism of ethanol-induced IL-8 production requires ethanol metabolism, and hepatocytes do not require the interaction among different populations of liver cells to respond.

Journal Article↗
PubMed2002

Trefoil factor 1 (TFF1/pS2) deficiency activates the unfolded protein response.

BACKGROUND: The trefoil factor 1 (TFF1/pS2) is a secreted gastrointestinal peptide that is often altered or lost in human gastric cancers. Consistently, mouse TFF1 deficiency leads to antropyloric tumors. MATERIALS AND METHODS: To investigate the gene expression alterations in response to the lack of TFF1, we performed differential expression analyses of TFF1 null antropyloric tumors using an array containing 588 cDNAs. RESULTS: Using total and enriched probes, 22 genes were found to be up-regulated. The identification of the genes for endoplasmic reticulum (ER)-resident GRP78, ERp72, and p58IPK proteins connected TFF1 deficiency to the unfolded protein response (UPR). Accordingly, CHOP10, a transcription factor induced early in response to ER stress, and the pleiotropic Clusterin, involved in protein folding, were also overexpressed. Northern blot analyses of 8 weeks and 1 year TFF1 null tumors confirmed that GRP78, ERp72, p58IPK, CHOP10, and Clusterin overexpression is a common and permanent feature shared by all TFF1 null antropyloric tumors. Finally, consistent with UPR, ultrastructural analyses showed that tumor rough ER was enlarged and contained dense material, supporting the hypothesis that TFF1 deficiency leads to the accumulation of misfolded proteins in the ER. CONCLUSION: Together, our data provide the first evidence of a relationship between a member of the TFF family and the ER machinery. Whereas to date TFF1 is believed to act as an extracellular molecule, our results suggest a possible additional function for TFF1 in protein folding and/or secretion.

Animals↗
PubMed2002

[Mechanisms and cofactors of hepatitis C fibrosis].

The development of quantitative methods to measure the degree of necrosis, inflammation and fibrosis in liver biopsies favored the knowledge of the natural course of liver fibrosis. Two of the most important methods are the Knodell index and the Metavir index. These indexes are also useful to monitor the effects of the diverse therapeutic alternatives. There are no satisfactory studies that confirm why progression of fibrosis is slower in women, or why it's faster when the diagnosis is made at an older age. All the therapeutic schemes decrease the progression of fibrosis, in at least one degree compared with the degree of fibrosis before the treatment. Moreover, combination therapy with pegylated interferon and ribavirin reduces the progression of fibrosis even more in patients with hepatitis C.

Hepatitis C↗
PubMedDate not supplied

Emerging concepts in inflammation and fibrosis.

Hepatic and pancreatic response to several insults commonly includes similar pathways of inflammation, fibrogenesis/regeneration, which may occur simultaneously and without appropriate coordination, resulting in chronic inflammation, scarring, and organ dysfunction. This review highlights the opinion of experts gathered for the Mexican Digestive Disease Week (2001) to analyze these molecular events with emphasis on identifying possible therapeutic opportunities. Inflammatory response encompasses leukocyte infiltration, favored by adhesion molecules of the selectin family, chemokines, integrins, and activated stellate cells (SC). Quiescent SC undergo activation mediated by mechanical stress and expression of cytokines, oxidative stress products, and growth factors and play a significant role in fibrosis and in reparation toward synthesis of extracellular matrix components. Also, hepatocytes and acinar cells contribute to the inflammatory and fibrotic response. Molecules that down-regulate this response are overexpressed. Therapeutic strategies with targeting to such mechanisms underlying chronic hepatic and pancreatic injury are an emerging reality.

Fibrosis↗
PubMedDate not supplied

Health-related quality of life and depression in patients with chronic hepatitis C.

BACKGROUND: Hepatitis C is a major cause of liver disease worldwide. It has been associated with decreased health-related quality of life (HRQL) and psychiatric symptoms. Our aim was to assess HRQL, depression, and illness understanding in patients with chronic hepatitis C without previous interferon therapy. METHODS: Consecutive patients attending a referral center were enrolled. HRQL was measured using SF-36 questionnaire, depression with Zung self-rating depression scale, and illness understanding with self-applied knowledge test. RESULTS: Of 157 patients enrolled, 112 were female (71%) and 45 male (29%). Ninety-seven patients (61.8%) had cirrhosis. HRQL was significantly decreased in chronic hepatitis C patients compared to historical normal controls in all eight domains of the SF-36 (p < 0.001). In hepatitis C cirrhotic patients, HRQL was significantly lower among Child-Pugh class B and C subjects in domains reflecting physical health (p <0.05). Ninety-two patients (58.6%) had depression that resulted in lower HRQL when compared to nondepressed patients (p <0.05). One hundred fourteen patients (72.6%) had poor illness understanding of hepatitis C. These subjects had significantly lower HRQL scores in six of eight SF-36 domains when compared to patients with better understanding of the disease (p <0.05). CONCLUSIONS: Chronic hepatitis C patients attending a tertiary-referral center had significant decrease in HRQL associated with depression (58.6%) and poor illness understanding (72.6%). Educational programs and their impact on HRQL need to be addressed in detail, particularly for the pre-treatment scenario.

Attitude to Health↗
PubMedDate not supplied

Early HCV RNA changes in patients with chronic hepatitis C treated with peginterferon alfa 2b and ribavirin.

INTRODUCTION: Currently, interferon alfa and ribavirin are the mainstay of therapy for patients with chronic hepatitis C. Recently the pegylation of interferon has allowed a once weekly application, resulting in an increased sustained viral response rate. The analysis of serum HCV dynamics has been shown to be useful in predicting clinical effects and optimizing the treatment regimen. AIM: The aim of the present study was to assess early serum HCV RNA changes in patients with chronic hepatitis C treated with peginterferon alfa 2b plus ribavirin. METHODS: Male and female patients aged 18 to 65 years with chronic hepatitis C were eligible for the study. All patients received peginterferon alfa 2b 1.5 micrograms/kg once-weekly for 4 weeks and then peginterferon alfa 2b 0.5 microgram/kg once-weekly until the completion of the 48 week trial period, plus ribavirin orally with meals, adjusted to body weight. HCV RNA was determined at base-line, 48 hours, 4 and 12 weeks of therapy. RESULTS: Data were obtained from 20 patients with chronic hepatitis C treated with peginterferon alfa 2b and ribavirin; 16 male, 4 female, with a mean age of 44.4 +/- 11.9 years, 16 patients (80%) were infected with HCV genotype 1, the remainder were infected with genotype 2. Mean baseline HCV RNA for the total group was 1,091,405 +/- 972,715 IU/mL. Mean reductions in viral load at 48 hours, 4 and 12 weeks for the 20 patients were 1.31 +/- 0.91 log, 1.99 +/- 1.27 log and 2.31 +/- 1.25 log, respectively. A > 2 log reduction in HCV RNA was noticed in 12/20 patients (60%) at 4 weeks (early viral responders), in 9 of them (45%) HCV RNA was undetectable. This response in HCV RNA persisted at 12 weeks of therapy. Early viral responders had a significant reduction in HCV RNA at 48 hours after the initial peginterferon alfa 2b injection (> 1 log reduction). Early viral response was observed in 8/16 patients with HCV genotype 1, and in all genotype 2 patients. CONCLUSION: Treatment with peginterferon alfa 2b and ribavirin produces significant changes in the early HCV viral dynamics supporting the concept that such changes may be pivotal in achieving a sustained viral response.

Adolescent↗