studies

HEPATOLOGY, VOLUME 62, NUMBER 1 (SUPPL) AASLD ABSTRACTS 373A
318
Uncertainty and Hepatitis C: A Correlational Study
Examining Mishel’s Uncertainty in Illness Theory
Humberto Reinoso; Nursing, Mercer University, Atlanta, GA
Background: Hepatitis C is the most common blood-borne infection
worldwide. It is estimated that some 5.3 million Americans
are living with hepatitis C. Some studies predict up to
7.1 million individuals affected including high-risk populations
(Chak, Talal, Sherman, Schiff, & Saab, 2011). Individuals born
between 1945 and 1965, those from the baby boomers generation,
account for approximately three-fourths of all hepatitis C
cases in the U.S. (Centers for Disease Control and Prevention
[CDC], 2012). Purpose: The purpose of this study was to examine
Mishel’s Uncertainty in Illness Theory among individuals
with hepatitis C. The study focused on the relationship a set
of variables prescribed by the model had on individual’s perception
of uncertainty. Methods: A cross-sectional design was
used to study the relationship between uncertainty and a set
of variables prescribed by Michel’s Uncertainty in Illness Theory
(i.e. educational attainment, healthcare authority figures,
social network, years since diagnosis, treatment attempts, and
treatment experience). Results: Data were collected over an
8-week period from a convenience sample of participants born
between 1945 and 1965, who self-identified as having hepatitis
C (n = 146). The relationship between perceived uncertainty
and a set of variables prescribed by the theory was investigated
using Pearson product-moment correlation coefficients.
Preliminary analyses were preformed to ensure no violation of
the assumptions of normality, linearity, and homoscedasticity.
Educational attainment (r = .2, p = < .05) as well as treatment
experience (r = .27, p = < .05) shared a positive relationship
with the individual’s perception of uncertainty. Social network
(r = -.51, p = < .01) shared a strong negative or inverse relationship
with participant’s perception of uncertainty. Furthermore,
there was a strong positive relationship between the
perception of uncertainty experienced by those individuals with
hepatitis C and information provided by healthcare authority
figures (r = .73, p = < .01). Conclusion: The results of this study
suggest that the perception of uncertainty experienced by those
individuals with hepatitis C may be influenced positively or
negatively by information provided by their healthcare authority
figures as well as their social network. Further research is
recommended, in the form of a multiple regression analysis, of
those variables identified of having strong relationships with an
individual’s perception of uncertainty in order to identify their
predictive ability.
Disclosures:
The following authors have nothing to disclose: Humberto Reinoso
319
Small Anti-Warburg Molecules Kill Hepatocarcinoma
Cells by Opening Voltage Dependent Anion Channels
and Promoting Mitochondrial Oxidative Stress
David N. DeHart 1 , Monika Gooz 1 , John J. Lemasters 1,2 , Eduardo
N. Maldonado 1 ; 1 Drug Discovery & Biomedical Sciences, Medical
University of South Carolina, Charleston, SC; 2 Biochemistry &
Molecular Biology, Medical University of South Carolina, Charleston,
SC
BACKGROUND: Enhanced aerobic glycolysis and suppressed
mitochondrial metabolism characterize the Warburg metabolism
of tumors. Flux of metabolites across mitochondrial outer
membranes occurs through voltage dependent anion channels
(VDAC). Dimeric α,β-tubulin closes VDAC in planar lipid
bilayers (PNAS 105:18746) and limits ingress of respiratory
substrates and ATP through VDAC that support mitochondrial
membrane potential (ΔΨ) formation in cancer cells (Cancer
Res. 70:10192). The small molecule erastin opens VDAC by
antagonizing the inhibitory effect of tubulin on VDAC (JBC
288:11920). Here, we hypothesized that small molecules that
antagonize VDAC-tubulin interaction increase mitochondrial
formation of reactive oxygen species (ROS), decrease glycolysis,
and activate c-jun N-terminal kinase (JNK), leading to
mitochondrial dysfunction, cell death and tumor growth inhibition
in hepatocarcinoma (HCC). Our AIM was to evaluate
the effects of VDAC-tubulin antagonists on mitochondrial ΔΨ,
ROS and lactate generation, JNK activation and cell killing
in HepG2 and Huh7 HCC cells and in a xenograft model
of Huh7 cells. METHODS: Confocal/multiphoton fluorescence
microscopy assessed ΔΨ (tetramethylrhodamine methylester)
and ROS (chloromethyldichlorofluorescein [cmDCF], MitoSOX
Red). JNK was assessed by Western blotting and cell killing
by propidium iodide fluorometry. Subcutaneous xenografts of
Huh7 cells were developed in nude mice. RESULTS: Erastin
and small molecules X1 and X2 identified in a high-throughput
screen increased ΔΨ and prevented mitochondrial depolarization
caused by cytosolic high free tubulin. Increased ΔΨ
was followed by mitochondrial depolarization occurring 1-2
h after X1 and X2 and 3-4 h after erastin. Lactate generation
after X1 decreased by 60%. ROS increased 30 min after X1
and 60 min after X2 and erastin, as assessed with cmDCF
and MitoSOX. The mitochondrially targeted antioxidant MitoQ
blocked this ROS increase. Additionally, erastin caused JNK
phosphorylation within 1 h. X1 and X2-dependent cell killing
of HCC cells was blocked by the antioxidant N-acetylcysteine.
By contrast, X1 and X2 caused