Endocrine,
Metabolic & Immune Disorders - Drug Targets
ISSN: 1871-5303
OPEN ACCESS ARTICLES
Contents
Isoforms of Vitamin E Differentially Regulate Inflammation, 2010, 10, 348-366
Joan M. Cook-Mills and Christine A. McCary
[Abstract] [Full
Text Article]
Implications of the Obesity Epidemic for Statin
Therapy: Shifting Cholesterol Metabolism to a High Synthesis
and Low Dietary Absorption State, 2007, 7, 153-166
M.R. Hoenig, K.M. Kostner, S.J. Read, P.J. Walker and J.J.
Atherton
[Abstract] [Full
Text Article]
CXCR3 Axis: Role in Inflammatory Bowel Disease and
its Therapeutic Implication, 2007, 7, 111-123
U.P. Singh, C. Venkataraman, R. Singh and J.W. Lillard,
Jr.
[Abstract] [Full
Text Article]
Abstracts
[Back to top]
Isoforms of Vitamin E Differentially Regulate Inflammation
Joan M. Cook-Mills and Christine A. McCary
[Full
Text Article]
Vitamin E regulation of disease has been extensively studied in humans, animal models and cell systems. Most
of these studies focus on the α-tocopherol isoform of vitamin E. These reports indicate contradictory outcomes for
anti-inflammatory functions of the α-tocopherol isoform of vitamin E, especially with regards to clinical studies of asthma
and atherosclerosis. These seemingly disparate clinical results are consistent with recently reported unrecognized properties
of isoforms of vitamin E. Recently, it has been reported that physiological levels of purified natural forms of vitamin
E have opposing regulatory functions during inflammation. These opposing regulatory functions by physiological levels
of vitamin E isoforms impact interpretations of previous studies on vitamin E. Moreover, additional recent studies also
indicate that the effects of vitamin E isoforms on inflammation are only partially reversible using physiological levels of a
vitamin E isoform with opposing immunoregulatory function. Thus, this further influences interpretations of previous
studies with vitamin E in which there was inflammation and substantial vitamin E isoforms present before the initiation of
the study. In summary, this review will discuss regulation of inflammation by vitamin E, including alternative interpretations
of previous studies in the literature with regards to vitamin E isoforms.
[Back to top]
Implications of the Obesity Epidemic for Statin Therapy:
Shifting Cholesterol Metabolism to a High Synthesis and Low
Dietary Absorption State
M.R. Hoenig, K.M. Kostner, S.J. Read, P.J. Walker and J.J.
Atherton
[Full
Text Article]
Obesity and the metabolic syndrome are becoming one of the
biggest health challenges of the 21st
century. Cholesterol metabolism is significantly altered in
both obesity and metabolic syndrome in that cholesterol synthesis
is increased and absorption reduced and this has important
implications for the treatment of lipid disorders in both
obesity and the metabolic syndrome. In the present review
we discuss these changes in detail especially in the context
of a more standardized approach for cholesterol reduction
like the TARGET LDL trial. Customized care is topical in lipidology
as we strive to achieve LDL cholesterol and non-HDL cholesterol
targets in every patient.
[Back to top]
CXCR3 Axis: Role in Inflammatory Bowel Disease
and its Therapeutic Implication
U.P. Singh, C. Venkataraman, R. Singh and J.W. Lillard,
Jr.
[Full
Text Article]
There is a great need for new intervention and prevention
strategies against Crohn’s disease (CD), a chronic,
relapsing tissue-destructive inflammatory bowel disease (IBD).
Estimates indicate more than 1 million cases of IBD in the
United States occur annually, with 50% involving CD. The clinical
features of CD correlate with certain mouse models of colitis,
including the spontaneous colitis observed in interleukin-10
deficient (IL-10-/-), senescence accelerated mice
(SAMP1/Yit) and trinitrobenzene sulfonic acid (TNBS)-treated
mice. Chemokines undoubtedly play a pivotal role in the regulation
(i.e., initiation, maintenance, and suppression) of mucosal
inflammation and tissue destruction. A number of key advances
have led to greater understanding of the steps responsible
for colitis and the roles played by chemokines. In fact, CXCR3
and the ligands for this chemokine receptor, monokine-induced
by interferon-γ
(IFN-γ)
(MIG/CXCL9), IFN-γ-inducible
10 kDa protein (IP-10/CXCL10), and IFN-γ-inducible
T cell α-chemoattractant
(I-TAC/CXCL11) are differentially expressed at sites of colitis
in IL-10-/- mice and in clinical cases of CD. While
we have demonstrated that antibodies directed against CXCL10
could both prevent the onset and cure of pre-existing colitis
in IL-10-/- mice, studies by other investigators
have shown the efficacy of CXCR3 blockade to mitigate colitis
and other inflammatory diseases. This review describes the
hallmarks of IBD, CXCL9-11, and CXCR3 expression during murine
colitis and IBD, gives an over-view of the antagonist therapies
targeting the CXCR3 axis, details current and pending bio-therapies
for IBD, and discusses what is known about the cellular and
CXCR3-mediated mechanisms of colitis. |
