Current
Contents
Insulin Resistance and Type 2 Diabetes – An
Adipocentric View Pp.107-125
Anna
Cederberg and Sven Enerback
Atopic Dermatitis: Molecular Mechanisms,
Clinical Aspects and New Therapeutical Approaches Pp.127-138
E.
Galli, R. Cicconi, P. Rossi, A. Casati, E. Brunetti and G. Mancino
Chemokines in Cardiovascular Remodeling:
Clinical and Therapeutic Implications Pp.139-147
Gerasimos
Filippatos, John T. Parissis, Stamatis Adamopoulos and Fotios Kardaras
Potential Mechanisms of Cancer
Chemoprevention by Anthocyanins
Pp.149-159
De-Xing
Hou
Inflammatory Mediators and the Failing Heart:
A Translational Approach
Pp.161-182
Abhinav
Diwan, Tony Tran, Arunima Misra and Douglas L. Mann
Abstracts
[Back to top] Insulin Resistance and Type 2 Diabetes – An
Adipocentric View
Anna
Cederberg and Sven Enerback
As a result of
selecting triglycerides as the major vehicle for storing superfluous energy,
evolution came up with a specialized cell type, the adipocyte, equipped to
handle triglycerides and its potentially toxic metabolites – fatty acids. For
the first time in history large human populations are subjected a wealth of cheap,
accessible and palatable calories. This has created a situation, on a large
scale not previously encountered, in which the capacity to store triglycerides
in adipocytes is an important determinant of human health. Too few adipocytes
(e.g. lipodystrophia) or a situation in which all adipocytes are filled, to
their maximum capacity (e.g. severe obesity), will create very similar and
unfavorable metabolic situations in which ectopic triglyceride stores will
appear in tissues like liver and muscle. This review sets out to discuss the
adipocyte and its role in metabolism as well as the consequences of a metabolic
situation, in which the adipocyte has lost its fat storing monopoly.
[Back to top] Atopic Dermatitis: Molecular Mechanisms,
Clinical Aspects and New Therapeutical Approaches
E.
Galli, R. Cicconi, P. Rossi, A. Casati, E. Brunetti and G. Mancino
Atopic dermatitis
(AD) is a genetically determinated, chronic inflammatory skin disorder
associated with cutaneous erythema and severe pruritus, affecting 10-15% of
children with increasing incidence and socio-economical relevance. Frequently,
AD is associated with development of allergic rhinitis and/or asthma later in
childhood. In most of patients AD is associated with a sensitization to food
and/or environmental allergens and increased serum-IgE, while only a fewer
percentage missed links to the classical atopic diathesis.
Currently
investigated pathogenetic aspects of AD include imbalanced Th1/Th2 responses,
altered prostaglandin metabolism, intrinsic defects in the keratinocyte
function, delayed eosinophil apoptosis, and IgE-mediated facilitated antigen
presentation by epidermal dendritic cells. An inflammatory response of the
two-phase-type and the effects of staphylococcal superantigens (SAgs) are also
reported.
At present a
standardized cure of AD and a consensus on therapeutical approach of the severe
form of the disease have not been established. Current management of AD is
directed to the reduction of cutaneous inflammation and infection, mainly by S.
aureus, and to the elimination of exacerbating factors (irritants, allergens,
emotional stresses). Since patient with AD show abnormalities in
immunoregulation, therapy directed to adjustment of their immune function could
represent an alternative approach, particularly in the severe form of the
disease.
In this review, we
analyse the clinical and genetic aspects of AD, the related molecular
mechanisms, and the immunobiology of the disease, focusing our attention on
current treatments and future perspectives on this topic.
[Back to top] Chemokines in Cardiovascular Remodeling:
Clinical and Therapeutic Implications
Gerasimos
Filippatos, John T. Parissis, Stamatis Adamopoulos and Fotios Kardaras
Chemokines are
newly discovered molecules that mediate the migration of leukocytes into
inflammed tissues and control the inflammatory reactions in various
immune-mediated diseases. Both in animal models and in human specimens,
chemokine expression is associated with atherosclerotic lesion development and
vascular remodeling and restenosis after angioplasty. Furthermore, recent
studies have demonstrated that chemokines play an important role in the
pathophysiology of acute coronary syndromes, post-infarction left ventricular
remodeling and chronic heart failure. The capacity to control activation and
movement of inflammatory cells suggests that chemokines and their receptors
might provide novel targets for therapeutic intervention in a number of conditions
characterized by chronic inflammation, including cardiovascular diseases. The
present review summarizes current knowledge regarding the potential pathogenic
role of chemokines in major cardiovascular disorders, as well as the modulation
of the chemokine network as a novel, interesting therapeutic modality in this
field.
[Back to top] Potential Mechanisms of Cancer
Chemoprevention by Anthocyanins
De-Xing
Hou
Anthocyanins are
the chemical components that give the intense color to many fruits and
vegetables, such as blueberries, red cabbages and purple sweet potatoes.
Epidemiological investigations have indicated that the moderate consumption of
anthocyanin products such as red wine or bilberry extract is associated with a lower
risk of cardiovascular disease and improvement of visual functions. Recently,
there is increasing interesting in the pharmaceutical function of anthocyanins.
This review summarizes current knowledge on the various molecular evidences of
cancer chemoprevention by anthocyanins. These mechanisms can be subdivided into
the following aspects: 1) the antioxidation; 2) the molecular mechanisms
involved in anticarcinogenesis; 3) the molecular mechanisms involved in the
apoptosis induction of tumor cells. Finally, the bioavailability and
structure-activity relationship of anthocyanins are also summarized.
[Back to top] Inflammatory Mediators and the Failing Heart: A Translational Approach
Abhinav Diwan, Tony Tran, Arunima Misra and Douglas L. Mann
Recent studies
have identified the importance of proinflammatory mediators in regulating
cardiac structure in health and disease. Recent studies suggest that cytokines
that are expressed within the myocardium in response to a environmental injury,
namely tumor necrosis factor-alpha (TNF), interleukin-1 (IL-1) and the
interleukin-6 (IL-6) family of cytokines play an important role in initiating
and integrating homeostatic responses within the heart. However, these
"stress-activated" cytokines all have the potential to produce
cardiac decompensation when expressed at sufficiently high concentrations.
Indeed, there is now a growing appreciation that these molecules may play an
important role in mediating disease progression in the failing heart. The
growing appreciation of the pathophysiological consequences of sustained
expression of proinflammatory mediators in pre-clinical and clinical heart
failure models culminated in a series of multicenter clinical trials that
utilized “targeted” approaches to neutralize tumor necrosis factor (TNF) in
patients with moderate to advanced heart failure. However, these targeted
approaches have resulted in worsening heart failure, thereby raising a number
of important questions about what role, if any, proinflammatory cytokines play
in the pathogenesis of heart failure. This review will summarize the tremendous
growth of knowledge that has taken place in this field, with a focus on what we
have learned from the negative clinical trials, as well as the potential
direction of future research in this area.