Cytokine Inhibition

The cytokine insulin-like growth factor-1 (IGF-1) mediates the mitogenic effect of growth hormone (GH). IGF-1 appears to play a permissive role in the development of ischemia-induced retinal neovascularization and is able to induce retinal neovascularization directly 49 . Both local and systemic expression of IGF-1 appear to contribute to its intraocular levels. IGF-1 inhibition by a receptor antagonist suppresses experimental retinal neovas-cularization. This approach can offer a beneficial...

Altered Proteins and ROS

The conventional view of the free-radical theory of aging seems to assume that increased ROS generation modifies intracellular proteins to such an extent that the chaperone and proteolytic activities are unable to cope with the increased load of oxidatively damaged polypeptides. While there is much evidence that ROS do damage proteins 101, 102 , it is also known that some altered proteins can induce ROS generation. For example, it has long been known that the amyloid peptide which is associated...

Biological Evidences

Lipid oxidation and formation of oxygen radicals are important elements of arterial plaque formation and atherosclerosis, and are involved in the pathophysiology of cardiovascular disease. Several potential mechanisms have been suggested to play a potential role in the antiatherogenic and cardioprotective effects of bilirubin (as schematically summarized in Table 1). Bilirubin has been considered a toxic by-product associated with the potentially fatal conditions of neonatal...

Sarika Arora1 Richa Vaishyat PK Dabla and Bhawna Singht

*Department of Biochemistry, Lady Hardinge Medical College & Associated Hospitals, New Delhi, India department of Biochemistry, G.B. Pant Hospital, New Delhi, India . 1. 3. NAD(P)H 4. Structure of NAD(P)H 5. NAD(P)H Oxidases in Coronary Artery 6. NAD(P)H Oxidases in 6.1. Angiotensin II-Related 6.2. NAD(P)H Oxidase-Derived Oxidative Stress in 6.3. NAD(P)H Oxidase and Endothelial Dysfunction in Hypertension 72 6.4. NAD(P)H Oxidases in Experimental Hypertension Models 73 7. NAD(P)H-Derived ROS...

Mitochondrial Inactivity and ROS Generation

It has been apparently assumed by many gerontologists that increased oxygen utilization by mitochondria will automatically increase ROS formation. This assumption is reported to be incorrect 22-25,209,210 . Even from first principles one would predict that an incompletely reduced oxygen molecule (i.e., an oxygen free-radical) would be more likely to be produced when few electrons are passed down the electron transport chain (i.e., in resting mitochondria), compared to when there is a ready...

Conclusion

Aging is often associated with both mitochondrial dysfunction and accumulation of aberrant proteins, although it remains uncertain as to which, if either, is the initiating event. For example, it has recently been suggested that activation of mitochondrial biogenesis may delay aging 215 and furthermore that brain mitochondria should be targeted in treatment of Alzheimer's disease, as amyloid b-peptide-induced damage to these organelles is a particularly early event in a mouse model of...

Circulating Biomarkers for Vulnerable Plaques

Circulating biomarkers that are involved in inflammation, endothelial damage, or hemostasis are recognized as potential biomarkers for CV risk and plaque vulnerability. For many of these molecules there is a mixture of data that is both supportive, and not, for their linkage to CVD and their role as biomarkers. Table 2 summarizes representatives of those peripheral blood biomarkers 59-81 . 5.1. Nonspecific Inflammatory Biomarkers C-reactive protein (CRP), a member of the pentraxin family, is...

NADPH Oxidases in Hypertension

Maintenance of blood pressure is essential to health, and any gross deviations of blood pressure from normal can be life-threatening. The various mechanisms by which NADP(H) oxidases may lead to hypertension are discussed in the following subsections. 6.1. Angiotensin II-Related Hypertension In landmark studies investigating the source of vascular ROS, Pagano et al. 38 showed that a constitutively active phagocyte-like (NOX2-based) NAD(P)H oxidase is present in aortic adventitial fibroblasts...

Hp and Vaccination

Louagie et al. investigated the Hp polymorphism and the immune response after a recombinant hepatitis B vaccination. In comparison with Hp 1-1 and 2-1, the Hp 2-2 phenotype was associated with a significantly lower hepatitis B antibody titer. The magnitude and the kinetics of the anti-HBs response were determined by the Hp polymorphism. The Hp concentration and immune response to the vaccine behaved independently 130 . In accordance, an inferior immune response of Hp 2-2 subjects has also been...

Angiogenic Factors Involved in Ocular Angiogenesis

Several factors are known to play a role in ocular angiogenesis, VEGF plays a central role in this process. VEGF is produced in the eye by RPE cells and is upregulated by hypoxia. There are four major biologically active human isoforms, of which VEGF165 is predominant in the human eye and appears to be responsible for pathological ocular neovascularization. Besides being a potent and specific mitogen for endothelial cells, VEGF increases vascular permeability, inhibits endothelial cells...

Conclusions

Although it was long thought bilirubin to be a nonfunctional waste product of metabolism and hyperbilirubinemia to be even neurotoxic, there is now increasing experimental evidence that moderately increased serum bilirubin concentration (especially unconjugated bilirubin) might act as a powerful chain-breaking antioxidant in biological systems, contributing to plasma, cellular, tissue protection, and thereby contributing to prevent the development and progression of cardiovascular disease and...

Aging and Autophagy of Mitochondria

Evidence is accumulating to support the idea that aging is associated with compromised autophagic elimination of dysfunctional mitochondria 60-65, 130, 131 . It is possible therefore that the age-related accumulation of dysfunctional mitochondria could simply be a consequence of age-related autophagic insufficiency the problem then becomes what causes the age-related autophagic dysfunction 132-134 . Alternatively, excessive generation of dysfunctional mitochondria may overload the autophagic...

Hp Polymorphism and Infections

Since 1955, when Smithies reported on Hp polymorphism 9 , studies have been carried out to examine the role of Hp polymorphism in disease. A number of reports on the association of Hp polymorphism and these infections have been published (Fig. 2 and Table 2). 4.1. Hp Polymorphism and Streptococcus pyogenes Streptococcus pyogenes or Group A Streptococcus is a human pathogen producing a diverse array of diseases, ranging from self-limited conditions (pharyngitis, impetigo, erysipelas) to severe...

Experience with the Microarray at the University of Antwerp

Excema Iga Deficiency

When discriminating between sensitization and genuine allergy, traditional IgE assays have repeatedly been demonstrated to be of limited value. Therefore, in order to assess the potential of the microarray in discriminating between clinically relevant and irrelevant sIgE antibodies, we conducted several evaluations. In a first study 37 we evaluated whether CRD by microarray could constitute a reliable instrument in the diagnosis of applemediated oral allergy syndrome OAS in birch...

Imaging Biomarkers for Vulnerable Plaques

Multiple diagnostic imaging modalities have been developed and applied to detect atherosclerotic plaques. Table 1 summarizes key features of each modality, including advantages and limitations of their applications in atherosclerosis 12-27 . While earlier methods provided anatomical information, the field is currently shifting toward imaging techniques that provide information on plaque and vessel composition as well. The imaging modalities are summarized as invasive and noninvasive categories,...

NADPH Oxidase and Plaque Formation in Coronary Artery Disease

The original hypothesis that atherosclerosis is an inflammatory disease centered on oxidized LDL as the main effector. It is clear, however, that oxidative stress plays a much broader role in the pathogenesis of this disease. Animal models of atherosclerosis have documented that all of the constituents of the plaque produce and use ROS 18, 20, 38, 39, 119 . Analysis of coronary arteries indicated that O2 is distributed homogeneously throughout normal vessels, whereas intense ROS production is...

Working together to grow libraries in developing countries

Numbers in parentheses indicate the pages on which the authors' contributions begin. Sarika Arora 65 , Department of Biochemistry, Lady Hardinge Medical College amp Associated Hospitals, New Delhi, India C.H. Bridts 87 , Department of Immunology-Allergology-Rheumatology, Faculty of Medicine, University of Antwerp, Antwerpen, Belgium Thomas M. Connolly 1 , Discovery Translational Medicine, Wyeth Research, Collegeville, Pennsylvania, USA P.K. Dabla 65 , Department of Biochemistry, Lady Hardinge...