Drom Test

ROMs can be measured in blood samples by the Diacron (FRAS-3) reactive oxygen metabolites (D-ROM) test. This test is based on the ability of transition metals to catalyze, in the presence of peroxides, the formation of free radicals, which are trapped by an alchilamine. The alchilamine reacts forming a colored radical detectable at 505 nm. The utilized reagents are the chromogen (R1, an alchilamine) and a pH 4.8 buffer (R2). Heamolyzed blood (10 L) is mixed with 1 mL buffer, and 10 L of R1 is...

Neuronal Death The Final Pathway

The nature, time course, and molecular causes of cell death in neurodegenerative diseases and their relations to basic processes discussed above are still a matter of controversy. Based on distinct morphologic criteria and biochemical features, three major mechanisms of neuronal demise are discussed apoptosis, a specific form of gene-directed programmed cell death (PCD) (oncotic) necrosis, a passive killing of the cell and autophagic degeneration (256,257). Morphologically, apoptotic cell death...

Oxidative Stress

Oxidative stress is a marker of aging and has been recently shown to be also involved in the early stages of the pathogenesis of various neurodegenerative disorders including AD, PD, ALS, and others (80,81). The nervous system is particularly vulnerable to the deleterious effects of reactive oxygen species (ROS) because the brain contains high concentrations of polyunsaturated fatty acids that are highly susceptible to lipid peroxidation moreover it utilizes, compared to other tissues, the...

Cell Cycle Regulators And Neurodegeneration

Consistent with reactivation of cell cycle components and uncoordinated cell cycle reentry playing a role in neuronal death, the up-regulation of cell cycle-related proteins, have been found in terminally differentiated neurons committed to or undergoing apoptotic cell death in a number of neurodegenerative models and diseases. In the two mouse neurological mutants, staggerer and lurcher, for example, which are characterized by Purkinje cell deficiencies and substantial cerebellar granule...

Susceptibility Genes In Neurodegeneration

Environmental risk factors alone cannot be responsible for the majority of sporadic forms of neurodegenerative diseases, whose etiology is most likely due to the contribution of several susceptibility genes at multiple loci and interaction between them and or environmental factors. Late onset Alzheimer's disease represents the vast majority of all AD cases with an age at onset of 65 years or older. Studies on both twins and first-degree relatives indicate the existence of a contribution of...

Therapy Of Increased Homocysteine Levels In Pd Patients

Putative therapeutic approaches for the reduction of homocysteine levels are additional folic acid supplementation, since folic acid catalyzes and enhances metabolism of homocysteine to methionine and then S-adenosylmethionine or vitamin B complex administration or the application of COMT inhibitors as adjuncts to levodopa DDI treatment (39,48,62,63). On the one hand, peripherally acting COMT inhibitors increase the bioavailability of levodopa, but on the other hand combination of levodopa DDI...

Conclusion And Therapeutic Outlook

Numerous evidence exists on the pivotal role of OS in the pathogenesis of PD. Research on monogenetic forms of PD in the last few years has provided an increasing understanding of genetic contribution to idiopathic PD also. Moreover, the importance of proper mitochondrial function for the integrity of the nigrostriatal system is obvious, and it has been shown that this vital system affect plays a role in all forms of PD. All three factors leading to pathological cascades - redox imbalance,...

Oxidative Stress In Ms

Recent studies suggest that glutamate plays a role in MS pathophysiology. Oligoden-drocytes, the myelin-producing cell of the CNS, are highly vulnerable to glutamate excitotoxicity, mainly via the AMPA kainate receptors (30,31), which have higher permeability to Ca2+ (32). Demyelinating lesions caused by excitotoxins can be similar to those observed in MS, causing histological damage (30,31,33). Moreover, treatment with AMPA kainate receptor antagonists was found to ameliorate axonal damage and...

Reactive Oxygen Metabolites ROMs as an Index of Oxidative Stress in Obstructive Sleep Apnea Patients

Gourgoulianis OBSTRUCTIVE SLEEP APNEA (OSA) SYNDROME Obstructive sleep apnea syndrome, a common disorder characterized by repetitive pharyngeal collapse during sleep, is receiving increased attention because of convincing data showing important neurocognitive and cardiovascular sequelae (1-9). Dilator muscles and soft tissues are crucial to maintenance of pharyngeal patency since there is no bony support in the region behind the tongue and soft palate (10-12). Change in the...

MtDNA mutagenesis in the brain

MtDNA alteration are possibly associated with neurodegenerative diseases The discovery that mtDNA mutations are of pathological importance (82,129,130), and that mitochondria play an important role in the mechanisms of aging ((131-133), reviewed in (2)) and cell death (7,134) shows the importance of mitochondria in pathological research. The spectrum of phenotypes has expanded from rare myopathies to multiple diseases representing virtually all branches of medicine. The possibility that some of...

Oxidation And Reduction Prooxidants And Antioxidants

Oxidation is defined as a loss of electrons, and reduction is a gain of electrons (87). An oxidant is a substance that is reduced by donating electrons, thus causing a reductant to be oxidized by the donated electrons. Reductant and oxidant are chemical terms, whereas antioxidant and pro-oxidant, or simply oxidant, have meaning in the context of a biological system. An antioxidant can be defined as a substance that, when present at low concentrations as compared to those of an oxidizable...

References

Teran-Santos J, Jimenez-Gomez A, Cordero-Guervara J. The association between sleep apnoea and the risk of traffic accidents. Cooperative Group Burgos-Santader. N Engl J Med. 340 847-851, 1999. 2. Jenkinson C, Davies RJ, Mullins R, Stradling JR. Comparison of therapeutic and subtherapeutic nasal continuous positive airway pressure for obstructive sleep apnoea a randomised prospective parallel trial. Lancet 353 2100-2105, 1999. 3. Faccenda J, Boon NA, Mackay TW, Douglas NJ. CPAP effects on blood...

S N

Neuroinflammation, free radicals, and A -induced neurotoxicity A 42, the primary constituent of A plaques in AD, is hypothesized to cause neuronal damage and cognitive failure via the generation of free radicals, mitochondrial oxidative damage, and inflammation (69-74). Several studies have shown that A fragments induce generation of free radicals under in vitro conditions (75-77), which subsequently leads to membrane lipid peroxidation and toxicity (76,79). Using multiphoton imaging, McLellan...

Introduction

The brain utilizes about 20 of respired oxygen, even though it represents only 5 of the body weight. Free radicals are generated in the brain during normal intake of oxygen, during infection, and during normal oxidative metabolism of certain substrates. Oxidative damage is highly relevant in the brain (1) because it (1) is a post-mitotic tissue with a high energy demand (2) is exposed to high oxygen concentrations, utilizing about one-fifth of the oxygen consumed by the body (3) contains...

Heme Oxygenase

Until 1997, two HO isoforms were described an inducible isoform, HO-1 and a constitutive isoform HO-2. These isoforms are the products of different genes and share only 43 homology. A 24-amino-acid segment, which forms a hydrophobic pocket within the tertiary structure of the protein, is common to both the isoforms and is considered the active center of the enzyme (67). Metalloporphyrins such as Zn-protoporphyrin-IX and Sn-protoporphyrin-IX (Zn-PP-IX and Sn-PP-IX, respectively) bind to the...

Mitochondrial Dna Damage And Repair

MtDNA mutation rate is faster than alterations in nuclear DNA In 1979, it was estimated that nucleotide substitutions are present at a 10-fold higher frequency in mtDNA than in nuclear DNA. The rate of mtDNA evolution is faster than that of nuclear DNA (13,14), which may reflect an increased susceptibility to mutations (15). The mtDNA undergoes a continuous turnover both in mitotic and post-mitotic cells that increases the chance of mutations. Alterations to the structure of mtDNA during aging...

Info

Chemokines and disease. Nat Immunol. 2 108-115, 2001. 156. Banisadr G, Queraud-Lesaux F, Boutterin MC, Pelaprat D, Zale B, Rostene W, Haour F, Parasadaniantz SM. Distribution, cellular localization and functional role of CCR2 chemokine receptors in adult rat brain. J Neurochem. 81 257-269, 2002. 157. Nordal RA, Nagy A, Pintilie M, Wong CS. Hypoxia and hypoxia-inducible factor-1 target genes in central nervous system radiation injury a role for vascular endothelial...

Contributors

Numbers in parentheses indicate the pages on which the authors' contributions begin Galip Agaoglu, (543), The Cleveland Clinic, Department of Plastic and Reconstructive, Surgery Microsurgery, The State University of Cleveland, USA. Margarita L. Alexandrova, (313), Department of Biophysics, Medical University, 1 Kliment Ohridsky str., 5800 Pleven, Bulgaria. Gjumrakch Aliev, (267), Department of Pathology, Case Western Reserve University, Cleveland, OH 44106, USA. Michael Aschner, (433), Life...

Mapt

Multiple system degeneration, balloned neurons, tau plaques Frontotemporal atrophy, Pick bodies, Pick cells, hippocampal atrophy, argyrophilic grains Alzheimer or other pathologies Mild cognitive impairment, normal cognition or dementia Frontotemporal dementia + parkinsonism (FTDP 17)

Antioxidants As Possible Treatment For Ms

Antioxidants are exogenous (natural or synthetic) or endogenous compounds acting to reduce or diminish the oxidative stress. The natural antioxidant system includes enzymes (i.e. superoxide dismutase (SOD), catalase, peroxidase, and some supporting enzymes), and low-molecular-weight antioxidants (LMWA), which contain ascorbic acid, lipoic acid, polyphenols, carotenoids, and vitamin E (14). The pathogenic role of oxygen and nitrogen free radicals in MS led to the recognition that antioxidants...

Genes and Oxidative Stress in Sporadic and Familial Parkinsonism cDNA Microarray Studies

Riederer, and M.B.H. Youdim INTRODUCTION In several neurodegenerative diseases, such as Parkinson's disease (PD), Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), prion disease and their models, oxidative stress (OS) mechanisms are thought to be involved, resulting in the generation of reactive oxygen species (ROS), as well as glutamate receptor abnormalities, ubiquitin-proteasome dysfunction, inflammatory and cytokine activation, dysfunction in...

The Role Of Oxidative Stress In Radiationinduced Late Effects

A number of factors contribute to the inherent vulnerability of the brain and neural tissue to oxidative stress. The brain represents one of the most metabolically active organs in the body, consuming an inordinate fraction 20 of the total O2 consumption for its relatively small weight 2 134 . This leads to a relatively high intracellular production of O2- and other ROS 2-5 of the O2 consumed in mitochondrial electron transport is converted to O2-. In addition, studies using isolated brain...

Cell Culture Models

Recent epidemiological studies have implied that heterogeneous environmental risk factors may potentiate unidentified genetic susceptibility component in PD 12 . These data encouraged the investigation of environmental factors influencing PD in cell culture models. Many epidemiological studies have pointed to several compounds involved as neurotoxicants in dopaminergic cells. These are such as paraquat a herbicide 13 , dieldrin an organochlorine pesticide 14 , salsolinol dopamine-derived...