Never Hire Me to do Research

Never hire me to do research. I am not trained in the scientific process as I am an engineer.  I take my research too personally and I jump to conclusions and become angry. Correlation is not causation, bla bla bla.  I make stupid jokes that nobody laughs at. I am predicting things due to dark energy when nobody knows what or where it is.  I get musicians to sing songs thinking they are more sensitive about life and dark energy then the rest of us. I send emails to scientists I don’t even know.  I have become obsessed with my research and I need to get a life. Phew, I feel better now.

Oxidative Stress Hypothesis in Alzheimer’s Disease

The major hurdle in understanding Alzheimer’s disease (AD) is a lack of knowledge about the etiology and pathogenesis of selective neuron death. In recent years, considerable data have accrued indicating that the brain in AD is under increased oxidative stress and this may have a role in the pathogenesis of neuron degeneration and death in this disorder. The direct evidence supporting increased oxidative stress in AD is: (1) increased brain Fe, Al, and Hg in AD, capable of stimulating free radical generation; (2) increased lipid peroxidation and decreased polyunsaturated fatty acids in the AD brain, and increased 4-hydroxynonenal, an aldehyde product of lipid peroxidation in AD ventricular fluid; (3) increased protein and DNA oxidation in the AD brain; (4) diminished energy metabolism and decreased cytochrome c oxidase in the brain in AD; (5) advanced glycation end products (AGE), malondialdehyde, carbonyls, peroxynitrite, heme oxygenase-1 and SOD-1 in neurofibrillary tangles and AGE, heme oxygenase-1, SOD-1 in senile plaques; and (6) studies showing that amyloid beta peptide is capable of generating free radicals. Supporting indirect evidence comes from a variety of in vitro studies showing that free radicals are capable of mediating neuron degeneration and death. Overall, these studies indicate that free radicals are possibly involved in the pathogenesis of neuron death in AD. Because tissue injury itself can induce reactive oxygen species (ROS) generation, it is not known whether this is a primary or secondary event. Even if free radical generation is secondary to other initiating causes, they are deleterious and part of a cascade of events that can lead to neuron death, suggesting that therapeutic efforts aimed at removal of ROS or prevention of their formation may be beneficial in AD. © 1997 Elsevier Science Inc.

Oxidative stress in autism

Autism is a severe developmental disorder with poorly understood etiology. Oxidative stress in autism has been studied at the membrane
level and also by measuring products of lipid peroxidation, detoxifying agents (such as glutathione), and antioxidants involved in the defense
system against reactive oxygen species (ROS). Lipid peroxidation markers are elevated in autism, indicating that oxidative stress is increased
in this disease. Levels of major antioxidant serum proteins, namely transferrin (iron-binding protein) and ceruloplasmin (copper-binding
protein), are decreased in children with autism. There is a positive correlation between reduced levels of these proteins and loss of previously
acquired language skills in children with autism. The alterations in ceruloplasmin and transferrin levels may lead to abnormal iron and copper
metabolism in autism. The membrane phospholipids, the prime target of ROS, are also altered in autism. The levels of phosphatidylethanolamine
(PE) are decreased, and phosphatidylserine (PS) levels are increased in the erythrocyte membrane of children with autism as compared to
their unaffected siblings. Several studies have suggested alterations in the activities of antioxidant enzymes such as superoxide dismutase,
glutathione peroxidase, and catalase in autism. Additionally, altered glutathione levels and homocysteine/methionine metabolism, increased
inflammation, excitotoxicity, as well as mitochondrial and immune dysfunction have been suggested in autism. Furthermore, environmental
and genetic factors may increase vulnerability to oxidative stress in autism. Taken together, these studies suggest increased oxidative stress
in autism that may contribute to the development of this disease. A mechanism linking oxidative stress with membrane lipid abnormalities,
inflammation, aberrant immune response, impaired energy metabolism and excitotoxicity, leading to clinical symptoms and pathogenesis of
autism is proposed. © 2006 Elsevier Ireland Ltd. All rights reserved

Free radicals, metals and antioxidants in oxidative stress-induced cancer

Oxygen-free radicals, more generally known as reactive oxygen species (ROS) along with reactive nitrogen species (RNS) are
well recognised for playing a dual role as both deleterious and beneficial species. The “two-faced” character of ROS is substantiated
by growing body of evidence that ROS within cells act as secondary messengers in intracellular signalling cascades, which induce
and maintain the oncogenic phenotype of cancer cells, however, ROS can also induce cellular senescence and apoptosis and can
therefore function as anti-tumourigenic species. The cumulative production of ROS/RNS through either endogenous or exogenous
insults is termed oxidative stress and is common for many types of cancer cell that are linked with altered redox regulation of cellular
signalling pathways. Oxidative stress induces a cellular redox imbalance which has been found to be present in various cancer cells
compared with normal cells; the redox imbalance thus may be related to oncogenic stimulation. DNA mutation is a critical step in
carcinogenesis and elevated levels of oxidative DNA lesions (8-OH-G) have been noted in various tumours, strongly implicating such
damage in the etiology of cancer. It appears that the DNA damage is predominantly linked with the initiation process. This review
examines the evidence for involvement of the oxidative stress in the carcinogenesis process. Attention is focused on structural,
chemical and biochemical aspects of free radicals, the endogenous and exogenous sources of their generation, the metal (iron,
copper, chromium, cobalt, vanadium, cadmium, arsenic, nickel)-mediated formation of free radicals (e.g. Fenton chemistry), the
DNA damage (both mitochondrial and nuclear), the damage to lipids and proteins by free radicals, the phenomenon of oxidative
stress, cancer and the redox environment of a cell, the mechanisms of carcinogenesis and the role of signalling cascades by ROS;
in particular, ROS activation of AP-1 (activator protein) and NF-
B (nuclear factor kappa B) signal transduction pathways, which
in turn lead to the transcription of genes involved in cell growth regulatory pathways. The role of enzymatic (superoxide dismutase
(Cu, Zn-SOD, Mn-SOD), catalase, glutathione peroxidase) and non-enzymatic antioxidants (Vitamin C, Vitamin E, carotenoids,
thiol antioxidants (glutathione, thioredoxin and lipoic acid), flavonoids, selenium and others) in the process of carcinogenesis as
well as the antioxidant interactions with various regulatory factors, including Ref-1, NF-
B, AP-1 are also reviewed.
© 2006 Elsevier Ireland Ltd. All rights reserved.