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The Effect of Cholesterol-Lowering and Antioxidant …

In a balanced cell state, ROS are produced as a byproduct of metabolic processes and the level of ROS can be controlled with antioxidants, such as small molecular weight dietary supplements, including vitamin E and vitamin C; small molecular weight peptides and cofactors, including glutathione and pyruvate; and enzymes, including superoxide dismutase and catalase (2). In a state of cellular imbalance, in which the levels of oxidants outweigh the levels of antioxidants, damage is caused to nuclear and mitochondrial DNA, proteins, and lipids. If this damage is irreparable, then injury, mutagenesis, carcinogenesis, accelerated senescence, and cell death can occur (2). Oxidative stress has been linked to diseases, including some allergic and inflammatory skin diseases (3), Alzheimers (4), atherosclerosis in diabetes patients (5), and Lou Gehrig disease (6).

23/02/1995 · Results

The antioxidants are essential molecules in human system but are not miracle molecules. They are neither performance enhancers nor can prevent or cure diseases when taken in excess. Their supplemental value is debateable. In fact, many high quality clinical trials on antioxidant supplement have shown no effect or adverse outcomes ranging from morbidity to all cause mortality. Several Chochrane Meta-analysis and Markov Model techniques, which are presently best available statistical models to derive conclusive answers for comparing large number of trials, support these claims. Nevertheless none of these statistical techniques are flawless. Hence, more efforts are needed to develop perfect statistical model to analyze the pooled data and further double blind, placebo controlled interventional clinical trials, which are gold standard, should be implicitly conducted to get explicit answers. Superoxide dismutase (SOD), glutathione peroxidase and catalase are termed as primary antioxidants as these scavenge superoxide anion and hydrogen peroxide. All these three enzymes are inducible enzymes, thereby inherently meaning that body increases or decreases their activity as per requirement. Hence there is no need to attempt to manipulate their activity nor have such efforts been clinically useful. SOD administration has been tried in some conditions especially in cancer and myocardial infarction but has largely failed, probably because SOD is a large molecule and can not cross cell membrane. The dietary antioxidants, including nutrient antioxidants are chain breaking antioxidants and in tandem with enzyme antioxidants temper the reactive oxygen species (ROS) and reactive nitrogen species (RNS) within physiological limits. Since body is able to regulate its own requirements of enzyme antioxidants, the diet must provide adequate quantity of non-enzymic antioxidants to meet the normal requirements and provide protection in exigent condition. So far, there is no evidence that human tissues ever experience the torrent of reactive species and that in chronic conditions with mildly enhanced generation of reactive species, the body can meet them squarely if antioxidants defense system in tissues is biochemically optimized. We are not yet certain about optimal levels of antioxidants in tissues. Two ways have been used to assess them: first by dietary intake and second by measuring plasma levels. Lately determination of plasma/serum level of antioxidants is considered better index for diagnostic and prognostic purposes. The recommended levels for vitamin A, E and C and beta carotene are 2.2–2.8 μmol/l; 27.5–30 μmol/l; 40–50 μmol/l and 0.4–0.5 μmol/l, respectively. The requirement and recommended blood levels of other dietary antioxidants are not established. The resolved issues are (1) essential to scavenge excess of radical species (2) participants in redox homeostasis (3) selective antioxidants activity against radical species (4) there is no universal antioxidant and 5) therapeutic value in case of deficiency. The overarching issues are (1) therapeutic value as adjuvant therapy in management of diseases (2) supplemental value in developing population (3) selective interactivity of antioxidant in different tissues and on different substrates (4) quantitative contribution in redox balance (5) mechanisms of adverse action on excess supplementation (6) advantages and disadvantages of prooxidant behavior of antioxidants (7) behavior in cohorts with polymorphic differences (8) interaction and intervention in radiotherapy, diabetes and diabetic complications and cardiovascular diseases (9) preventive behavior in neurological disorders (10) benefits of non-nutrient dietary antioxidants (11) markers to assess optimized antioxidants status (12) assessment of benefits of supplementation in alcoholics and heavy smokers. The unresolved and intriguing issues are (1) many compounds such as vitamin A and many others possessing both antioxidant and non-antioxidant properties contribute to both the activities in vivo or exclusively only to non-antioxidant activity and (2) since human tissues do not experience the surge of FR, whether there is any need to develop stronger synthetic antioxidants. Theoretically such antioxidants may do more harm than good.

Vitamin E, Heart Disease and Tocotrienols - Jeffrey …

Vitamin E, Heart Disease and Tocotrienols by Jeffrey Dach MD

In this study, we examined lipid peroxidation products, ie, thiobarbituric acid reactive substances (TBARS) and LDL-conjugated diene, formed as a result of oxidative stress generated in a hypercholesterolemic atherosclerosis model in rabbits. The antioxidant activity of defensive enzymes, including superoxide dismutase, catalase, and paraoxonase, was also investigated to determine oxidative status. The effects of atorvastatin, a potent HMG-Co A reductase inhibitor, with the longest half-life of its group, was evaluated for its influence on lipid profiles, lipid peroxidation, and the antioxidant system, as well as its impact on paraoxonase activity. In addition, atherosclerotic plaque formation and the outcome of atorvastatin treatment was assessed histopathologically.

Advances in the management of hypercholesterolemia are primarily due to the development of the 3-hydroxy-3-methylglutaryl coenzyme (HMG-Co A) reductase inhibitors, ie, the statins. Recently, many statins have been used for their overall antihypercholesterolemic action in patients with atherosclerosis. They are presumed to work by upregulating the LDL receptor, thereby lowering LDL cholesterol in particular. In addition to lowering cholesterol levels, statins seem to act on the formation and progression of atherosclerotic plaque through alternative mechanisms involved in progression of the disease. The various statins differ in their pharmacokinetics, therapeutic efficacy, drug interactions, dosage, and administration, and therefore they differ in their potential advantages and disadvantages. Reduction of lipid peroxidation may be one of the important features explaining the favorable effect of statins in preventing or reducing atherosclerosis. Even though some investigators have shown the antioxidant potential of statins in vitro, in vitro investigations may not be the best approach to evaluate the effects of these agents because many other relevant events may be taking place in vivo.

This article is part two of a series, for part one, click here

Vitamin C is an antioxidant that is required for at least 300 metabolic functions including tissue growth and repair, adrenal functioning, and oral health. It aids in the production of anti-stress hormones and the immune system protein, interferon. It is needed for the metabolism of folic acid, tyrosine, and phenylalanine. Vitamin C can reduce the symptoms of asthma, and protect against the effects of pollution. It is cancer preventative, protects against infection and boosts the immune system. Vitamin C is able to combine with certain heavy metals and other toxic substances, and escort them out of the body. It is instrumental in lowering blood pressure and helping to prevent atherosclerosis and blood clots. It has anti-aging properties and is essential in the formation of collagen.

The results of this study demonstrate the success of atorvastatin therapy in alleviating the production of LDL TBARS and LDL-conjugated diene. The oxidatively modified lipids and their degradation products are believed to have proinflammatory, immunogenic, and cytotoxic properties which contribute to both the initiation and progression of atherosclerotic lesions. It is reported that products of oxidatively modified LDL contribute to recruitment of monocytes and T cells, directly or indirectly, via induction of chemokines and endothelial cell adhesion molecules. The present study supports this hypothesis, with histopathological examination showing atherosclerotic plaque formation and nearly 50% luminal narrowing ( and ) in aortic tissue from the nontreated atherogenic diet group.

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Effects of Different Cooking Methods on Nutritional …

For the nutritional intervention, no significant difference (after 3 weeks of consumption of 96 g/day of tomato puree) was found between the two purees with regard to their ability to affect the plasma levels of the two major antioxidants, vitamin C and lycopene.

Herbs that help with Chemo & Radiation - distance …

Systemic Lupus Erythematosus (SLE) is a chronic, usually life-long, potentially fatal autoimmune disease, characterized by unpredictable exacerbations and remissions with protean clinical manifestations. There is a predilection for clinical involvement of the joints, skin, kidney, brain, serosa, lug, heart and gastrointestinal tract.

SLE is an autoimmune disease characterized by immune dysregulation, resulting in the production of antinuclear antibodies, generation of circulating immune complexes, and activation of the complement system. SLE is notable for unpredictable exacerbations and remissions and a predilection for clinical involvement of the joints, skin, kidney, brain, serosa, lung, heart, and gastrointestinal tract. The pathologic hallmark of the disease is recurrent, widespread, and diverse vascular lesions. The clinical features of SLE are protean and may mimic infectious mononucleosis, lymphoma, or other systemic disease. The etiology remains unknown. A genetic predisposition, sex hormones, and environmental trigger(s) likely result in the disordered immune response that typifies SLE.

The origin of auto-antibody production in SLE is unclear but a role is suggested for an antigen driven process, spontaneous B-cell hyper-responsiveness, or impaired immune regulation. Regardless of the etiology, SLE is associated with the impaired clearance of circulating immune complexes secondary to decreased CR1 expression, defective Fc receptor function, or deficiencies of early complement components such as C4A. More is known about the pathogenic cellular and molecular events responsible for vascular lesions than the origins of autoimmunity.

Disease manifestations result from recurrent vascular injury due to immune complex deposition, leukothrombosis, or thrombosis. Additionally, cytotoxic antibodies can mediate autoimmune hemolytic anemia and thrombocytopenia, while antibodies to specific cellular antigens can disrupt cellular function. The health status of a patient is related not only to disease activity, but to the damage that results from recurrent episodes of disease flare (deforming arthropathy, shrinking lung, end stage renal disease, organic mental syndrome, etc.), as well as the adverse effects of treatment (i.e. avascular necrosis of bone, infections, and precocious atherosclerosis, etc.).

Drugs such as procainamide or hydralazine can induce the production of antinuclear antibodies, especially anti-histone antibodies, and occasionally a SLE-like illness. Drug induced lupus is usually characterized by fever, hematological abnormalities such as an autoimmune hemolytic anemia or autoimmune thrombocytopenia, or serositis. Skin, renal and neurologic manifestations are uncommon. Neonatal or congenital lupus occurs when the transplacental acquisition of auto-antibodies produce in the neonate a transient photosensitive rash, confential complete heart block, thrombocytopenia or rarely hepatobiliary dysfunction.

Presenting Signs and Symptoms: 80% of patients with SLE will present with involvement of the skin or joints. A common presenting complaint is a photosensitive rash often with alopecia. Alternatively, patients may present with arthralgia or frank arthritis. However, patients may present with fever accompanied by single organ involvement, such as inflammatory serositis, glomerulonephritis, neuropsychiatric disturbance or hematological disorder (autoimmune hemolytic anemia or thrombocytopenia).

90% of patients with SLE experience fatigue. Arthralgia and myalgia often accompany complaints of malaise. Also common and a more serious constitutional feature of SLE is persistent fever and weight loss. Musculoskeletal: Approximately 90% of patients with SLE have musculoskeletal symptoms, typically arthralgia. Less common is frank inflammatory myositis, which occurs occasionally during the course of SLE.

Mucosal ulcers are not an infrequent complication of lupus, occurring in 30% of patients, painful when there is a secondary infection, such as oral candidiasis.

Approximately 80% of patients with SLE have dermatological manifestations during the course of their illness, manifest as a photosensitive rash. Alopecia occurs in 50% of patients, typically manifest as reversible hair thinning during periods of disease activity.

Anemia is a common feature of exacerbated SLE. Autoimmune thrombocytopenia purpura can be a presenting feature, as can thrombocytopenia and leukopenia with lymphopenia.

Although the majority of patients with SLE have glomeruplopathy, clinically relevant kidney disease occurs in about 50% of patients, a consequence of deposition of immune complexes containing anti-DNA in the kidney.

Central Nervous System:
Neuropsychiatric complications occur in 50% of SLE patients and include acute and chronic, as well as focal and diffuse manifestations. Seizures complicate the course in 25% of patients. Recurrent involvement of the central nervous system may result in an organic brain syndrome and dementia.

The most common involvement of the lung is inflammatory serositis, producing pleuritis. However, patients with lupus can develop transient hypoxia on the basis of pulmonary leukosequestration, inflammatory pneumonitis, interstitial pulmonary fibrosis, pulmonary hypertension, diaphragmatic dysfunction, and phrenic nerve palsy.

The most common cardiac manifestation is pericarditis and myocarditis.
Gastrointestinal: Medical peritonitis with or without ascites is a manifestation of lupus involving the peritoneum.

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