Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Restricting caloric intake to 60-70% of normal adult weight maintenance requirement prolongs lifespan 30-50% and confers near perfect health across a broad range of species. Every other day feeding produces similar effects in rodents, and profound beneficial physiologic changes have been demonstrated in the absence of weight loss in ob/ob mice. Since May 2003 we have experimented with alternate day calorie restriction, one day consuming 20-50% of estimated daily caloric requirement and the next day ad lib eating, and have observed health benefits starting in as little as two weeks, in insulin resistance, asthma, seasonal allergies, infectious diseases of viral, bacterial and fungal origin (viral URI, recurrent bacterial tonsillitis, chronic sinusitis, periodontal disease), autoimmune disorder (rheumatoid arthritis), osteoarthritis, symptoms due to CNS inflammatory lesions (Tourette's, Meniere's) cardiac arrhythmias (PVCs, atrial fibrillation), menopause related hot flashes. We hypothesize that other many conditions would be delayed, prevented or improved, including Alzheimer's, Parkinson's, multiple sclerosis, brain injury due to thrombotic stroke atherosclerosis, NIDDM, congestive heart failure. Our hypothesis is supported by an article from 1957 in the Spanish medical literature which due to a translation error has been construed by several authors to be the only existing example of calorie restriction with good nutrition. We contend for reasons cited that there was no reduction in calories overall, but that the subjects were eating, on alternate days, either 900 calories or 2300 calories, averaging 1600, and that body weight was maintained. Thus they consumed either 56% or 144% of daily caloric requirement. The subjects were in a residence for old people, and all were in perfect health and over 65. Over three years, there were 6 deaths among 60 study subjects and 13 deaths among 60 ad lib-fed controls, non-significant difference. Study subjects were in hospital 123 days, controls 219, highly significant difference. We believe widespread use of this pattern of eating could impact influenza epidemics and other communicable diseases by improving resistance to infection. In addition to the health effects, this pattern of eating has proven to be a good method of weight control, and we are continuing to study the process in conjunction with the NIH.
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PMID:The effect on health of alternate day calorie restriction: eating less and more than needed on alternate days prolongs life. 1652 78

Heat shock proteins (hsp's) are among the most conserved proteins in evolution. They have been identified as important pathogen-related antigens as well as autoantigens suitable for construction of novel vaccines. The high evolutionary homology of hsp's has raised the question about the safety of such vaccines. Experimental and clinical observations have confirmed that hsp proteins are involved in the regulation of some autoimmune disease such as autoimmune arthritis, type 1 diabetes mellitus, atherosclerosis, multiple sclerosis, and other autoimmune reactions. It has been shown in experimental animals that some hsp proteins (especially hsp60, hsp70, and hsp10) can either induce or prevent autoimmune reactions depending on the circumstances. This article discusses the involvement of hsp proteins in the etiology of autoimmune diseases and it presents promising experimental data on the effects of immunization with hsp proteins in the prevention and therapy of autoimmune diseases.
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PMID:Heat shock proteins in autoimmune diseases. 1660 63

In the past years, statins have emerged as the most important class of lipid lowering agents. Through inhibition of HMG-CoA reductase, they restrict the rate-limiting step of cholesterol synthesis, which leads to upregulation of LDL receptors on the cell membrane and thus reduction of atherogenic LDLs. This effect translates into clinical benefit by reducing cardiovascular events both in primary and secondary prevention settings. As an approximate rule, statin therapy leads to a relative risk reduction of 25-30% in most of the large randomised controlled trials. Stroke risk is reduced to a similar degree. Despite initial concerns, the currently available statins have a favourable safety profile; however, potential interactions with other drugs must be considered. Recently, characteristics unrelated to LDL lowering have been intensively studied. These pleiotropic statin effects result from decreased levels of isoprenoid intermediates of cholesterol synthesis. They include--among others--anti-inflammatory, anti-proliferative, and immunomodulatory actions. Pleiotropic effects favourably influence pathomechanisms of plaque formation. Furthermore, they may prove beneficial in the prevention or treatment of diseases unrelated to atherosclerosis, eg rheumatoid arthritis, multiple sclerosis, or cancer.
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PMID:The role of statins in clinical medicine--LDL--cholesterol lowering and beyond. 1663 45

Uncoupling protein 2 (UCP2) is a member of the mitochondrial transporter superfamily that is expressed in many tissues, including immune cells. UCP2 prevents oxidative stress by reducing reactive oxygen species. Using UCP2-deficient mice, it was shown that UCP2 is involved in the regulation of insulin secretion, in the resistance to infection, and in atherosclerosis. Here, we investigated the role of UCP2 in experimental autoimmune encephalomyelitis, a murine model of multiple sclerosis. Immunized C57BL/6J UCP2-deficient mice showed a slightly delayed onset during experimental autoimmune encephalomyelitis (13.0 +/- 0.6 versus 11.5 +/- 0.8 in wild-type controls) and developed significantly higher disease scores than littermate controls (maximum disease score of 2.9 +/- 0.2 versus 1.7 +/- 0.2, P = 0.001). Higher levels of infiltrating T cells into the spinal cord meninges and parenchyma were observed. The T-cell proliferative response to the specific antigen was increased in UCP2-deficient mice compared with littermate controls, and CD4 cells of UCP2 knockout mice produced significantly higher levels of pro-inflammatory cytokines, eg, tumor necrosis factor-alpha and interleukin-2, resulting from a Th1 response. Mice lacking UCP2 also developed a higher B-cell response. Concomitantly, CD4 and CD8 cells of the UCP2-deficient mice showed increased production of reactive oxygen species. These results suggest a protective function of UCP2 in chronic inflammatory diseases such as multiple sclerosis.
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PMID:Uncoupling protein 2 has protective function during experimental autoimmune encephalomyelitis. 1665 23

Matrix metalloproteinases (also named matrixin or MMPs) are a major group of enzymes that regulate cell-matrix composition by using zinc for their proteolytic activities. They are essential for various normal biological processes such as embryonic development, morphogenesis, reproduction tissue resorption, and remodeling. Metalloproteinases also play a role in pathological processes including inflammation, arthritis, cardiovascular diseases, pulmonary diseases and cancer. Herein we review the involvement of MMP-9 in a variety of autoimmune diseases including systemic lupus erythematosus, Sjogren's syndrome, systemic sclerosis, rheumatoid arthritis, multiple sclerosis, polymyositis and atherosclerosis. MMP-9 plays either a primary or secondary role in each one of those autoimmune diseases by its up or down-regulation. It is not expressed constantly but rather is induced or suppressed by many regulating molecules. This feature of MMP-9 along with its involvement in disease pathogenesis turns it into a target for therapy of autoimmune diseases.
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PMID:Matrix metalloproteinase-9 and autoimmune diseases. 1665 30

Habitual cannabis use has been shown to affect the human immune system, and recent advances in endocannabinoid research provide a basis for understanding these immunomodulatory effects. Cell-based experiments or in vivo animal testing suggest that regulation of the endocannabinoid circuitry can impact almost every major function associated with the immune system. These studies were assisted by the development of numerous novel molecules that exert their biological effects through the endocannabinoid system. Several of these compounds were tested for their effects on immune function, and the results suggest therapeutic opportunities for a variety of inflammatory diseases such as multiple sclerosis, rheumatoid arthritis, inflammatory bowel disease, atherosclerosis, allergic asthma, and autoimmune diabetes through modulation of the endocannabinoid system.
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PMID:The cannabinergic system as a target for anti-inflammatory therapies. 1691 57

Inflammation is traditionally viewed as a physiological reaction to tissue injury. Leukocytes contribute to the inflammatory response by the secretion of cytotoxic and pro-inflammatory compounds, by phagocytotic activity and by targeted attack of foreign antigens. Leukocyte accumulation in tissues is important for the initial response to injury. However, the overzealous accumulation of leukocytes in tissues also contributes to a wide variety of diseases, such as atherosclerosis, chronic inflammatory bowel disease, rheumatoid arthritis, multiple sclerosis, vasculitis, systemic inflammatory response syndrome, juvenile diabetes and psoriasis. Many therapeutic interventions target immune cells after they have already migrated to the site of inflammation. This review addresses different therapeutic strategies, used to reduce or prevent leukocyte-endothelial cell interactions and communication, in order to limit the progression of inflammatory diseases.
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PMID:Therapeutic targeting of molecules involved in leukocyte-endothelial cell interactions. 1695 69

The recent identification of cannabinoid receptors and their endogenous lipid ligands has triggered an exponential growth of studies exploring the endocannabinoid system and its regulatory functions in health and disease. Such studies have been greatly facilitated by the introduction of selective cannabinoid receptor antagonists and inhibitors of endocannabinoid metabolism and transport, as well as mice deficient in cannabinoid receptors or the endocannabinoid-degrading enzyme fatty acid amidohydrolase. In the past decade, the endocannabinoid system has been implicated in a growing number of physiological functions, both in the central and peripheral nervous systems and in peripheral organs. More importantly, modulating the activity of the endocannabinoid system turned out to hold therapeutic promise in a wide range of disparate diseases and pathological conditions, ranging from mood and anxiety disorders, movement disorders such as Parkinson's and Huntington's disease, neuropathic pain, multiple sclerosis and spinal cord injury, to cancer, atherosclerosis, myocardial infarction, stroke, hypertension, glaucoma, obesity/metabolic syndrome, and osteoporosis, to name just a few. An impediment to the development of cannabinoid medications has been the socially unacceptable psychoactive properties of plant-derived or synthetic agonists, mediated by CB(1) receptors. However, this problem does not arise when the therapeutic aim is achieved by treatment with a CB(1) receptor antagonist, such as in obesity, and may also be absent when the action of endocannabinoids is enhanced indirectly through blocking their metabolism or transport. The use of selective CB(2) receptor agonists, which lack psychoactive properties, could represent another promising avenue for certain conditions. The abuse potential of plant-derived cannabinoids may also be limited through the use of preparations with controlled composition and the careful selection of dose and route of administration. The growing number of preclinical studies and clinical trials with compounds that modulate the endocannabinoid system will probably result in novel therapeutic approaches in a number of diseases for which current treatments do not fully address the patients' need. Here, we provide a comprehensive overview on the current state of knowledge of the endocannabinoid system as a target of pharmacotherapy.
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PMID:The endocannabinoid system as an emerging target of pharmacotherapy. 1696 47

Changes in human DNA methylation patterns are an important feature of cancer development and progression and a potential role in other conditions such as atherosclerosis and autoimmune diseases (e.g., multiple sclerosis and lupus) is being recognised. The cancer genome is frequently characterised by hypermethylation of specific genes concurrently with an overall decrease in the level of 5 methyl cytosine. This hypomethylation of the genome largely affects the intergenic and intronic regions of the DNA, particularly repeat sequences and transposable elements, and is believed to result in chromosomal instability and increased mutation events. This review examines our understanding of the patterns of cancer-associated hypomethylation, and how recent advances in understanding of chromatin biology may help elucidate the mechanisms underlying repeat sequence demethylation. It also considers how global demethylation of repeat sequences including transposable elements and the site-specific hypomethylation of certain genes might contribute to the deleterious effects that ultimately result in the initiation and progression of cancer and other diseases. The use of hypomethylation of interspersed repeat sequences and genes as potential biomarkers in the early detection of tumors and their prognostic use in monitoring disease progression are also examined.
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PMID:DNA hypomethylation and human diseases. 1704 45

Matrix metalloproteinases (MMPs) are a family of zinc- and calcium-dependent secreted or membrane anchored endopeptidases. MMPs are involved in many physiological processes but also take part in the pathophysiological mechanisms responsible for a wide range of diseases. Pathological expression and activation of MMPs are associated with cancer, atherosclerosis, stroke, arthritis, periodontal disease, multiple sclerosis and liver fibrosis. Thus, noninvasive visualisation and quantification of MMP activity in vivo are of great interest in basic research and clinical application. This can be achieved by scintigraphic molecular imaging techniques such as single photon emission computed tomography (SPECT) and positron emission tomography (PET) provided suitable radiolabelled tracers exist, e.g. radioactive inhibitors of matrix metalloproteinases (MMPIs). The approach to monitor MMP activity in vivo using radiolabelled small molecule inhibitors suitable for SPECT and PET is summarised in this review. Briefly, latest advances in scintigraphic imaging are introduced and followed by a report about the enzyme class of MMPs. The involvement of MMPs in cancer and atherosclerosis is exemplified and small molecule MMPIs are classified. Subsequently, the development of radiolabelled small molecule MMPIs, their synthesis and in vitro and in vivo evaluation is reviewed. Finally, an outlook on the clinical potential of labelled MMPIs in diagnostic algorithms is given.
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PMID:Molecular imaging of matrix metalloproteinases in vivo using small molecule inhibitors for SPECT and PET. 1707 31


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