Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002736 (amyotrophic lateral sclerosis)
 19,048 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The possible role of trace elements in a pathogenesis of central nervous system (CNS) on degenerative and demyelinating diseases has been suggested. Simultaneous measurements of Zinc (Zn) and iron (Fe) concentration in CNS were undertaken by neutron activation analysis in CNS tissues: a patient with multiple sclerosis (MS), five patients with amyotrophic lateral sclerosis (ALS), five with spinocerebellar degeneration (SCD), and five with cerebral infarction (CVD) in non-invasive area of CNS as control. Although Zn and Fe concentration were present in white matter and gray matter of CNS in each disease, 1) Zn concentration showed no special pattern in gray matter among four diseases, but decreased more in white matter of MS and ALS than that of CVD (p less than 0.05); 2) Fe concentration in gray matter of SCD increased more than that in CVD (p less than 0.05), but Fe concentration in white matter of CVD was increased more than that of ALS (p less than 0.05); 3) Fe concentration of CNS in a patient with MS was not notable except for high Fe concentration in caudate nucleus and globus pallidus. The demyelinated pathological area in CNS of MS showed a decrease in Zn level but no change in Fe level. These results indicate that low Zn concentration in CNS tissues of MS seemed to be responsible for CNS demyelination, but not for undernutrition due to poor conditions of a patient with MS. It seems that Zn might be one pathogenetic factor of MS, but the action of Fe in MS can not be ruled out.
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PMID:[Zinc concentration in the central nervous system in a case of multiple sclerosis--comparison with other neurological diseases]. 179 99

Quality of life has been used as a primary outcome measure in the treatment of cancer and cardiovascular disease, and as a secondary outcome measure in therapy of Parkinson's disease. However, it has been relatively neglected in studies of amyotrophic lateral sclerosis (ALS). Although there is need for the development of an ALS-specific quality-of-life measure, it will be necessary, nonetheless, to continue to use generic measures in order to ensure comparability of measurement between disease states. An argument is put forward for the use of quality-of-life measures as a primary end-point in future clinical trials in ALS. A distinction is drawn between the demonstration of biological efficacy and clinically useful benefit. The most likely instruments to prove useful are briefly discussed.
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PMID:Health outcome and quality-of-life measurements in amyotrophic lateral sclerosis. 917 68

Exposures to extremely low-frequency electric and magnetic fields (EMF) emanating from the generation, transmission, and use of electricity are a ubiquitous part of modern life. Concern about potential adverse health effects was initially brought to prominence by an epidemiologic report two decades ago from Denver on childhood cancer. We reviewed the now voluminous epidemiologic literature on EMF and risks of chronic disease and conclude the following: a) The quality of epidemiologic studies on this topic has improved over time and several of the recent studies on childhood leukemia and on cancer associated with occupational exposure are close to the limit of what can realistically be achieved in terms of size of study and methodological rigor. b) Exposure assessment is a particular difficulty of EMF epidemiology, in several respects: i) The exposure is imperceptible, ubiquitous, has multiple sources, and can vary greatly over time and short distances. ii) The exposure period of relevance is before the date at which measurements can realistically be obtained and of unknown duration and induction period. iii) The appropriate exposure metric is not known and there are no biological data from which to impute it. c) In the absence of experimental evidence and given the methodological uncertainties in the epidemiologic literature, there is no chronic disease for which an etiological relation to EMF can be regarded as established. d) There has been a large body of high quality data for childhood cancer, and also for adult leukemia and brain tumor in relation to occupational exposure. Among all the outcomes evaluated in epidemiologic studies of EMF, childhood leukemia in relation to postnatal exposures above 0.4 microT is the one for which there is most evidence of an association. The relative risk has been estimated at 2.0 (95% confidence limit: 1.27-3.13) in a large pooled analysis. This is unlikely to be due to chance but, may be, in part, due to bias. This is difficult to interpret in the absence of a known mechanism or reproducible experimental support. In the large pooled analysis only 0.8% of all children were exposed above 0.4 microT. Further studies need to be designed to test specific hypotheses such as aspects of selection bias or exposure. On the basis of epidemiologic findings, evidence shows an association of amyotrophic lateral sclerosis with occupational EMF exposure although confounding is a potential explanation. Breast cancer, cardiovascular disease, and suicide and depression remain unresolved.
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PMID:Review of the epidemiologic literature on EMF and Health. 1174 9

Owing to improving preventative, diagnostic, and therapeutic measures for cardiovascular disease and a variety of cancers, the average ages of North Americans and Europeans continue to rise. Regrettably, accompanying this increase in life span, there has been an increase in the number of individuals afflicted with age-related neurodegenerative disorders, such as Alzheimer's disease, Parkinson's disease, and stroke. Although different cell types and brain areas are vulnerable among these, each disorder likely develops from activation of a common final cascade of biochemical and cellular events that eventually lead to neuronal dysfunction and death. In this regard, different triggers, including oxidative damage to DNA, the overactivation of glutamate receptors, and disruption of cellular calcium homeostasis, albeit initiated by different genetic and/or environmental factors, can instigate a cascade of intracellular events that induce apoptosis. To forestall the neurodegenerative process, we have chosen specific targets to inhibit that are at pivotal rate-limiting steps within the pathological cascade. Such targets include TNF-alpha, p53, and GLP-1 receptor. The cytokine TNF-alpha is elevated in Alzheimer's disease, Parkinson's disease, stroke, and amyotrophic lateral sclerosis. Its synthesis can be reduced via posttranscriptional mechanisms with novel analogues of the classic drug, thalidomide. The intracellular protein and transcription factor, p53, is activated by the Alzheimer's disease toxic peptide, Abeta, as well as by excess glutamate and hypoxia to trigger neural cell death. It is inactivated by novel tetrahydrobenzothiazole and -oxazole analogues to rescue cells from lethal insults. Stimulation of the glucagon-like peptide-1 receptor (GLP-1R) in brain is associated with neurotrophic functions that, additionally, can protect cells against excess glutamate and other toxic insults.
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PMID:New therapeutic strategies and drug candidates for neurodegenerative diseases: p53 and TNF-alpha inhibitors, and GLP-1 receptor agonists. 1568 14

Vascular endothelial growth factor (VEGF) has been implicated in neuronal survival, neuroprotection, regeneration, growth, differentiation, and axonal outgrowth, which are known to be involved in the pathophysiology of major depressive disorder (MDD). Recently, the VEGF mRNA expression in the peripheral leukocytes from Alzheimer's disease or cardiovascular disease was reported to be changed. We hypothesized that the expression of the VEGF mRNA in the peripheral leukocytes may be a good candidate for the biological marker for MDD. Thirty two patients with MDD and age- and sex-matched control subjects were included in this expression study. The VEGF mRNA levels in the peripheral leukocytes from drug-naive MDD patients were significantly higher than those from the control subjects and the magnitude of the decrease of VEGF mRNA after 8-week treatment significantly correlated with clinical improvement. Then, we genotyped two single nucleotide polymorphic markers of VEGF gene, which were reported to be associated with amyotrophic lateral sclerosis and Alzheimer's disease, in patients with MDD and control subjects (n=154, each). We did not find any significant association between these markers and MDD or its clinical subtypes. Our investigation indicates that the higher expression levels of VEGF mRNA in the peripheral leukocytes are associated with the depressive state and their recovery after treatment may be associated with the clinical improvement.
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PMID:Gene expression and association analysis of vascular endothelial growth factor in major depressive disorder. 1725 29

Statin drugs are widely prescribed to achieve aggressive low-density lipoprotein lowering in order to decrease cardiovascular disease. Although some of the immunomodulatory effects of statins may stabilize atherosclerotic plaque, they may be harmful in certain segments of the population. Recently, statins have been shown to increase the concentration of regulatory T cells (Tregs), in vivo. There is evidence that this increases the risk of many cancers, particularly in the elderly. Furthermore, a statin induced increase in Tregs may be detrimental in neurodegenerative disorders, such as amyotrophic lateral sclerosis; and a myriad of infectious diseases. These include, but are not limited to, human immunodeficiency virus, hepatitis B virus, hepatitis C virus, and varicella zoster virus. These issues need our attention, and call for a heightened state of vigilance among those prescribing statins.
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PMID:The double-edged sword of statin immunomodulation. 1857 Dec 56

The occupational epidemiological literature on extremely low frequency electric and magnetic fields (EMF) and health encompasses a large number of studies of varying design and quality that have addressed many health outcomes, including various cancers, cardiovascular disease, depression and suicide, and neurodegenerative diseases, such as Alzheimer disease and amyotrophic lateral sclerosis (ALS). At a 2006 workshop we reviewed studies of occupational EMF exposure with an emphasis on methodological weaknesses, and proposed analytical ways to address some of these. We also developed research priorities that we hope will address remaining uncertainties. Broadly speaking, extensive epidemiological research conducted during the past 20 years on occupational EMF exposure does not indicate strong or consistent associations with cancer or any other health outcomes. Inconsistent results for many of the outcomes may be attributable to numerous shortcomings in the studies, most notably in exposure assessment. There is, however, no obvious correlation between exposure assessment quality and observed associations. Nevertheless, for future research, the highest priorities emerge in both the areas of exposure assessment and investigation of ALS. To better assess exposure, we call for the development of a more complete job-exposure matrix that combines job title, work environment and task, and an index of exposure to electric fields, magnetic fields, spark discharge, contact current, and other chemical and physical agents. For ALS, we propose an international collaborative study capable of illuminating a reported association with electrical occupations by disentangling the potential roles of electric shocks, magnetic fields and bias. Such a study will potentially lead to evidence-based measures to protect public health.
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PMID:Future needs of occupational epidemiology of extremely low frequency electric and magnetic fields: review and recommendations. 1880 78

The Insulin-like growth factor-1 (IGF-1) system is dynamic and complex, involving many binding proteins, binding-protein-related proteases, and receptors. It has emerged in time as a powerful defence to life processes of many cytotypes, tissues and systems. Mainly in body metabolism, diabetes and cardiovascular system, but also in brain and kidney, IGF-1 plays a key role in maintaining homeostasis, increasing progenitor cell potential, and improving physiologic performance both in rest and stress conditions. Its vasculoprotective and insulin sensitizing ability exerts a protective role on flow-metabolism coupling and organs function. Therapeutical human use of recombinant human IGF-1 (rhIGF-1) has been widely applied only in Laron syndrome, while being verified in many randomized controlled trials to improve glycemic control in type 1 and type 2 diabetes, and proposed in neurological disease such as amyotrophic lateral sclerosis, multiple sclerosis and Alzheimer disease. Sparse evidence exists moreover about rhIGF-1 use in insulin resistance, burns, catabolic and post-surgery states, acute and chronic renal failure, amyotrophic lateral and multiple sclerosis, brain injury, and immunoincompetence. Along with these data, results are available on cardiovascular benefit of administration of other growth factors, such as erythropoietin and vascular endothelial growth factor, or on cardiovascular side effects of growth factor antagonists such as trastuzumab in cancer therapy. We intended therefore to summarize in this review available human and animals evidence about rhIGF-1 effects on different systems with insights on rhIGF-1 cardiovascular effects. In view of its ability to improve flow-metabolism coupling, IGF-1 could indeed represent a new cardiovascular disease treatment option for many cardiac disorders such as ischemic heart disease and heart failure.
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PMID:Recombinant human insulin-like growth factor-1: a new cardiovascular disease treatment option? 1885 38

RNA interference has been implicated in diverse biological process. It is a powerful method for specific gene silencing which may also lead to promising novel therapeutic strategies. The success of early studies of therapeutic RNAi in rodent models has generated considerable interest on the development of RNAi as a potential therapy. A number of recent patents have been published that deal with the use of siRNA as therapeutic tools for human diseases. In this review, I will comment on some of the patents issued on siRNA-based strategies for cancer, ocular diseases, cardiovascular disease, Alzheimer's disease, Parkinson's disease, bone healing, and monogenic diseases such as amyotrophic lateral sclerosis, Marfan syndrome or Huntingon's disease. Progress in developing RNAi-based drugs and potential obstacles will also be discussed.
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PMID:Recent patents relating to siRNAs and therapeutic strategies for genetic diseases. 1907 44

The understanding of the essential role of selenium (Se) in human health has increased substantially in recent decades. Micronutrient deficiencies are very common in the general population and may be even more common in patients with different pathologies due to genetic or environmental causes and prescription drug use. Selenium is used by people in the prevention and/or treatment of different disorders including cardiovascular disease, osteoarthritis, rheumatoid arthritis, hypothyroidism, stroke, atherosclerosis, cancer susceptibility and treatment, HIV, AIDS, neuronal diseases such as Alzheimer or amyotrophic lateral sclerosis, pancreatitis, depression, and diabetes amongst others. Several mechanisms have been suggested to mediate the biological effects of Se and these include antioxidant defence systems, synthesis and stability of metabolites that act as intermediates implicated in diverse selenoproteins expression pathways oxidative metabolism, immune system modulation, DNA intercalators, kinase regulation, enzymatic cofactor, and gene expression. A number of clinical trials in recent years have provided convincing evidence of the central role of this element, either alone or in combination with other micronutrients or antioxidants, in the prevention and treatment of multiple diseases. Based on these studies this review focuses on the advances made so far in the study of mechanisms and applications of selenium compounds that could be suitable for chronic diseases.
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PMID:Selenium and clinical trials: new therapeutic evidence for multiple diseases. 2186 84


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