UMLS:C0002736 - FACTA Search

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Query: UMLS:C0002736 (amyotrophic lateral sclerosis)
19,048 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We studied the energy metabolism of ALS patients under mechanical ventilation and tube feeding. Gas exchanges (O2 and CO2 content in expiratory and inspiratory gas) were measured all day long by DELTATRAC (Datex, Finland) in 11 ALS patients, and energy metabolism during 24 hours was calculated according to the next formula; 5.67 VO2 + 1.60 VCO2-2.17 UN (VO2; O2 consumption l/min, VCO2; CO2 production l/min, UN; urea nitrogen excretion in urine g/day). All patients were clinically stable under continuous mechanical ventilation and tube feeding, and did not have any infection such as pneumonia. The patients were 23-70 years old (mean 49.3), and had total clinical courses of 3-12 years (mean 7.1), and 2-8 year-long courses under mechanical ventilation (mean 4.6). They were classified into the next 3 groups: group I; totally locked-in state (2 patients), group II; complete tetraplegia (6 patients), group III; incomplete tetraparesis (3 patients). Basal metabolic rate (BMR) of each patient was also calculated from Harris-Benedict's formula; male = 66.47 + 13.75W + 5.0H - 6.76A, female = 665.10 + 0.567W + 1.85H - 4.68A (W; weight kg, H; height cm, A; body surface area m2). And the changes of the body weight by month were examined retrospectively in 26 ALS patients with at least 2 year-duration under mechanical ventilation, which include the previous 11 patients. The calorie consumption of 24 hours were 783.3 kcal (group I), 875.3 (group II), 974.9 (group III), which were all lower than BMR (I; -26.8%, II; -17.6%, III; -11.3%).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Energy metabolism of ALS patients under mechanical ventilation and tube feeding]. 190 43

Cognitive impairment in the absence of lesions indicative of Alzheimer's disease and other dementing conditions has long been recognized in a subgroup of patients with motor neuron disease MND), including amyotrophic lateral sclerosis. However, the mechanisms underlying this cognitive deterioration and its relationship with the relatively selective involvement of motor neurons remains elusive. We used histo- and immunocytochemical labeling methods to study the nitrogen monoxide (NO; a.k.a. nitric oxide) synthase (NOS)-/NADPH diaphorase-containing neurons (NOSN) in three patients with MND and dementia (MND+D), two patients with MND without dementia, and 19 controls that included patients with Alzheimer and non-Alzheimer dementias. Patients with MND+D, but not those with MND without dementia, exhibit numerous dystrophic perikarya and neurites throughout all sensory, motor, association, and limbic neocortices examined. Interestingly, affected NOSN appear to correspond to some subtypes (smooth stellate and spiny neurons), while other neurons containing the same molecular phenotype (such as layer I local circuit neurons and layer II granule cells) are either spared or significantly less affected. These observations indicate that cognitive impairment and dementia in MND may be due, at least in part, to a pancortical involvement of certain types of NOSN. Consequently, the elucidation of the factors that make NOSN vulnerable in MND, and the prevention or pharmacological palliation of their loss, may eventually help to prevent or ameliorate cognitive impairment in MND and may also shed some light on the nature of the insult that targets motor neurons.
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PMID:Alterations in nitrogen monoxide-synthesizing cortical neurons in amyotrophic lateral sclerosis with dementia. 855 69

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive muscle atrophy and weakness. Although dysphagia is a universal feature of this illness, the nutritional and metabolic status of ALS patients has received little attention. We performed serial measurements of muscle power, body composition, energy expenditure, nitrogen balance, and dietary intake on ALS patients on three occasions over 6 mo in the General Clinical Research Center of the University of Kentucky Medical Center. Data were analyzed in reference to the time of death. Regression analysis demonstrated progressive decreases in body fat, lean body mass, muscle power, and nitrogen balance and an increase in resting energy expenditure as death approached. The changes in body composition were greater in males. Energy and protein consumption averaged 84% and 126% of the recommended dietary allowances, respectively, but did not correlate with complaints of dysphagia. We conclude that ALS patients have a chronically deficient intake of energy and recommended augmentation of energy intake rather than the consumption of high-protein nutritional supplements.
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PMID:Nutritional status of patients with amyotrophic lateral sclerosis: relation to the proximity of death. 860 60

Nitric oxide contrasts with most intercellular messengers because it diffuses rapidly and isotropically through most tissues with little reaction but cannot be transported through the vasculature due to rapid destruction by oxyhemoglobin. The rapid diffusion of nitric oxide between cells allows it to locally integrate the responses of blood vessels to turbulence, modulate synaptic plasticity in neurons, and control the oscillatory behavior of neuronal networks. Nitric oxide is not necessarily short lived and is intrinsically no more reactive than oxygen. The reactivity of nitric oxide per se has been greatly overestimated in vitro because no drain is provided to remove nitric oxide. Nitric oxide persists in solution for several minutes in micromolar concentrations before it reacts with oxygen to form much stronger oxidants like nitrogen dioxide. Nitric oxide is removed within seconds in vivo by diffusion over 100 microns through tissues to enter red blood cells and react with oxyhemoglobin. The direct toxicity of nitric oxide is modest but is greatly enhanced by reacting with superoxide to form peroxynitrite (ONOO-). Nitric oxide is the only biological molecule produced in high enough concentrations to out-compete superoxide dismutase for superoxide. Peroxynitrite reacts relatively slowly with most biological molecules, making peroxynitrite a selective oxidant. Peroxynitrite modifies tyrosine in proteins to create nitrotyrosines, leaving a footprint detectable in vivo. Nitration of structural proteins, including neurofilaments and actin, can disrupt filament assembly with major pathological consequences. Antibodies to nitrotyrosine have revealed nitration in human atherosclerosis, myocardial ischemia, septic and distressed lung, inflammatory bowel disease, and amyotrophic lateral sclerosis.
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PMID:Nitric oxide, superoxide, and peroxynitrite: the good, the bad, and ugly. 894 24

Post-traumatic stress-induced disorders are still the focus of interest and most recently discussions are under way whether stress-induced cortisol excess leads to atrophy of the brain. In investigation on carcinogenesis the first reports were published on the use of antisense-oligonucleotides during inhibition of the development of tumours by a humoral mechanism and on the gene-based neuroendocrine differentiation of the lungs, perhaps associated with the basis for the development of small cell carcinoma. The oncogenic action of superoxides has also humoral mediators. Interest in nitrogen oxide is focused on two areas: inflammations and hypertension. Intraluminal NO concentrations increase in asthma 2-10x, in cystitis 30-100x, in Crohn's disease 20-200x. Humoral mechanisms in asthma offer new drugs--inhibitors of the development or action of leucotrienes. The basal NO production is reduced in "essential" hypertension but it is not known whether it is the cause or consequence. IGF-I increases the formation of NO in the vascular wall and thus perhaps reduces vascular contractility. As far as IGF is concerned, it is obvious that if recombinant preparations will be available, they will be tested in amyotrophic lateral sclerosis, myotonic dystrophy, multiple sclerosis, catabolic conditions, osteoporosis, in renal failure and to promote wound healing. STH may also prove useful in cardiac failure, in particular in cardiac cachexia. That TRH has receptors in the gut is not surprising, it acts, however, even there via TSH. Thrombopoietin is being tested in clinical trials. Neocytolysis is a new phenomenon: when erythropoietin secretion declines new erythrocytes disappear and only old ones remain in the blood stream. Alpha-adducin is a renal tubular protein, regulating the sodium balance.
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PMID:[Endocrinology 1996-1997]. 965 Mar 40

Copper-zinc superoxide dismutase (Cu,ZnSOD) is the antioxidant enzyme that catalyzes the dismutation of superoxide (O2*-) to O2 and H2O2. In addition, Cu,ZnSOD also exhibits peroxidase activity in the presence of H2O2, leading to self-inactivation and formation of a potent enzyme-bound oxidant. We report in this study that lipid peroxidation of L-alpha-lecithin liposomes was enhanced greatly during the SOD/H2O2 reaction in the presence of nitrite anion (NO2-) with or without the metal ion chelator, diethylenetriaminepentacetic acid. The presence of NO2- also greatly enhanced alpha-tocopherol (alpha-TH) oxidation by SOD/H2O2 in saturated 1, 2-dilauroyl-sn-glycero-3-phosphatidylcholine liposomes. The major product identified by HPLC and UV-studies was alpha-tocopheryl quinone. When 1,2-diauroyl-sn-glycero-3-phosphatidylcholine liposomes containing gamma-tocopherol (gamma-TH) were incubated with SOD/H2O2/NO2-, the major product identified was 5-NO2-gamma-TH. Nitrone spin traps significantly inhibited the formation of alpha-tocopheryl quinone and 5-NO2-gamma-TH. NO2- inhibited H2O2-dependent inactivation of SOD. A proposed mechanism of this protection involves the oxidation of NO2- by an SOD-bound oxidant to the nitrogen dioxide radical (*NO2). In this study, we have shown a new mechanism of nitration catalyzed by the peroxidase activity of SOD. We conclude that NO2- is a suitable probe for investigating the peroxidase activity of familial Amyotrophic Lateral Sclerosis-linked SOD mutants.
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PMID:Nitration of gamma-tocopherol and oxidation of alpha-tocopherol by copper-zinc superoxide dismutase/H2O2/NO2-: role of nitrogen dioxide free radical. 978 14

The present report proposes the hypothesis that increased levels of neurodegenerative disorders in humans may have arisen due to inclusion in the diet of methionine sulfoximine (MSO), a byproduct of the bleaching of flour by nitrogen trichloride. This method of bleaching, the 'agene process' was in use from early in the century and continued until at least 1949/1950. Estimates indicate that, at least in the UK, as much as 80% of all flour during this period was produced by this process. MSO acts directly to inhibit the production of two crucial molecules, glutathione (GSH) and glutamine. Decreases in GSH, a key antioxidant and free radical scavenger, diminish the body's antioxidant defenses and may lead to increased oxidative stress. Decreases in glutamine synthesis may act to increase free glutamate and give rise to increased levels of ammonia. Cells in the nervous system are particularly sensitive to a decline in either GSH or glutamine. The combined effects of decreases in these molecules, particularly with long-term exposure to MSO in bleached flour, may have had quite drastic effects on neuronal health and survival. The present hypothesis may provide clues to the etiology of neurological disorders such as Alzheimer's disease (AD), Parkinson's disease (PD) and amyotrophic lateral sclerosis (ALS), suggesting that such disorders may arise in part due to toxic actions of some compounds in processed human foods.
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PMID:Did consumption of flour bleached by the agene process contribute to the incidence of neurological disease? 1005 66

Neuronal loss, synaptic disconnection and neuritic sprouting correlate with dementia in Alzheimer's disease (AD). Nitric oxide (NO) is an important synaptic plasticity molecule generated by nitric oxide synthase (NOS) oxidation of a guanidino nitrogen of L-arginine. Experimentally, the NOS III gene is modulated with neuritic sprouting. In a previous study, NOS III expression was found to be abnormal in cortical neurons, white matter glial cells, and dystrophic neurites in AD and Down syndrome brains. The present study demonstrates the same abnormalities in neuronal and glial NOS III expression with massive proliferation of NOS III-immunoreactive neurites and glial cell processes in other neurodegenerative diseases including: diffuse Lewy body disease, Pick's disease, progressive supranuclear palsy, amyotrophic lateral sclerosis, multiple system atrophy, and Parkinson's disease. However, each disease, including AD, was distinguished by the selective alterations in NOS III expression and sprouting in structures marred by neurodegeneration. Double label immunohistochemical staining studies demonstrated nitrotyrosine and NOS III co-localized in only rare neurons and neuritic sprouts, suggesting that peroxynitrite formation and nitration of growth cone proteins may not be important consequences of NOS III enzyme accumulation. The results suggest that aberrant NOS III expression and NOS III-associated neuritic sprouting in the CNS are major abnormalities common to several important neurodegenerative diseases.
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PMID:Neuritic sprouting with aberrant expression of the nitric oxide synthase III gene in neurodegenerative diseases. 1020 79

The age-related neurodegenerative diseases exemplified by Alzheimer&hyp;s disease (AD), Lewy body diseases such as Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and Huntington&hyp;s disease are characterized by the deposition of abnormal forms of specific proteins in the brain. Although several factors appear to underlie the pathological depositions, the cause of neuronal death in each disease appears to be multifactorial. In this regard, evidence in each case for a role of oxidative stress is provided by the finding that the pathological deposits are immunoreactive to antibodies recognizing protein side-chains modified either directly by reactive oxygen or nitrogen species, or by products of lipid peroxidation or glycoxidation. Although the source(s) of increased oxidative damage are not entirely clear, the findings of increased localization of redox-active transition metals in the brain regions most affected is consistent with their contribution to oxidative stress. It is tempting to speculate that free radical oxygen chemistry plays a pathogenetic role in all these neurodegenerative conditions, though it is as yet undetermined what types of oxidative damage occur early in pathogenesis, and what types are secondary manifestations of dying neurons. Delineation of the profile of oxidative damage in each disease will provide clues to how the specific neuronal populations are differentially affected by the individual disease conditions.
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PMID:Chemistry and biochemistry of oxidative stress in neurodegenerative disease. 1137 46

Oxidative stress, reactive oxygen (ROS), and nitrogen (RNS) species have been known to be involved in a multitude of neurodegenerative disorders such as Parkinson's disease (PD), Alzheimer's disease (AD), and amyotrophic lateral sclerosis (ALS). Both ROS and RNS have very short half-lives, thereby making their identification very difficult as a specific cause of neurodegeneration. Recently, we have developed a high performance liquid chromatography/electrochemical detection (HPLC/EC) method to identify 3-nitrotyrosine (3-NT), an in vitro and in vivo biomarker of peroxynitrite production, in cell cultures and brain to evaluate if an agent-driven neurotoxicity is produced by the generation of peroxynitrite. We show that a single or multiple injections of methamphetamine (METH) produced a significant increase in the formation of 3-NT in the striatum. This formation of 3-NT correlated with the striatal dopamine depletion caused by METH administration. We also show that PC12 cells treated with METH has significantly increased formation of 3-NT and dopamine depletion. Furthermore, we report that pretreatment with antioxidants such as selenium and melatonin can completely protect against the formation of 3-NT and depletion of striatal dopamine. We also report that pretreatment with peroxynitrite decomposition catalysts such as 5, 10,15,20-tetrakis(N-methyl-4'-pyridyl)porphyrinato iron III (FeTMPyP) and 5, 10, 15, 20-tetrakis (2,4,6-trimethyl-3,5-sulfonatophenyl) porphinato iron III (FETPPS) significantly protect against METH-induced 3-NT formation and striatal dopamine depletion. We used two different approaches, pharmacological manipulation and transgenic animal models, in order to further investigate the role of peroxynitrite. We show that a selective neuronal nitric oxide synthase (nNOS) inhibitor, 7-nitroindazole (7-NI), significantly protect against the formation of 3-NT as well as striatal dopamine depletion. Similar results were observed with nNOS knockout and copper zinc superoxide dismutase (CuZnSOD)-overexpressed transgenic mice models. Finally, using the protein data bank crystal structure of tyrosine hydroxylase, we postulate the possible nitration of specific tyrosine moiety in the enzyme that can be responsible for dopaminergic neurotoxicity. Together, these data clearly support the hypothesis that the reactive nitrogen species, peroxynitrite, plays a major role in METH-induced dopaminergic neurotoxicity and that selective antioxidants and peroxynitrite decomposition catalysts can protect against METH-induced neurotoxicity. These antioxidants and decomposition catalysts may have therapeutic potential in the treatment of psychostimulant addictions.
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PMID:Methamphetamine-induced dopaminergic neurotoxicity: role of peroxynitrite and neuroprotective role of antioxidants and peroxynitrite decomposition catalysts. 1146 92

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