Metabolic impairment

Cytotoxicity assays employ mammalian celk in culture to measure cellular metabolic impairment and death resulting from exposure in vitro to soluble and particulate toxicants. Mammalian cells derived from various tissues and organs can be maintained as short term primary cultures or, in some cases, as continuous cell strains or lines. The cytotoxicity assays, incorporated as part of Level 1 analysis, employ primary cultures of rabbit alveolar (lung) macrophages (RAM) and maintenance cultures of strain WI-38 human lung fibroblasts. 

Zanella, A., Izzo, C., Meola, G., Mariani, M., Colotti, M. T., Silani, V., Pellegata, G. Metabolic impairment and membrane abnormality in red cells from Hunting-ton s disease./. Neurol. Sci. 1980,47 93-103. 

Mitochondrial dysfunction has been linked to the causes of metabolic impairment following TBI (41). Xiong et al. (42) demonstrated that... 

Vanadium Vanadium is believed to be essential in certain animals, although there is still no evidence of this in humans. A V deficiency may alter Fe metabolism, impair heme synthesis, and affect lipid metabolism [15]. 

Central nervous system and neuromuscular junction. A remarkable number of alkaloids interfere with the metabolism and activity of neurotransmitters in the brain and nerve cells, a fact known to man for a thousand years (Table IV). The cellular interactions have been discussed above. Disturbance of neurotransmitter metabolism impairs sensory faculties, smell, vision, or hearing, or they may produce euphoric or hallucinogenic effects. 

Abnormal response to a metabolic load, such as the inability to metabolize a test dose of histidine in folate deficiency (Section 10.10.4), or tryptophan in vitamin Be deficiency (Section 9.5.4), although at normal levels of intake there may be no metabolic impairment. 

Mirzaei S, Rodrigues M, Koehn H, Knoll P, Bruecke T (2003) Metabolic impairment of brain metabolism in patients with Lewy body dementia. Eur J Neurol 10 573-575. 

Protein oxidation is certainly one of the most predominant protein modifications in neurodegeneration. On the other hand, a possible way by which a protein aggregate could lead to neurotoxicity would be via mediation of radical formation due to metabolic impairment of affected cells. This process again leads to secondary protein oxidation and aggregate modification. One of the best-studied proteins is the amyloid peptide, which seems capable of inducing free radical production in Alzheimer s disease [134]. Amyloid peptide is able to bind metals and these are able to produce radicals through the Fenton reaction [135,136]. 

Apoptosis mediated by p75 requires specific conditions, with regard to cell type, cell cycle stage, developmental stage, injury or stress. This could be due to time in culture, metabolic impairment, hypoxia, or other types of stress signals, such as nerve injury or trauma (Gu et al., 1999). Sensitive cells may be highly susceptible to injury and inflammation and may become more reactive to released growth factors and cytokines by upregulating receptor expression at the site of injury. 

FIGURE 4 Changes in free Mg + (AMg) during a reduction in MgATP (AMgATP) during metabolic impairment of bladder smooth muscle. The dashed line indicates the line of unity expected if all the liberated Mg + appeared as free Mg +. 

VI. A, using NMR to measure the effect on force generation requires metabolic impairment. 

Biochemical-cellular Toxication Metabolic impairment Cellular damage Detoxication... 

Falk et al., 1976). Thus, the highly reproducible acute and chronic changes make TD an attractive model to ask mechanistic questions about how mild impairment of oxidative metabolism impairs brain function. 

Scurvy is a fatal disease. It is characterized by structural and metabolic impairment of the human body, particularly by the destabilization... 

Symptoms of deficiency. Scurvy fatigue, bleeding gums, muscle pain, depression, dry skin, impaired iron absorption, impaired folate metabolism, impaired wound healing. 

Metabolism Impaired glucose homeostasis in renal transplant recipients receiving... 

Cystinuria is a hereditary disease characterized by the excessive excretion of cystine, lysine, ornithine, and arginine in the urine, probably resulting from a deficiency in the renal tubular transport mechanism. Sir Archibald E. Garrod postulated that cystinuria resulted from a metabolic block involving the oxidation of cystine to sulfate. Later investigations of the pathogenesis of cystinuria demonstrated that the hereditary deficiency does not involve a metabolic block. If a metabolic impairment existed, cystine would be expected to accumulate in the plasma of cystinurics, but plasma levels of cystine are normal or low in cys-... 

An object of controversy is whether GNE mutations lead to reduced sialylation of muscle glycoproteins and this has a pivotal role in h-IBM pathogenesis. Although numerous Unes of evidence corroborate this hypothesis, other investigators believe that hyposialylation of mnscle glycoproteins represents only a minor by-product of a metabolic impairment that may instead crucially affect other subcellular compartments. Below are summarized the main experimental data available that support each hypothesis. 

If future studies prove that GNE/MNK has a role in cellular pathways other than that of sialic acid and possibly more relevant for maintaining skeletal muscle homeostasis, then this will also provide valuable clues to understanding the specific susceptibility of muscle to a generalized metabolic impairment that is peculiar to h-IBM. 

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