Metabolic disturbances

A second problem concerns delimiting the mechanisms of action which should be included in the definition, to exclude effects which are a secondary consequence of overt toxicity in other body systems. For example, disruption to the endocrine system caused by general metabolic disturbance, such as in severe liver damage, should not be grounds for calling a chemical an ED. 

Exposure to estrogenic compounds through diet will differ for herbivores and carnivores, the latter being most likely to encounter endogenous steroids in their prey. Efficient uptake of steroids in mammals is illustrated by the use of the contraceptive pill, but routes of absorption in invertebrates remain to be determined. The relationship between endocrine disruption and metabolic toxicity, with reduced reproductive viability a secondary consequence of metabolic disturbance, also merits further study in invertebrate species. 

In addition to direct effects of chemical compounds on the fetus, metabolic disturbances in the mother, such as diabetes or hyperthermia, or deficiencies of calories or specific nutrients such as vitamin A, zinc, and folic acid may lead to teratogenesis. Compounds that inhibit placental functions may also induce malformations, e.g., by inhibiting placental circulation. For example, hydroxyurea disrupts the placental circulation and induces malformations. In addition, it also induces DNA damage. 

Type 2 diabetes is a heterogeneous and progressive endocrine disorder associated with insulin resistance (impaired insulin action) and defective function of the insulin-secreting (3-cells in the pancreatic islets of Langerhans. These endocrine disorders give rise to widespread metabolic disturbances epitomised by hyperglycaemia. The present classes of antidiabetic agents other than insulin act to either increase insulin secretion, improve insulin action, slow the rate of intestinal... 

Epileptic seizures affect 0.5% of the population, are more common in the young and, except for partial seizures, often decrease with age. Convulsions associated with metabolic disturbances are not considered to be epileptic. 

Metabolic acidosis and alkalosis result from primary disturbances in the serum H CO., concentration. Respiratory compensation of metabolic disturbances begins within minutes and is complete within 12 hours. 

Isolated seizures that are not epilepsy can be caused by stroke, central nervous system trauma, central nervous system infections, metabolic disturbances (e.g., hyponatremia and hypoglycemia), and hypoxia. If these underlying causes of seizures are not corrected, they may lead to the development of recurrent seizures I or epilepsy. Medications can also cause seizures. Some drugs that are commonly associated with seizures include tramadol, bupropion, theophylline, some antidepressants, some antipsy-chotics, amphetamines, cocaine, imipenem, lithium, excessive doses of penicillins or cephalosporins, and sympathomimetics or stimulants. 

Foscarnet 40 mg/kg IV q8—12hours x 2-3 wkor until clinical resolution is attained Renal insufficiency, metabolic disturbances, hypophosphatemia... 

Lu, M. L. et al. (2004). Adjunctive fluvoxamine inhibits clozapine-related weight gain and metabolic disturbances. /. Clin. Psychiatry, 65, 766-71. 

Breves G, Faul K, Schroder B, Holst H, Caspa-ry WF, Stein J Application of the colon-simulation technique for studying the effects of Sac-charomyces boulardii on basic parameters of porcine cecal microbial metabolism disturbed by clindamycin. Digestion 2000 61 193-200. 

The rapid progress in proteomics and peptidomics during the last decade offers us new possibilities to study clinical aspects of disorders and diseases related to the brain [1], These strategies also offer new tools to follow chemical modifications and altered metabolic disturbances that may be indicative of pathophysiological adaptations related to environmental and psychosocial prolonged stress. These techniques can contribute to developments in the diagnostic and therapeutic fields of psychiatric... 

The establishment of quantitative methods for the determination of vitamins in body fluids and tissues by microbiological assay techniques should stimulate the search for the significance of vitamins in disease, not only in nutritional deficiency, but in the much wider field of all metabolic disturbances. Functional vitamin deficiencies are produced by malabsorption, by inhibitors of the vitamin function through products of the body, and particularly through drugs and other toxic substances. Vitamin deficiencies may be relative deficiencies whenever an individual s metabolism is deranged so as to require enhanced quantities of a given vitamin to cure or to counteract certain symptoms as, e.g., in Darier s disease (keratosis follicularis) (P2a). 

Persons with a metabolic disturbance in the conversion of cyanide to thiocyanate may be at greater risk. A defect in the rhodanese system and vitamin B12 deficiency have been associated with tobacco amblyopia and Leber s hereditary optic atrophy in persons exposed to cyanide in tobacco smoke (Wilson 1983). 

Frontotemporal dementias are characterized by gross structural changes in the frontal and anterior temporal lobes, metabolic disturbances, and involvement of certain subcortical structures as well (Ishii et al. 1998). Whereas in Alzheimer s disease the early cognitive disturbances are in memory, in frontotemporal dementias the early manifestations are in executive and behavioral function (Pfeffer et al. 1999 Varma et al. 1999). This relative cognitive distinction persists throughout the course of the two disorders (Pachana et al. 1996). Disinhibition and disorganization are common, and psychotic symptoms may be prominent in frontotemporal dementia. 

Cardiovascular and cerebrovascular disorders associated with lipid metabolism disturbance and atherosclerosis represent major risk factors for dementia (3,25,59). Atherosclerosis is the primary cause of heart disease and stroke in which genetic and environmental factors converge (553). More than 90% of patients older than 70-80 yr with dementia show signs of atherosclerosis in their arteries and a clear cerebrovascular component in their dementia process. It is very likely that pure AD is practically absent in octogenarians, in whom the prevalent diagnosis is vascular or mixed dementia (3,25,59), in which the APOE-4 allele also accumulates (18-20,554). 

Delirium. Delirium is an abrupt change in mental status often accompanied by agitation and seemingly psychotic symptoms that may resemble mania. Unlike mania, however, delirium is commonly characterized by a fluctuating level of consciousness and disorientation. The chief precipitants of delirium include infections, medications, and metabolic disturbances. Therefore, all patients who present in an acutely agitated state should undergo a comprehensive yet expeditious medical evaluation to rule out potential causes of delirium. This evaluation must include a thorough physical examination and a battery of laboratory tests. 

The metabolic disturbances in these conditions are as expected from a shortage of oxygen dependence of tissues on glycogen conversion to lactate (which results in lactic acido-... 

Intense research has revealed much about the molecular mechanisms involved in tumour development but much less is known about the metabolic changes in cancer. Nonetheless, most deaths from cancer are caused not directly by the tumour but by infections due to an immune system that has been impaired by metabolic disturbances in the whole... 

The sequence of events from mutations or damage to proto-oncogenes and leads to tumour suppressor genes, loss of development of cancer, with its metabolic disturbances and cachexia. Finally these changes can lead to... 

For patients who have ingested more than 30 ml of (pure) methanol or ethylene glycol, dialysis is recommended, and haemodialysis is more effective than peritoneal dialysis. Dialysis both removes the alcohols and their metabolites, and corrects the renal and metabolic disturbances and so is the preferred treatment in severe poisoning. The maintenance dose of ethanol required may be tripled during haemodialysis as ethanol is also removed. Early treatment is indicated if ethylene glycol concentrations are above 20 mg/100 ml (200 mg/1), if the arterial pH is below 7.3, if serum bicarbonate concentrations are less than 20 mM/1, and when there are oxalate crystals in the urine. 

Prolonged use or overdose may result in electrolyte or metabolic disturbances (such as hypokalemia, hypocalcemia, and metabolic acidosis or alkalosis), as well as persistent diarrhea, vomiting, muscle weakness, malabsorption, and weight loss. 

Doses above 250 mg provide no further blood pressure reduction, but are more likely to induce metabolic disturbance (hypokalemia, hyperuricemia, etc.)... 

To correct metabolic disturbance caused by opiate dependence... 

Their relative blood concentrations are an expression of nutritional balance, providing a view of the metabolic disturbances arising in a patient. In conjunction with the measurement of unesterified fatty acids (UEFA) and glucose, they are useful tools with which to investigate intermediary metabolism in health and disease, particularly in inherited metabolic diseases. 

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