Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0020473 (hyperlipidemia)
 15,891 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have experienced with 50 cases of parasellar tumors, four cases of which had persistent thirst, polydipsia, polyuria, and reversible temporary hyponatremia secondary to hypernatriuresis. The mechanism of the syndrome in these four cases could not be explained by either that of the syndrome of hypernatremia or of the so-called SIADH. We tentatively named this syndrome as "CEREBRAL POLYURIC HYPONATREMIA" and the criteria of this syndrome as as follows: 1) persistent thirst, polydipsia polyuria, 2) reversible temporary hyponatremia secondary to hypernatriuresis, 3) exception of the following items--administration of uretic drugs, renal and adrenal dysfunction, hyperglycemia, hyperlipemia, overadministration of water, and poor administration of NaCl. The mechanism of this syndrome is presumed as follows: 1) compression by a tumor or surgical attack to the anterior hypothalamus, 2) disturbance of the mechanism of ADH secret-on, 3) extrasecretion of natriuretic factor possibly produced in the anterior hypthalamus, and 4) preservation of the thirst center.
 ...
PMID:[Cerebral polyuric hyponatremia--discussion of a new syndrome with disturbance of electrolyte balance of central origin (author's transl)]. 55 42

Chronic "neurogenic" hypernatremia is the consequence of defective thirst mechanism either alone or in combination with impaired osmoregulation of ADH release. Both the specific receptors and the structures involved in hormonal secretion are localised in the hypothalamic area. "Neurogenic" hypernatremia can be secondary to a hypothalamic lesion of different type (neoplastic, vascular, malformative) or rarely it can be idiopathic. We present three cases: two females 4 and 5 months old, affected by cerebral malformations involving midline structures of the brain (III ventricule, corpus callosum etc.) and a male 4 years old with a idiopathic form. We discuss the relationship between the origin of the cerebral malformations and the ontogeny of the structures involved in the control of the osmolarity. Moreover we have observed that the hypernatremia in associated with hyperlipemia: the pathogenetic hypothesis explaining this abnormality are discussed.
 ...
PMID:[Neurogenic hypernatremia syndrome in children]. 203 94

Advances in our knowledge of the microsomal metabolism of ethanol enable us to understand a number of complications that develop in the alcoholic. After chronic ethanol consumption, microsomal ethanol-oxidizing system (MEOS) activity increases with an associated rise in microsomal cytochrome P-450, including a form different from that induced by phenobarbital and methylcholanthrene and which has a high affinity for ethanol, as shown in reconstituted systems. The role of this MEOS in vivo and its increase after chronic ethanol consumption was most conclusively shown in alcohol dehydrogenase-negative deer mice. Microsomal induction is also associated with enhanced metabolism of other drugs, resulting in metabolic drug tolerance. Furthermore, there is increased conversion to toxic metabolites of known hepatotoxic agents (such as CCl4), which may explain the enhanced susceptibility of alcoholics to the toxicity of industrial solvents. Furthermore, the ethanol-induced form of cytochrome P-450 has a high capacity for the conversion to toxic metabolites of some commonly used drugs, such as acetaminophen, and also carcinogens, such as dimethylnitrosamine which is activated at concentrations much lower than those required for other microsomal inducers. Moreover, catabolism of retinol is accelerated through a newly discovered microsomal pathway, thereby contributing to hepatic vitamin A depletion and possibly vitamin A toxicity. There is also induction of microsomal enzymes involved in lipoprotein production, resulting in hyperlipemia. Contrasting with the chronic effects of ethanol consumption, acutely, ethanol inhibits the metabolism of other drugs through competition for an at least partially shared microsomal detoxification pathway.
 ...
PMID:Microsomal ethanol-oxidizing system. 310 31

In vivo ethanol given acutely or chronically by two dietary means resulted in significant increases in [1-(14)C]palmitate incorporation into triglyceride by intestinal slices or microsomes derived from intestinal slices. In vitro, 2.6 percent ethanol, an amount comparable to that found in t..e intestinal lumen of social drinkers, also resulted in significant increases in [1-(14)C]palmitate incorporation into triglyceride. Pyrazole, an inhibitor of alcohol dehydrogenase, diminished the stimulatory effect of ethanol both in vivo and in vitro. These data may provide a new insight into the effects of alcohol, and specifically on the possible contribution of intestinal triglyceride synthesis to alcoholic hyperlipemia and the alcohol-induced fatty liver.
 ...
PMID:Ethanol stimulates triglyceride synthesis by the intestine. 513 47

Although alcohol is likely to have direct effects on the subcellular integrity of the pancreas, other factors arising outside the pancreas may modulate or potentiate alcohol-induced damage. Among these factors are the hepatic metabolism of ethanol to acetaldehyde (via isoenzymes of ADH), the hepatic production of free radicals, the release of G.I. hormones, pancreatic ischemia (and reperfusion injury), hyperlipemia, diet and smoking. This article summarises what is known about these extrapancreatic factors. It is suggested that the pathogenesis of alcoholic pancreatitis is multifactorial but that many studies in this field are difficult to interpret because of methodological problems, particularly with regard to inadequate controls.
 ...
PMID:An overview of extrapancreatic factors in the pathogenesis of alcoholic pancreatitis. 897 59

Creatinine clearance decreases with age by 1 ml/min/year after 40 years of age, although serum creatinine remains constant because of reduction of muscle mass. Reduction of water intake may occur in the elderly because of a reduced sensation of thirst; this is associated with a tendency to lose water with urine. The capacity to respond to sodium load is impaired in aged kidneys, thereby leading to ECV expansion and hypertension. But there is also, in the elderly, a reduced capacity for retaining sodium (FENa is higher than in young subjects), making old subjects sensitive to salt depletion and ECV contraction. Hypernatraemia (Nas > 150 mmol/l) is not infrequent in the elderly (1%) and is usually due to water deficiency (old subjects should be forced to drink), and rarely to iatrogenic excess of sodium. It is the abrupt occurrence of severe hypernatraemia that causes neurological symptoms due to dehydration and brain shrinking, which may lead to cerebral haemorrhage and death. Hyponatraemia (Nas < 130 mmol/l) is frequent among the elderly (7-11%) and is mainly due to water overload, which is usually iatrogenic. Hypovolaemic hyponatraemia occurs when salt depletion causes ECV contraction > 10%, and is due to water retention in an attempt to normalize ECV. Hypervolaemic hyponatraemia is due to ADH hypersecretion because of a decrease in 'effective' circulating blood volume. 'Pseudohyponatraemia' may occur because of hyperlipidaemia or hyperproteinaemia. It is the abrupt occurrence of severe hyponatraemia that causes neurological symptoms (water intoxication), secondary to the oedomatous swelling of the brain within the skull. While rapidly occurring hyponatraemia may be lethal, slowly occurring hyponatraemia is usually asymptomatic. Rapid correction of hyponatraemia may cause cerebral dehydration and 'osmotic demyelination syndrome' ('central pontine myelinosis'). Decrease (e.g. by diuretics) or increase (e.g. by ACE-inhibitors, non-steroidal anti-inflammatory drugs, beta-blockers) or serum potassium may occur in the elderly. Diuretics should be used with caution in elderly subjects to avoid salt depletion, hypotension and renal function impairment.
 ...
PMID:Some sodium, potassium and water changes in the elderly and their treatment. 905 29

The objective of this study was to determine the effects of a country liquor Toddy (Coconut palm wine) and an equivalent quantity of ethanol on liver function and lipid metabolism in utero. Female albino rats with an average weight of 125 +/- 5 g were exposed to Toddy from coconut palm (24.5 ml/kg body weight/day) and ethanol (0.52 ml/kg body weight/day) for 15 days before conception and during pregnancy. On day 13 and day 19 of gestation, altered liver function and hyperlipidemia were seen in the fetuses of both the treated groups. Altered liver function was evidenced by the increased activity of alcohol dehydrogenase, aldehyde dehydrogenase, glutamic oxaloacetic transaminase (aspartate amino transferase (GOT)), glutamic pyruvic transaminase (alanine amino transferase (GPT)). Hyperlipidemia was caused by increased biosynthesis since the incorporation of 14C acetate into lipids and activities of HMG CoA reductase and lipogenic enzymes were elevated. Toddy treated fetuses were more severely affected than those exposed to an equivalent quantity of ethanol. Toddy seemed to potentiate the toxicity induced by alcohol suggesting the role of non alcoholic components. Hepatic functions of the day 13 fetuses were effected to a lesser degree than those in the day 19 hepatic liver.
 ...
PMID:Effect of in utero exposure of Toddy (coconut palm wine) on liver function and lipid metabolism in rat fetuses. 995 82

Oxidation of ethanol via alcohol dehydrogenase (ADH) explains various metabolic effects of ethanol but does not account for the tolerance and a number of associated disorders that develop in the alcoholic. These were elucidated by the discovery of the microsomal metabolism of ethanol. The physiologic role of this system comprises gluconeogenesis from ketones, fatty acid metabolism, and detoxification of xenobiotics, including ethanol. After chronic ethanol consumption, the activity of the microsomal ethanol-oxidizing system (MEOS) increases, with an associated rise in cytochromes P-450, especially CYP2E1. This induction is associated with proliferation of the endoplasmic reticulum, both in experimental animals and in humans. The role of MEOS in vivo and its increase after chronic ethanol consumption was shown most conclusively in alcohol dehydrogenase-negative deer mice. Enhanced ethanol oxidation is associated with cross-induction of the metabolism of other drugs, resulting in drug tolerance. Furthermore, there is increased conversion of known hepatotoxic agents (such as CCl4) to toxic metabolites, which may explain the enhanced susceptibility of alcoholics to the adverse effects of industrial solvents. CYP2E1 also has a high capacity to activate some commonly used drugs, such as acetaminophen, to their toxic metabolites, and to promote carcinogenesis (e.g., from dimethylnitrosamine). Moreover, catabolism of retinol is accelerated and there also is induction of microsomal enzymes involved in lipoprotein production, resulting in hyperlipemia. Contrasting with the chronic effects of ethanol consumption, acute ethanol intake inhibits the metabolism of other drugs through competition for the at least partially shared microsomal pathway. In addition, metabolism by CYP2E1 results in a significant free radical release and acetaldehyde production which, in turn, diminish reduced glutathione (GSH) and other defense systems against oxidative stress. Acetaldehyde also forms adducts with proteins, thereby altering the functions of mitochondria and of repair enzymes. Increases of CYP2E1 and its mRNA prevail in the perivenular zone, the area of maximal liver damage. CYP1A2 and CYP3A4, two other perivenular P-450s, can also sustain the metabolism of ethanol, thereby contributing to MEOS activity and possibly liver injury. By contrast, CYP2E1 inhibitors oppose alcohol-induced liver damage, but heretofore available compounds were too toxic for clinical use. Recently, however, polyenylphosphatidylcholine (PPC), an innocuous mixture of polyunsaturated lecithins extracted from soybeans, was discovered to decrease CYP2E1 activity. PPC (and its active component dilinoleoylphosphatidylcholine) also oppose hepatic oxidative stress and fibrosis. PPC is now being tested clinically for the prevention and treatment of liver disease in the alcoholic.
 ...
PMID:Microsomal ethanol-oxidizing system (MEOS): the first 30 years (1968-1998)--a review. 1039 83

The objective of this study was to determine the effects of a country liquor (Arrack) and the equivalent quantity of ethanol on liver function and lipid metabolism in utero. Female rats of average weight 125 g were exposed to Arrack (12 ml/kg body weight/day) and ethanol (3.2 ml/kg body weight/day) for 15 days before conception and throughout gestation. On 13th day and 19th day of gestation, altered liver function and hyperlipidemia was seen in the fetus of both the treated groups. Altered liver function was evidenced by the increased activity of alcohol dehydrogenase and glutamic pyruvic transaminase or alanine amino transferase (GPT). Hyperlipidemia was caused by increased biosynthesis since the incorporation of 14C acetate to lipids and activities of HMG CoA reductase and lipogenic enzymes were elevated. Arrack seemed to potentiate the toxicity induced by alcohol indicating the role of non ethanolic portion. Hepatic functions of the 13th day fetuses were effected to a lesser degree than the 19th day hepatic liver.
 ...
PMID:Prenatal exposure of an alcoholic beverage (Arrack) on fetal lipid metabolism in rats. 1094 14

The objective of this study was to determine the effects of country liquor Toddy and its equivalent quantity of ethanol on lipid metabolism during gestation in rats. Female rats weighing an average of 125 g were exposed to Toddy (24.5 ml/body weight/day) and ethanol (0.52 ml/kg body weight/day) for 15 days before conception and throughout gestation. On the 19th day of gestation, altered liver function and hyperlipidemia was seen in both the treated groups. Altered liver function was evidenced by the increased activity of alcohol dehydrogenase, aldehyde dehydrogenase, glutamic oxaloacetic transaminase or aspartate amino transferase (GOT), glutamic pyruvic transaminase or alanine amino transferase (GPT) and gamma glutamyl transpeptidase (GGT). Hyperlipidemia was caused by increased biosynthesis and decreased degradation of lipids. The incorporation of 14C acetate in lipids and activities of HMG CoA reductase and lipogenic enzymes were elevated and activity of LPL and bile acids contents were decreased. Toddy treated rats were more severely affected than those receiving an equivalent quantity of ethanol. Toddy seemed to potentiate the toxicity induced by alcohol indicating the role of the nonethanolic portion. Hepatic functions were also affected.
 ...
PMID:Effect of exposure to a country liquor (Toddy) during gestation on lipid metabolism in rats. 1131 2


1 2 Next >>