Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027497 (nausea)
 23,468 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Liver alcohol dehydrogenase (ADH) represents the main enzyme of normal alcohol metabolism. Total activity of this enzyme varies largely due to the occurrence of isoenzymes and of genetic polymorphisms. One genetic variant, called "atypical", is characterized by a higher specific activity. In carriers of this variant enzyme an initially faster rate of ethanol metabolism leads to higher blood acetaldehyde levels. Acetaldehyde, as a toxic intermediary metabolite, causes tachycardia, nausea and flushing of the face. A high frequency for "atypical" ADH is observed in mongolid races and consequently a hypersensitivity to alcohol is often observed in Orientals. Hence, certain genetically determined enzyme patterns may represent an aversive factor with regard to alcohol consumption. In Caucasians the phenotypes with "atypical" ADH are less frequent. However, in individuals with the "atypical" variant regular intake of alcohol may lead to an increased organotoxicity due to acetaldehyde.
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PMID:[Pathobiochemistry of alcoholism]. 45 82

A 46-year-old man, presenting with headache, nausea, and lassitude, was diagnosed as having diabetes mellitus and hyponatremia, and admitted to Tohoku University Hospital. Insulin treatment improved the hyperglycemia but aggravated hyponatremia, which was proved to be elicited by the inappropriate secretion of antidiuretic hormone (SIADH). An acute water load failed to suppress ADH release in the supine posture but slightly increased plasma atrial natriuretic peptide (ANP). On the other hand, plasma ADH markedly increased in response to an upright posture, accompanied by a fall in blood pressure and a rise in heart rate. After treatment with droxidopa "a sympathomimetic drug", ambulatory blood pressure gradually increased and hyponatremia disappeared. However, blood pressure and ADH responses to upright posture were not improved by treatment with the drug. Moreover, plasma ADH was still not sufficiently suppressed by acute water loading in the supine position, but plasma ANP markedly increased, thereby resulting in urinary dilution and natriuresis. These results suggest that exaggerated ADH release (SIADH) was brought about by the baroreceptor reflex stimulated by the postural hypotension, and also by the impaired osmoregulation associated with diabetic neuropathy, and that droxidopa improved cardiovascular function and increased ANP release with resultant urinary dilution and natriuresis in spite of slightly increased ADH release.
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PMID:A case of syndrome of inappropriate secretion of antidiuretic hormone associated with diabetes mellitus. 179 39

Two female patients are described with an unusual clinical presentation of a small-cell bronchogenic carcinoma. Patient A, 61 years old, had a one week history of epigastric pain and nausea accompanied by dizziness and periods of unconsciousness. Patient B, 48 years old, had suffered for four days of general malaise, abdominal pains, nausea and vomiting. The symptoms of both patients could be attributed to severe hyponatraemia, most probably a consequence of the inappropriate ADH syndrome. After correction of the hyponatraemia and treatment of the underlying carcinoma the serum sodium remained normal and symptoms did not recur. The patients died 14 months and 9 months after the diagnosis respectively. In the Netherlands about 2000 small-cell bronchogenic carcinomas are diagnosed each year. About 14% of these are associated with the inappropriate ADH syndrome. The presence of the syndrome implicates a much graver prognosis.
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PMID:[Small-cell lung carcinoma with hyponatremia]. 184 17

4-Methylpyrazole (4-MP), an inhibitor of alcohol dehydrogenase, is a possible future drug for the treatment of methanol and ethylene glycol intoxications and the severe ethanol-disulfiram reaction. Therefore a placebo-controlled, double-blind, single-dose, randomized, sequential, ascending-dose "Phase I study" was performed in healthy volunteers in order to determine the tolerance of 4-MP at dose levels of 10 (n = 4), 20 (n = 4), 50 (n = 4), and 100 mg/kg (n = 3). Along with each dose group, there were two placebos except with the 100 mg/kg group where there was only one placebo. In the 10 and 20 mg/kg group there were no side-effects in any subject. At the 50 mg/kg level, three out of four subjects experienced slight to moderate nausea and dizziness from 0 to 2.5 h after dosing. In the 100 mg/kg group all three subjects reported side-effects like nausea, dizziness, and vertigo, that were short-lived in two subjects, but lasted up to 30 h in one subject. The study was stopped after evaluation of the latter subject, so fewer subjects were completed in this last group. Despite these subjective side-effects, there were no significant changes in objective clinical parameters like pulse, blood pressure, body temperature, or blood and urine chemistries. We conclude that at a single dose of 4-MP (10-20 mg/kg) producing plasma levels within a probable therapeutic range, no side-effects were attributed to 4-MP.
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PMID:4-Methylpyrazole: a controlled study of safety in healthy human subjects after single, ascending doses. 305 73

Differences in the pharmacokinetics of alcohol absorption and elimination are, in part, genetically determined. There are polymorphic variants of the two main enzymes responsible for ethanol oxidation in liver, alcohol dehydrogenase and aldehyde dehydrogenase. The frequency of occurrence of these variants, which have been shown to display strikingly different catalytic properties, differs among different racial populations. Since the activity of alcohol dehydrogenase in liver is a rate-limiting factor for ethanol metabolism in experimental animals, it is likely that the type and content of the polymorphic isoenzyme subunit encoded at ADH2, beta-subunit, and at ADH3, the gamma-subunit, are contributing factors to the genetic variability in ethanol elimination rate. The recent development of methods for genotyping individuals at these loci using white cell DNA will allow us to test this hypothesis as well as any relationship between ADH genotype and the susceptibility to alcoholism or alcohol-related pathology. A polymorphic variant of human liver mitochondrial aldehyde dehydrogenase, ADLH2, which has little or no acetaldehyde oxidizing activity has been identified. Individuals with the deficient ALDH2 phenotype do not have altered ethanol elimination rates but they do exhibit high blood acetaldehyde levels and dysphoric symptoms such as facial flushing, nausea and tachycardia, after drinking alcohol. Because acetaldehyde is so reactive, it binds to free amino groups of proteins including a 37 kilodalton hepatic protein-acetaldehyde adduct and may elicit an antibody response. We would predict that individuals who have low ALDH2 activity because of liver disease or because they have the inactive ALDH2 variant isoenzyme might form more protein-acetaldehyde adducts and elicit a greater immune response. These adducts may represent good biological markers of alcohol abuse and may also play a role in liver injury due to chronic alcohol consumption.
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PMID:Genetic polymorphism of enzymes of alcohol metabolism and susceptibility to alcoholic liver disease. 306 25

A tilt-table test was administered to five young men before (test 1) and after (test 2) 8 days of heat acclimation (2-h daily exercise at 50% VO2max at 40 degrees db, 30 degrees C wb) and to five other young men before and after the same exercise at 24 degrees C to determine fluid-electrolyte and endocrine responses in orthostasis in fainters and nonfainters. Half of the 10 subjects showed improved orthostatic reactions from test 1 to test 2 (disappearance of nausea and dizziness and improved heart rate and blood pressure), and the other 5 subjects showed no improvement. The improvement, especially in the nonfainters, was related to increases in posttilt plasma volume (PV) and plasma concentration of potassium. During test 1, plasma renin activity (PRA) increased five times from supine to orthostatis, with a corresponding increase in plasma vasopressin (ADH) of 50 times. The corresponding increases in test 2 were lower by 50 and 75% compared with those occurring in test 1 for PRA and ADH, respectively. PRA was five times higher in nonfainters than in fainters in test 1, whereas ADH showed an opposite trend. The orthostatic-induced increase in ADH seems to be related to volume control independent of PRA. This increase is reduced with improvement in orthostatic reactions, probably because of an increase in PV.
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PMID:Orthostatic fluid-electrolyte and endocrine responses in fainters and nonfainters. 731 73

A case of isolated ACTH deficiency with hyporeninemic hypoaldosteronism, presenting severe hyponatremia, is described. A 57-year-old man complaining of nausea, vomiting and fatigability was admitted to our hospital because of hyponatremia (114 mEq/I). The low levels of serum cortisol and urinary 17-OHCS suggested glucocorticoid deficiency, and that the glucocorticoid deficiency was due to isolated ACTH deficiency was confirmed by a continuous ACTH loading test and pituitary gland stimulation tests. Although the low level of serum sodium was normalized after the administration of cortisone acetate (50 mg/day) combined with an increase in oral salt intake, urinary sodium loss persisted by the results of hypertonic saline infusion test. Treatment led to improvement of impairment of water diuresis due to hypersecretion of ADH. Hyporeninemic hypoaldosteronism persisted after treatment. We have shown that severe hyponatremia that occurs with combined deficiency of glucocorticoids and mineralocorticoids can be corrected with high salt intake and glucocorticoid replacement without correcting mineralocorticoid deficiency.
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PMID:A case of isolated ACTH deficiency with hyporeninemic hypoaldosteronism. 877 60

A case of isolated ACTH deficiency who developed autoimmune-mediated hypothyroidism and still showed impaired water diuresis during glucocorticoid replacement therapy is reported. A 45-year-old woman was initially admitted for nausea, vomiting, and general malaise. Her serum sodium and plasma osmolality, ACTH and cortisol values were low, but her urine osmolality was high. Other pituitary hormone levels, thyroid hormone levels, and a computed tomogram of the pituitary gland were normal. The patient was treated with hydrocortisone and followed in the outpatient clinic; however, she was lost to follow up 18 months after admission. Three years later she presented with hypoglycemia and hyponatremia. Her serum or plasma ACTH, FT3, FT4, cortisol levels were low and her serum TSH level was high. Pituitary stimulation tests revealed a blunted response of ACTH to CRH and an exaggerated response of TSH to TRH. Plasma ADH was inappropriately high, and a water-loading test revealed impaired water diuresis and poor suppression of ADH. Although ADH was suppressed, impaired water diuresis was observed in the water loading test after hydrocortisone supplementation. Thyroxine supplementation completely normalized the water diuresis. Her outpatient clinic medical records revealed a gradual increase in TSH levels during follow up, indicating that she had developed hypothyroidism during glucocorticoid replacement therapy. The hyponatremia on the first admission was due to glucocorticoid deficiency, whereas the hyponatremia on the second admission was due to combined deficiencies of glucocorticoid and thyroid hormones.
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PMID:A case of isolated ACTH deficiency who developed autoimmune-mediated hypothyroidism and impaired water diuresis during glucocorticoid replacement therapy. 1122 40

Pharmacokinetic models for ethanol metabolism have contributed to the understanding of ethanol clearance in human beings. However, these models fail to account for ethanol's toxic metabolite, acetaldehyde. Acetaldehyde accumulation leads to signs and symptoms, such as cardiac arrhythmias, nausea, anxiety, and facial flushing. Nevertheless, it is difficult to determine the levels of acetaldehyde in the blood or other tissues because of artifactual formation and other technical issues. Therefore, we have constructed a promising physiologically based pharmacokinetic (PBPK) model, which is an excellent match for existing ethanol and acetaldehyde concentration-time data. The model consists of five compartments that exchange material: stomach, gastrointestinal tract, liver, central fluid, and muscle. All compartments except the liver are modeled as stirred reactors. The liver is modeled as a tubular flow reactor. We derived average enzymatic rate laws for alcohol dehydrogenase (ADH) and acetaldehyde dehydrogenase (ALDH), determined kinetic parameters from the literature, and found best-fit parameters by minimizing the squared error between our profiles and the experimental data. The model's transient output correlates strongly with the experimentally observed results for healthy individuals and for those with reduced ALDH activity caused by a genetic deficiency of the primary acetaldehyde-metabolizing enzyme ALDH2. Furthermore, the model shows that the reverse reaction of acetaldehyde back into ethanol is essential and keeps acetaldehyde levels approximately 10-fold lower than if the reaction were irreversible.
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PMID:A physiologically based model for ethanol and acetaldehyde metabolism in human beings. 1592 32

It has been shown that stress changes stimulated pro-inflammatory cytokine production and the sensitivity of stimulated cytokine production to glucocorticoid suppression. While glucocorticoid secretion habituates in response repeated stimulation, it is not known whether stimulation and suppression of cytokine production are also subject to adaptation. Eight healthy young subjects were exposed to repeated nauseogenic body rotation on four consecutive days. On each day subjects were rotated around the vertical axis up to five times for a period of 1 min or until subjects chose to stop due to nausea. Blood and saliva samples were obtained before and after rotation for assessment of cortisol, ACTH, plasma vasopressin (ADH), in vitro TNF-alpha and IL-6 production and glucocorticoid sensitivity of TNF-alpha and IL-6 production. Rotation induced increases of ACTH, cortisol, and ADH in the first session. All endocrine responses habituated over time, except for the free cortisol response in men. Pro-inflammatory cytokine production showed a sex-specific response pattern with increases in men and decreases in women in the first session vs. increases in men and women in the last session. Response patterns of GC sensitivity also changed over time: in the first session, sensitivity increased only in men, but in the last session, GC sensitivity decreased in all subjects. In conclusion, in response to repeated nausea induction, habituation occurs only in the endocrine system and predominantly in women. In the immune system, response patterns change in the favor of inflammatory conditions, with increases in stimulated IL-6 and TNF-alpha and decreases in the effectiveness of glucocorticoid suppression of these cytokines. These presumably unfavorable changes in the inflammatory system are more pronounced men.
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PMID:Sex-specific adaptation of endocrine and inflammatory responses to repeated nauseogenic body rotation. 1614 52


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