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Biomedical subjects

W M Doizaki

Publications and source records attributed to W M Doizaki.

18 recordsLinked to original sources
PubMed1984

Brain methanethiol and ammonia concentrations in experimental hepatic coma and coma induced by injections of various combinations of these substances.

In normal rats in a coma induced by NH+4 alone or by methanethiol alone, the brain and blood levels of ammonia or methanethiol are much higher than those observed in rats in experimental hepatic coma. When various smaller dosage combinations of NH+4, methanethiol, and octanoic acid were injected simultaneously, coma occurred at lower brain and blood concentrations of ammonia and methanethiol. Brain ammonia and methanethiol concentrations in normal rats receiving 0.75 mmol NH+4 plus 0.15 mmol octanoic acid plus 18 mumol methanethiol were comparable with those observed in 24 rats in hepatic coma after fulminant hepatic failure caused by acute massive ischemic liver necrosis. The normal rats became comatose. In these rats and in the rats in hepatic coma, the ammonia level in the brain was increased threefold and the methanethiol level in the brain was increased fivefold. Because these levels of ammonia and methanethiol were sufficient to induce coma in normal rats, they should also have been sufficient to induce coma in rats with damaged livers. Therefore, the accumulation of ammonia and methanethiol in the central nervous system after the acute massive ischemic necrosis may have been sufficient to account for the coma that ensued, without the involvement of other factors.

Ammonia↗
PubMed1983

Gas chromatographic method for the determination of the lower volatile alcohols in rat blood and in human stool specimens on a fused silica capillary column.

A method is described for the simultaneous quantitation of the lower volatile alcohols in stool specimens and rat blood. The addition of potassium carbonate to the assay mixture markedly increased the sensitivity in the detection of these compounds. The method is shown to be simple and reproducible and is suitable for following the metabolism of ethanol in human stool specimens.

Alcohols↗
PubMed1980

Blood methanethiol in alcoholic liver disease with and without hepatic encephalopathy.

Blood methanethiol and ammonia concentrations were measured in 16 healty volunteers, 52 consecutive alcoholic cirrhotics without overt hepatic encephalopathy (HE), and 42 consecutive patients with alcoholic liver disease and overt HE. The mean concentration of blood methanethiol was significantly greater than normal in the cirrhotics without overt HE, and the means of both methanethiol and ammonia were significantly greater in the patients with than in those without overt HE. Only one patient with overt HE had both normal ammonia and methanethiol blood concentrations. Twenty of the patients with HE were followed serially. The directions of change in methanethiol and ammonia were consistent with the direction of change in mental status in 85% adn 60% respectively. All of the patients who deteriorated and died had changes in blood methanethiol that correlated with the change in mental status. We conclude that blood methanethiol is a valuable adjunct to the ammonia determination in the evaluation of the patient with possible HE. It is especially helpful in following the course of a patient with hepatic encephalopathy, both as to prognosis and as an indicator of response to therapy.

Adult↗
PubMed1980

Blood mercaptan and ammonia concentrations in cirrhotics after a protein load.

Measurements of blood ammonia and methanethiol were made in 17 moderate or severe alcoholic cirrhotics without overt hepatic encephalopathy under fasting conditions and 2, 3 1/2 and 5 hours after ingestion of a hamburger containing 80 gm. protein. At every time interval the average blood methanethiol in the cirrhotics was significantly higher than in 11 normal controls. The average blood ammonia in the cirrhotics was also higher than in the controls but only at five hours was the difference statistically significant. Fasting blood ammonia and methanethiol values were not strikingly effective in separating the normals and cirrhotics. After the protein load, however, the peak values of these measurements completely separated the cirrhotics from normals on a two-dimensional plot of methanethiol vs. ammonia. In our sample of patients, the peak postprotein load measurements were not effective in predicting which cirrhotics may develop overt encephalopathy. Utilization of the area under the curve of values obtained after the protein load did not appreciably improve on the results with the single peak value.

Adult↗
PubMed1979

Reversal of ammonia coma in rats by L-dopa: a peripheral effect.

Ammonia coma was produced in rats within 10 to 15 minutes of an intraperitonealinjection of 1.7 mmol NH4CL. This coma was prevented with 1.68 mmol L-dopa given by gastric intubation 15 minutes before the ammonium salt injection. The effect of L-dopa was correlated with a decrease in blood and brain ammonia, an increase in brain dopamine, and an increase in renal excretion of ammonia and urea. Intraventricular infusion of dopamine sufficient to raise the brain dopamine to the same extent did not prevent the ammonia coma nor affect the blood and brain ammonia concentrations. Bilateral nephrectomy eliminated the beneficial effect of L-dopa on blood and brain ammonia and the ammonia coma was not prevented. Thus, the reduction in blood and brain ammonia and the prevention of ammonia coma after L-dopa, can be accounted for by the peripheral effect of dopamine on renal function rather than its central action. These results provide a reasonable explanation for the beneficial effects observed in some encephalopathic patients receiving L-dopa.

Ammonia↗
PubMed1977

An improved method for measuring blood mercaptans.

An improved method for measuring MT in the blood is described which uses zinc as a reducing agent and utilizes a more sensitive gas chromatograph. The method measures covalently bound MT that was not previously detected and permits determinations in patients for the first time. The average normal whole blood MT in rat blood was 200 +/- 42 pmol/ml and in human blood 229 +/- 29 pmol/ml. Eleven rats in experimental hepatic coma following acute massive hepatic necrosis had blood levels four to 18 times the average normal, and seven cirrhotic patients with hepatic encephalopathy or coma had blood levels four to five times the average normal.

Animals↗
PubMed1975

Methionine-induced hepatic coma in dogs.

Oral methionine is noncomatogenic in normal dogs, but it is consistently comatogenic in dogs with portacaval shunts in the presence of elevated ammonia levels. Such action appears to be enhanced by the ammonia itself, since relatively small doses of oral methionine can induce coma when baseline levels of ammonia are above 1,000 mug/100 ml; much higher doses are nesessary for near normal ammonemia. The methionine-induced coma closely reproduces the clinical and electroencephalographic picture of coma in other canine models. Oral methionine does not significantly increase the ammonia levels, but its action is probably mediated by the release of methanethiol (and other less active compounds) from the bowel. Methanethiol levels tend to increase in proportion to the amount of methionine administered, and its comatogenic action may be amplified, up to one hundredfold, by high ammonia levels. Methanethiol levels in comatose patients and the concept of the synergistic effect with ammonia may lead to a clearer understanding of certain enterogenous and dietetic forms of hepatic encephalopathy in cirrhotic patients. The lowering of ammonia levels by hemodialysis or methanethiol levels by activated charcoal hemoperfusion, as attempts to reverse such forms of coma, warrants further investigation.

Administration, Oral↗