[Dynamic study of ammonia metabolism after rectal administration of 13N-ammonia (author's transl)].
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Biomedical subjects
Publications and source records attributed to N Fukuda.
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Enhancement by TRH of the dopamine(DA) agonist-induced circling behavior and effect of TRH itself on circling behavior were investigated. TRH(2.5--20 mg/kg, i.p.) remarkably enhanced the circling behavior induced by apomorphine or-L-DOPA in the mice lesioned unilaterally in the caudate nucleus by injection of 6-hydroxydopamine (60OHDA) or by tissue aspiration with subsequent reserpinization. TRH also enhanced the apomorphine-induced stereotypy in reserpinized normal mice. The above TRH-enhancing action of the circling behavior was potentiated, suppressed or unaffected by alpha-methyl-para-tyrosine (alpha-MT) or GABA-ergic drugs. In the 6-OHDA lesioned mice treated with TRH, the cyclic AMP formation by DA or apomorphine was clearly enhanced in the triatal slices taken from the lesioned side but not from the intact side. In the rats lesioned unilaterally in the nigrostriatal DA pathway by 6-OHDA, high doses of TRH injected i.p. (100 mg/kg) or into the non-lesioned caudate nucleus (50 micrograms) produced circling toward the lesioned side, which was suppressed by haloperidol or alpha-MT. TRH(10(-5)--10(-3)M) increased the 14C-DA release from the rat striatal slices in vitro. These results suggest that TRH at low doses facilitates the DA postsynaptic transmission in association with an increase of DA-stimulated cyclic AMP formation in the striatum under supersensitization of the DA receptors, and also at high doses enhances the DA neuronal activity by increasing the DA release from the striatal nerve terminals.
A flow diagram for the automated determination of ferricyanide reductase activity in red blood cells was prepared in the modules from AutoAnalyzer AA I (Technicon Instruments Inc). Ferricyanide reductase assay can be substituted for assay of cytochrome b5 reductase (EC 1.6.2.2), which plays a major role in reducing methaemoglobin in erythrocytes, and is defective specifically in the erythrocytes of patients with hereditary methaemoglobinaemia. The effective sampling rate of the analysis is 30/h, and less than 0.05 ml of whole blood is required. Interference of haemoglobin with absorption by potassium ferricyanide at 420 nm is effectively exculded by dialysis. This automated method was compared with the accepted diaphorase method, and it distinguished clearly the ferricyanide reductase activity of cord bloods from that of adult bloods. The activity of the blood from a patient with hereditary methaemoglobinaemia was only residual. It is suggested that the method is useful as a mass screening test for hereditary methaemoglobinaemia.
The effects of treadmill exercise on hepatic cholesterogenesis and fecal steroid excretion were studied using male Wistar rats fed a commercial pellet ration. Exercise, in comparison with ad libitum or pair-feeding sedentary groups, caused the following significant changes: (i) a reduction in the concentration of plasma triglyceride, phospholipid and cholesterol; (ii) a reduction in liver weight; (iii) increases in hepatic 3-hydroxy-3-methylglutaryl-CoA reductase activity and incorporation of mevalonate into digitonin precipitable sterol; (iv) increases in excretion of neutral and acidic steroids into the feces; (v) the increase in lipoprotein lipase activity in the cardiac muscle, and (vi) the decrease in the concentration of carcass triglyceride but not of cholesterol. These data suggest that the mechanism responsible for the plasma cholesterol-lowering effect of exercise is attributable to an increase in exretion of fecal neutral and acidic steroids accompanied by an acceleration of cholesterol turnover in the body.
Behavioral and EEG changes induced by brain stem compression and the effect of TRH were studied. The compression was given for 1 to 6 min by inflating a balloon chronically implanted on the dorsal surface of the cat brain stem in the 4th ventricle via cisterna magna. Within 10 to 36 sec after the start of the compression, the cats turned sideways and became motionless in a spastic extension of four legs, and thereafter all reverted to a normal position, after 45 to 120 min, although slight movements or head-up position was observed in some animals. The cortical EEG patterns observed after the compression were initially a brief rush of low amplitude-fast waves (EEG arousal) followed by a flattened and/or spike pattern, and subsequently these shifted to high amplitude-slow waves with or without an accompanying EEG arousal. These behavioral EEG alterations were remarkably improved by i.v. administration of TRH as follows: eight of 12 cats with 1 mg/kg and one of 4 cats with 0.5 mg/kg promptly changed from the lateral to a crouching or abdominal position, and thereafter never turned sideways again. Partial recovery such as movements of forelegs, struggling or head-up in the lateral position, rolling or slight shift of position was also observed within several min in three cats with 1 mg/kg as well as in two cats with 0.5 mg/kg. Furthermore, TRH induced a dose dependent, persistent EEG arousal in all cats. These results show that TRH ameliorates deterioration in behavior and the EEG, this deterioration being similar to clinical states of disturbance in consciousness induced by compressing the brain stem.
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Ammonia has been known to be an inducing agent of hepatic coma associated with liver cirrhosis. In order to establish a non-invasive method of investigating the portal circulation and the metabolism of ammonia at liver the following studies were performed, by using cyclotron produced 13N-labeled ammonia and delayed line-camera interphased with on-line computer system. 1) Animal experiment. Dynamic scintigraphy of thoraco-abdominal region of a rabbit after intrasigmoidal as well as intravenous administration of 13N-ammonia were performed. 2) Theoretical consideration on the functional image of liver: According to the results of the animal experiments, a model of ammonia metabolism having the minimal complexity necessary to represent data in the case of intrasigmoidal administration was proposed. Starting from the solution to the differential equation describing the model, relevant parameters characterizing the dynamic curve of liver were duded.
1) Clinical application: Dynamic scintigraphy of liver and heart of a patient having liver cirrhosis after intrasigmoidal administration of 13N-ammonia (pH 8.1) were performed. Simultaneously, continuous measurments of radioactivity at the left side abdomen and the left temporal region were done by using a scintillation detector for renography. Successive measurement of radioactivity of blood was also carried out. 2) Comstruction of functional images of liver and heart: By using digital radioisotope image of liver and heart of the patient after intrasigmoidal administration of 13N-ammonia, the maps with respect to parameters described in the pervious paper were constructed.
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Ten cases of various kinds of dermatoses underwent cephradine by injection. Two cases injected cephradine intramuscularly resulted in severe pain. Three of 4 cases with pyogenic skin infection revealed excellent results. Three cases were prevented from secondary infection. Adverse effects such as vertigo were avoided by lowering the speed of intravenous injection. No abnormal findings of serum GOT and GPT levels after the completion of the treatment was noted in 7 of 8 cases, but one case which was administrated large dosis of corticosteroid concomitantly revealed elevated level in this finding.
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A theoretical analysis was made on the optimum Bleomycin treatment regimen on the basis of the "binding-saturation model" which was proposed for the Bleomycin dose-cell survival relation. The surviving fraction of tumor cells decreased as a function of the number of fractionated treatments up to the optimum fractionation number if the tumor was treated with the same total dose. The effect of cellular sensitivity to the antibiotic, tumor doubling time, treatment interval, and total doses on the optimum regimen was analyzed. The importance of treatment interval and tumor doubling time was emphasized and the short treatment interval was recommended for the clinical use of this antibiotic. The optimum number of fractions increased linearly with the increase of the total dose while the optimum single dose was independent of the total dose. A concept of the tumor control probability of tumors treated with the optimum fractionation regimen was introduced and implications of these analyses in the clinical cancer chemotherapy were discussed.