Effect and metabolism of 1 alpha,24-dihydroxyvitamin D3 in hepatectomized rats.
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Biomedical subjects
Publications and source records attributed to T Noguchi.
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The distribution of enzymes involved in purine degradation in fish and crustaceous liver was examined by centrifugation in a sucrose density gradient. In mackerel, yellow mackerel, and prawn liver and mantis club hepatopancreas, uricase and allantoinase were located only in the peroxisomes and in the soluble fraction from broken peroxisomes, and allantoicase was located only in the peroxisomes. Uricase and allantoinase seem to be located in the peroxisomal matrix and allantoicase in the peroxisomal membrane. Adenase, guanase, and xanthine oxidase were present only in the soluble fraction of mackerel liver.
A factor responsible for stimulating an increase in ornithine decarboxylase activity in the liver of mice was found in tumor cell-free ascites fluid of mice 3 days after inoculation of tumor cells. The factor was purified about 70-fold in 25% yield from tumor cell-free ascites fluid. As little as 1 microgram of protein of purified fraction, injected intraperitoneally into normal mice, significantly increased the activity of ornithine decarboxylase in the liver. The most active preparation of the factor formed two major protein bands on analytical polyacrylamide gel electrophoresis and both these bands stained with periodic acid-Schiff's reagent. The factor was a heat-labile, alkaline-stable, acidic protein with a molecular weight of more than 300 000. It was inactivated by treatment with 10 mM dithiothreitol, 5 M urea, pronase or mixed glycosidase, but was stable on treatment with DNAase, RNAase or neuraminidase.
The correlation between the dissolution rate and bioavailability of griseofulvin tablets was studied in stomach-emptying-controlled rabbits and in humans. Three different test tablets, each consisting of two dose levels (62.5 or 125 mg) of griseofulvin, were used. The dissolution rates in 0.5 hr were approximately 75, 40, and 12%. With oral administration at 62.5 mg/rabbit, the ratio of peak plasma level, Cmax, was 1.00:0.66:0.40 and that of the area under the curve (AUC) was 1.00:0.73:0.46 for the three tablets. The corresponding C'max ratio was 1.00:0.74:0.34 and the AUC ratio was 1.00:0.72:0.33 in humans at the dose level of 500 mg. A good correlation was observed for the rank order of Cmax and AUC between rabbits and humans, but such a correlation was not seen between in vivo data and in vitro data at a larger dose of 125 mg/rabbit. This finding was attributable to the dose, which exceeded the GI drug dissolution or absorption capacities. These results suggest that the stomach-emptying-controlled rabbit is useful for evaluating oral dosage forms for human use and that dose level selection is important in the bioavailability study of a barely water-soluble drug.
Hepatic functional reserve was evaluated in 76 patients with known liver, biliary tract or pancreas diseases using kinetic analysis of removal of indocyanine green (ICG) with special reference to maximal removal rate (Rmax). In surgery other than hepatectomy, if ICG Rmax is below 0.4 mg/kg/min the operative risk should be considered high. In hepatic surgery, even if ICG Rmax is above 0.4 mg/kg/min the operative risk was high and it should be required to be above 1.0 mg/kg/min for extended lobectomy or hepatectomy. Furthermore, prior to hepatectomy the functional reserve of the remnant liver was estimated from an effective liver volume rate, calculated from the rate of uptake of radioisotope as measured by on-line computer system, and ICG Rmax. The functional reserve of the remnant liver was compared with the operative results, such as morbidity or mortality for each patient. When ICG Rmax of the remnant liver was below 0.4 mg/kg/min the prognosis was poor in hepatic surgery, because of there were three postoperative death and seven complications such as ascites or liver failure in the ten cases. On the other hand, when above 0.4 mg/kg/min, the prognosis was good without any postoperative death or complications in the twelve cases of hepatic surgery, as the completely same results for general surgery, in which it is as well when ICG Rmax of whole liver is above 0.4 mg/kg/min.
Fifty-five dogs were used to evaluate the resectability of the liver with obstructive jaundice. Cholecystectomy and ligation of the distal common bile duct were used to produce obstructive jaundice. It was found that 40 per cent of the liver with obstructive jaundice was resectable with biliary decompression 2 weeks after ligation. At 1 week after induction of obstructive jaundice, 70 per cent hepatectomy with biliary decompression may be tolerated with careful postoperative management. From serum chemical studies it was found that if the serum albumin level was below 2.0 g/dl, 60 per cent of the dogs died after 40 per cent hepatectomy and all died after 70 per cent hepatectomy. From the standpoint of hepatic functional reserve 40 per cent hepatectomy is successful if the maximal removal rate of indocyanine green is above 0.14 mg/kg/min. Hepatic functional reserve is reliable for predicting the risk of hepatectomy, and it correlates well with the rate of hepatic regeneration after hepatectomy.
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In rats fed ad libitum, a marked circadian rhythm with a peak at night was observed in the hepatic level of ornithine decarboxylase (ODC) [EC 4.1.1.17], the enzyme for the first step of polyamine synthesis. A similar rhythm was found in the hepatic content of putrescine, but not of spermidine or spermine. The mitotic activity of the liver also exhibited a clear rhythm with a peak in the daytime. The rhythms of both ODC and mitosis were generated by cyclic ingestion of proteinous food, since the peaks shifted when rats were meal-fed and both activities disappeared on starvation or protein deprivation. The close parallel between the rhythms suggested that synthesis of polyamine, especially that of putrescine, was a prerequisite for the rhythmic growth of liver. The dietary induction of hepatic ODC depended on the nutritive value of dietary protein; zein or gelatin was effective only when supplemented with limiting amino acids and there was a good correlation between the hepatic ODC level and the relative growth rate.
7 patients with primary humoral immunodeficiency were given an S-sulfonated IgG preparation, 100 mg/kg i.v. at intervals of 3--4 weeks, for treatment of, or prophylaxis against, infection. The clinical effects and metabolism of S-sulfonated IgG were studied. No side reactions attributable to S-sulfonated IgG occurred in any of the patients. The S-sulfonated IgG was completely transformed into intact IgG within 24 h after administration, and had a mean half-life of 21 days, comparable to that of intact IgG. Complete restoration of IgG Fc fragment activity occurred within 24 h following injection, as assessed by reversed passive cutaneous anaphylaxis.
The patellar tendon was tapped by random impulses of triangular waveform and motor unit spikes were recorded from the quadriceps femoris muscle. The cross-correlogram of the taps and the motor unit spikes revealed a primary correlation kernel, the width of which was interpreted as an indicator of the mean time-to-peak of excitatory postsynaptic potentials (EPSPs) elicited monosynaptically in an alpha-motoneurone by the triangular taps. The mean time-to-peak was 7.6 +/- 1.3 ms in normal subjects and 9.0 +/- 1.8 ms in spastic patients (P less than 0.005). The prolonged time-to-peak of EPSP in spastic patients is consistent with the hypothesis that as a result of degeneration of the corticomotoneuronal tract the Ia axons sprout and form more synaptic contacts on distal portions of the dendrites of alpha-motoneurones.
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Thyroxine (T4)-prolactin interactions on hepatic arginase and ornithine transcarbamylase (OTC) as well as hind legs, tail, digestive tract and median eminence were investigated in tadpoles, Rana catesbeiana. Prolactin completely blocked T4-induced tail resorption, but failed to suppress hind-leg growth, shortening of digestive tract and promotion by T4 of the median eminence development. Prolactin blocked T4-induced increase in hepatic arginase activity but not in hepatic OTC activity. A possibility that T4 and prolactin are regulating the hepatic arginase indirectly is discussed.
Pyruvate (glyoxylate) aminotransferase is found in the peroxisomal and mitochondrial matrices, and in soluble fractions of rat liver homogenates. Soluble activity is from broken peroxisomes. Differential solubility of the mitochondrial and peroxisomal enzymes in digitonin can be used to assay the two activities separately.
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TEI-1194, sodium 6-[D-(-)-alpha-(coumarin-3-carboxamide)-phenylacetamide] penicillanate and TEI-2012, sodium 6[D-(-)alpha-(8-hydroxy-coumarin-3-carboxamide)-phenylacetamide] penicillanate are new semisynthetic penicillin derivatives both possessing a broad spectrum of in vitro antibacterial activities. Minimal inhibitory concentrations of both agents were compared with carbenicillin. TEI-1194 and TEI-2012 were clearly found to have more potent activities especially against Pseudomonas aeruginosa than carbenicillin. At a concentration at 6.25 micrograms/ml, 85 approximately 90% of a total of 50 strains of clinically isolated P. aeruginosa were inhibited by TEI-1194 and TEI-2012, whereas carbenicillin had no effect. Evaluation of the antibacterial activity against a series of mutants producing different levels of beta-lactamases and test of the susceptibilities to some beta-lactamases demonstrated that TEI-1194 and TEI-2012 had low susceptibility to various cephalosporinases. However, both compounds were susceptible to penicillinase from Klebsiella pneumoniae H-2 at a rate of about 15% of penicillin-G taking its absolute rate as 100.