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Biomedical subjects

M Nakano

Publications and source records attributed to M Nakano.

At least 919 records · Page 51Linked to original sources

Age-related alteration of renal brush border leucine aminopeptidase in rat kidney cortex.

Renal brush border enzyme activities were significantly decreased with age. The decrease was observed in the homogenate and brush border fractions. Purified leucine aminopeptidase was significantly decreased in Vmax and Km value for leucyl-beta-naphthylamide in the old rats. Heat stability of leucine aminopeptidase from both old and young rats showed biphasic, and the enzyme from old rats was more stable at 60 degrees C than that of the young. However, other properties such as molecular weight, antigenicity, charge, and optimum pH were not significantly different between young and old rats. From these results, it is suggested that age-related alteration of leucine aminopeptidase is due to a conformational change of enzyme molecule; the conformational change might occur at the active sites of the enzyme.

Aging↗

Isolation and identification of beta-nitrostyrene from smoked chicken.

Extraction and identification of beta-nitrostyrene from smoked chicken is described. Commercially obtained smoked chicken was homogenised and extracted with chloroform-methanol (2:1). The extracts were fractioned by silicic acid column chromatography. The purified extract using thin-layer chromatography was identified by a colour reaction (this qualitative method for some nitrated compounds is developed this time), high pressure liquid chromatography and gas chromatography/mass spectrometry. The concentration of beta-nitrostyrene in the smoked chicken was 94 ppb. The average recovery of added beta-nitrostyrene was 107%. However, the toxicity of this material was not tested in the present paper.

Journal Article↗

Increased platelet thromboxane synthesis in renal glomerular diseases.

Washed platelets were prepared from healthy children and adults, and patients with renal glomerular diseases, and incubated with [1-14C] arachidonate to measure the generation capacities of thromboxane (Tx) A2 and 12-hydroxyeicosatetraenoate (12-HETE). Tx generation capacity of platelets was significantly higher in patients with chronic glomerulonephritis, purpura nephritis and lupus nephritis than in healthy control subjects. There was no significant increase in minimal change nephrotic syndrome. 12-HETE showed a decreasing tendency in the glomerular diseases, which was restored to normal level by in vitro addition of indomethacin. Such increased Tx generation capacity of platelets may cause abnormal enhancement of platelet functions and conceivably constitute an aggravating factor of glomerular and microvascular damage in the affected kidney.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗

Long-term results of jejunal replacement of the esophagus.

Since 1969, jejunal interpositions have been carried out in 19 patients for esophageal replacement. A segment of the upper jejunum was used to bridge the gap in the right thoracic cavity. The distal esophagus and its sphincteric mechanism was preserved in all but four patients, who had peptic strictures. Early postoperative complications such as total necrosis of the graft, perforation of the graft, and anastomotic leak developed in three patients (16%). There were no operative deaths but there were two later deaths (11%). We were able to follow 12 patients over a long term. Among these 12 patients there were two anastomotic strictures, one of which was dilated successfully by bouginage, and one marked redundancy of the jejunum which necessitated surgical correction. Both height and weight were lower than -2 SD on a Japanese standard growth curve in two patients who had anastomotic strictures. Transient stagnation of swallowed barium at the lower esophagus was the common finding; it was observed in seven cases (58%). Only three patients (25%) complained of occasional feelings of delay in swallowing. Stagnation with a mildly redundant jejunum was the common radiologic finding in these three patients. Reflux of the gastric content into the esophagus did not occur. All the patients, except one who still has dysphagia due to anastomotic stricture, can eat anything they wish at almost normal speed. These long-term results indicate that jejunal interposition with preservation of the lower esophagus is a recommendable procedure for esophageal replacement.

Adolescent↗

Adrenal cortical carcinoma. A clinicopathological and immunohistochemical study of 91 autopsy cases.

The clinicopathological and immunohistochemical features of 91 patients with adrenal cortical carcinoma (ACC) are presented. This series included 52 men and 39 women with a mean age of 45.7 years. According to the extent of cellular pleomorphism, it was possible to define ACC as Grade 1, 2 or 3. There was a correlation between the grading and mitotic activity (P less than 0.05). Median survival of patients with G2 or G3 tumors was only 4.3 months, while that of patients with G1 tumors was 24.3 months (P less than 0.05). The histological grading of ACC was thus shown to be an important prognostic factor. In most cases of ACC, silver impregnation demonstrated zona fasciculata-like structures. Immunohistochemically, vimentin-positive tumor cells could be detected in 41 of 56 cases (73.2%) of ACC, while only 6 of 43 cases (14.0%) of adrenal cortical adenoma showed scattered vimentin-positive cells (p less than 0.01). Considering the fact that the adrenal cortex is of mesodermal origin, this finding may suggest dedifferentiation of the tumor to fetal tissue. Twenty-four of 62 cases of ACC showed cytokeratin-positive cells. Vimentin and silver staining are useful for the diagnostic differentiation of ACC from other carcinomas. In the present study, there was no histologic differentiation between clinically functional and nonfunctional ACC.

Adolescent↗

Dose-dependency in the exsorption of theophylline and the intestinal dialysis of theophylline by oral activated charcoal in rats.

The elimination half-life of theophylline in serum after intravenous (i.v.) administration of aminophylline increased with increase in dose. Exsorption of theophylline from blood to the gastrointestinal tract was investigated after i.v. administration of aminophylline (10-50 mg kg-1) to rats by the in-situ single-pass perfusion technique. The exsorption rate of theophylline into the intestinal lumen also increased with increase in dose. When the dose of aminophylline was increased five-fold from 10 to 50 mg kg-1, the amount of theophylline exsorbed in 120 min was proportionally increased from 450 to 2300 micrograms. The average extent of theophylline exsorbed into the intestinal lumen was 12-15% after doses from 10-50 mg kg-1, while the extent of the drug excreted into the bile varied from 0.17-0.30% after doses from 10-50 mg kg-1. However, intestinal and biliary clearance of theophylline did not change significantly in the range 10 to 50 mg kg-1. Oral administration of multiple doses of activated charcoal reduced the serum theophylline levels after i.v. administration of aminophylline (50 mg kg-1) to rats. The serum half-life and the area under the serum concentration-time curve of theophylline were decreased to 52 and 50% by the charcoal treatment, respectively, while the total body clearance of the drug was increased to 188% compared with the corresponding control experiments. The volume of distribution was not significantly different between treated and control rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Transport of furosemide into the intestinal lumen and the lack of effect of gastrointestinal dialysis by charcoal in rats with acute renal failure.

The characteristics of exsorption and/or excretion of furosemide into the small intestinal lumen in rats with acute renal failure (ARF rat) were investigated by an in situ single-pass perfusion technique. The amount of furosemide, which was exsorbed into the intestinal lumen after an intravenous administration of the drug to rats was only very slight. The exsorption rate of the drug was significantly increased in ARF rats as compared with normal rats. The average amount of the drug exsorbed into the perfusate in normal rats was 0.83% of dose, whereas that in ARF rats was 1.83% of dose. The amounts of furosemide excreted into the bile in normal rats and ARF rats were 1.53% and 2.64%, respectively. The increased exsorption of furosemide in ARF rats appeared to be due primarily to the decreased binding of the drug to the serum protein, because only the unbound drug permeates through the intestinal membrane into the gastrointestinal (g.i.) tract, and, to some extent, to the increased nonrenal excretion caused by poor renal excretion. Oral activated charcoal had little effect on the serum furosemide levels after intravenous administration of the drug at a dose of 10 mg/kg in ARF rats. The lack of effect of activated charcoal on the elimination of the drug may be due to the small amount of the drug excreted into the g.i. tract.

Acute Kidney Injury↗

Relative bioavailability of midazolam following sublingual versus oral administration in healthy volunteers.

The extent of bioavailability of midazolam following sublingual and oral administration were evaluated. Three healthy volunteers received a single 15-mg dose of midazolam maleate by sublingual and oral routes on two occasions in a ossover design. Concentrations of midazolam in plasma during 4 h after each dose were measured by gas-liquid chromatography with an electron-capture detector. The mean AUC0-4 value following sublingual administration was significantly greater than that following oral administration (14889 vs 3594 ng. min/ml, p less than 0.05). The peak plasma concentration after sublingual dose was also significantly higher than that after oral administration (p less than 0.05). The mean AUC0-4 value of midazolam after sublingual administration was increased four times compared with that after oral administration, possibly due to avoidance of first-pass effect. Thus, the clinical effects of midazolam may likewise be enhanced by sublingual administration of midazolam.

Administration, Oral↗

Transport of procainamide and N-acetylprocainamide from blood into the intestinal lumen and intestinal dialysis by oral activated charcoal in rats with acute renal failure.

The characteristics of exsorption and/or excretion of procainamide and its metabolite, N-acetylprocainamide (NAPA), into the small intestinal lumen in both normal rats and rats with acute renal failure (ARF rats) induced by uranyl nitrate were investigated by an in situ single-pass perfusion technique. The exsorption of procainamide and NAPA from blood into the intestinal lumen was increased in ARF rats compared with normal rats. The mean apparent renal, biliary and intestinal clearance values of procainamide were 186, 1.83 and 73.9 ml/h/kg in normal rats, respectively, and were 2.02, 1.37 and 55.8 ml/h/kg in ARF rats respectively. Furthermore, the mean renal, biliary and intestinal clearance values of NAPA were 35.2, 19.4 and 21.1 ml/h/kg in normal rats, respectively, and were 1.12, 21.0 and 26.0 ml/h/kg in ARF rats, respectively. There was little difference in the intestinal clearance values of procainamide and NAPA between normal and ARF rats. The ratio of nonrenal clearance/total body clearance was greater in ARF rats than in normal rats. Treatment with oral activated charcoal reduced the serum NAPA levels in both normal and ARF rats, and had little effect on the serum procainamide levels in normal rats, while it reduced the serum drug levels in ARF rats. Consequently, the increase in both drugs transported into the intestinal lumen induced by renal failure may enhance the intestinal clearance of the drug by oral administration of activated charcoal.

Acecainide↗

Enhanced faecal excretion of 2,3,4,7,8-pentachlorodibenzofuran in rats by a long-term treatment with activated charcoal beads.

1. The effect of activated charcoal beads on the faecal excretion of 2,3,4,7,8-pentachlorodibenzofuran (PenCDF), a causal agent of yusho, which accumulates in the body, was studied for 12 weeks in rats. 2. Diets supplemented with 1% and 5% activated charcoal beads stimulated faecal excretion of PenCDF about 2- and 4-fold, respectively. The concentration of PenCDF in liver, the major storage site, was decreased significantly and dose-dependently by the treatment. 3. The charcoal bead treatment decreased the extent of fatty liver, thymic atrophy, and induction of hepatic benzo[a]pyrene hydroxylase.

Animals↗