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Biomedical subjects

K Shirai

Publications and source records attributed to K Shirai.

At least 181 records · Page 10Linked to original sources
PubMed1987

[Fundamental and clinical studies of flomoxef in the pediatric field].

Fundamental and clinical studies of flomoxef (FMOX, 6315-S) were conducted and the obtained results are summarized as follows. For the pharmacokinetic investigation, FMOX at 10 or 20 mg/kg was administered by intravenous drip infusion over 30 minutes. In the 10 mg/kg group, the maximum blood concentration was reached just after completion of the drip infusion with the mean concentration of 30.3 +/- 4.5 micrograms/ml, and the mean half-life was 0.734 +/- 0.196 hour. The 6-hour urinary excretion rate was 72.3%. In the 20 mg/kg group, which also showed the peak concentration immediately after completion of the drip infusion, the mean peak blood concentration was 54.3 +/- 9.7 micrograms/ml and the mean half-life was 0.628 +/- 0.185 hour. The 6-hour urinary excretion rate was 69.3%. The urinary recovery tended to be lower in children than in adults. Between 10 mg/kg and 20 mg/kg, a definite correlation was observed between dose levels and blood concentrations. In the clinical investigation conducted with a total of 30 patients (22 with respiratory tract infection, 3 with lymphadenitis, 2 each with urinary tract infection and cellulitis, and 1 with acute osteomyelitis), FMOX was found to be excellent in 14 cases, good in 9, fair in 1, poor in 1, and not evaluable in 5. The efficacy rate was, therefore, 92.0%. In the bacteriological evaluation, 8 out of 12 clinically isolated strains were eradicated, 2 unchanged and 2 unknown. The elimination rate was 80.0%. Regarding side effects, no abnormal clinical symptoms were observed. As abnormal laboratory values, eosinophilia, prolongation of APTT, increased platelet count, and a slight elevation of GOT were observed.

Adolescent↗
PubMed1987

Impaired intermediate-density lipoprotein triglyceride hydrolysis in familial lecithin:cholesterol acyltransferase (LCAT) deficiency.

A new lecithin:cholesterol acyltransferase (LCAT)-deficient family was found in Japan. In the proband, both LCAT activity and LCAT mass were deficient. The patient's parents, child, and sister, diagnosed as heterozygotes, had half-normal LCAT activity and LCAT mass. In the patient, an increase of intermediate-density lipoprotein (IDL, 1.006 less than d less than 1.019) fraction was observed. In postheparin plasma, both lipoprotein lipase and hepatic triglyceride lipase activities were low. Hydrolysis of [14C] triolein by human hepatic triglyceride lipase in patient IDL was decreased compared to that in IDL from normal postprandial serum. Preincubation of these IDL with normal plasma in the absence of 5,5'-dithiobis-(2-nitrobenzoic acid) (DTNB) increased the rate of hydrolysis, in the presence of DTNB, this increment was not observed. These results suggest that one cause of IDL increase in the LCAT-deficient patient might be the difficulty of hydrolysis of these lipoprotein particles by hepatic triglyceride lipase.

Adult↗
PubMed1987

Effect of pirozadil on lipids, lipoproteins and apolipoproteins in Japanese with type IIa hyperlipoproteinemia.

Pirozadil (pyridine 2,6-dimethanol-bis(3,4,5-trimethoxybenzoate), Pemix) was administered for 16 weeks at a dose of 1.5 or 2.0 g/d to 15 adults with Type IIa hyperlipidemia. All patients had achieved a stable weight and were given a diet before treatment. Plasma lipids, lipoproteins and apolipoproteins were measured at 4-week intervals. Pirozadil reduced the mean total cholesterol (TC) level from 291.0 mg/dl to 260.8 mg/dl in 16 weeks (p less than 0.05). The mean percentage decrease was 8.5% in week 16. Low density lipoprotein (LDL)-cholesterol and apolipoprotein B (apoB) decreased 9.7% and 8.5%, respectively, in week 16. A decrease of more than 10% in TC, representing a decrease of more than 30 mg/dl, was observed in 12 of the 15 patients. These 12 patients, who were regarded as responders, showed mean decreases in the levels of TC, LDL-cholesterol and apoB of 13.7%, 10.4% and 11.7%, respectively, but no significant change in the level of high density lipoprotein (HDL)-cholesterol or serum triglycerides. Eight of 11 patients in the lower dose group (1.5 g/d) and all 4 patients who had obtained the higher dose (2.0 g/d) were responders. Suspected side effects of pirozadil were edema, numbness of the extremities and palpitation. The results obtained suggest the beneficial effect of pirozadil on serum lipids in patients with Type IIa hyperlipoproteinemia.

Apolipoproteins↗
PubMed1986

Serum cholinesterase in patients with fatty liver.

In search of a practical biochemical test that will reflect hepatic steatosis, we assessed the significance of serum cholinesterase activity in 48 patients with nonalcoholic fatty liver, 16 obese subjects without fatty liver, 30 cases of chronic persistent hepatitis, 38 cases of chronic active hepatitis, and 20 cases of liver cirrhosis. Increased cholinesterase activity was observed in nonobese as well as obese patients with fatty liver, whereas obese subjects without fatty liver showed levels in the upper normal range. When we set a cutoff level above the upper normal limit, half of the patients with fatty liver showed values above it, with only a few overlaps with other patients. When obese patients with fatty liver took a low-caloric diet, cholinesterase activity decreased, clearly reflecting improvement of hepatic steatosis. Thus, measurement of cholinesterase activity is of diagnostic value and an alternative to computed tomography in hepatic steatosis, and will provide a practical measure for the assessment of effects during follow-up.

Cholinesterases↗
PubMed1986

Effect of glycyrrhizin on lysosomes labilization by phospholipase A2.

The influence of glycyrrhizin on the effect of phospholipase A2 on lysosomes was studied. Treatment of rat liver lysosomes with venom phospholipase A2 caused release of acid phosphatase. This release of acid phosphatase was inhibited by 0.1 mM glycyrrhizin. Glycyrrhizin also inhibited acid phospholipase A2 with pH optimum of 4.5, which is thought to be present in the lysosomal membrane. These results suggest that glycyrrhizin stabilizes lysosomes by inhibiting phospholipase A2 activity in the lysosomal membrane.

Acid Phosphatase↗
PubMed1986

Effect of glycyrrhizin on stability of lysosomes in the rat arterial wall.

Studies were made on the effect of phospholipase A2 on the stability of arterial wall lysosomes, and the influence of glycyrrhizin on this effect. Lysosomal phospholipase A2 activity was found to be increased in the aorta of hypercholesterolemic rats. Treatment of the lysosomal fraction of the arterial wall with venom phospholipase A2 resulted in release of acid phosphatase, and addition of glycyrrhizin (0.1 mM) inhibited this release. Lysosomal phospholipase A2 in the arterial wall was also inhibited dose-dependently by glycyrrhizin. These results suggest that lysis of lysosomes was due to increase in phospholipase A2 activity, and that glycyrrhizin stabilized the lysosomes by inhibiting phospholipase A2 activity.

Acid Phosphatase↗
PubMed1986

Existence of lipoprotein lipase in rat brain microvessels.

To clarify the possibility that brain microvessels could utilize very low density lipoprotein (VLDL)-triglyceride, the hydrolysis of [14C] triolein in VLDL by rat brain microvessels was examined. The rat brain microvessels were prepared under microscopy. In the homogenate, triolein hydrolyzing activity was observed only in the presence of apolipoprotein C-II. That activity was diminished by the addition of 1 M NaCl. [14C] triolein incorporated in VLDL was hydrolyzed time- dependently. These results suggested that there exists lipoprotein lipase in brain microvessels and the brain can utilize VLDL triglyceride as a source of fatty acids.

Animals↗
PubMed1986

[Clinical evaluation of CMA in the treatment of prostatic cancer].

Forty five patients with previously untreated prostatic cancer were given chlormadinone acetate (CMA) at a dose of 100 mg/day (mean 12.6 months), and 42 of them were evaluated for effectiveness. Overall response evaluation revealed 19 complete responses (45.2%), 14 partial responses (33.3%), 4 minor responses (9.5%), and 5 were unresponsive (11.9%). Consequently CMA was judged to be effective in 33 patients (78.6%, complete and partial responses). Response rate was 100.0% for stage A, 88.9% for stage B, 77.8% for stage C, and 57.1% for stage D. The response rate for stage D was relatively high, possibly because the time of judgement of effectiveness was a little too early. As side effects, elevated triglyceride level, impaired liver function and impotence were noted in one patient each. All of them were slight. The testosterone level in both castrated and non-castrated patients were not higher than that in women, and no significant difference in the level was noted between the groups. Nevertheless, the clinical usefulness of castration is not denied. CMA is considered useful as an endocrine therapeutic drug, though its effect on the disease at stage D was insufficient. The administration method, such as sequential treatment and combination treatment of CMA and estrogen preparations, is a future subject.

Aged↗
PubMed1985

Human plasma carboxyl esterase-catalyzed triolein hydrolysis. Existence of promoting factor in serum.

The possibility that some factor in serum changes the substrate specificity of purified human plasma carboxyl esterase, which hydrolyzes the short chain fatty acid ester, tributyrin, was investigated. The purified carboxyl esterase from human plasma hydrolyzed 48 mmol of tributyrin/mg of protein/h, monoolein at 1560 mumol of released fatty acids/mg of protein/h, diolein at 133 mumol of released fatty acids/mg of protein/h, and triolein at less than 10 mumol of released fatty acids/mg of protein/h. When human serum was applied to phenyl-Sepharose, a triolein hydrolysis-promoting factor (THPF) for purified carboxyl esterase was bound to the gel and was eluted with water. This partially purified human serum THPF enhanced carboxyl esterase-catalyzed triolein hydrolysis about 30-fold, diolein hydrolysis 2-fold, and monoolein hydrolysis 1.5-fold. Hydrolysis of triolein in very low density lipoproteins (d less than 1.006) and intermediate lipoproteins (1.006 less than d less than 1.019) by carboxyl esterase was also enhanced by addition of THPF. THPF activity was reduced by treatment of delipidation, but resistant to trypsin treatment or heating at 50 degrees C. These results indicated that serum carboxyl esterase can hydrolyze the long chain fatty acid ester, triolein, in the presence of triolein hydrolysis-promoting factor in serum.

Carboxylic Ester Hydrolases↗
PubMed1985

Studies on cholesterol esterase in cultured rabbit smooth muscle cells.

Acid and neutral cholesterol esterases (CEases) in cultured rabbit smooth muscle cells (SMC) were examined. The optimal pH of acid CEase was 4.5 and its apparent Km was 83 microM. The optimal pH of neutral CEase was 7.5 and its apparent Km was 38 microM. CEases were most active with substrate vesicles prepared with phosphatidylcholine. Acid CEase hydrolyzed cholesteryl [1-14C]oleate labeled LDL (LDL-CE), but neutral CEase did not. Incubation with LDL increased the acid and neutral CEase activities of SMC, but incubation with acetylated-LDL did not increase their activities.

Animals↗
PubMed1985

Metabolism of n-3 polyunsaturated fatty acids and modification of phospholipids in cultured rabbit aortic smooth muscle cells.

The metabolism of the linolenic acid family (n-3) of fatty acids, e.g., linolenic, eicosapentaenoic, and docosahexaenoic acids, in cultured smooth muscle cells from rabbit aorta was compared to the metabolism of linoleic and arachidonic acids. There was a time-dependent uptake of these fatty acids into cells for 16 hr (arachidonic greater than docosahexaenoic, linoleic, eicosapentaenoic greater than linolenic), and the acids were incorporated mainly into phospholipids and triglycerides. Eicosapentaenoic and arachidonic acids were incorporated more into phosphatidylethanolamine and phosphatidylinositol plus phosphatidylserine and less into phosphatidylcholine than linolenic and linoleic acids. Docosahexaenoic acid was incorporated into phosphatidylethanolamine more than linolenic and linoleic acids and into phosphatidylinositol plus phosphatidylserine less than eicosapentaenoic and arachidonic acids. Added linolenic acid accumulated mainly in phosphatidylcholine and did not decrease the arachidonic acid content of any phospholipid subfraction. Elongation-desaturation metabolites of linoleic acid did not accumulate. Cells treated with eicosapentaenoic acid accumulated both eicosapentaenoic and docosapentaenoic acids mainly in phosphatidylethanolamine and the arachidonic acid content was decreased. Added docosahexaenoic acid accumulated mainly in phosphatidylethanolamine and decreased the content of both arachidonic and oleic acids. The following conclusions are drawn from these results. The three n-3 fatty acids are utilized differently in phospholipids. The arachidonic acid content of phospholipids is reduced by eicosapentaenoic and docosahexaenoic acids, but not by linolenic acid. Smooth muscle cells have little or no desaturase activity, but have significant elongation activity for polyunsaturated fatty acids.

Animals↗