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Biomedical subjects

K Saku

Publications and source records attributed to K Saku.

At least 127 records · Page 7Linked to original sources

Mechanism of action of gemfibrozil on lipoprotein metabolism.

Gemfibrozil is a potent lipid regulating drug whose major effects are to increase plasma high density lipoproteins (HDL) and to decrease plasma triglycerides (TG) in a wide variety of primary and secondary dyslipoproteinemias. Its mechanism of action is not clear. Six patients with primary familial endogenous hypertriglyceridemia with fasting chylomicronemia (type V lipoprotein phenotype) with concurrent subnormal HDL cholesterol levels (HDL deficiency) were treated initially by diet and once stabilized, were given gemfibrozil (1,200 mg/d). Each patient was admitted to the Clinical Research Center with metabolic kitchen facilities, for investigation of HDL and TG metabolism immediately before and after 8 wk of gemfibrozil treatment. Gemfibrozil significantly increased plasma HDL cholesterol, apolipoprotein (apo) AI, and apo AII by 36%, 29%, and 38% from base line, respectively. Plasma TG decreased by 54%. Kinetics of apo AI and apo AII metabolism were assessed by analysis of the specific radioactivity decay curves after injection of autologous HDL labeled with 125I. Gemfibrozil increased synthetic rates of apo AI and apo AII by 27% and 34%, respectively, without changing the fractional catabolic rates. Stimulation of apo AI and apo AII synthesis by gemfibrozil was associated with the appearance in plasma of smaller (and heavier) HDL particles as assessed by gradient gel electrophoresis and HDL composition. Postheparin extra-hepatic lipoprotein lipase activity increased significantly by 25% after gemfibrozil, and was associated with the appearance in plasma of smaller very low density lipoprotein particles whose apo CIII:CII ratio was decreased. These data suggest that gemfibrozil increases plasma HDL levels by stimulating their synthesis. Increased transport (turnover) of HDL induced by gemfibrozil may be significant in increasing tissue cholesterol removal in these patients.

Apolipoprotein A-I↗

Laryngoplasty using suprahyoid muscles--hyoid transposition laryngoplasty.

A new technique of laryngoplasty using the function of the suprahyoid muscles (hyoid transposition laryngoplasty) was reported. Total laryngectomy is carried out as usual and the tracheal stump is anastomosed directly to the hypopharynx. The hyoid bone is cut medially, then transpositioned and sutured to the posterolateral margins of the tracheal stump. With this procedure, the new glottis is pressed strongly to the tongue base during swallowing and aspiration is avoided. Postoperative swallowing and speech in the cases operated on with this method were satisfactory, and even nasal respiration was possible in some cases.

Aged↗

C-II anapolipoproteinemia and severe hypertriglyceridemia. Report of a rare case with absence of C-II apolipoprotein isoforms and review of the literature.

A new case of C-II anapolipoproteinemia (complete apolipoprotein C-II deficiency) as the cause of severe hypertriglyceridemia with chylomicronemia (type I lipoprotein phenotype) is described. The patient was a five-year-old boy living in Connecticut. He had splenomegaly, episodic abdominal pain, and bloody stools. Absence of apolipoprotein C-II (and its isoforms C-II1 and C-II2) was documented by a sensitive and specific radioimmunoassay, analytical isoelectric focusing, and in vitro lipolytic assay. Decreased levels of high- and low-density lipoprotein cholesterol and apolipoproteins A-I and A-II and increased levels of plasma triglycerides and apolipoprotein E were found. Post-heparin extra-hepatic lipoprotein lipase activity was within normal range. Incorporation of exogenous purified human apolipoprotein C-II to an incubation mixture of purified lipoprotein lipase and the patient's triglyceride-rich lipoproteins resulted in a dramatic increase in the catabolic rate of the defective triglyceride-rich lipoproteins. The absence of the isoforms of apolipoprotein C-II in this patient indicates that a common gene exists for the C-II isoproteins, which appear to be necessary for normal triglyceride transport in humans. A literature review of 23 reported cases indicates that xanthomas and hepatosplenomegaly are less common in C-II anapolipoproteinemia than in lipoprotein lipase deficiency, the other major etiologic cause of genetic chylomicronemia.

Adolescent↗

Renal handling of high-density lipoproteins by isolated perfused kidneys.

Recent studies show that the normal and diseased kidney is an important organ in the catabolism of high-density lipoproteins (HDL). However, little is known about the renal handling of HDL. To investigate this aspect, kidneys were isolated from normal rats and rats made nephrotic with puromycin aminonucleoside. They were perfused in a chamber at 37 degrees C with a modified Krebs-Hensleit Bicarbonate Buffer containing 1%, 3%, 6%, and 10% Bovine Serum Albumin (BSA). Presence of 10% BSA in the perfusate prevented glomerular filtration and urine formation. Thus, the filtering and the nonfiltering kidney perfusion models distinguish the renal parenchymal function independently of luminal events that follow filtration. 125I-labeled rat HDL was injected into the perfusate and radioactivity in perfusate, urine, and kidney was examined. At the end of perfusion (30 minutes or four hours), each kidney was flushed with 125I-HDL-free perfusate and kidney radioactivity was measured. At four hours, 1.9% +/- 0.5% of injected radioactivity was present in urine from kidneys perfused with 6% BSA. Kidneys with intact glomerular filtration sequestered significantly more radioactivity (1.1% +/- 0.2% of injected radioactivity) than nonfiltering kidneys (0.7% +/- 0.2%); P less than 0.05. Radioactivity in filtering kidneys was significantly higher than in nonfiltering kidneys (33.9 +/- 7.8 v 15.6 +/- 2.6 cpm/mg kidney tissue protein, respectively; P less than 0.001). Nephrotic kidneys (filtering and nonfiltering) sequestered two to four times more 125I-HDL than normal kidneys. These data support the hypothesis that prior to urinary excretion, partial reabsorption of filtered HDL (or subfractions) occurs in the normal kidney.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

[MIC test of Campylobacter jejuni/coli].

Using 3 kinds of medium, Mueller-Hinton (M-H) agar, M-H agar added with defibrinated horse blood and lysed horse blood, susceptibilities of Campylobacter were tested quantitatively to 12 antibacterial agents. The result showed no remarkable difference between them. MIC was examined with the cell concentration of McFarland unit 0.5 and 100-times dilution, and there was no significant difference between them except for 2 strains, on which erythromycin showed MIC of 6.25 micrograms/ml at McFarland unit 0.5 and 0.39 micrograms/ml at 100-times dilution. Eighty-two clinical isolates of C. jejuni and 6 of C. coli were tested for their susceptibility to 12 antibacterial agents. These strains were most susceptible to gentamicin and amikacin and less susceptible to benzylpenicillin, carbenicillin and cephaloridine with the MIC of 25 micrograms/ml. There were 2 peaks of susceptibility distribution to minocycline (0.2 and 50 micrograms/ml). In tests for beta-lactamase of C. jejuni and C. coli, 3 strains obtained from 1 patient were positive.

Anti-Bacterial Agents↗

Bacteriostatic and bactericidal activities of beta-lactam antibiotics enhanced by the addition of low concentrations of gentamicin.

The combined effects of low concentrations of gentamicin on certain beta-lactam antibiotics were studied by the agar plate method. the combination of gentamicin with cephalothin produced synergism against 17 of 26 strains of Escherichia coli and 19 of 27 strains of Klebsiella sp. if assessed at the bacteriostatic (minimal inhibitory concentration) level. Synergy against many more strains was apparent when bactericidal concentrations were used. Synergy against most of these strains was observed if bactericidal concentrations with brief exposure times (3 h) to the antibiotics were used for measurement. Additive effects were observed in almost all of the remaining strains. The combination of gentamicin and carbenicillin were synergistic against most strains of Pseudomonas aeruginosa when any bacteriostatic or bactericidal measurement was used as the criterion.

Bacteria↗

Serological typing of Pseudomonas aeruginosa--comparison of various antigenic schema.

Serotyping sera for both the agglutination (using IMSUT sera) and slide agglutination (using TIBS sera) were succesfully prepared using Homma's serotype strains. They were proved to be type specific and distinct. The two typing sera (IMSUT and TIBS) were used to determine the correspondence of major O-antigens among the different kinds of serotype schema which are used at present throughout the world. The serotype sera of Lanyi, Liu and Meitert were also used for the same purpose. The relationships among serotypes of the seven schemata were clarified as shown in tables in the text. Cross-reactions were found among several serotypes in each of several serotype schemata was suggested.

Agglutination Tests↗

Passive hemagglutination reaction test using formalinized sheep erythrocytes treated with tannic acid and coated with proteast or elastase of Pseudomonas aeruginosa.

Methods were established for estimating antibodies of protease and elastase of Pseudomonas aeruginosa by passive hemagglutination (HA) tests using fixed sheep erythrocytes coated with each of the two enzymes. High antibody titers of protease and elastase were found in the HA tests on sera in some cases suffered from P. aeruginosa infection. The evaluation of the HA tests was discussed.

Animals↗

Effects of high-dose troglitaz one on insulin sensitivity and beta-cell function in Watanabe heritable hyperlipidemic rabbits.

UNLABELLED: To clarify the dose-response effects of troglitazone on insulin sensitivity and beta-cell function, we examined the effects of high-dose troglitazone (100 mg/day per animal, administered as a food admixture) on glucose and insulin metabolism in hyperinsulinemic Watanabe heritable hyperlipidemic (WHHL) rabbits, and compared the results with our previous results with low-dose troglitazone (10 mg /day per animal). MATERIALS AND METHODS: Glucose and insulin metabolism were quantitatively characterized by a minimal model technique as reported previously. RESULTS: When troglitazone was administrated at a high dose for 6 months, it reduced hyperinsulinemia as reflected by a reduced basal (steady-state) insulin concentration lb and the insulin response to a glucose load, improved beta-cell function as reflected by decreased second-phase post-hepatic insulin delivery to glucose phi2, and reduced insulin resistance as reflected by increased insulin sensitivity to glucose disposal Si, without affecting glucose tolerance as reflected by an unchanged rate of glucose utilization Kg or insulin-independent glucose disposal Sg. The reductions in Ib and phi2 and the increases in Si in WHHL rabbits treated with a high dose of troglitazone were greater (p<0.05) than those observed in WHHL rabbits treated with a low dose of troglitazone, as assessed by a two-way repeated measures analysis of variance and the Wilcoxon-Mann-Whitney test. CONCLUSION: In WHHL rabbits, troglitazone dose-dependently reduced hyperinsulinemia, improved beta-cell function, and increased insulin sensitivity.

Animals↗

Effects of lisinopril and bisoprolol on lipoprotein metabolism in patients with mild-to-moderate essential hypertension.

The short- and long-term effects of the angiotensin-converting enzyme inhibitor lisinopril and the cardioselective beta-blocker bisoprolol on serum lipids, lipoproteins, apolipoproteins, and lipoprotein(a) (Lp[a]) levels were investigated in patients with mild-to-moderate essential hypertension. Fifty-two patients completed the 12-month, randomized, multicenter trial. After administration of lisinopril (10 to 20 mg/d; n = 24) and bisoprolol (2.5 to 10 mg/d; n = 28), systolic and diastolic blood pressures decreased significantly (P < 0.01) from baseline in both groups at 3, 6, and 12 months. The reduction in diastolic blood pressure was significantly (P < 0.05) greater in the lisinopril group than in the bisoprolol group only at 6 months. Heart rates dropped significantly in the bisoprolol group but not in the lisinopril group. No significant changes in lipids, lipoproteins, apolipoproteins, or Lp(a) levels were observed with either drug at 3, 6, or 12 months, and no significant differences were noted between the two drugs for these parameters. We conclude that lisinopril and bisoprolol are effective as antihypertensive drugs without adverse metabolic effects after short- and long-term treatment in patients with mild-to-moderate essential hypertension.

Adrenergic beta-Antagonists↗

Effects of manidipine and delapril on serum lipids, lipoproteins, and apolipoproteins in patients with mild to moderate essential hypertension: a randomized trial with one-year follow-up.

Forty-five patients with mild to moderate essential hypertension were randomly assigned to receive 10 to 40 mg of manidipine HCl or 15 to 60 mg of delapril daily for 12 months. In the manidipine-treated group were 13 women and 5 men (mean age, 48.2 years) and in the delapril-treated group 11 women and 11 men (mean age, 53.7 years). Blood samples were taken at baseline and after 6 and 12 months of treatment and again at 2 months after treatment discontinuation. Significant reductions in blood pressure were observed in both treatment groups. The reduction in diastolic blood pressure was significantly greater in the manidipine-treated patients than in the delapril-treated patients; no significant between-groups differences in systolic blood pressure were noted. Heart rate increased significantly in the manidipine group. No changes in serum levels of total cholesterol, triglycerides, and high-density and low-density lipoprotein cholesterol were noted during or after treatment. In the manidipine group, a small but significant decrease in apolipoprotein (apo) A-I and an increase in lipoprotein(a) were found at 6 months and a significant increase in apo A-II and apo E at 12 months; in the delapril group a significant decrease in apo A-I was found at 6 months. The results indicate that both manidipine and delapril are lipid-neutral antihypertensive drugs, since neither drug greatly affected serum lipid metabolism.

Adult↗

Effects of polydextrose on serum lipids, lipoproteins, and apolipoproteins in healthy subjects.

The subjects were 61 healthy volunteers who received 15 gm of polydextrose daily for two months. A significant increase in the incidence of soft feces and diarrhea and in the volume of feces was reported during polydextrose treatment. These had returned to normal one month after treatment. Serum levels of total cholesterol, triglycerides, and low-density lipoprotein cholesterol did not change during treatment. Levels of apolipoprotein (apo) A-I and A-II were significantly lowered at one month and high-density lipoprotein cholesterol (HDL-C) and apo A-I were significantly decreased at two months; these returned to normal after treatment. Levels of HDL2-C decreased and HDL3-C levels increased significantly during treatment. The results indicate that polydextrose selectively affected the metabolism of HDL and its major proteins, apo A-I and A-II.

Adult↗