[Drug therapy of hyperlipidemia].
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Biomedical subjects
Publications and source records attributed to I Horiuchi.
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In order to ascertain the most effective index for predicting coronary sclerosis, the concentration of lipids, lipoproteins, and apoproteins in serum were determined in 45 males aged over 44 with angiographically diagnosed effort angina and in 153 male controls aged over 44 without ischemic heart disease (IHD) on physical examination. The results of our study are summarized as follows. 1) Alcohol intake of 25 g/day or more and smoking of 20 cigarettes/day or more showed significant odds ratios of 0.47 and 2.33, respectively. 2) By decrease of 10 mg/dl in HDLC level or of 10 mg/dl in Apo-AI level, the possibility of coronary sclerosis increases twofold after adjusting the effects of confounders. 3) LDLC/HDLC and Apo-B/Apo-AI are effective indices for predicting coronary sclerosis and, in particular, the probability of coronary sclerosis increases 3.8 times by increase of 0.5 in Apo-B/Apo-AI.
Male golden hamsters fed a glucose diet as a model for cholesterol gallstone formation were used to investigate the effect of CS-514 on the lithogenicity of bile. Treatment with 0.05% (w/w) CS-514 in the diet for 1-4 weeks caused a decrease in plasma cholesterol and triacylglycerol levels. A marked increase in hepatic hydroxymethylglutaryl-CoA reductase activity in vitro and also an increased de novo cholesterol synthesis in the liver were induced by treatment with CS-514 for 1-4 weeks. The concentration of free cholesterol in liver microsomes and the cholesterol 7 alpha-hydroxylase activity were both decreased by treatment with CS-514 for 1 week, but were not affected by treatment for 4 weeks. The cholesterol output into bile and the lithogenic index of bile were double those of the control (glucose diet only) following treatment with CS-514 for 4 weeks, and the subsequent incidence of cholesterol gallstone formation was elevated. The content of free cholesterol and cholesterol ester in the liver was not affected by treatment with CS-514 for 4 weeks. These results suggest that long-term treatment with CS-514 causes a compensatory increase in the synthesis of hydroxymethylglutaryl-CoA reductase which leads to augmented hepatic de novo cholesterol synthesis and subsequent increased cholesterol output followed by an increase in the lithogenicity of bile. CS-514 apparently does not prevent cholesterol gallstone formation in those examples where the mechanism is thought to be due to augmented hepatic de novo cholesterol synthesis (type IV hyperlipidemia).
The object of this study was to determine the effects of ursodeoxycholic acid administration on metastability in human gallbladder bile, as reflected by nucleation time. Bile samples from 10 patients with cholesterol gallstones who underwent preoperative ursodeoxycholic acid treatment exhibited a significantly longer median nucleation time (16 days) than those from 11 patients with cholesterol gallstones who received no preoperative treatment (4 days) (p less than 0.01). On the other hand, the median nucleation times of bile samples from 15 patients with noncholesterol gallstones and 24 patients without gallstones were 15 and 14 days, respectively. In addition, 3 mo of treatment with ursodeoxycholic acid significantly elevated the serum concentration of the antinucleating factor apolipoprotein A-I, from 133.3 +/- 12.3 to 148.6 +/- 13.2 mg/dl (p less than 0.05). These findings suggest that ursodeoxycholic acid retards cholesterol crystal nucleation, thereby inhibiting cholesterol gallstone formation. It is also possible that serum apolipoprotein A-I plays a role in this process.
We measured aortic pulse wave velocity (PWV) in 168 male adult cases of various arteriosclerotic diseases. In order to evaluate the effects of age, smoking habits, alcohol intake, and blood pressure, we applied the least median of squares (LMS) regression which was considered to be very useful for data analysis. The results showed that PWV level increased with age. Furthermore smoking was associated with increasing PWV level and this effect was also related to age. We concluded that the PWV was valuable as an index of arteriosclerosis, and instead of the classical least squares method, LMS regression was very useful for analysis of medical data.
We studied the preferential distribution patterns of cholesterol and proteins to biliary lipid particles isolated from human gallbladder bile by gel permeation chromatography. In addition nucleation times of those bile samples were determined to estimate the metastability of bile cholesterol. Cholesterol dominantly incorporated into a non-micellar fraction in bile from cholesterol gallstone patients with and without preoperative treatment with ursodeoxycholic acid, whereas nucleation time was significantly longer in cholesterol gallstone patients with a preoperative treatment with ursodeoxycholic acid than that of those without any preoperative treatment (p less than 0.01). Furthermore the induced incorporation of apolipoprotein A-1 into a non-micellar fraction was found in bile from cholesterol gallstone patients with ursodeoxycholic acid. These results suggest that stabilizing effects of apolipoprotein A-1 on a non-micellar fraction has been induced by ursodeoxycholic acid treatment resulting in the retardation of cholesterol nucleation in bile.
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Ceftizoxime (CZX) were administered and tested for the efficacy and safety in 80 elderly patients who were older than 65 years of age with infections. The sensitivity of bacteria found in these infections to CZX was examined before the administration of the drug. Serum concentrations and the rate of urinary output of the drug were examined in 3 cases. The clinical effect of CZX was as follows: 29 cases (36.3%) of excellent effectiveness and 31 cases (38.8%) showed moderate effectiveness. The patients were divided into 2 groups depending on the presence or the absence of other diseases in their backgrounds. Effectiveness of CZX for patients with and without other diseases were 74.0% and 85.7%, respectively. The effectiveness of CZX in patients with other diseases in their background was lower than the group without other diseases. Other antibiotics were used in 16 cases before the use of CZX. The effectiveness of CZX for these patients was 62.5%. Infecting bacteria were detected in a total of 46 cases (19 cases of respiratory infections and 27 cases of urinary tract infections). Among the respiratory cases, 8 were due to Gram-positive bacteria and 11 were due to Gram-negative bacteria. No Gram-positive organisms were detected from urinary tract infections, which were all due to Gram-negative bacteria. Sensitivities of isolates of these infecting bacteria to CZX were very sensitive 3 isolates, sensitive (++) 8 and slightly sensitive (+) 1 isolate. It was found that CZX was effective against 39 of 46 cases from which causative organisms were identified. The effectiveness ratio was 84.8%. Serum concentration of CZX was determined after a drip injection of 1 g CZX for 1 hour. The half-lives of CZX in plasma in healthy subjects and aged patients were 1.33 hours and 2.15 hours, respectively. The rate of urinary output of CZX during 6 hours after the injection was 76.4% in healthy subjects. Delayed urinary output which was 58.2% during 7 hours after injection was observed in aged patients. Fever in 1 patient and eosinophilia in 3 cases were observed after administration of CZX.
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The effects of glia maturation factor (GMF) on cell proliferation and differentiation were investigated with 3 astroglioma cells (GE-12, C6, and GA-1), Schwannoma-like cells (354A), and mixed glioma cells (LRM-55). In the exponentially growing phase the growth rates of all glioma cells were enhanced by GMF regardless of the presence or absence of serum, but the factor failed to make the saturation density surpass the control level observed in the medium without GMF even in the chemically defined medium (N2 medium). GMF markedly lowered the saturation density of Schwannoma-like cells in N2 medium. Although GMF increased the intracellular content of S-100 protein 10-fold and 2',3'-cyclic nucleotide phosphohydrolase activity 1.5-fold in Schwannoma-like cells, GMF conversely decreased the S-100 contents and glycerol phosphate dehydrogenase activity in astroglioma cells. All the astroglioma cells secreted into the culture medium large quantities of a growth-promoting factor(s) which had similar chemical properties to those of GMF and stimulated the proliferation of normal glioblasts; but Schwannoma-like cells did not, although they produced a small amount of such a factor(s). These findings imply that astroglioma cells are deprived of the differentiation-promoting response to GMF while Schwannoma-like cells still preserve the response in addition to the proliferative response to GMF.
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