The purpose of the present study was to investigate the role of Ca in the adrenergic neurotransmission in hypertension. The perfused mesenteric vasculatures were prepared in spontaneously hypertensive rats (SHR, Okamoto & Aoki, 7-9 weeks old) and age-matched normotensive Wistar Kyoto rats (WKY).
(1) The pressor responses to the electrical nerve stimulation were significantly greater in SHR than in WKY. The norepinephrine overflow during the nerve stimulation was also enhanced in SHR compared with WKY (15Hz stimulation: SHR 2.43±0.23ng/g of wet tissue weight, n=6, WKY 1.16±0.22ng/g of wet tissue weight, n=4, p<0.02).
(2) When Ca concentration was reduced in the perfusion medium, the pressor responses and norepinephrine overflow induced by the electrical nerve stimulation were decreased, and the suppressive magnitudes were significantly greater in SHR than in WKY.
These results demonstrated that the vasoconstriction and neurotransmitter release were enhanced in SHR, and that the marked reduction of the pressor responses and norepinephrine overflow by Ca-depletion in SHR might explain the higher Ca-dependency in the adrenergic neurotransmission in hypertension.

抄録全体を表示

Calcium playes an important role in pathogenesis of atherosclerosis. During the past few years, attenuation in development of experimental atherosclerosis by calcium antagonists has been reported. But, most of these studies, degree of atherosclerosis was determined by morphological methods. Present study was intended to determine effects of diltiazem on contractile responses of the arteries induced by hypercholesterolemia.
Eighteen male albino rabbits weighing 2.5kg were devided into three groups, i. e. control, 1% cholesterol fed and cholesterol fed with diltiazem (100mg/kg/day) administration. Rabbits were sacrified at the end of twelve weeks, and aorta, coronary arteries and basilar arteries were removed. The arteries were cut into helical strips and suspended in tissue bath filled with oxygenated Krebs-Ringer's solution kept at 37°C. The strips were attached to force displacement transducer for recording the isometric tension. Contractiondeveloped tension by KCl, norepinephrine (NE), 5-hydroxytryptamine (5-HT) and histamine (His), were determined. In the aorta, tension developed by His was increased, but tension developed by 5-HT was decreased in the cholesterol group. In the diltiazem group, tension developed by His and 5-HT was reduced to the level of the control. In the coronary and basilar arteries, tension developed by KCl and His were higher in the cholesterol group than in the control. Tension generated by KCl and 5-HT from diltiazem treated rabbits, were same level of the cholesterol fed (See Fig. 1).
Median effective concentration (ED50) for KCl and 5-HT to the aorta, for 5-HT to coronary, for NE and 5-HT to the basilar artery were increased in the cholesterol group. ED50 for His to the aorta, coronary and basilar arteries were decreased in the cholesterol group, although significant difference did not exist except to the aorta. In the diltiazem group, ED50 for 5-HT and His to the aorta were not different from that in the control. On the other hand, ED50 for 5-HT to the coronary and basilar arteries in the diltiazem group were apparently elevated as compared with the cholesterol feeding (See Table 1).
Passive tension to the aorta and coronary artery was increased in order of the control, cholesterolfed, diltiazem-treated. To the basilar artery, passive tension was increased in the diltiazem group, but the difference was not significant (See Fig. 2).
This study demonstrates that diltiazem can suppress the change of vasoreactivities induced by hypercholesterolemia in the aorta, but not in the coronary and basilar arteries. This difference of the effect of diltiazem may associate with the difference in atherogenic mechanisms between the arteries.

抄録全体を表示

The abnormalities of calcium binding and transport have been reported in patients with essential hypertension and in spontaneously hypertensive rats (SHR). In this study, intracellular free calcium concentration in platelets of SHR and DOCA-salt hypertensive rats (DOCA-salt HT) was examined using the fluorescent calcium indicator quin 2.
The systolic blood pressure of SHR and DOCA-salt HT was significantly higher than that of control rats. The intracellular free calcium concentration in platelets of 14-week-old male SHR was significantly increased compared with that of WKY (124.5±8.3nM vs. 103.8±4.0nM, mean±SEM, p<0.05). The intracellular free calcium concentration in platelets of DOCA-salt HT and salt-loaded rat (Nx+1% NaCl) was significantly increased in comparison with unilaterally nephrectomized rats (Nx)(152.4±5.8, 150.8±4.9 and 127.6±6.5nM, respectively, p<0.05) 10 days after the operation. However, this difference was not found 8 weeks after the operation (123.7±9.0, 111.6±7.4, 122.6±7.1nM).
The increase in cytosolic sodium of DOCA-salt HT was reported. The initial increase in intracellular free calcium in platelets of DOCA-salt HT and Nx+1% NaCl might be due to enhancement of sodium-calcium exchange caused by sodium retension. After long term treatment, a certain compensatory mechanism could normalize intracellular free calcium.
On the other hand, intracellular free calcium concentration in platelets of 14-week-old SHR was increased significantly in comparison with WKY. The increase in intracellular free calcium of SHR is not thought to be the secondary change caused by high blood pressure, because intracellular free calcium of DOCA-salt HT after 8 weeks treatment was not increased in spite of high blood pressure. It is considered that there could be hereditary abnormalities of cell membrane permeability for calcium in SHR.

抄録全体を表示

Atherosclerosis begins with a degenerative change of endothelial cell, manifesting itself in various events such as platelet adherence and aggregation at the site of injury, release of a platelet derived growth factor (PDGF), accelerated migration of smooth muscle cells under the intima, cell division and proliferation and increased foam cells, and ending up with connective tissue proliferation, fragmentation and loss of elastic fibers and calcification in the arterial wall. Of these events, calcification is yet to be clarified regarding its mechanism. Our study was undertaken with a view to elucidating its pathogenetic mechanism.
Thoracic and abdominal aortas were harvested from autopsied 70-year or older patients who had been claimed by a cardiovascular disease, and portions of aortas centering around atheromas were examined histologically in relation to atheromas for changes in elastic and collagen fibers and calcification. Elastic fibers were stained with a stain of Van Gieson type and a stain of Kossa type was used to determine calcification.
Calcification was classified into (1) particulate, (2) granular, (3) humped, (4) streaky and (5) mixed types. The findings of calcification can be summarized as follows in relation to atheromas.
When stained with a stain of Kossa type, calx of particulate type was revealed to be comprised of fine-grained particles with fatty streaks. Calx of this type was noted around early atheromas with underdeveloped fibrosis. Calx of granular type was somewhat larger in size than the particulate type and was found around atheromas and immediately under the intima in most cases. Calx of humped type was larger in size than the granular type and had been formed around atheromas at sites of collagen and elastic fiber fragmentation. Streaky type calx was comprised of thick, plate-like streaks of uniform calcium deposits. It was found in deep parts of atheromas and intimas and in the area of transition to the media, covering degenerated elastic and collagen fibers around atheromas. The mixed type, a combination of various forms of calcification, was noted at and around lesions of atheromas and in the intima and media with marked swelling or fragmentation of elastic and collagen fibers.

抄録全体を表示

We investigated the influence of lanthanum (La³⁺) as a channel blocker of calcium ion on the experimental atherosclerosis in rabbit.
Twenty male rabbits were divided into three groups (A-, B- and C-groups). A- and C-groups were fed on a basal diet and B group were fed on a basal diet plus 0.12% LaCl₃ through experimental period. A- and B-groups (experimental group) were injected with nor-epinephrine by drip infusion from 14 to 16 weeks. At 18 weeks, they were autopsied.
1) Increases of body weight did not show significant difference among three groups.
2) Incidence of grossly visivle atherosclerotic rabbits were found 0% in C-group, 57% (4 out of 7 rabbits) in A-group and 37.5% (3 out of 8 rabbits) in B-group.
3) There were no differences in serum total cholesterol, triglyceride and phospholipid among three groups. On the other hand, HDL cholesterol was significantly lowered in B-group than in A-group (p<0.05).
4) There were no differences in serum calcium, magnesium, sodium and potassium among three groups, while inorganic phosphorus in A-group was significantly higher than that in C-group (p<0.05).
5) Significant differences were obtained that total cholesterol in the kidney was higher in A-group than in B-group (p<0.01) and in the thoracic aorta higher in B-group (p<0.05).
6) Significant differences were found that calcium content in the thoracic aorta was higher in B-group than in C-group (p<0.05) and magnesium in the myocardium was higher in B-group than in C-group (p<0.01), and sodium in the liver were higher in B-group than in C-group (p<0.05) and higher in A-group than in B-group (p<0.05), and sodium in the adrenal were higher in B-group than in C-group (p<0.01) and higher in A-group than in B-group (p<0.01). Potassium in the liver was higher in B-group than in A-group (p<0.05).
From the above results, it was suggested that lanthanum chloride might have suppressive effect on the incidence of significant atherosclerosis induced by nor-epinephrine. Nevertheless, inhibition effect on the calcification of thoracic aorta were not at all observed.

抄録全体を表示

We have studied the effects of elastase on the development of atherosclerosis in 6 patients with essential hypertension, 5 patients with ischemic heart disease, 3 patients with diabetes mellitus and 4 patients with hyperlipidemia type II. Elastase was orally administered to the patients at the dose of 5, 400U/day for 1 or 1.5 years. Before and after the treatment, the following determinations were carried out: Aortic calcification index (ACT) and pulse wave velocity (PWV), the indicators of atherosclerosis, and serum levels of lipids, apolipoproteins (apo), lipoprotein (Lp) electrophoresis and Ca.
The results obtained from the differences between before and after elastase administration were as follows.
Elastase administration caused the significant decrease of both percent ACT and PWV.
There were no significant changes in terms of serum lipids such as triglycerides, HDL-C, malondialdehyde and Ca except cholesterol which was significantly elevated.
The percent changes of apo A-I were slightly elevated while apo B/A-I ratio tended to be decreased. In addition, there was a significant increase α-Lp or a significant decrease in both β- and pre β-Lps.
The present observations indicate that elastase could be a protective drug against the progression of atherosclerosis even though calcified atherosclerosis.

抄録全体を表示

It is well known that pyridoxal phosphate (PAL-P) works as a cofactor of lysyl oxidase, an enzyme that is absolutely necessary to form the crosslinking in collagen and elastin and β-aminopropionitrile (BAPN) produces dissecting aneurysm in aorta of rats and another animals, because it inhibits the activity of lysyl oxidase. But the direct relationship between PAL-P and BAPN is unknown, thus authors studied physiological effects of PAL-P on enzymatic reactions of cross-linking formation.
In this study, authors observed that PAL-P combined with BAPN and considerably inhibited the depression of activities of vitamin B₆ dependent enzymes by BAPN in vitro. In addition, allylamine and cysteamine that have been reported as toxic agents for vascular wall, also inhibited the activities of vitamin B₆ dependent enzymes as same as BAPN and INH.
From the above results, it was assumed that BAPN inhibited the lysyl oxidase by binding with PAL-P that is necessary for the activation of lysyl oxidase.

抄録全体を表示

To investigate the effect of aging on prostaglandin synthesis, urinary excretion of prostaglandin (PG) E and thromboxane (TX) B₂ were measured in normal subjects of different age groups and PG synthetic profile was examined in subcultured vascular smooth muscle cells from rat mesenteric artery. While urinary excretion of PGE was decreased in the groups of 60-79 and 80-93 year of age as compared with younger age groups, urinary excretion of TXB₂ was increased in the group of 60-93 year of age. Vascular smooth muscle cells produced mainly PGI₂ (measured as 6-keto-PGF_1α) followed by PGF_2α>TXB₂≅PGE₂. Synthetic ability for PGI₂ was greater in cells of passage 3 and remained unchanged in cells up to 24th passage (162 days after the isolation of cells). The ability of PGI₂ synthesis in response to hormonal (angiotensin II, arginine vasopressin) or non-hormonal (arachidonic acid, calcium ionophore) stimulation was higher in cells of passage 3 and remained constant in cells of later passages. These results may suggest that an imbalance between PGE₂ or PGI₂ and TXA₂ may contribute to the pathogenesis of cardiovascular diseases and impaired renal function in the elderly.

抄録全体を表示

Since more than 30 years, we have reported that experimental atherosclerosis similar to that of human beings was produced in monkeys by Vitamin B₆ deprived diet. However, the mechanism of forming atherosclerotic lesion in Vitamin B₆ deficiency was not obvious. On the other hand, the endothelial and smooth muscle cell were suspected to play an important role in the initiation and its development of atherosclerosis. Also, some investigators began to be interested in the role of thromboxane A₂ and prostacyclin in the formation of atherosclerotic lesion. Therefore, by using Vitamin B₆ antagonists, we examined the effect of Vitamin B₆ deficiency on prostacyclin production by the cultured endothelial cells from fetal bovine aorta. We assayed the prostacyclin production by measuring the 6-keto-PGF_1α, a stable metabolite of prostacyclin.
On the other hand, it is reported that the patients with homocystinuria, who lack the activity of cystathionine synthetase which needs Vitamin B₆ as a cofactor, have the tendency to suffer from atherosclerosis in their early life. So we also studied the effect of homocysteine on prostacyclin production. To evaluate the degree of cell damage, we also measured the level of LDH in the culture media.
As Vitamin B₆ antagonists, we used deoxypyridoxine HCl and Isoniazid. No difference was detected between control and Vitamin B₆ antagonists added group in LDH level. When dl-homocysteine at various doses as follows was added, LDH levels were 1.1±0.4, 16.0±2.2, 115.0±7.4, 201.2±3.2 (Wroblewski unit) at 0mM (control), 2mM, 5mM, 10mM, respectively.
6-keto-PGF_1α production was expressed as percentage to control. When isoniazid was added, the results were 125.0±2.8% or 146.4±55.0% at concentration of 0.1mM or 1mM, respectively. When deoxypyridoxine HCl was added, the results were 132.4% or 106.7% at concentration of 2.5mM or 5mM, respectively. When dl-homocysteine was added, the results were 58.4±22.8% or 41.6±9.7% at concentration 5mM or 10mM, respectively.
We already reported that homocysteine had endothelial cell detaching potential and increased the number of circulating endothelial cells when it was injected into experimental animals. Jones reported homocysteine inhibited prostacyclin production by rat aortic ring. In this study, homocysteine gave injury to endothelial cells and suppressed prostacyclin production in a dose dependent manner. Therefore, it was suggested from above results that the homocysteine might contribute to the cell damaging. However, because it was supposed that the atherosclerosis might be caused by the impairment of multiple factors, for example, endothelial cells, smooth muscle cells, platelets, coagulants and their interactions in vivo, further investigations would be necessary.

抄録全体を表示

The serum lipids and apoproteins were determined in 218 male patients including 146 cases with ischemic heart disease and the results were compared with the coronary arteriographic findings. The serum total cholesterol, LDL cholesterol, apoprotein B, apoprotein C-II and triglycerides were significantly elevated in ischemic heart disease. There was a significant positive correlation between the serum apoprotein B levels and the severity of stenosing lesions of coronary arteries. There was also a significant positive correlation between the serum LDL cholesterol level and the LDL particle size in the patients with ischemic heart disease.

抄録全体を表示

Proline-rich protein (PRP) is a human serum protein which exists in chylomycron and d>1.21g/ml fraction. PRP levels were significantly higher in inflammatory diseases such as infectious diseases and autoimmune diseases compared to controls without inflammation. PRP levels significantly correlated to erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and serum α₁-, α₂-globurins. These data suggest that PRP is an acute phase reactant as well as an apolipoprotein.

抄録全体を表示

Since apo B-48 retention in triglyceride (TG) rich lipoproteins was noted in uremics, correlation of apo B-48 in VLDL and IDL to serum levels of lipids, apolipoproteins (apo) and lipoproteins, and activities of LCAT, LPL and H-TGL was investigated in 18 hemodialysis patients.
Apo B-48 ratio was calculated from the formula: apo B-48/(apo B-100+apo B-48)×100.
The apo B-48 ratio in VLDL showed a significantly positive correlation to serum TG, apo C-II, apo C-III and total amounts of VLDL and VLDL/IDL ratio.
In the low TG groups, the apo B-48 ratio in VLDL tended to be correlated with serum LCAT activity.
No significant relationship between the apo B-48 ratio in IDL and other parameters was observed.
These results suggest that apo B-48 retentions in uremics is closely related to VLDL metabolism involving both TG and apo C but not to IDL or LDL metabolism.

抄録全体を表示

Daily losses of apolipoproteins into dialysate were measured in 5 patients on continuous ambulatory peritoneal dialysis (CAPD). The mean excretion of apolipoprotein (apo) A-I and apo A-II, major proteins of high density lipoproteins (HDL), were 84 and 17mg/day, respectively, while that of apo B, a major protein of LDL was 39mg/day. The peritoneal clearance of apo A-I and apo A-II were similar; however, these were significantly greater than that of apo B. The fractional catabolic rates of various proteins through CAPD dialysate showed molecular sieving effects of peritoneal membrane; the data indicated that apolipoproteins were excreted as lipoproteins.
These data suggest that continuous and selective loss of HDL compared to LDL may also increase predisposition of these patients to atherosclerosis.

抄録全体を表示

It has been reported that physical exercise decrease plasma-cholesterol (Ch), plasma triglyceride (TG), very low density lipoprotein (VLDL)-TG, and low density lipoprotein (LDL)-Ch in young and middle-age men. However, the effects of physical exercise on plasma lipoprotein and apolipoprotein metabolism have not been investigated in the older men. In the present study, we measured plasma concentrations of lipids, lipoproteins and apolipoproteins (apo) in 12 welltrained, older male runners. There were no significant differences in age, height and body mass index between runners and sedentary men of old and young groups. Old runner (OA) and young runner (YA) showed higher VO₂ max and VO₂ max/weight than old (OC) and young (YC) respective controls. There were no significant differences in plasma levels of cholesterol, triglyceride and phospholipid between two old groups and between two young groups. Runners of both old and young groups, however, had decreased levels of VLDL-and LDL-Ch, and a significantly increased levels of HDL-Ch. Among apolipoproteins, plasma apo A-I and A-II concentrations of runner were significantly higher than those of control in old group, but significant differences were not observed in young groups. Atherogenic index (LDL-Ch/HDL-Ch) of OA was significantly lower than that of OC (2.09 vs. 3.04). Atherogenic index of YA was also lower than that of YC, but differences were not significant.
Ratio of apo A-I+A-II/apo B both in runners of the old and young groups was higher than that of respective controls. Ratios of apo A-I/HDL-Ch and apo A-I+A-II/HDL-Ch in runners were significantly lower than those in controls. However, apo B/LDL-Ch was not significantly different.
Physical training significantly increased plasma HDL levels and significantly decreased plasma concentrations of LDL and VLDL. It appears that physical exercise affects more HDL-lipids than HDL-proteins. The data presented indicate that regular exercise has favorable effects on plasma concentrations of lipids, lipoproteins and apolipoproteins levels in the old runner as reported in younger runner. The effects of exercise in old-age group were greater than in younger group.

抄録全体を表示

The levels of serum lipoproteins and apolipoprotein in 113 peoples undertaking coronary angiography were examined, and their correlation between the severity of coronary stenosis were evaluated. Stenosis score caliculated from angiography were higher in IIb>IIa>IV hyperlipoproteinemia. In type IIa, the stenosis scores were not correlated with each levels of lipoprotein cholesterol, and apo A-I and apo B. But the ratios of LDL-C/apo B, LDL-C/apo A-I and apo B/apo A-I were significantly correlated with stenosis scores. These results suggest that the combination of apo B, apo A-I and LDL-C were useful indicator for forcasting the degree of coronary stenosis.

抄録全体を表示

The particle size of HDL was measured in 68 diabetics, 42 patients with coronary heart disease (CHD), and 121 normal subjects by high performance liquid chromatography.
In 121 normal subjects there was a significant correlation between the particle size of HDL and the concentration of plasma HDL cholesterol (r=0.201, p<0.05), or the concentration of plasma triglyceride (r=-0.241, p<0.02). The particle size of HDL became smaller as the plasma triglyceride increased or the plasma HDL cholesterol decreased. The particle size of HDL did not correlate with the concentration of plasma cholesterol.
The mean concentration of plasma cholesterol and triglyceride was higher and the mean concentration plasma HDL cholesterol was lower in diabetics and patients with CHD than that in normal subjects. However the mean particle size of HDL in diabetics and patients with CHD was significantly larger than that in normal subjects. The mean particle size of HDL in male diabetics with normolipidemia (TC<220mg/dl and TG<150mg/dl) was also significantly larger than that in male normal subjects.
From these results it is suggested that the larger particle size of HDL is characteristic of dial etes or CHD, and related to the high incidence of CHD in diabetics.

抄録全体を表示

The Maillard reaction, a nonenzymatic glycosylation is nonspecific binding reaction of sugar to protein. The extent of this glycosylation was estimated by determining furosine, which is a hydrolysate of fructose-lysine. Nonenzymatic glycosylation of the rat aorta increased with advancing age in the range of up to 50 weeks. Nonenzymatic glycosylation level of aorta in streptozotocininduced diabetic rats also increased with advancing age in the range of up to 50 weeks. No significant difference was found in hemoglobin A₁ levels among rats at different weeks of age, except rats at 4 weeks of age. However, nonenzymatic glycosylation level in diabetic rats was significantly higher than that found in normal rats at the same weeks of age. It is considered that the Maillard products can be regarded as a sort of cross-linking compounds between protein and sugar. Furthermore, the Maillard reaction proceeds slowly over a long period of time. Therefore, these results suggested that nonenzymatic glycosylation of artery may become an accelerating mechanism of arteriosclerosis in diabetic patients.

抄録全体を表示

The present study was carried out to examine the effects of diabetes mellitus and of insulin treatment on the cholesterol ester (CE) synthetase and the neutral CE hydrolase activities in rat aortic wall. Male rats of Wistar-King strain were divited into three groups; control (C), streptozotocin-induced diabetic (D) and insulin-treated diabetic (I) groups. CE synthetase activity was assayed by determining CE synthetized from [1-₁₄C] palmitic acid as the method of Shirai, et al. Neutral CE hydrolase activity was assayed by determining fatty acid released from cholesterol [1-₁₄C] oleate with an optinum pH of 7.4 as a slight modification of the method of Brecher, et al.
CE synthetase activity in D-group was significantly lower than that in I-group and was slightly lower than that in C-group. Neutral CE hydrolase activity was slightly low in D-group and in I-group, as compared with C-group. The ratio of CE synthetase activity to neutral CE hydrolase activity in D-group was one half of I-group, and was two third of C-group, although both differences were not significant.
These results involve that the risk of atherosclerosis concerning to be reduced in experimental diabetic animals may be increased by being treated insulin.

抄録全体を表示

To elucidate the initial compositional changes in cell lipids and the progress of atherosclerosis in diabetics, we analyzed lipid fractions in intimamedia tissues separated from the arch, renal and abdominal portions of aorta from 8 non-diabetic and 4 type-2 diabetic autopsy cases. Intima-media was homogenized in 0.13M Tris-HCl buffer and centrifuged. Total lipids (sulfo-phospho-vanillin method), lipid fraction (TLC), phospholipid fraction (TLC) and protein (Lowry's method) in the supernatant were measured.
Total lipid content was 7.8±1.1mg/g wet weight (M±SE) in non-diabetics and it raised significantly (p<0.02) to 15.0±3.3mg/g wet weight in diabetics. Cholesteryl ester was dominant and triglyceride raised most remarkably to 1.9±0.6mg/g wet weight in diabetics (non-diabetics: 0.5±0.1mg/g wet weight). Phospholipids reduced significantly (p<0.05) to 1.3±0.3mg/g wet weight in diabetics (non-diabetics: 2.2±0.2mg/g wet weight). In phospholipid subfraction, phosphatidylcholine reduced significantly (p<0.05) to 0.30±0.29mg/g wet weight (non-diabetics: 0.55±0.05mg/g wet weight) and sphingomyelin (p<0.005) to 0.96±0.25mg/g wet weight (non-diabetics: 1.57±0.19mg/g wet weight). But, there were no differences between diabetics (0.53±0.09) and non-diabetics (0.52±0.06) in phosphatidylcholine/sphingomyelin ratio.
We supposed the decrease of phospholipids might cause the disorder of permeability in the aortic cell membranes, resulting in the accumulation of the TG-rich lipoproteins that are known to increase in diabetics.

抄録全体を表示

There is increasing agreement about the atherogenicity of intermediate density lipoprotein (IDL). Our previous work demonstrated abnormal accumulation of IDL (Sf 12-60) in normocholesterolemic NIDDM. Diabetics under insulin treatment had no abnormal lipoprotein profile if they were normocholesterolemic. On the other hand, it is well recognized that hyperinsulinemia has a role in atherogenesis. In order to explore the possibility that there is any relationship between residual endogenous insulin response and IDL metabolism in NIDDM, an oral glucose tolerance test was performed in 61 patients. Forty-one of them were treated on diet and the other by sulphonylureas (SU). Patients who were hyperinsulinemic, with thyroid, renal or hepatic disease and those taking steroids or hypolipidemic drugs were excluded. Cholesterol (Ch) and triglyceride (Tg) levels were measured in three subclasses of Tg-rich lipoprotein fraction—very low density lipoprotein (VLDL): Sf 60-400, intermediate density lipoprotein₁ (IDL₁): Sf 20-60, IDL₂: Sf 12-20. HDL fraction was separated from the plasma by precipitation.
Oral glucose tolerance test performed in NIDDM on diet showed significant correlation between ΣIRI/ΣPG and IDL₁-Ch/Tg or IDL₁₊₂-Ch/Tg. Since hyperinsulinemic subjects were excluded from the study ΣIRI/ΣPG ratio may represent the insulin sensitivity rather than insulin resistance. The significant correlations shown here suggest the importance of insulin sensitivity for the metabolism of IDL. In SU treated group, there was an inverse relationship between insulinogenic index and HDL-Ch, suggesting the atherogenicity of endogenous insulin. Negative correlation between ΣIRI and HDL-Ch in all the diabetics in this study supports this suggestion. Thus, we demonstrate here the new evidence linking insulin with atherosclerosis.

抄録全体を表示

It is our purpose to investigate the effects of dietary regimens on serum lipid levels in patients with glucose intolerance.
By 75g oral GTT diabetic type, borderline type and renal glycosuria were determined, who accepted mainly dietary treatments of 1, 600 kcal, 1, 800 kcal or 2, 000 kcal, respectively.
1) Male outpatients aged 41 to 60 years were used, including 23 diabetics, 23 borderlines or 14 renal glycosuria. They showed normal findings in ST·T segments of both resting and Master loading ECG. The three groups were almost same in relative body weight ratio (RBWR), Serum cholesterol (Chol), triglyceride (TG), atherosclerotic index ((Chol-HDL-C)/HDL-C), β-lipoprotein, apoprotein A-I, A-II, B or B/A-I tended to be higher in both diabetic and borderline types than in renal glycosuria.
2) 28 male diabetics aged 52.9±10 years (M±SD) and 39 male borderlines aged 48.1±11.1 years showed the decreased tendencies of RBWR, TG, atherosclerotic index, apoprotein B in the periods of about three months. Moreover, the decrements of apoprotein B were accompanied by the decrements of RBWR, Chol, TG or atherosclerotic index.
3) In diabetics who showed the decrements of FBS, TG or Chol without drugs in about five months, prescribed diets were 1, 563±49 kcal, and dietary intakes were 1, 626±226 kcal, consisting of 228±42g of carbohydrate, 67.1±15.8g of protein, 39±10.4g of fat and 269±131mg of cholesterol. Food intakes were less in rice, potatoes, sugars, cakes, oils or fruits in diabetics than in general peoples.
4) Addition of combined vegetable oils to prescribed diets, which consisted of rice oil (70%) and safflower oil (30%), made serum cholesterol decrease significantly in 15 cases with glucose intolerance including 4 female cases, who were 51.7±12.3 years old. This decrements were accompanied by the decrements of TG, atherosclerotic index, β-lipoprotein, apoprotein A-II, B or B/A-I in 2.3 months.
It was evaluated that prescribed diets for diabetic patients might effect a good influence on serum lipids, especially when combined vegetable oils were added to prescribed diets.

抄録全体を表示

Plasma concentrations of lipids, lipoproteins and apolipoproteins were measured before and at 4 weeks after treatment with eptastatin (10mg orally twice daily), an inhibitor of HMG CoA reductase, in patients with non-familial Type II hyperlipoproteinemia. Eptastatin produced a decrease in total cholesterol by 20%, whereas HDL-cholesterol and triglyceride did not change. These responses to eptastatin were found in Type ha as well as Type Jib hyperlipoproteinemia. A reduction in total cholesterol was due to a fall in LDL-cholesterol which was associated with a decrease in apolipoprotein B. These results indicate that eptastatin will be a useful drug in reducing the risk of coronary heart disease by lowering LDL-cholesterol without a reduction in HDL-cholesterol.

抄録全体を表示

Cord serum lipoproteins were characterized in terms of lipid and apoprotein compositions in comparison with adult lipoproteins.
Cord sera were obtained from normal babies of normal mothers and sera were also taken from the same babies one and five days after the births. Adult sera were obtained from normal subjects. Lipoproteins were separated by sequential ultracentrifugation by adjusting density with KBr, and in some experiments a density gradient centrifugation was used to obtain each lipoprotein. Apoprotein (apo) A-I, A-II, B, C-II, C-III, and E were determined by single radial immunodiffusion method. Apo B subclasses were analyzed by polyacrylamide gel electrophoresis in the presence of SDS. HDL subclasses were separated by gradient gel electrophoresis using Pharmacia PAA 4/30 gels. Cord serum total cholesterol (TC), triacylglycerol (TG) and phospholipid (PL) levels were significantly lower than those of adult serum; one-third, one-fourth, and a half of that of adult serum respectively. Baby serum lipid levels increased rapidly with time in as few as five days. Lipid contents of each lipoprotein in cord serum were significantly lower than those of adult lipoproteins, but HDL lipids were in a lower range of normal adult HDL lipids, while cord serum VLDL and LDL lipids were extremely lower. The same amount of TC was found in HDL and LDL in cord serum, which shows that cord serum is relative hyperalpha-lipoproteinema. Cord serum VLDL contains less TG/protein compared with adult VLDL, while the TC/protein ratio was comparable to that of adult VLDL. In cord LDL TC/protein was similar to that in adult LDL, but the PL/protein was twice as high as that of adult LDL. Apoprotein composition of each lipoprotein in cord serum was very similar to that in adult serum. However, cord serum HDL contained more apo E than adult HDL. Cord serum HDL was rich in smaller-sized subclasses compared with adult HDL. SDS-PAGE disclosed that the molecular weight of apo B of both adult and cord sera was mainly composed of a 290k to 300k dalton particle corresponding to apo B-48. In adult apo B a band of 120k dalton, which was thought of as apo B-48, was recognized. In cord serum apo B, there was a trace amount of B-48.
Cord serum was poor in VLDL and rich in HDL, and the amount of TC in HDL and in HDL was the same. Cord serum HDL contained more apo E than adult HDL. These data may imply that HDL can play a role in cholesterol supply to peripheral cells by virtue of apo E in fetus, because apo E is able to bind apo B, E receptor in peripheral cells. The fact that fetus serum contains apo B-48 shows that apo B-48 could be also synthesized in fetal liver or secreted from the intestine without food ingestion. Lipoprotein metabolism in fetus should be further investigated in a system including cells.

抄録全体を表示

To elucidate the relationship between the metabolic abnormalities of VLDL and cerebral infarction (CI), we measured lipid concentrations of VLDL and IDL in male survivors of CI and in age-matched healthy males. VLDL was subfractionated by heparin-Sepharose affinity chromatography into heparin unbound fraction (UBF) and heparin bound fraction (BF).
We found 1) VLDL concentration was increased in CI patients as compared with controls, although IDL concentration was not increased in CI patients. 2) VLDL-CE/TG ratio and IDL-CE/TG ratio were increased in CI patients. 3) BE was increased in CI patients and BF-CE/TG ratio was higher in CI patients than in controls.
We suggest that in CI patients VLDL catabolism by lipoprotein lipase is retarded and that CE is excessively transferred from HDL to VLDL forming the CE-rich lipoprotein particles.

抄録全体を表示

The bile of homozygous WHHL-rabbit (Watanabe Heritable Hyperlipidemic rabbit) was analyzed and compared with Japanese White rabbits. There is no significant difference in bile acid and cholesterol concentration of both hepatic and gallbladder bile. And among the bile acids composition of hepatic bile, deoxycholic acid occupied the dominant portion, about 85 per cent. In the rest small portion, a small quantity of cholic acid, allodeoxycholic acid and lithocholic acid were existed. The composition of bile acids was almost the same in the two groups except for the decrease of cholic acid in WHHL-rabbit. In perfusion experiment of isolated rabbit liver, no difference was observed in the serial bile flow, biliary cholesterol and bile acid concentrations in the two groups. Lipid concentrations of perfusate and cholesterol contents of liver, which were measured after perfusion, showed no difference in the two groups. Synthesis of cholesterol was measured in WHHL-rabbit by the sterol balance technique. Newly cholesterol synthesis decreased by one thirds in WHHL-rabbit, but not significantly. These results revealed that hepatic handling of bile acids in WHHL-rabbit was almost the same as in normal rabbit, while it is well known that homozygous human subjects with familial hypercholesterolemia show decrease of biliary cholic acid. WHHL-rabbit, which possess a nearly complete deficiency of LDL-receptor, tend to reduce cholesterol synthesis with little influence on catabolism of cholesterol to bile acid.

抄録全体を表示