A total of 20 subjects (10 control subjects and 10 non-insulin dependent diabetic patients), aged 40-65 years old, was investigated for fasting plasma lipids and lipoproteins. All subjects showed the normal levels of lipids including HDL-choles-terol. However, the sialic acid content (per mg protein) was significantly reduced in HDL₂ and HDL₃ fractions of the diabetic patients. Thus, sialic acids in HDL seem to have no influence on HDL concentration in plasma. The fact that there was a significant positive correlation between the sialic acid and cholesterol contents either in HDL₂ or in HDL₃ might be accounted for by the known evidence that the sialoapoproteins (apo C and E groups) and free cholesterol are transfered simultaneously between VLDL and HDL particles, together with phospholipids.

抄録全体を表示

Fibromuscular dysplasia is characterized to be thickened in vessel wall by hyperplasia of both smooth muscle cells and fibrous elements of the affected artery. Stenosis of the arterial lumen may develop by diffuse proliferative change in smooth muscle cells and fibrous tissue of the media. Its importance is usually related to its partial obstruction of renal blood flow resulting in hypertension.
According to the part of the arterial wall affected, fibromuscular dysplasia is classified into three type, intimal, medial and adventitial type-the medial type being by far the most common. The lesion, as a whole, are common in younger age groups, especially young female, and tend to occur in only renal artery. The etiology of fibromuscular dysplasia of the renal arteries is unknown. But etiologic factors of this pathological abnormalities are speculated to hormone, organic change of vasa vasorum, hypermobility of kidney (nephroptosis), and hereditary developmental weakness of renal artery.
An autopsy findings of 49-year-old male with reno-vascular hypertension associated with cerebral infarction was studied clinicopathologically. The patient had a history of hypertension of 30 years duration. He suffered from cerebrovascular sttack 2 times, 9 and 4 years before death.
At postmortem examination, fibromuscular dysplasia were found out in right renal artery and right common carotid artery. It showed that renovascular hypertension and old cerebral infarction caused by obstruction of both right renal artery and right common carotid artery respectively. This case report is rare and interesting for cardio-vasology.
As referred to earlier, certain varieties are associated with involvement of other vessels in the body. Case have indeed been described, but the number are small. From present study, it is to suggest that fibromuscular dysplasia may represent a general arterial dysplasia rather than a lesion limited to renal arteries. Fibromuscular dysplasia would have been considered as a cause of curious hypertension and cerebral infarction in young adults which have increased the frequency in the future.

抄録全体を表示

We tried to prove the hypothesis that apolipoproteins, the protein constituents of plasma lipoproteins, are secreted into bile. We examined human gallbladder bile obtained at surgery (N=54) from subjects with (N=44) and without (N=10) gallstones and hepatic bile collected by T-tube drainage (N=9) after cholecystectomy.
Using specific radioimmunoassays for human apolipoproteins A-I and A-II, the major apolipo-proteins of high density lipoproteins, for apolipo-proteins C-II and C-III, major apolipoproteins of very low density lipoproteins, we found immuno-reactivity for these four apolipoproteins in every bile samples.
Using immunodiffusion technique, we observed complete lines of identity between bile samples and purified apolipoproteins A-I and A-II, or C-II.
Using molecular sieve chromatography, we found identical elution profiles of biliary apolipo-proteins A-I and A-II, as those of apolipoproteins A-I and A-II purified from human plasma.
When we added high density lipoproteins purified from human plasma to lipoprotein-free solutions perfusing through isolated rat livers, we detected apolipoproteins A-I and A-II in bile.
These data indicate that apolipoproteins can be transported across the hepatocyte and secreted into bile.

抄録全体を表示

To investigate the possible mechanism of lipid abnormality in nephrotic syndrome, we have determined plasma and urinary lipid, particularly urinary phosphatidyl ethanolamine (PE), levels in control and puromycin aminonucleoside induced nephrotic rats.
In nephrotic rats, there was a significant increase both in plasma total cholesterol (TC), triglycerides (TG) and phospholipids (PL) and in urinary cholesteryl ester (CE), phosphatidyl choline (PC) and PE.
The following relationship among daily urinary excretion rates and plasma levels of various parameters was summarised:1) Urinary protein had a significant negative correlation to plasma protein and a positive correlation to plasma TC and TG, which showed a negative correlation to plasma protein. 2) Correlation of urinary CE, PC and PE to urinary protein and plasma protein, TC and TG was significant except between plasma TG and urinary PE. Urinary PE had a higher correlation to urinary and plasma protein than that of urinary PC, while the correlation of urinary PC to plasma TC and TG was higher than that of urinary PE.
These results suggest that the mechanism of urinary PE excretion may be different from that of other lipids in nephrotic rats. However, further investigation needs to clarify the detail mechanism in terms of urinary PE metabolism in nephrotic syndrome.

抄録全体を表示

Fecal sterols of human subjects, aged 0-80 years old, were analyzed by thin-layer chromatography and gas-liquid chromatography, in order to clarify the role of intestinal flora in the metabolism of cholesterol. It is known that cholesterol is transformed into coprostanol, an unabsorbable sterol, by the intestinal flora. The coprostanol was not detected in the meconium and neonatal feces. This sterol was detected in the feces of subjects over 2 years old and the content increased with age. In contrast, the content of cholesterol decreased with age, so that the coprostanol/cholesterol ratio increased. Over 92% of the cholesterol in feces was non-esterified, indicating the active sterol metabolism by the intestinal flora, because cholesterol is transformed into coprostanol only when cholesterol is free form. The feces of aged subjects contained some unidentified neutral sterol-like substances other than cholesterol, coprostanol and plant sterols, suggesting that the sterol metabolism is complicated by many species of intestinal flora such as Clostridium. The longer transit time through the gut of aged subjects than younger subjects may also contribute to the complex metabolism of sterols by intestinal flora. It is suggested that the transformation of cholesterol into coprostanol and other sterol metabolism by intestinal flora may play an important role in the sterol metabolism of whole body.

抄録全体を表示

It is our purpose to clarify the relationship between serum triglyceride levels and the incidence of cardiovascular lesions.
1) 166 male outpatients of average age of 51.2 years were investigated for mean period of 36.8 months, who showed diabetic type in 50g OGTT.
2) 86 male outpatients of average age of 47.7 years were investigated for mean period of 46.9 months, who showed borderline type in 50g OGTT.
In 1) and 2), blood samples in fasting were used for measuring biochemical data. Four groups were subdivided by serum triglyceride levels. Group A was under 120mg/dl of serum triglyceride, group B more than 120mg/dl and under 160mg/dl, group C more than 160mg/dl and under 200mg/dl, and group D more than 200mg/dl. As compared with group A, group D showed higher levels of serum cholesterol, uric acid, fasting blood sugar, relative body weight and systolic or diastolic blood pressure in cases with diabetic type, while higher levels of those except serum cholesterol and fasting blood sugar in cases with borderline type. The ranges in the changes of serum triglyceride levels were shown by the standard deviation, and were wider when serum triglyceride levels were higher in cases with diabetic type. Higher serum triglyceride levels such as group C and D were accompanied by frequent incidences of ST depression and of advanced Keith Wagner degrees.
3) 25 male outpatients with glucose intolerance in 75g OGTT were investigated for one to 4 months. The increments or decrements of serum triglyceride levels were accompanied by those of β-lipoprotein or VLDL levels, while those of cholesterol levels by those of LDL levels. There were significant positive correlations (r=0.89) between serum triglyceride and VLDL, and (r=0.83) between serum cholesterol and LDL.
4) Male outpatients with glucose intolerance in 50g OGTT were investigated for 6 months. 21 cases received clinofibrate in the dosage of 600 to 1, 200mg per day, 46 cases received riboflavin tetrabutyrate in the dosage of 120 to 180mg per day, and 21 cases were under dietary treatment. Although serum triglyceride levels tended to decrease by these drugs, serum triglyceride more than 200mg/dl decreased significantly with riboflavin tetrabutyrate. Serum cholesterol levels and cholesterol/HDL-cholesterol ratio decreased significantly with clinofibrate. Higher serum triglyceride levels tended to be accompanied by the risk factors of atherosclerosis such as obesity, hypertension, serum cholesterol, uric acid et al.

抄録全体を表示

Impaired glucose tolerance (IGT) as well as diabetes mellitus (DM) are known to carry increased atherosclerotic risk. However, the mechanism is unclear. The purpose of this study is to clarify the relationship between IGT and plasma lipid as an atherosclerotic risk factor.
Fifty seven men matched for age and %IBW were divided into four groups: normal, IGT, DM and borderline group according to WHO diagnostic criteria for evaluation of 75g OGTT. DM group was newly diagnosed at start of this study. Borderline group was “not diagnosed” group which showed slightly impaired glucose tolerance. We examined plasma lipids, lipoproteins and basal insulin levels in four groups.
1) Mean plasma triglyceride and total cholesterol levels were 165^* and 202mg/dl, respectively in DM group, 150^* and 178mg/dl in IGT group, 135 and 180mg/dl in borderline group, and 117 and 182mg/dl in normal group (^*p<0.05 vs. normal). The incidence of hyperlipemia increased with increasing degree of glucose intolerance, that is, in order of DM, IGT, borderline and normal group.
2) Plasma basal insulin level in IGT group was significantly higher than that in DM group.
3) Plasma LDL-Cholesterol level in DM and IGT group, and atherogenic index (LDL/HDL-Cholesterol ratio) in IGT, DM and borderline group were higher than in normal group, but it was not significant.
4) Only IGT group showed a tendency to have lower level of plasma HDL-Cholesterol than normal group. Plasma HDL₂-Cholesterol level and HDL₂/HDL₃-Cholesterol ratio in DM, IGT and borderline group were lower than in normal group, but it was not significant. There was no difference in plasma HDL₃-Cholesterol level in four groups.
The present results suggest that IGT and borderline group have alterations in lipid metabolism of intermediate degree between normal group and diabetic group. These alterations might partly contribute to increased atherosclerotic risk in IGT.

抄録全体を表示

It is widely accepted that diabetics often have hyperlipemia and atherosclerosis. In order to study the changes in lipid metabolism in diabetes mellitus, the plasma lipids, lipoproteins and apoproteins were measured in spontaneously diabetic Chinese hamsters in the Asahikawa colony.
Plasma TG, TC, PL and FFA, and blood lipoperoxide levels in diabetic hamsters significantly increased as compared with those of the nondiabetic controls. Plasma HDL-Cholesterol level in diabetic hamsters was significantly higher than in the non-diabetic controls. Gradient gel electrophoretic analysis revealed the increase of plasma VLDL, LDL and HDL in the diabetic hamsters. Furthermore, by ultracentrifugation we showed
that there was much chylomicron in the plasma from the diabetic hamsters.
A relative increase in apoprotein A-I in HDL from the diabetic hamsters was found by polyacrylamide gel electrophoresis in 8 M urea, and relative increases in apoprotein C-II, C-III₀ and C-III_1-2 in VLDL from the diabetic hamsters were found by isoelectric focusing.
Finally we examined morphologically the descending thoracic aortas of non-diabetic and diabetic hamsters. The aortas of the non-diabetic controls were normal, but slight thickening and proliferation of the intima of the diabetic hamsters were found.
The present results suggest that there are alterations in lipoproteins and apoproteins, and some morphologic changes in the aorta in spontaneously diabetic Chinese hamsters. The relation of these findings to atherosclerosis is, however, unknown.

抄録全体を表示

Experimental atherosclerosis was induced in rats by feeding the animal with vit. D₂ and atherogenic diet, which was reported previously. In order to examine the mechanism of action of elastase preparation (Eisai, 450 ELU/kg b.w./day), in terms of anti-atherosclerotic effect, calcitonin, an antagonist of vit. D₂ in the calcium metabolism, was administered to the experimentally induced athero-sclerotic rats (calcitonin in the form of elcatonin, a derivative of calcitonin, 0.4 MRCU/kg b.w./day, i. m. injection, made by Toyo Jozo Co.).
1) In the experimentally induced atheroscle-rosis, serum lipids as well as cholesterol, as the total cholesterol, in the artery and in the heart were increased. Cholesterol levels in the artery and in the heart after the fractionation, mainly present in the elastin fraction, were also increased. For such lipids increasing tendency in the experimental stherosclerosis elastase and calcitonin was tend to decrease their levels.
2) In the experimentally induced atheroscle-rosis, the content of the bridge components of lysine origin (isodesmosine, desmosine, merodesmosine, and lysinonorleucine) of the artery was decreased or at least tend to be decreased. Administration of elastase or calcitonin was tend to improve, or normalize such ill tendency.
It may be said that elastase and calcitonin have similar mechanism in the anti-atherosclerotic effect, and metabolic regulation of calcium may be partly related.

抄録全体を表示

We observed the effect of elastase (10800 E. I. U./day, orally) in 58 hyperlipidemic patients with diabetes mellitus for a period of 2 to 6 months. To estimate the effect, the data were analysed at two stages, that is, from 2 to 3 months (A group), from 4 to 6 months (B group) after administration of elastase.
The results: (1) Total serum cholesterol was decreased in both groups, but it was not significant statistically. On the other hand, the patients whose serum levels were above 250mg/dl showed significant fall in both groups (p<0.05). (2) The serum triglyceride was decreased, but it was not significant in A group, while B group showed signifi cantly fall (p<0.01). The patients whose serum levels were above 150mg/dl showed significant fall in both groups (A group p<0.05, B group p<0.01). (3) The serum level of HDL-cholesterol was increased in both groups, but it was not significant. On the other hand, the patients whose serum levels of HDL-cholesterol were under 40mg/dl showed significant increase in both groups (A group p<0.001, B group p<0.01). (4) The serum levels of β-lipoprotein, BUN (blood urea nitrogen), FPG (fasting plasma glucose), and others showed no significant changes in both groups. (5) Only one patient felt abnormal thirst, but he recovered after stop of administration. (6) These data demonstrate that elastase is effective in the treatment of hyperlipidemic patients with diabetes mellitus.

抄録全体を表示

Because it has been established that the pathogenesis of familial hypercholesterolemia is related to the defect of the LDL receptors, we studied the effect of an antihyperlipidemic drug, clinofibrate, on the activity of LDL receptor in lymphocytes.
18 male subjects including 11 hyperlipidemic patients (3 type IIa, 1 type IIb and 7 type IV) and 7 normolipidemic persons were administered clinofibrate (200mg t.i.d.) for six or eight weeks. This treatment lowered serum cholesterol (from 204.1±40.9 to 178.9±35.7mg/dl, p<0.01), phospholipids (from 244.3±30.2 to 226.5±36.6mg/dl, p<0.05) and triacylglycerols (from 171.8±101.0 to 125.9±93.2mg/dl, p<0.05). LDL-cholesterol was also decreased from 125.4±44.2 to 106.0±38.6mg/dl (p<0.05), and HDL-cholesterol tended to increase (48.8±10.0 to 51.0±11.2mg/dl) which, however, was not significant.
The activity of LDL receptor was examined as the degradation of ¹²⁵I-labeled low density lipoprotein (¹²⁵I-LDL) in lymphocytes which were obtained from the peripheral blood and cultured for 3 days in 10% lipoprotein-deficient serum as previously described. 10 μg/ml of ¹²⁵I-LDL were added to the medium in the presence or absence of 250 μg/ml nonlabeled LDL and then the lymphocytes were incubated for 5 hours. The radioactivity of the trichloroacetic acid-soluble fraction of the medium was measured. The experimental lymphocytes and the control ones were run simultaneously and the value was expressed as the percentage to the control. The mean activity of LDL receptor in lymphocytes from 18 subjects was 78.3±18.3% before drug therapy, and it significantly increased to 88.3±21.8% (p<0.05) after therapy. It is difficult to decide only by these data whether clinofibrate had an influence directly on lymphocytes or the increase of the activity of LDL receptor was resulted from the changes in serum lipids, but the former may be possible since another derivative of clofibrate, bezafibrate, was reported to reduce serum cholesterol by the increase of the LDL receptor-mediated catabolism by the use of the kinetic study in vivo. Though the positive correlation was shown between the increment of the activity of LDL receptor in lymphocytes and the decrement of serum cholesterol, it was not significant. This may be at least partly due to the heterogeneity of the subjects in terms of hyperlipidemic pattern.
The result of this study may support the hypothesis that raising the activity of LDL receptor is one of the most effective way for lowering serum cholesterol.

抄録全体を表示

Effect of clinofibrate on post heparin lipolytic activity and serum lipid in hyperlipidemic patients were studied. Twenty two patients were given 1, 200mg clinofibrate daily for 16 to 32 weeks.
1. Total cholesterol and triglyceride (TG) were reduced by 7.1 and 15.7%, respectively and phospholipid was increased by 8.8% after treatment for 32 weeks.
2. No significant correlation between serum TG or VLDL-TG and lipoprotein lipase (LPL) was observed before treatment. However after treatment, negative correlation between serum TG or VLDL-TG content and LPL activity was observed.
3. There is closely negative correlation between changes in VLDL-TG concentration (ΔVLDL-TG) and LPL activity (ΔLPL) during treatment.

抄録全体を表示

Sulfonylurea has been reported sometimes to reduce plasma HDL-cholesterol concentrations. In this study, 17 sulfonylurea-treated diabetics with sustained hyperlipemia under the steadystate blood glucose control received clinofibrate, an antilipemic agent, with a dose of 600mg/day for approximately one year or more. As controls of hyperlipemics, 33 normolipemic diabetics taking sulfonylurea were studied. Blood cholesterol, HDL-cholesterol and triglyceride were measured before and after 2, 4 weeks and thereafter each 2 months administration of clinofibrate. Seven hyperlipemic diabetics with dietary treatment were also investigated in the same manner as in the sulfonylurea-treated diabetics. The following results were obtained.
1. Plasma HDL-cholesterol concentrations under the continuous treatment of sulfonylurea are not lower than the concentrations of untreated diabetics or dietary-treated patients.
2. Serum cholesterol and triglyceride decreased 2 weeks after the administration of clinofibrate in sulfonylurea-treated diabetics and maintained the same or more lowered level throughout the observation period. Clinofibrate tends to increase plasma HDL-cholesterol concentration approximately 2 months after administration, followed by a gradual increase until the end of experiment in sulfonylurea group. The final HDL-cholesterol concentration was shown to be 117% of the initial level, slightly higher than the rate of increase in dietary-treated group.
3. The effect of clinofibrate on improving lipid metabolism in sulfonylurea-treated diabetics appears to last for a long period, and does not disappear at least after one year's administration.

抄録全体を表示

Effects of clinofibrate on serum lipids and lipoproteins were studied in 56 patients with hyperlipidemia and/or with hypo HDL cholesterolemia. The patients received 600mg of clinofibrate every day for 16 weeks. Levels of serum lipids, HDL cholesterol and apoprotein A-I, A-II and B were measured at every four weeks during the treatment. By the treatment, cholesterol levels decreased by 13% of the initial value and triglyceride decreased by 33%. HDL cholesterol increased by 10% of the initial value. Increase of HDL cholesterol observed mainly in HDL₃ fraction. By apoprotein measurement, an increase of apo A-I and a decrease of apo B were observed in the course of treatment.

抄録全体を表示

It has been reported that patient with Type IIa Hyperlipidemia which results in metabolic abnormarities of serum Prostanoids are prone to have Arteriosclerosis.
Tremori et al reported a positive correlation between serum Cholesterol levels and plasma Thromboxane B₂ levels. Serum Cholesterol levels have a close relationship to prostaglandin metabolism in platelets. In the case of Type ha Hyperlipidemia, we have found both platelet aggregation and Thromboxane B₂ levels to be significantly elevated compared to controls.
In addition, the ratio of C_{20: 4}of phospholipid, P. E., P. C. and NEFA in platelets were significantly elevated in Type IIa Hyperlipidemia. This implies that abnormalities of Cholesterol metabolism affect C_{20: 4}levels in platelets, and therefore the process of prostaglandin metabolism.
After administering Clinofibrate, a lipid lowering agent, to patients with Type ha Hyperlipidemia, there was a significant improvement of the ratio of TX B₂ to 6-Keto-PGF_1α, a significant reduction in TX B₂, platelets aggregation and C_{20: 4} levels of P. E. in platelets phospholipids, consistent with a decrease in serum Cholesterol. We conclude these strongly suggest the relation of occurance of thrombosis and abnormalities of serum lipid through Prostanoids metabolism.

抄録全体を表示

The effect of Clinofibrate on lipids in plasma and lipoprotein, plasma apoproteins and the proportion of apo C subspecies in VLDL was studied. Eleven hyperlipidemic patients, consisting of 5 type IIa, 3 type IIb and 3 type IV, were given 600 mg of Clinofibrate per day or placebo, each for 8 weeks by cross-over design.
Following change was obseved after the Clinofibrate treatment.
1. Mean plasma cholesterol, triglyceride decreased significantly.
2. VLDL-chol, VLDL-TG and LDL-TG decreased significantly and HDL₂-chol tended to increase and HDL₃-chol tended to decrease.
3. Plasma apo C-II decreased significantly.
4. The relative proportion of apo C-III₀ in VLDL decreased and that of apo C-II in VLDL increased.
5. Atherogenic index decreased.

抄録全体を表示

Incorporation of LDL (Cholesterol [1-¹⁴C] oleate labelled LDL) was enhanced by the addition of pantethine in rabbit smooth muscle cells (SMC). The incorporated LDL was metabolized in the cells and the radioactivities were found in the various lipids, suggesting the hydrolysis of cholesterol oleate and the incorporation into the lipids from the liberated oleic acid. The ratio of the radioactivities in the cholesterol ester to that in other lipids was decreased by the addition of Pantethine. These results suggest that Pantethine might protect the accumulation of cholesterol ester in the SMC.
Incorporation of acetylated LDL (aLDL) was inhibited by the addition of pantethine in rat peritoneal macrophages. The incorporated LDL metabolism was not affected by the addition of pantethine. The inhibition of incorporation by pantethine might cause the protection of cholesterol ester accumulation in macrophages.

抄録全体を表示

Recent studies suggest that long term therapy of hypertension with thiazide may result in a decrease of serum levels of HDL-cholesterol. The present paper describes the effects of cross-over administration of trichlormethiazide alone (A) and the combination of trichlormethiazide and pantethine (B) on the serum levels of total cholesterol (TC), HDL-cholesterol (HDL), triglyceride (TG), low density lipoprotein (LDL) and very low density lipoprotein (VLDL) in essential hypertensives. Pantethine, which is one of the components of Co-enzyme A and acyl carrier protein, has been known to improve the serum levels of some lipid fractions such as HDL, TG, or TC in hypertensives and hyperlipidemic patients.
A or B was administered for 4 months. Each lipid fraction was determined under hunger condition at early in the morning before and after A or B. TC was not altered significantly in this study. HDL was decreased by A and increased by B, thus atherogenic index (A.I., (TC-HDL)/HDL) was increased by A, and decreased by B. Mann-Whitney analysis of the changes of HDL (ΔHDL) and A. I. (ΔA.I.) revealed that these changes were statistically significant at the level of p<0.05. The other lipid fractions were not significantly changed in this study.
These results suggest that to combine pantethine with trichlormethiazide in the therapy of essential hypertention maintains the HDL levels higher.

抄録全体を表示

Diets high in cholesterol (Ch) have been shown to cause significant elevations in plasma Ch in several animals including man. Elevated plasma Ch has been shown to be an independent risk factor for coronary heart disease.
Consistent features of Ch-induced hypercholes-terolemia in several animals are the occurrence of β-VLDL in the d<1.006g/ml fraction, an increase in the IDL and LDL, a decrease in the typical HDL and the appearance of HDLc.
Plasma lipoprotein abnormalities are common in the patients with diabetes mellitus. They are of considerable clinical interest because of the higher incidence of atherosclerosis in the diabetics.
Recently we have found that Ch-fed diabetic rat had marked elevations of plasma Ch and triglyceride (TG) and had higher concentrations of lipoproteins of VLDL (d<1.006g/ml), IDL (1.006<d<1.019g/ml) and LDL (1.019<d<1.063g/ml) as compared with Ch and propylthiouracil (PTU)-fed non-diabetic rat. Insulin treatment was highly effective to improve hyperlipoproteinemia of Ch-fed diabetic.
The present study was designed to investigate the effect of pantethine on plasma lipids and plasma lipoproteins of Ch-fed rat, diabetic rat and Chfed diabetic rat. Non-diabetic control rats and streptozotocin-induced diabetic rats were fed the diet containing 1% Ch, 1% lard and 0.3% sodium taurocholate for 4 weeks. In non-diabetic rats, 0.1% PTU was added.
Pantethine-treated rats were fed the diet containing 1% pantethine. Ch and PTU-fed rats had features of plasma lipoproteins as described previously.
Pantethine treatment significantly decreased plasma Ch (617±84.6→275±45.0mg/dl) and plasma TG (164±16.9→100±10.4mg/dl). VLDL-Ch, VLDL-TG, VLDL-protein, IDL-Ch, IDL-TG, LDL-Ch, LDL-TG and LDL-protein were decreased significantly. Furthermore, HDL-Ch, HDL-PL (p<0.05) and HDL-protein showed the tendency to decrease. However, pantethine did not affect plasma lipids and lipoprotein profiles in the labo chow-fed and Ch-fed diabetic rats except that pantethine increased significantly HDL-PL (p<0.05).

抄録全体を表示

In order to evaluate the effect of anti-hyperten-sive drugs to levels of serum lipids, fasting concentration of total cholesterol (TC), triglyceride (TG) and HDL-cholesterol (HDL-C) was measured before and during therapy in 80 patients with essential hypertension. The patients were divided into 9 groups according to administrated drugs including thiazide, α-methyl-dopa, nifedipine, diltiazem and alprenolol. Observation periods were 1 to 4 years.
No significant changes of serum TC, TG and HDL-C levels were found in all 9 groups during the study. However, patients who were treated with thiazide tend to show increased level of TC and decreased level of HDL-C. Those who were treated with nifedipine tend to show increased level of HDL-C. Patients who showed elevated serum TG were mainly found in groups of patients treated with α-methyl-dopa.
These results suggest that it may be important to know serum lipids levels when anti-hypertensive drugs are administrated to patients for a long period of time.

抄録全体を表示

It has been reported that Dilazep, [tetrahydro-1H-1, 4-diazepine-1, 4 (5H)-dipropranol bis (3, 4, 5-trimethoxy benzoate) dihydrochloride monohy-drate], a coronary vasodilator, has a potent antiaggregatory effect in vivo and in vitro studies. However, the exact mechanism of antiaggregatory effect of Dilazep has not been determined yet. In this experiment, in vitro effect of Dilazep on the metabolism of membrane phospholipids and arachidonic acid (AA) cascade in human platelets was studied. Dilazep inhibited in a dose dependent manner platelet aggregation and tromboxane B₂(TXB₂) formation when stimulated by ADP, epinephrine and collagen.
Dilazep inhibited thrombin-induced release of [¹⁴C] arachidonic acid ([¹⁴C]AA) from both of phosphatidylcholine and phosphatidylinositol fractions of [¹⁴C]AA prelabeled platelets. The appearance of [¹⁴C]AA in 1, 2-diacylglycerol and phosphatidic acid in response to thrombin was inhibited by Dilazep. The conversion of endogenous and exogenous [¹⁴C]AA to cyclo-oxygenase products was inhibited by Dilazep. Cyclic AMP and cyclic GMP levels in washed platelets were not affected by the addition of Dilazep. These results indicate that Dilazep may inhibit the release of AA from platelet membrane phospholipids, e. g. most likely inhibition of phospholipases and reduce the formation of TXA₂ from released AA.

抄録全体を表示

Fifteen risk factors for atherosclerosis were studied on the 758 female subjects. Age, obesity, ECG, ocular fundus, blood pressure, GOT, total choresterol, triglyceride, HDL-cholesterol, the numbers of leucocyte and erythrocytes, hematocrit, hemoglobin, blood sugar, uric acid were determined. Higher cholesterol risk factor index (CRFI, >0.8) was counted 65 subjects (8.6%). Significant correlations were noted among the CRFI-age-uric acid-blood pressure and age-triglyceride-ocular fundus. Serum triglyceride was also related to systolic blood pressure. Abnormal data seemed to correlated each other when LDL-C level was exceeded 120mg/100ml.

抄録全体を表示

Relationships between ECG findings and serum lipids were studied in 4503 healthy male industory employees.
Results were as follows:
1) Total cholesterol and LDL-cholesterol increased with increasing the age.
2) HDL-cholesterol in old myocardial infarction group (MI) was 35.60±19.17mg/dl and lower than that of non ischemic heart disease group (IHD) (111.53±34.78).
3) LDL-cholesterol and atherogenic index 1 and 2 in the old MI group were 147.64±19.47, 6.97±4.483 and 6.29±4.073, respectively. These values were higher than those of non IHD group (111.53±34.78, 3.341±3.067, 2.748±2.723, respectively).
4) Increase in blood pressure, total cholesterol, triglycelide and LDL-cholesterol tended to increase in rate of ischemic ECG changes.
5) In combinations of 2 items examined, hypertension and hypercholesterolemia were most responsible to increase in ischemic ECG changes.

抄録全体を表示

The purpose of this study was the simultaneous measurement of triglyceride, total cholesterol, phospholipid, very low density lipoprotein cholesterol (VLDL-C), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C) and basal insulin levels from carefully selected patients with diabetes mellitus who were under treatment for a long period (7.2±0.8yr.).Subjects included patients with middle-aged type II diabetes (51.2±0.8yr.: Group A) together with healthy individuals matched for sex, age and body weight (47.8±1.6yr.: Group B). In diabetic patients, all the above-mentioned variables were examined according to the difference of blood sugar control, treatments for diabetes mellitus, and the existence of diabetic retinopathy. Furthermore, it was studied that the relationship betweenthese variables and the existence of ischemic heartdisease (IHD) in old type II diabetes (69.8±1.8yr.: Group C).
1) Fasting plasma glucose in Group A was significantly elevated compared with that in Group B (p<0.01). No difference in plasma lipids, lipoproteins and basal insulin levels was found between Group A and B. But triglyceride and LDL-C/HDL-C ratio showed a tendency to increase in Group A.
2) Diabetic patients treated with insulin showed elevated fasting plasma glucose and basal insulin level compared with patients of groups treated either with sulfonylurea or diet only (p<0.05, p<0.05; respectively). And the patients treated with sulfonylurea or insulin showed a tendency to increase of HDL-C compared with the diet therapy patients.
3) Total cholesterol, triglyceride LDL-C and HDL-C increased more in the groups with advanced hyperglycemia. So, LDL-C/HDL-C ratio did not differ according to blood sugar control.
4) The group of patients with proliferative retinopathy showed significantly elevated triglyceride level compared with groups of patients either with background retinopathy or without retinopathy (p<0.05, p<0.05; respectively). No significant difference in other lipids, lipoproteins was observed among these three groups.
5) Triglyceride, LDL-C and LDL-C/HDL-C ratio showed a tendency to increase in Group C compared with those in Group A. Furthermore, patients with IHD showed a tendency to still more elevated level compared with those without IHD in Group C. But no difference in other lipids and lipoproteins was found between patients with IHD and without IHD.
From these data, it was thought that correction of plasma lipids and lipoproteins as well as plasma glucose level was very important to prevent against both arteriosclerosis and microangiopathy with diabetes mellitus.

抄録全体を表示

Diabetes is frequently complicated with the arteriosclerotic disease, with leads to short average spans of life of its patients. Not a few fundamental, clinical and epidemiological reserches have so far been made on this disease, however, its pathogenesis is still unknown. In the present study histochemical determinations and observations were made of elastin and collagen aortic media in order to examine the pathology of the macroangiopathy in the diabetes.
Subjects were human thoracic aortic media from a total of 226 cases (179 of control and 47 of diabetes). Elastin and collagen were stained with Weigert's and Van Gieson's stain, respectively, and histochemical observations were made on the architecture of both compornents, which were further determined by microspectrophotometry (MSP). Comparisons of the histological findings in elastic fiber revealed that compared with control group diabetic group had aortic medial architectural disturbances such as fibrous irregular running and increment of collagenous fiber. The amount of elastin for control group was 28.4v/v% at forties, 28.9v/v% at fifties, 29.0v/v% at sixties and 21.3v/v% at seventies, while for diabetic group it showed significant decrements (8.8v/v at forties, 9.7v/v% at fifties, 13.6v/v% at sixties and 8.4v/v% at seventies). The amount of collagen was 21.7%E at forties, 20.3%E at fifties and 22.5%E at sixties, and 27.7%E at forties, 26.1%E at fifties and 27.5%E at sixties for control group and for diabetic group, respectively, showing significant increments.
It was suggested that quantitative and qualitative changes of aortic medial elastin and collagen played an important role in the pathogenesis of arteriosclerosis in diadetes.

抄録全体を表示

Serum apolipoprotein and lipid levels have been studied in type 2 diabetic subjects.
1) In type 2 diabetic subjects, apo A-I, A-II, B, C-II, E are all significantly elevated compaired with that in control subjects.
2) Positive correlation was observed between apo A-I and FPG level.
3) Apo B level was correlated with total cholesterol, TG and LDL-Chol level. The elevation of apo B levels was also observed in subjects with normolipidemia and therefore serum apo B level seems to be an important marker for deranged lipid metabolism.
4) Apo C-II level was correlated with TG level, but not with T. chol level, and it did not increase in those with insulin therapy. Thus, the elevation of Apo C-II level seemed to be secondary to the elevation of serum TG level.
5) App E level was correlated with T, chol as well as TG levels, and it did not increase in normolipidemic subjects. This suggests that the elevation of apo E level is also secondary to the elevation of serum T.chol and TG level.
In type 2 diabetic subjects serum levels of apoprotein were all elevated. Since apo C-II & E were normalized in those on insulin treated, while elevation was noted for serum apo B level, changes of apo A-I & B level may serve as an metabolic and atherogenic marker.

抄録全体を表示

1. Contents and distributions of acid mucopolysaccharides and glycoprotein were histochemically assayed in the coronary artery (LAD seg. 6) in 54 cases of WKY, from 35 to 800 days, and in 59 cases of SHRSP, from 45 to 650 days.
2. Acid mucopolysaccharides (AMPS) contents in WKY did not show the pattern of aging, and they were around 10 %E in all age populations. AMPS in SHRSP increased with aging, reaching to the level 11.5 to 30.6 %E. When the both group were compared, SHRSP showed higher value, after 300 days, in each 100 days with p<0.01-0.05. When the both groups were compared for all cases, it was found that WKY 9.7±2.8%E and SHRSP 13.4±5.1%E (p<0.001).
3. There was no distinct effect of aging in Glycoprotein (GP) content in WKY, and it was within the range of 37 to 42%E. However, in SHRSP, effect of aging was remarkably shown, 44.0 to 77.1%E, showing higher value in SHRSP in each 100 days with p<0.01-0.001. When the both group were compared with all cases, WKY was 37.1±4.5%E and SHRSP was 57.5 ±13.0%E (p<<0.001).
4. AMPS and GP levels in SHRSP showed, in a half cases of death for marked hypertension within 300 days, destruction and decrease, and the remaining half cases showed ill increasing process after 300 days.

抄録全体を表示

1. Histochemical observation and assay of the smooth muscle cells (SMC) were performed for 57 cases of SHRSP and 49 cases of WKY from 35 to 600 days old, 106 cases in total using the coronary arterial descending branch seg. 6.
2. SMC in WKY, from birth to 199 days was higher, 92.3-87.7%E, not changed during 200-499 days, (79.1-82.8%E), and lowered gradually after 500 days, 60%E.
3. SMC in SHRSP was 60%E within 100 days, 50%E after 200 days, showing remarkable decrease. Comparing the SMC levels in each stage (each 100 days) in the both group, SHRSP showed lower level with p<0.05-0.001. When SMC was copared in the whole age group, WKY was 86.3±16.3%E and SHRSP was 63.0±18.8%E (p<0.001).

抄録全体を表示

We investigated the effect of hyperlipidemic serum on CAMP accumulation, determined by adenine prelabeling technique in intact vascular smooth muscle cells cultured from rabbit aorta. The cells were grown to confluence, then cultured for 24 hours in hyperlipidemic medium (total cholesterol: 0.8mg/ml). These cells enhanced cAMP accumulation in both basal levels and response to isoproterenol 10^-6M, as compared with control cells. Enhancement of cAMP accumulation in the cells cultured in hyperlipidemic medium was still detected in the presence of IBMX 10^-3M, a potent inhibitor of phosphodiesterase. Moreover, application of propranolol 10^-4M at 5 minutes after isoproterenol showed similar rate constant for cAMP disappearance.
The phosphodiesterase activity in 40, 000g supernatant of the Triton X-100 solubilized homogenates of the cells in hyperlipidemic medium revealed no changes. Thus, enhanced production rather than decreased destruction of cAMP was evident in the cells preincubated in hyperlipidemic medium for 24 hours. β-receptor assay showed an increased B_max with a similar Kd, and such may contribute, at least in part, to the increased adenylate cyclase activity as a compensatory phenomenon. A longer incubation with hyperlipidemic medium showed an attenuated CAMP accumulation in the cells; and under such conditions, there was an increased deposition of fat, which may reflect developing atherosclerosis.

抄録全体を表示

Comparative study on natural history of coronary atherosclerosis in 83 patients with effort angina between medical and surgical group were designed based on two coronary arteriograms.
The second coronary arteriograms were performed averaged 9 months after the initial angiography. Progression or regression were defined as 6 categories in severity of each coronary artery based on Kramer's criteria.
1) Incidence of progression was found in 50 of all patients with no relation to the age. Especially, the types of that were most frequently recognized as the categories of a) less than 100 to 100%, b) less than 30% to greater than 50%.While, the incidence of regression was found in only 4% with the non-infarcted patients.
2) As for progression in relation to the interval, the peak of that's incidence was recognized as one year later after CABG, however, these incidences were significant within 6 months in both groups.
3) In relation to coronary artery, the incidence of progression was highest in right coronary artery with medical group. On the other hand, that was significantly high in left circumflex coronary artery of the non-grafted vessels surgically.
4) As conclusion, serial coronary arteriograms are very important to evaluate the progressive arterial change or regression in patients with the ischemic heart disease.

抄録全体を表示

Serum apolipoprotein A-I and A-II levels were determined by a single radial immunodiffusion method for fasting sera of 308 normal healthy subjects, 160 males and 148 females, with a total mean age of 48±21, 50±21 for male and 47±20 for female. The relation of apoprotein levels with age, sex difference, mean normal values and correlation with serum lipids were examined.
Apo A-I and A-II did not change with age both in male and female. Apo A-I averaged as 135±20mg/dl for male and as 132±20mg/dl for female.The total mean for A-I was 133±18mg/dl. Apo A-II averaged as 32±6mg/dl for male and as 32±5mg/dl for female. The total A-II was 32±6mg/dl. The A-I/A-II ratio was 4.2±0.7 for male, 4.2±0.7 for female, and 4.2±0.7 for the total. No sex difference was seen in A-I and A-II levels and in the A-I/A-II ratio. Both A-I and A-II had a positive correlation with serum HDL-cholesterol, but no significant correlation seen with total cholesterol and triglycerides. Despite these correlations, there were certain cases whose apo A-I level had a discrepancy with HDL-cholesterol. These, taken together, indicated that the measurements of apoproteins widen the scope of studies on serum lipid and lipoproteins.

抄録全体を表示