Since Harman proposed the free radical theory of aging, this theory receives an attention widespread and numerous reports on lipoperoxide (Px), the product of free radical, appears. In order to study the clinical significance of these changes, we measured Px, lipid fraction and vitamin E (VE) in human serum with reference to age in 398 patients admitted to the Department of Medicine, Wakayama Medical College Hospital and Fuchu Hospital in Osaka and 76 healthy working subjects examined on a mass healthy survey. Methods of Px measure are modified TBA spectrometry by Naito (Px spectro) and modified TBA fluorometry by Yagi (Px fluoro). By spectrometry, serum Px in hospital patients was 13.0±2.45nmole/ml, significantly higher than 11.32±1.92nmole/ml in healthy subjects. Prior to the age of 70, serum Px value tended to increase with age, while it tended to fall after this age. Such tendency was most clearly seen in Px fluoro in healthy working subjects. Cases with abnormally high values of Px spectro (above m+2SD) included those of gastric cancer, myocardial infarction and heart failure, especially those under serious conditions. Concerning the relationship between lipid fraction and Px value, a positive correlation was found between Px spectro on one hand, and β-lipo, β-lipoprotein fraction and NEFA on the other in 398 hospital patients. A positive correlation was also found between Px fluoro and β-lipo in 76 healthy working subjects. No correlation was found between serum VE and Px, suggesting the presence of antioxidants other than VE in blood. Serum Px spectro was 10 times as high as Px fluoro and no correlation was found between two, suggesting that spectrometry also measures some non Px material such as sialic acid in serum.
Nandy and Bourne (1966) reported that the centrophenoxine (dimethylaminoacetyl-p-chlorophenoxy-acetate, Lucidril) showed an action to remove the lipofuscin from the aged guinea pig nerve cells. The purpose of this paper is to confirm the above result and to observe the ultrastructural changes of the lipofuscin by centrophenoxine administration. After intraperitoneal injection of 20mg/ml solution of centrophlnoxine or physiological saline to the young (6 months-old) and the aged (2 years-old) guinea pigs for 90 or 127 days, the animals were sacrified and various organs were investigated light and electron microscopically. The electron microscopy was performed on the hypothalamus, thalamus, ammon horn, anterior horn of spinal cord. Light microscopic observation revealed no change between centrophenoxine and saline groups in the amount of lipofuscin in the nerve cells of pontine trigeminal nucleus, hypothalamus and Purkinje cell layer of cerebellum. Electron microscopically, some lipofuscin granules showed vacuolation, especially in the anterior horn cells in both aged groups, with slightly high incidence in the centrophenoxine group. In the hypothalamus the amount of the monophasic type lipofuscin increased in the centrophenoxine group. The distribution of lipofuscin in the cytoplasm changed to rather disperse form than aggregated form in the anterior horn cells in the centrophenoxine group. From above results the effect of centrophenoxine for dissolution and removal of lipofuscin in the nerve cell could not be confirmed, but some changes on the structure and distribution of lipofuscin were observed. It is uncertain, however, whether these changes are direct effect of centrophenoxine on the lipofuscin metabolism.
Metabolic relationship among plasma lipoproteins was investigated on 11 hyperlipoproteinemic subjects under the accelerated condition of lipoprotein breakdown by the administration of dextran sulfate (MDS). Oral (3.6g) or intravenous administration of MDS (300mg) induced the reduction of triglyceride in very low density lipoprotein (VLDL) with concomitant fall of cholesterol in this lipoprotein. Mild reduction of protein in VLDL was also observed. Phospholipids in various lipoproteins remained unchanged. The ratio of VLDL-triglyceride/VLDL-protein showed rather increase in the process of VLDL catabolism. These results suggested that core lipids in VLDL were likely to be removed readily on the catabolic pathway. Correlation between the fall of VLDL-triglyceride and low density lipoprotein (LDL)-cholesterol was noted in this study, indicating that MDS-initiated breakdown of VLDL accelerated the cholesterol removal in LDL. Cholesterol content in high density lipoprotein (HDL) increased in 8 cases among 11 subjects after the administration of MDS. This would indicate that catabolic process of VLDL by MDS could be beneficial for the prevention of atherosclerotic vascular disease by decreasing VLDL-triglyceride, VLDL-cholesterol and LDL-cholesterol, and increasing HDL-cholesterol. This should be investigated by further epidemiological study.
It has been reported that the incidence of calcification of the abdominal aorta is greater in women over sixty than that in men, and that the incidence of atherosclerosis suddenly increases after the menopause. The purpose of this report is to investigate the interrelationship between estrogen deficiency and atherosclerosis. We have measured serum estradiol levels and checked the presence of arterial calcification in 53 postmenooausal women over sixty (mean age, 71.7±0.8 years). Serum estradiol levels were measured by radioimmunoassay and the calcifications of the thoracic, abdominal aorta and the iliac artery were examined by X-ray films. The results were as follows: 1) Mean value of serum estradiol was significantly lower in women with calcification of the iliac artery (5.5±1.64pg/ml) than in women without calcification (16.2±2.01pg/ml). (p<0.01). Mean value of serum estradiol tended to be lower in women with calcification of the thoracic or abdominal aorta than those without it. Furthermore mean value of serum estradiol was significantly lower in women with calcification of the iliac artery than those in women with calcification of the thoracic or abdominal aorta. 2) Calcifications of all three arteries, including the thoracic, abdominal aorta, and the iliac artery, were significantly more frequent in women with calcification of the iliac artery, 14/16(87.5%) than in women with calcification of the thoracic aorta, 14/35(40%), or the abdominal aorta, 14/30(46.7%).(p<0.01). 3) The incidence of glucose intolerance and hypertention was not significantly different from that in women with arterial calcification to that in those without it. Mean age was significantly lower in women with arterial calcification than those without. Serum estradiol levels did not change from sixty to eighty years old in women. 4) These data indicate the possibility that the incidence of calcification of the iliac artery reflects the severity of arterial calcification, and that estrogen deficiency might accelerate arterial calcification in postmenopausal women.