1) The clinical effects of citicoline on apoplectic patients with long standing, fixed symptoms were evaluated by means of double-blind, cross-over methods and the difference in effects between citicoline and placebo were statistically examined by technique of sequential analysis. 2) The determination of orders of administration and selection of 10 out of 40 subjects were according to the randomized number table, while both orders of administration were planned to be equalized. 3) Activity of daily living (ADL), general improvement rating (GIR) and global comparative judgement (GCJ) were employed as criteria for the evaluation of symptoms and assesment of preferences. 4) The effect of citicoline on motor paralyses, especially rigidity of muscles and contracture of joints, was significantly better than that of placebo by assesment of either ADL, GIR or GCJ. 5) Neither abnormalities in laboratory tests nor subjective side effects were observed. 6) From these results, citicoline was evaluated to be significantly effective against motor paralyses, one of the main symptoms of post cerebral apoplexy.
The purpose of this study is to evaluate “nail bed capillary examination” for the control of hypertension and arteriosclerosis. The morphologic findings of the capillaries were investigated in these diseases and correlated with their blood pressure levels and ocular fundus camera findings. Subjects and method: The subjects were 623 cases, from 40 to 90 years, in Asahi Town, Aichi prefecture, and 401 high school students, from 16 to 17 years. in Nagoya city Japan. The subjects in the town were thoroughly checked up on their cerebro-and cardio-cvasular function, and students had the blood pressure measurement and physical examinations. Nail bed capillaries and micrometer were photographed through microscope with magnification of 40× and 60×, and the enlarged prints were made for measurement and classification. Average A/V ratio, average ratio of the width of the arterial limb to the venous limb, were calculated in each picture. All the pictures were classified into one of the ten types bases on their dominant pattern which exceeded 50 per cent in the field, but some pictures which contain several patterns in a field without predominance were classified as o-type. On the other hand, the frequencies of the person with the specific rare patterns were calculated. Ocular fundus findings were classified according to Keith-Wagener's classification system. Results: The straight hairpin-like shape of the capillary pattern was the most frequent in the students and the residents under 50 years, but it became significantly less frequent with advancing age. The frequency of the twisted capillary pattern was very low in the students, but in the residents over 40 years it became significantly high with advancing age. The capillary pattern which showed marked bendings without twist or torsion was found more frequently in the students than in the residents over 40 years. The pictures with various kinds of capillary patterns were more frequently seen in the residents over 40 years than in the students and significantly increased with advancing age. In the students, the pictures with various kinds of capillary patterns. A/V ratio of 1/2 or less and appearance of subpapillary plexus were significantly more frequent in the hypertensives than in the normotensives. In the residents over 40 years, the pictures which had the dominant pattern with twist or torsion, A/V ratio of 2/3 or less and appearance of sub-papillary plexus were significantly more frequent in the hypertensives than in the normotensives. Normal ocular fundus findings were frequent in the subjects with the dominant pattern of straight hairpin-like shape. Ocular fundus abnormalities were frequent in the subjects whose pictures had the dominant pattern with transformations, especially with twist or torsion and Grade II or more advanced changes were also highly frequent in this group. In the subjects with ocular fundus abnormality, A/V ratio of 2/3 or less and recognition of sub-papillary plexus were also more frequent, and there was a tendency that A/V ratio of nail bed capillary became smaller with advance of ocular fundus abnormality.
Recently, investigators in the fields of basic and clinical medicine have begun to place more emphasis on the studies of arteriosclerosis. In view of this, we investigated the lipid metabolism, blood coagulation, fibrinolytic system, and platelet system in various arteriosclerotic diseases (diabetes, cardiac infarction, encephalomalacia, etc.) from clinical aspects. Simultaneously, using Dextran sulfate, antilipemic agent, we studied fluctuation of lipids, and changes in the blood coagulation, fibrinolytic system, and platelet system in various arteriosclerotic diseases showing hyperlipemia. In this investigation we made comparative study on individual lipid fractions from such group with hyperlipemia and corresponding individual fractions from those with normal lipid-blood level, as well as the coagulation-fibrinolytic systems. As a result, it was found that the total lipid contents, cholesterol, triglyceride, and phospholipids as revealed by the screening tests of the coagulation system and the fibrinolytic system in these diseases, proved to be identically the same. However, by individual estimations of coagulations factor of the total lipids, TGT, in comparing the hyperlipemic group with normal lipid-blood group, the former group had more marked activities of Factor II and Factor V, BaSO4-adsorbed plasma factor and serum factor. In other words, among these arteriosclerotic patients the group showing hyperlipemia had accelerated coagulability of blood as compared with those having normal lipid-blood level. As for the platelet system, factor-3 and adhesiveness are also enhanced in the group with hyperlipemia. In the application of Dextran sulfate (MDS) to the group of hyperlipemia for its effect on the coagulation system, it has been found that there is prolongation of r and k by TEG, and shortening of ma. i.e. an inhibitory effect on the blood coagulation system. Especially noteworthy is the fact that the fall in the blood cholesterol level parallels with the inhibitory effect of MDS on the coagulation system. With respect to the coagulation factors, activities of F-V, F-VII and the platelt factor-3 are decreased.
In order to examine aminoacid metabolism in osteoporosis, oral amino acid loading tests were performed in 7 normal old men, 11 severely osteoporotic and 5 mildly osteoporotic patients. All subjects were free of other important diseases including liver or renal disorders. When the ratio of vertebral density to disc density in the lateral tomogram of the lumbar spine was less than 1.0, the patients were considered osteoporotic. Presence of compression fracture indicated “severe” osteoporosis, while the absence spoke for “mild” osteoporosis. Fasted subjects were orally loaded with amino acid mixtures in an amount corresponding to the body weight. Blood samples were drawn before and 1, 2, 3 and 4 hours after the loading. One ml of serum specimen was subjected to gaschromatographic analysis of amino acids. Although the fasting levels of serum valine were not different between the normal and osteoporotic subjects (63±7.7γ/ml and 76±8.0), the one-hour (151±9.0 and 215±21.3) and four-hour levels (139±8.7 and 178±16.3) were significantly higher in the severely osteoporotic subjects. The peak value of serum valine was also shown to be significantly higher in the severely osteoporotic group (normals 192±9.5, osteoporotics, 263±24.6). Mild osteoporotics gave intermediate values. As for leucine and phenylalanine levels, no difference was noted between the groups. Since valine is most rapidly absorbed from the gastrointestinal tract and most slowly metabolized in the liver among various amino acids, the behavior of valine might serve as a sensitive detector of abnormal amino acid metabolism, especially in demonstrating the difference between normals and osteoporotics.
Thyrocalcitonin (TCT) is the hormone that lowers blood calcium by inhibiting bone resorption. Effect of TCT on protein and amino acid metabolism was studied in the light of the proposed effect of TCT in the treatment of osteoporosis. Male Wistar rats were subcutaneously injected with 50mMRC units of TCT daily for three weeks, at the end of which part of the animals were sacrificed in groups at one-hour interval over four hours for obtaining blood speciments. Femurs were removed from animals without valine-loading to measure relative cortical thickness in the Softex films. The femurs were cleaned of soft tissues and bone marrow, dried, decalcified and hydrolysed. The hydroysates were analysed for amino acids with gaschromatography. In the curves of valine loading no difference was demonstrated between TCT-treated and control groups. Relative cortical thickness was greater in TCT-treated rats (27±0.6% (16)) than in the control group (25±0.4 (13)). Among the amino acids of the metaphyses which were measurable with the method employed, i. e., alanine, glycine, valine, leucine, hydroxyproline, aspartic acids and phenylalanine, only phenylalanine increased significantly in TCT-treated group (10±0.6μg/mg dry weight (5)) as compared with the controls (7±0.6 (5)). Non-fasted and fasted rats were intravenously injected with 5 or 20mMRC units of TCT and venous blood specimens were obtained to be analysed for amino acids 1 hour later. In non-fasted rats, injection of 20mMRC units of TCT caused a significant depression of plasma levels of alanine (control 135±17g/ml (5), TCT-injected 74±16 (5)), glycine (116±17 and 53±7), leucine (65±16 and 25 5), and phenylalanine (25±1 and 19±2), while 5 mMRC units caused a significant decrease of only phenylalanine (20±1 (5)). At fasting, no significant difference in plasma amino acids was noted between the TCT-injected and control groups. The action of TCT to lower the concentration of some plasma amino acids and to raise the concentration of phenylalanine in the bone might suggest the possibility that TCT is not only involved in calcium metabolism, but also affects protein and amino acid metabolism in the bone.
The incidence of cardiovascular complications of diabetes mellitus was studied for four groups as defined based on blood glucose level, a) advanced diabetes (525 cases), b) mild (318 cases), c) borderline (362 cases) and d) normal (313 subjects). The association with hypertension was much more frequent in diabetic groups than in a normal group, the incidence increasing as blood glucose level elevated. It was found that the rate of retinal arteriosclerosis on SCHEIE's classification was highest in advanced rgoup patient, as well as in the hypertensive and aged. This finding was likewise reflected in proteinuria. Abnormalities in PSP test and renal clearance test seemed to be less dependent on disturbed carbohydrate metabolism than hypertension and aging. Hypertension was responsible but not elevated blood sugar level for abnormal ECG. In Japanese diabetics, unlike Western-type diabetics, hypertension and proteinuria were closely associated, and hypertension and aging seemed to have more influence than diabetes itself on the development of arteriosclerotic changes in the heart, the kidney and the retina.