A β-blockade, propranolol, was found to reduce lipogenesis from glucose stimulated by insulin in mice, suggesting that it inhibited an insulin action in vivo. When nicomol was administered with the blockade, its inhibitory action on insulin was remarkably relieved. It was demonstrated that propranolol also inhibited insulin-stimulated lipogenesis from glucose in isolated fat cells. In contrast to the in vivo experiments, nicomol did not relieve the inhibitory action on insulin in the fat cell system. On the other hand, nicotinic acid, one of metabolites of nicomol, was found to reduce the inhibitory action of propranolol on insulin. Then experiments were carried out to clarify the effect of micomol and its metabolites on PGI₂ and TXA₂ formation in the platelet rich plasma-arterial ring system. Nicomol was found to elevate PGI₂ level and reduce TXA₂ level in this system. On the other hand, nicotinic acid did not affect both PGI₂ and TXA₂ formation. Nicotinamide, one of metabolites of nicomol, increase PGI₂ formation, but did not affect TXA₂ content. Based on these experimental results, clinical effects of nicomol were discussed.

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An acid stable phosphoprotein was formed as a reaction intermediate of Ca²⁺-dependent ATPase of bovine aortic microsomes. The Ca²⁺-dependence of phosphoprotein formation was not affected by the addition of diltiazem (10μg/ml), nifedipine (100ng/ml), vanadate (10μM), nicotinic acid (10μg/ml) or nicotinamide (10μg/ml). Nccomol increased the phosphoprotein level at 1μM Ca²⁺. The rate of phosphoprotein formation was not changed, but the rate of its decomposition was decreased by 65% in the presence of 10μg/ml of nicomol. A high activity (3.89unit/mg) of adenylate kinase in the mitochondrial fraction isolated from bovine aortic smooth muscle was observed. The adenylate kinase activity was not affected by nicomol (10μg/ml) and nicotinamide (10μg/ml), but it was stimulated by 158% by 10μg/ml of nicotinic acid.

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To assess the effects of nicomol, an ester derivative of nicotinic acid synthesized in Japan, on the lipoprotein abnormalities found in patients with ischemic heart disease, plasma lipoprotein fractions were ultracentrifugally separated and examined before and after three months administration of this drug in a dose of 1.2 grams a day.
The subjects examined were 8 survivors of myocardial infarction and 6 patients with angina pectoris. Each fraction of ultracentrifugally separated VLDL and LDL was mixed with heparin Ca solution and then filtered with a Millipore filter. Fractions retained on the filter were used for the determination of their chemical composition. The HDL₂ and HDL₃ subfractions were delipidated with tetramethylurea and then electrophoresed on a polyacrylamide gel. The densitometry of these electrophoretograms permited us to determine the proportion of contaminating albumin.
The plasma triglyceride level was significantly decreased, whereas the total cholesterol levels remained unchanged. VLDL-triglyceride concentration was significantly decreased. Percentage content of triglyceride was also significantly decreased but percentage contents of phospholipid and protein were significantly increased. The LDL level was almost unchanged. Either HDL-cholesterol level or HDL: LDL-cholesterol ratio was increased. Their increases were small but reached a statistically significant level. The HDL subfractions, HDL₂ and HDL₃-cholesterol levels were also increased. The increase of the former level was greater than that of the latter level, resulting in the slight increase of HDL₂ to HDL₃-cholesterol ratio. In the HDL₂ subfraction, percentage contents of phospholipid and triglyceride were decreased whereas the percentage content of protein was increased. The percentage content of cholesterol remained unchanged. The chemical composition of HDL₃ subfraction changed in almost the same way as that of HDL₂ subfraction. No significant side effects were observed.
It was clearly shown that nicomol administration considerably affected the lipoprotein profile in patients with ischemic heart disease. The level of VLDL was decreased in association with the significant elevation of the HDL, particularly HDL₂-cholesterol level. Therefore, the changes in the lipoprotein profile found in the present study seem beneficial for protecting against the atherosclerotic vascular disease.

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Recently, nonprescription switch OTC drugs have attracted a great deal of attention, and many such drugs are being developed. Among these drugs, ibuprofen is contained in many brands and various dosage forms on the market. Dissolution tests were performed for ibuprofen preparations both by the paddle (PD) method described in the Japanese Pharmacopoeia (JP) and by the rotating dialysis cell (RDC) method. Dissolution behavior tested by the RDC method more accurately represented pharmaceutical characteristics of these preparations than that when tested by the PD method.

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Isolated dog cardiac microsomes (CSR) showed Ca²⁺ uptake by adding ATP, which was measured with the optical density change of Arsenazo III (Ca²⁺-sensitive dye) using Hitachi dual wave length spectro photometer at 30°C. Maximal Ca²⁺-uptake (18.5±1.4nmol/mg) was attained at 1min after adding 0.1mM ATP to 1 mg/ml of CSR in the presence of 50μM Arsenazo III. This Ca²⁺-uptake was inhibited by 0.5mM Nicomol (about 39%) and Nicotinic Acid Amid (about 28%) but not by Nicotinic Acid. It was suggested that the Nicomol and Nicotinic Acid Amid possibly delay the cardiac muscle contraction and relaxation.

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Nicomol [2, 2, 6, 6-tetrakis (nicotinyloxymethyl)-cyclohexanol], a derivative of nicotinic acid, was given to 25 patients with hyperlipidemia of type II_a, II_b or IV at a level of 0.6-1.2g per day for 8-32 months. Facial flush, erythema and itching of the skin temporarily occurred as side effects in 11 patients. Lowering of the plasma cholesterol level more than 50mg/100ml was attained in 35-50% of the cases. Decreases in plasma triglyceride concentration were observed in almost all of the cases of type II_b and IV in which the triglyceride level before treatment was more than 150mg/100ml. However, in several cases in which the triglyceride level was previously normal, that is, in type II_a hyperlipidemia, plasma triglyceride showed a slight or moderate increase and there was a change in lipoprotein lectrophoretic pattern from type II_a to type II_b or IV.
In three cases of alcoholics (one female and two males) which presented type II_a or II_b hyperlipidemia before treatment, a sever hyperlipemia of type IV or V appeared during the course of the treatment. Prohibition of alcohol brought a prompt healing and the withdrawal of the drug also resulted in a recovery of plasma lipid level.

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The actual state of high density lipoprotein-cholesterol levels (in part, total cholesterol ratio) among rural inhabitants in Akita Prefecture is discussed in this report based on the findings of our extensive research work from basic statistics to experiments to improve the HDL-cholesterol level.
In the basic study, we checked up on errors in measuring HDL-C levels or instrumental errors. Variations during a day (before, after eating), daily variations (five consecutive days) and seasonal variations (spring, summer, winter) were also examined. In actual fact, errors of measurement were not found, but significant errors caused by measuring instruments (precipitation method) were observed. There is no variation during a day. Daily and seasonal variations were significant.
The mean value of HDL-C levels among 386 males examined was 57.5 mg/dl±14.7, while the mean value among 359 females was 55.2 mg/dl±14.0. A normal distribution with 50-59 mg/dl as the most commonly occurring values was shown in the frequency table for both sexes. By body build, obese persons, both male and female, showed significantly lower levels than the standard value.
Geographical variations did not make any significant difference in the HDL-C level. However, the levels for those who engage in hard labor were high.
By type of disease, the group of healthy, normal persons showed higher HDL-C levels than the groups of hypertension, cerebral apoplexy, hypercholesterolemia, hypertriglyceridemia, ischemic heart disease, liver ailment and anemia. There was no significant differential between the healthy normal group and the diabetes group.
Retinal and electrocardiographical findings revealed that the normal group has higher levels than the abnormal group. It was also found that the HDL-C level has positive correlation with GOT and negative correlation with the triglyceride value.
The HDL-C level was the highest among those who drink sake and do not smoke cigarettes, and the lowest among those who smoke but do not drink sake. The difference was significant. Linkings for coffee, juice and sweets did not affect the HDL-C level.
A study was made of the changes in HDL-C levels in relation to drug administration and exercise.
For eight weeks before administration, examinations were made to find changes in the HDL-C levels of healthy normal persons. However, their mean value did not fluctuate. Eight weeks after administration, it was found that the HDL-C levels of healthy, arteriosclerotic disease and hyperliPoproteinemia groups of persons rose significantly. Diabetics and cigarette smokers showed some improvement, thought not significantly.
Exercise was rope skipping. The subjects were asked to do the light physical activity for four minutes a day over a period of four weeks. The experiment brought about significant improvements in the HDL-C levels.

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