(1) Free and conjugated histamine in the human urine were measured by a modified McIntire's ion exchange method. (2) The urinary excretion of free histamine in normal adults, measured by this method, ranged from 0.8 to 1.5μg per hour. (3) Conjugated histamine excretion was usually variable and decreased by oral administration of chloramphenicol. It was suggested that under physiological conditions, in normal adults, most conjugated histamine excreted in the urine was produced as a result of bacterial activity in the intestine. On the contrary, free histamine excretion was remarkably constant for a given subject. Subcutaneous injection of 500μg of histamine chloride led to an excretion of about 6.5μg of free histamine. Probably urinary free histamine excretion reflects the intrinsic histamine metabolism. (4) Change of urinary free histamine excretion by thermal baths of the Ito Spa was observed. On the first day, the urinary free histamine excretion increased about 0.4μg per 2hrs. after a hot spring bathing (at 41-42°C for 10 minutes). After 8 days an increased excretion, which reached to about 8μg per day, was observed, and the increase by thermal bath almost disappeared after 22 days. (5) A similar but stronger change was observed by vapor bath, but no change was seen after a hot plain water bath (at 41°C or 37°C for 10 minutes). It was concluded that the effect of the natural thermal baths on histamine metabolism was caused not only by heat but by the chemical constituents in the spring water. (6) The free histamine excretion was increased about 0.8μg per 2hrs. by a cold plain water bath at 20°C for 10 minutes. (7) No significant change was observed by steam douche, ultrashort wave therapy. and ultrasound therapy. (8) A series of ultraviolet irradiations increased free histamine excretion in the urine. namely after 15 days.
In the previous paper the author proved a diurnal variation in the serum iron and copper. It was reported also that acetylcholine increased and adrenalin decreased both serum iron and copper. In the present paper effects of season, bathing, ultra-short wave diathermy, chlorpromazine, and prednisone were studied with following results: Chlorpromazine, 50mg daily given per orally in healthy adults, inhibited the diurnal variation in serum iron, but the inhibitory effect was not so evidently seen in serum copper. Seasonal variation was observed in the serum iron of healthy adults. Namely, serum iron level was higher in autumn and winter, and lower in summer, with an average difference of 17γ/100ml. Serum copper level also showed seasonal variation, being higher in winter and lower in summer, with an average difference of 10γ/100ml. Thermal bath in the Spa Ikaho (an iron and CO2 containing calcium sulfate water) at 42.5°C for 10min. showed no influence on serum iron. But Iwakiri proved with Fe59 a percutaneous absorption of iron into the body from the iron containing bath water. Therefore the effect of bathing in iron containing earthy water (Fe ion, 10.5mg/l) was investigated again, but no remarkable change either in serum iron or in serum copper was proved in the healthy adults. Administration of prednisone to healthy adults produced a transient decrease in serum iron, and a slight transient decrease in serum copper too. Bathing in plain water at 45°C and 20°C, for 5 minutes respectively, produced no change in the rabbit either in serum iron or in serum copper. In the 2nd week after injection of typhoid vaccine agglutinin titre in the rabbit serum attained a maximum, and thereafter declined gradually. Serum iron began to diminish with an increase of antibody titre, attaining a minimum in the 2nd week, and then increasing gradually with decrease in the immunebody titre. Namely, there was an inverse relation between serum iron and the antibody titre. Serum copper decreasad also with the increase in the immunebody, attaining a minimum in the 2nd week, then increased gradually but it showed a decrease once more in the 5th week. Thus no definite relation was established between the serum copper and antibody titre. When rabbits, pretreated with typhoid vaccine, were bathed in plain water at 45°C for 5 minutes, a transient increase in serum agglutinin titre together with a decrease in serum iron was observed, but no change in serum copper. The vaccinated rabbits were bathed in plain water daily at 45°C for 14 days. Then the transient increase in serum agglutinin titre after a bath became no more observed. Thus a series of hot baths for 14 days changed the mode of biological reaction observed in serum iron against a single bath. Application of ultra-short wave current to the liver and spleen region of the rabbits decreased serum iron transiently (-18γ/100ml), and tended to increase serum copper transiently. The same procedure, administered to the vaccinated rabbits, increased serum agglutinin titre and serum copper (+8γ/100ml), and decreased serum iron (-28γ/100ml) transiently.
The author investigated the effects of a series of various artificial and natural thermal baths (at 37°C for ten minutes every day during ten days) on the blood picture and fat index of liver in X-irradiated mice (130KV, 10mA, Cu 0.3mm, Al 0.5mm, Focus-Skin distance 40cm). Thermal waters which were tested were as follows: Artificial thermal waters: 1) plain water 2) 15mg/l H2S solution 3) 1g/l alum solution 4) 1g/l iron alum solution 5) normal saline (9g/l NaCl solution) 6) 1g/l NaCl solution 7) 1g/l NaHCO3 solution 8) 1g/l monazite suspension (artificial radioactive water) Natural thermal waters: 1) ASAMA Hot Spring (simple thermal spring) 2) AKAKURA Hot Spring (sodium chloride containing sulphur spring) 3) DOKUZAWA Mineral Spring (acid alum-vitriol spring) 4) TAKAHAMA Hot Spring (weak common salt spring) 5) IRIYAMABE Mineral Spring (earthy carbondioxated spring) 6) MASUTOMI Mineral spring (radioactive spring) A. Preventive effect of thermal baths against X-irradiation. Thermal baths for ten days were carried out prior to total body X-irradiation (50r per day for ten days) and the blood picture before and after the irradiation and fat index of the liver were examined. A marked preventive effect was revealed in the following groups: groups bathing in 1) plain water 2) 1g/l NaCl solution 3) 1g/l NaHCO3 solution 4) ASAMA Hot Spirng 5) TAKAHAMA Hot Spring. An unfavorable effect was revealed in the following groups: groups bathing in 1) normal saline 2) 15mg/l H2S solution 3) 1g/l alum solution 4) artificial radioactive water 5) AKAKURA Hot Spring 6) DOKUZAWA Mineral Spring. B. Therapeutic effect of thermal baths for X-irradiation. Total body X-irradiation (25r per day for ten days) were carried out and a series of ten days' thermal baths were started at the eleventh day after the last irradiation. The blood picture before and after the baths and fat index of the liver were examined. A marked therapeutic effect was recognized in the following groups: groups bathing in 1) plain water 2) 1g/l NaCl solution 3) ASAMA Hot Spring 4) TAKAHAMA Hot Spring. No favorable effect was proved in the group bathing in 15mg/l H2S solution and even injurious effect was revealed in the group bathing in the artificial radioactive water. With these results it is concluded that a favorable effect of thermal baths on X-irradiated mice may be expected when the thermal water contains no distinctive constituents or is mild in its biological action. Special constituents such as H2S and alum, or radioactivity have no favorable, and rather injurious effect.
Few attempts have been made to study the metabolism of vitamine B1 in spa treatment, though a large quantity of vitamine B1 is used in combination in balneotherapy of various diseases, especially neuritis, neuralgia and rheumatic diseases. A number of reports have been made by workers in our laboratory on the effects of hotspring bathing on the liver function, carbonhydrate metabolism and pituitary adrenocortical function. And a number of reports have also been made on the close association that exists between them and vitamine B1. Taking into account these reports, the author attempted to study the effect of hot-spring bathing on metabolism of vitamine B1 by performing experiments with healthy rabbits and then with healthy persons. By using fou, hot springs at Narugo Spa, examinations were made of the effects of single and successive bathing on quantity of blood vitamine B1 and on the quantity of vitamine B1 excreted in urine, and further study was made on the effect of hot-spring bathing on the injected or orally administered vitamine B1. Vitamine B1 was measured by means of Permutite-Thiochrom Flourescence method. The results obtained may be summarized as follows: 1) Blood vitamine B1 decreases immediately after hot-spring bathing, but gradually increases above the value before bathing, returning to the former value 60 to 90 minutes after bathing. Such variations are found to be greater in hot-spring bathing than in fresh-water bathing, especially so in hot springs strong in stimulation. 2) Such variations in blood vitamine B1 as observable in single bathing show gradual decrease by successive bathings, consequently, a gradual decrease in the difference among individuals and in the nature of hot springs. 3) The greater effect of hot-spring bathing can be seen in the case of intracutaneous injection or oral administration of vitamine B1 than in the case of no bathing in an increase of blood vitamine B1. 4) The effect of hot-spring bathing on the quantity of B1 excreted in urine during 3 hours after administration of vitamine B1 is irregular either in increase or decrease, but successive bathings show decrease in vitamine B1 in all cases. 5) It is seen from these experimental results that hot-spring bathing, especially successive bathings, is favorable to the metabolism of vitamine B1 in the body. In particular, it increases the utility of B1. 6) It is difficult to reach any conclusion as to the mechanism of the effect of hot-spring bathing on the metabolism of vitamine B1, but an influence can be made from the author's study as well as from a series of studies made in the laboratory of which the author is a member that the controlling action of the function of autonomic nervous system due to unspecific stimuli of hot-spring bathing and the vitalizing stimulation of the liver function and pituitary adrenocortical function due to hot-spring bathing play important parts in them.
One of the difficult problems that practioners come across daily in their work is how to deal with bathing or hot-spring bathing for tuberculous patients. Hardly any literature has been found on hot-spring bathing for tuberculous patients, though we find a number of reports dealing with climatic factors and tuberculosis. In order to meet in part the requirement of medical circles, a systematic research has been in progress at our balneological institute to study (1) whether tuberculous patients shall be prohibited from bathing in hot springs or not; (2) if hot-spring bathing is not always necessarily prohibitive, where the line of demarcation between indication and contraindication of hot-spring bathing should be drawn; (3) the basis on which prohibition or permissibility is to be made; (4) whether there is probability where favorable effect on tuberculosis will be observable or not. In the present paper, the author gives report on the results obtained until now. Classification of pulmonary tuberculosis is based on that of the American Preventive Association for Tuberculosis published in 1953. The results obtained may be summarized as follows: 1) As far as the changes in clinical conditions are concerned, no unfavorable effect was detectable from hot-spring bathing twice a week or every other day in the medium T. B. slight T. B. group; favorable effect may rather be expected. In the group, temporary variations in the value of blood sedimentation rate were observed, but no unfavorable effect was detectable. In the advanced T. B. group, there were some cases where unfavorable effect was observed, showing that they should he cautious of hot-spring bathing. 2) Tuherculous patients showed greater variations in the changes in body temperature, pulse. respiration, vital capacity, body weight and Donaggio value caused by hot-spring bathing than healthy persons. These variations are proportional to aggravation of tuberculosis and the time required for the restoration to the conditions before bathing is also proportional to aggravation of the disease. 3) These variations caused by hot-spring bathing will be smaller through the administration of successive hot-spring bathing. This may he interpreted as being an adaptation phenomenon of human body to stimulation caused by hot-spring bathing. 4) The decrease in blood glutathione (reduced form) and blood catalase caused by hot-spring bathing will be great in proportion to the exacerbation of disease, and the restoration to the values before bathing will be slower. Similar to the various reactions mentioned above, defects can be seen in the adaptation phenomenon observable in bathing cure. 5) The basal metabolic value of tuherculous persons are generally higher than that of healthy persons. The increase in basal metabolic value after bathing in the slight T. B. group is about the same as that of healthy persons, but in some of the group of secondary grade and in the group of advanced grade it is remarkable and the restoration to the value before bathing is slower. 6) These experiments show that the adaptation phenomenon to stimulation induced by hot-spring bathing is approximately proportional to the degree of changes in tuberculosis; that is, the more aggravated the disease is, the greater is the defect in the adaptation phenomenon to stimulation caused by hot-spring bathing, and clinical observation shows that unfavorable effects of hot-spring bathing are frequently seen in those who have such defects. 7) Consequently, observations of these variations in the reactions both before and after bathing and determination of the adaptation faculty by examining their changes in bathing cure will he good guide in deciding whether tuherculous patients should have hot-spring bathing or not. 8) Generally speaking, hot-spring bathing once or twice a week, or every other day has no unfavorable effect on the slight T. B. group; instead, some favorable effects may he expec
The total serum lipids and lipoproteins were studied with turbidimetry and paper electrophoresis. 1) In 31 patients with hypertension, the β/α lipoprotein ratio was significantly higher than in the healthy control persons (average of the total lipids 563±182mg/dl, average of the lipoprotein ratio 2.2±0.4). 2) The total lipids and lipoprotein ratio in 43 patients with apparent arteriosclerosis were examined and they were also higher than those in the healthy controls (average of total lipids 691±178mg/dl, average of the lipoprotein ratio 2.5±0.4). 3) No signifcant difference was observed between the average total lipids and lipoprotein ratio in the healthy controls and those in the patients with rheumatoid arthritis. The total serum lipids in rheumatoid arthritis decreased in the Stage II as compared with the level in the Stage I, but the, β/α lipoprotein ratio showed a gradual increase after the Stage II. From 1 to 3 years after the onset of the disease, the total lipids level proved to be comparatively lower. No definitely abnormal values were found in other collagen diseases and Behçet's disease. 4) Intravenous administration of ACTH (20mg) in 6 patients resulted in no significant change of the total lipids and lipoproteins, but prolonged per oral use of Prednisolone (10-20mg daily for 3 weeks) had a tendency to increase them. Prolonged use of Ca-pantothenate produced a tendency to decrease the total lipids and lipoprotein ratio in hypertensive subjects. Chondroitin sulfate showed also a decreasing effect on the total serum lipids, but on the lipoprotein ratio clinically. 5) In cholesterol fed animals a tendency to decrease serum lipids was proved with sulfated polysaccharides such as chondroitin sulfate, glucosamin monosulfate, and Carrageeninsubstances. But the effects of the latter two were insignificant. 6) In 8 patients no significant difference was observed in the total lipids and lipoprotein ratio between before and after a full immersion plain water bath at 39°C for 15 min. After a cabinet vapour bath at 45°C for 15 min.. the total lipids and lipoprotein ratio of 13 patients significantly decreased as compared with intial values. 7) No significant difference was observed in the total lipids and lipoproteinratio in 7 healthy subjects between before and after an ultraviolet radiation (I. S. E. D.). 8) At Spa Kusazu (a strongly acid spring containing H2S), a significant decrease of total lipids and lipoprotein ratio was shown in 16 patients after a series of daily baths at 46°C for 5 min. for a week. Saito and his co-workers proved also an elevation of PBI and increases in the sensitivity against insulin, and in urinary excretion of estrogen, 17 KS and 17 OHCS in the early stage of the spa treatment in Kusazu. 9) At Spa Kageyu (a simple thermal spring), a significant decrease of the total lipids was shown in 15 patients after a series of daily baths at 39°C for 20 min. for a week. But after two weeks serum lipids returned to the normal levels.
In the previous paper the author reported that the serum cholesterol values of patients taking “Time Limit Bath” treatment in Kusazu Hot Springs decreased in about a week after the start of serial bathings, kept on low till the end of the second week, and tended to rise again in the third week. This was interpreted as a process of adaptation to the spa treattment. In the present report the same phenomenon was studied by means of animal experiment. 1) Eight mature male rabbits were divided into two groups. The first group was used for control, and the second was bathed in Kusazu Hot Spring at 47°C for three minutes, twice a day for four days. On the fifth day they were sacrificed and the cholesterol content of the left adrenal was measured by Sperry-Webb's method. While ascorbic acid content was measured in the right adrenal. It was revealed that in the second group both cholesterol and ascorbic acid contents were found lower than in the control group. Significant was the difference in the total cholesterol amount. 2) Twenty-seven mature male rabbits were divided into five groups. The first group with five rabbits was used as control. Seven rabbits of the second group were bathed once everyday in tap water at 36°C for twenty minutes, this group being called “Tap Water (Bathed) Group”. Five rabbits of the third group were bathed in the hot spring at 36°C for twenty minutes once everyday, this group being called “Hot Spring (Bathed) Croup”. Four rabbits of the fourth group were given 10c. c. of fresh water per Kg of body weight per orally with stomach tube and were called “Fresh Water Drinking Group”. Six rabbits of the fifth group were given thermal water, diluted in equal amount by fresh water, in the same way as with the fourth group, and were called “Thermal Water Drinking Group”. All the rabbits of the five groups were given 0.1g/kg of Cholesterol with basal diet. Their serum cholesterol values were measured by Sperry-Webb's method before starting the experiment and then every tenth day. This experiment was continued for sixty days. No significant difference was noted in the serum cholesterol values between Hot Spring Bathed Group and control group. But in Tap Water Bathed Group and in Thermal Water Drinking Group an apparent tendency to suppress hypercholesterolemia was seen compared with the control group. In Fresh Water Drinking Group a slight hypercholesterolemia suppressing effect was noted till about the thirtieth day, but after the fortieth day serum cholesterol reached the level of the control group, and after the sixtieth day it went beyond that of the control group. Histological investigation revealed that atherosclerotic changes were most markedly proved in the control group, followed by Fresh Water Drinking Group, Hot Spring Bathed group, less in Tap Water Bathed Group and Theremal Water Drinking Group. As a whole the serum cholesterol values and the atherosclerosis-grades ran parallel with each other. 3) a) Nineteen mature male rabbits were divided into four groups. Two rabbits of the first group were bathed in the natural hot spring. Eight rabbits of the second group were bathed in sodium sulphate solution. Four rabbits of the third group were bathed in sodium sulphate+chloride solution. And five rabbits of the fourth group were bathed in sodium sulphate+silicate solution. These solutions were of same ionic concentration as in the natural hot spring water. All the rabbits of the four groups were bathed at 36°C for twenty minutes every day. And all the rabbits were given cholesterol in the same way as in the last experiment. Their serum cholesterol values were measured every tenth day, and killed on the sixty first day to examine atherosclerotic changes in the aorta. Average serum cholesterol values in the sodium sulphate+silicate water bathed group proved lower than in the natural hot spring water bathed group. There was no mar