下部尿路における治療其他の薬物溶液の吸收に関する実験的研究(第IX篇) : 膀胱における各濃度硫酸マグネシウム溶液の吸收(態度)に関する生化学的研究
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Since the urinary bladder is an organ provided with an extensive mucous membrane as its important structure, numerous investigators have utilized it for a long time in the study of the absorption of water and various therapeutic solutions. Such a situation has naturally stimulated many others to investigate in real earnestness the problems related to the absorptive function of the bladder. However, the conclusions derived from these studies are far from being unanimous and much controversy still exists in the literature. It has often been presumed that the absorptive function of the bladder is selective in nature, since this organ behaves differently depending upon the nature of the drug solutions under investigation. The early workers proposed the positive absorption theory, which, however, was later denied, although again today the absorption is considered to be entirely possible. For this reason, we have been engaged in experimental studies employing many kinds of drug solutions and endeavored to elucidate the basic theory of absorption on the basis of the data we have obtained. For preliminary investigations, we have made observations on 19 varieties of drugs, and discovered 8 of these to be absorbed, 8 to be rather attended by exudation, while the remainder to be entirely indifferent. Subsequently, biochemical as well as histological investigations in detail have been carried out on silver nitrate solution, protein silver solution, saline solutions of different concentration and sugar solution by Oi (1952), Sahako (1954), Sasaki (1955), Morishima (1955) and Goto (1955). The results of these studies indicate positive absorption of the solutions in comparatively large amounts in accordance to certain definite rules. The author has devised a series of experiments by attempting to approach the problem in a somewhat reversed manner by using solutions of magnesium sulfate, a drug which is generally considered to be absorbed with difficulty through the mucous membrane. The method consisted of isolating the bladders of rabbits weighing over 2kg, and 20cc each of magnesium sulfate solutions prepared to represent concentrations of 0.5, 1.0, 2.0, 5.0 and 10.0 per cent were introduced into these organs. The content of each bladder was collected at intervals of 30 minutes, 1, 2, 4, 6, 12 and 24 hours afterwards and examined as to quantitative changes as well as biochemical fluctuations of the actual amount of magnesium (Mg). The disapearance rate of Mg from the bladder content was followed by the new Sobel's method which was also utilized for the determination of this element in the serum. A total of 84 rabbits was used in these experiments and the results are shown in 7 tables and 18 figures. Since the isotonic zone of magnesium sulfate solution in the bladder is presumed to lie in the neighborhood of 2.0 per cent, the higher limit of concentration of the test solution was set at 5.0〜10.0 per cent, and the lower at 0.5〜1.0 per cent. With solutions of lower concentration the absorption of Mg takes place, and it is most active in 4〜6 hours. The fluctuations of Mg are relatively slight with solutions approaching isotonicity, the three curves for the quantity, Mg content and its concentration describing almost parallel gradients. The amount of water shows a slight increase in about 2 hours, but Mg is clearly absorbed from the beginning, the 24 hour averages being approximately 20.3mg against the initial value of 40 mg. However, since water absorption occurs simultaneously, the calculated concentration for magnesium sulfate is 1.156 per cent. This means that the bladder either absorbs or excretes water and Mg in a highly sensitive manner for a given stretch of time in order to bring the concentration of the injected solution to the isotonic zone. This phenomenon is most marked with the high as well as the low concentration of the test solution, while it is least apparent with isotonic solutions. The results of observations made at 2〜4 hours, at which these reactions are seen to occur most vigorously, may be summarized as follows: With 0.5 per cent solution the average value of water content at 2 hours was 18.0cc (10% decrease), at 4 hours 15.5 cc (22.5% decrease), while with 1.0 per cent solution the 4 hour average value was 16.0 cc (20% decrease). With 2.0 per cent solution the 2-hour average value was 19.7 cc (only 1.5% decrease), but at 4 hour's it was 16.0 (20% decrease). With 2.0 per cent solution, however, there was a slight exudation at 2 hours and no appreciable changes were noted thereafter. On the contrary, with 5.0 per cent solution the 2-hour average value was 23.5 cc (17.5% increase), and at 4 hours it was 22.5 cc (12.5% increase). The exudation phenomenon was observed to a most remarkable degree with 10.0 per cent solution, the values being 27.0 cc (35% increase) and 27.5 cc (35.5% increase) at 2 and 4 hours respectively. The Mg content of the exudate fluid showed almost constant decrease, indicating absorption of this element with the lapse of time. The 2-hour average values were 7.6 mg (24.4% decrease), 17.5mg (12.5% decrease), 31.0mg (22.5% decrease), 88.25mg (11.7% decrease) and 145.6mg (27.2% decrease) with 0.5, 1.0, 2.0, 5.0 and 10.0 per cent solutions respectively. Likewise, at 4 hours the average values of Mg content were 6.3mg (37% decrease), 14.5mg (27.5% decrease), 32.0mg (20% decrease), 68.5mg(31.5% decrease) and 118.1 mg (40.75% decrease) with 0.5, 1.0, 2.0, 5.0 and 10.0 per cent solutions respectively. At 24 hours the values indicated marked decrease in each instance. Looking at the calculated magnesium sulfate concentration in the exudate at the final examination (24 hours), there is noted slight dilution in each of the solutions, namely, 0.304%, 0.592%, 1.156%. 2.052% and 2.250% with 0.5, 1.0, 5.0 and 10.0 per cent solutions respectively. These results indicate that absorption of magnesium sulfate did take place, the amount absorbed being in direct proportion to its concentration in the solution. Thus, at 24 hours, the intravesical concentration (injection tests of various concentration) appears to lie in the range of 0.304〜2.250%. When compared with the results reported in previously published experimental data using saline and sugar solutions, the range with the former lies between 0.92 and 0.59%, while with the latter between 2.74 and 0.461%. These findings clearly indicate that the range curves for saline solution lie in the narrow zone, followed by these of sugar solutions, while the magnesium sulfate solutions occupies the two outer zones. The difference among the range curves of all these solutions appears to be related to the isotonicity of each drug solution in the bladder, its pharmacological property and the amount and distribution in the body. Furthermore, there seems to be a definite interrelationship between the fluctuations of magnesium sulfate solution introduced into the bladder and its concentration in the serum. In conclusion, it may be stated that magnesium sulfate solution, hitherto considered to be absorbed with difficulty through the bladder wall, has been found to show good absorbability in the present absorption experiments, this explaining the increased value of this drug in the serum. However, it is necessary to note that the range of absorption curves lies slightly outside those of saline and sugar solutions. This slight difference is thought to represent the peculiar property of magnesium sulfate solution.
- 社団法人日本泌尿器科学会の論文
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