Since the discovery of antileprotic agents like "Promin" interest has been stimulated in the study of other antibiotics and synthetic compounds (sulfone and thiourea derivertives) in regard to their antileprotic activity. Studies of the synthesis and antibacterial action of the new compound were made, has been published in "Studies on antileprotic agents, report No. 3".*
Structure of the compound is as follows and the term of this compound will given as "Thiozamin" in this paper.
NH2- -SO2 - -CH=N NH CS NH2
The present auther has accordingly examined on the pharmacological actions of Thiozamin and has got the following results.
1. The suspension of Thiozamin was administered subcutaneously to mice. LD50……1705.5mg/kg=
2. No hemolytic action.
3. No change of respiratory action and blood pressure even with such a large dose.
4. Actions on the intestine of the rabbit caused spasmogenic activity in very little dose and decreased in the tone of intestine were used large.
From the results described above, it will be possible to the drug for a treatment of leprosy.

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By the end of World War II, a specific disease, which might have existed in the past, yet was not known to the public, was found in the down-stream basin of the Pa-Chang River on the south west coast of Taiwan. The disease was found to cause gangrene of the extremities, especially the foot, and mutila-tion, and was called the "black-foot" disease by the local people, though it could probably be arsenical gangrene by nature. This disease has been feared by the people for, once infected, patients suffer as much as the lepers. In fact, several clinical symptoms of this specific disease, such as red swelling of toes and fingers, the initial stage of paresthesia, breaking of fingers and toes, the later stage of mutilation, resemble some symptoms of leprosy. Therefore, the dif-ferential diagnosis of this "black-foot" disease in the course of the diagnosis of leprosy has become quite necessary in this country. Since few health workers in the field of leprosy control in this country have encountered this disease, it is helpful to describe the similarity and differences of these two diseases for reference.
1. Paralysis and gangrene found in black-foot disease patients are caused by long-term intake of arsene with a result in changes primarily in the blood system, such as intimal arteritis, particularly capillar sclerosis, obliterans, and even thrombosis. Peripheral nerves are injured to cause peripheral multiple neuritis, and therefore paralysis. The trophic nerves are then injured, and the deep tissue therefore becomes necrotic, resulting in gangrene and mutilation
2. Leprosy is the only bacillary infection which attacks the peripheral nerves. Paresthesia occurs naturally. The Mycobacterium leprae parasitizes and multiplies in the small arteria, the round cells are then infiltrated, and the con-nective tissue becomes thicker. As a result, the arterial lumen becomes nar-rower, and macula circumscripta and paralysis occur. The severity and the frequency of the red-swelling of fingers and toes in leprosy are less than seen in Black foot disease.
3. Although these two diseases are caused by different agents, their local symptoms, such as the red-swelling of fingers and toes, numbness, cold feeling, contraction of fingers and toes, dwindle and remnant of nails, are similar.
4. While anhidrosis is found in the leprosy patients, hyperidrosis is found in the black-foot disease patients,
5. Other symptomatological, and bacteriological findings mentioned in this article can be of reference to the differential diagnosis of these two diseases. In one word, there is neither superficial nerve hypertrophy, nor leprotic erup-tion in the black-foot disease. At the ulcerous lesions, hyperesthesia instead of anesthesia occurs. Since the black-foot disease is a nonbacillary disease, no acid-fast bacilli can be found.
6. It was found in this study that the increase of arsenical content in water in these areas might probably have something to do with earthquakes.
Acknowledgement: This work was aided by grants from the Natioual Council on Science Development of the Republic of China.

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The in vitro cultivation of the murine leprosy bacillus is being investigated from the aspect of the energy production mechanism and it has been shown that electron transmission system stops at the stage of reduced flavin due to the absence of the cytochrome system. Under such a condition, it would be impossible for the murine leprosy bacillus to grow in vitro. Since the organisms have an enzyme, which promotes production of ATP by accepting a high energy phosphate from polyphosphate, the elongation of the murine leprosy bacillus without increase in number in Hart-Valentine medium, may be explained by a using up of the polyphosphate in the cell. Since the Douglas strain of murine leprosy bacillus was not used, this cannot accurately be considered a reinvestigation but an elongation equal to that reported by Hart & Valentine was not found using the Hawaiian strain. The marked elongation may be due to a difference in method of collection and the condition of the murine leproma. This, however, should not be considered a constant phenomenon and it was impossible to investigate factors essential for energy production or growth by using this phenomenon as an index. Table 1 and Fig. 1 show the average length, RNA, DNA, hydrolyzed inorganic phosphate, free inorganic phosphate and optical density at 260 mμ from 0 to 8 weeks. A slight elongation of the organism is apparent but since the same organism was not followed, it is not clear whether an actual elongation had taken place or short cells had disappeared by autolysis and only one remained. The RNA level showed no change up to 2 weeks but a rapid decrease took place thereafter and a course toward destruction was taken. DNA is relatively stable but there is a gradual decrease. Up to 5 weeks, there is a difference between the hydrolyzed inorganic phosphate and the free inorganic phosphate but after 7 weeks, this difference is no longer apparent. This finding suggests that high energy phosphate is present in the cell up to 5 weeks but is depleted after 7 weeks and a poor condition for survival occurs. Sucrose is one of the constituents in the Hart-Valentine medium and if this aids in the elongation of the murine leprosy bacillus, it may have to be restudied. The cell lysis of the protoplast or spheroplast of other bacteria is prevented by the addition of 20% sucrose to the medium. The cellular components of the murine leprosy bacillus may leak out if biosynthesis in the cell wall dose not parallel the in vitro elongation and fissures occur in the cell wall in medium lacking sucrose. This is an intersting problem in the light of Johne bacillus which is difficult to cultivate in artificial synthetic media. Difco (Bacto) casamino acids and asparagine are used as the nitrogen source in the Hart-Valentine medium but if this medium is utilized for supplying amino acids, casamino acids do not contain tryptophan and tryptophan must be added separately. If it is the aim to supply the materials for biosynthesis of the cell wall, DNA and RNA, bouillion which contains polysaccharides, lipids, purine and pyrimidine derivatives would be much more advantageous.

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When leprolin antigen is injected repeatedly into BCG sensitized guinea pigs, the leprolin reaction relatively easily becomes negative although the tuberculin reaction is not affected. When viable peritoneal cells of the tuberculin positive-leprolin negative guinea pig, sensitized with BCG, are transplanted to the normal guinea pig, the recipient showed negative leprolin and positive tuberculin reactions.
Furthermore, both tuberculin and leprolin reactions in the BCG sensitized guinea pig, repeatedly desensitized with tuberculin antigen, gradually subsided, and positive tuberculin and leprolin reaction was not induced in the recipient guinea pig by the passive peritoneal cell transfer from the guinea pig which had been desensitized with tuberculin.
The above mentioned and previously reported finding that the inactivation of common reacting factors, corresponding to tuberculin and leprolin antigens, occurs as a result of the combination of the peritoneal cells of guinea pig, either sensitized and non-sensitized with BCG, with leprolin antigen in vitro. These experimental findings may offer a clue for the difficulty in sensitizing the guinea pig with human leprosy bacilli.

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Leprosy infection in married couple is relative rare and of about 6000 patients in the Tama Zenshoen Leprosarium, 20 cases (0.33%) has been observed. The husband was the source of infection in 12 of the 20 cases (60%) and the wife in 8 cases (40%); the wife being infected in 60% and the husband in 40%.
The type of infection in the source was lepromatous (L) for the most part and 1 case of the tuberculoid (T) type, and moderate to severe in degree. In those that had become infected, the (T) type was predominant with 14 (70%) and there were 6 cases (30%) of the (L) type. Compared to the ratio of (T) 33.5% and (L) 66.5% among all the cases in the leprosarium, these findings are worthy of note. The predominance of the (T) type may be due to early dis-covery before progression to (L), greater resistance in the adult, less sensitivity or other factors but further study is required.

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