Hansen's disease is caused by an infection with an intracellular pathogen, Mycobacterium leprae, which mainly inhabits macrophages and Schwann cells. However, little is known about the survival or growth mechanisms of the bacilli in mouse and human macrophages. In the present study, by using radiorespirometry analysis for the evaluation of the viability of M.leprae, we observed that in vitro incubation of M.leprae-infected macrophages at 35°C was more growth permissive than at 37°C, and supplementation with the immunosuppressive cytokine IL-10 supported the survival of the bacilli in the macrophages for 3 weeks, whereas viability of the bacilli was gradually lost if cultured without IL-10. In human macrophages, M.leprae retained its viability when cultured at 35°C for at least 4 weeks without IL-10. However, the viability of M.leprae was almost lost within 2 weeks if cultured at 37°C. These data suggest that temperature is a crucial factor for the survival of M.leprae in host cells.

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Due to the emergence of drug resistant M.leprae , there is a need to look for new drugs for the treatment of leprosy. We evaluated the effectiveness of new quinolones in vitro as well as in vivo. The in vitro and in vivo results suggested that a cyclopropyl group at the 1-position, COOH at the 3-position, OH at the 4-position, NH₂ or OH-substitutions at the 5-position, F at the 6-position, 5- and 6-membered rings at the 7-position, halogen (F or Cl) or OCH₃ at the 8-position of the quinolone core structure, remarkably enhance ant-M.leprae activities of the drug.

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The epidemiological situation of leprosy is reported by the health division of each country to WHO. The reported data is collected by WHO and is immediately run on the Weekly Epidemiological Record. On this latest edition, data from the beginning of 2008 was reported. In almost all of the highly endemic countries, control activities have been integrated within the general healthcare system. However, maintaining political interest and mobilizing the necessary funds to implement activities in the field are challenges for many national programmes as the burden of disease declines further.

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Average age of residents living in National sanatorium Hoshizuka-Keiaien where people have past history of Hansen disease is around 80 years old at present, and many of them spend their whole days in watching TV or sleeping almost alone in their rooms. Therefore music therapy was introduced in order to improve their daily activities in our sanatorium. Singing, listening to music, playing the musical instruments, and dancing were performed, either in a group or individually. Reactivation of their brain function such as recollection, sense of unity and relaxation were expected. Improvement of cardiopulmonary function was also expected. Solidarity and relaxed state were observed by being with the other participants in the group therapy. For example, when using musical instruments, some participants with hesitation tried to use their instruments, and had good performance. They seemed to be satisfied and became confident with the musical instruments. Then their confidence and satisfaction activated the group. After the sessions, mutual conversation increased. These processes obtained a synergy effect, which means that a group affects of individuals at first and next alteration of individual behavior influences the group. We could observe a better effect in their motivation and activity in their daily life in the individual therapy. The music therapy was applied to the senior participants by the music therapist in this study. The participants could easily reinforce their mind and body through this therapy. Music therapy will be continued for the improvement of quality of life of residents in the sanatorium.

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Nitric oxide (NO) produced by inducible NO synthase (iNOS) during infection plays a crucial role in host defense mechanisms, via its antimicrobial and cytoprotective activities. Infection of Salmonella typhimurium in mice induces excessive production of NO, as a host defense response. We found much greater bacterial growth and apoptotic changes in iNOS-deficient (iNOS^-/-) mice than in wild-type mice. However, the mechanism of NO-mediated cytoprotection during Salmonella infection remained unclear. An important signaling mechanism induced by NO is heme oxygenase (HO)-1, a significant cytoprotective molecule produced by oxidative stress. Thus, we sought to clarify NO-dependent cytoprotective and antimicrobial host defense, with a particular focus on the signaling mechanism of HO-1 induction. We recently discovered a nitrated cyclic nucleotide, 8-nitroguanosine 3',5'-cyclic monophosphate (8-nitro-cGMP), which is formed via NO possibly with reactive oxygen species. We observed strong immunoreactivity for 8-nitro-cGMP in Salmonella -infected wild-type mouse liver and peritoneal macrophages in culture but not in iNOS^-/- mouse liver and macrophages. Moreover, a higher apoptosis was observed in iNOS^-/- macrophages compared with wild-type macrophages after Salmonella infection, but the difference was nullified when iNOS^-/- cells were treated with 8-nitro-cGMP. Finally, authentic 8-nitro-cGMP induced HO-1 in cultured macrophages infected with Salmonella . The signaling function of 8-nitro-cGMP appears to be mediated by its unique reaction with the sulfhydryl group of cysteine, thus forming a protein- S-cGMP adduct, which is an important mechanism of post-translational modification of proteins called protein S-guanylation. More importantly, we found 8-nitro-cGMP-dependent S-guanylation of Keap1, a regulatory protein of transcription factor Nrf2, which regulates the transcription of HO-1. In this review, we focus on a unique mechanism of NO-mediated host defense via formation of a novel signaling molecule, 8-nitro-cGMP in microbial infections.

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Completion of Mycobacterium leprae genome sequence revealed that there are many pseudogenes and non-coding regions, but rather small numbers of protein-coding genes. Although it was thought that pseudogenes and non-coding regions were silent and junk, our previous studies indicated that RNA expression was detected from these regions. To elucidate comprehensive RNA expression pattern on M. leprae whole genome, tiling array was designed and total RNA of M. leprae Thai-53 strain was analyzed. As a result, highly expressed regions were detected among not only the gene regions but also pseudogenes and non-coding regions. Since some of the RNA expression levels were modulated by MDT, evaluation of RNA expression pattern might be a good indicator for the treatment of leprosy.

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Minamata disease (MD) was first recognized in May 1956. Its first recognized victims were 3 and 5 years old children. Environmental contamination most rapidly and seriously affected the physiologically and socially weak among the residents. Methylmercury (MeHg) had accumulated in fishes and shellfishes and those who ate them had been poisoning with it.MD is an indirect poisoning by MeHg through the food chain as a result of environmental contamination, and is the first known disease to cause abnormalities in the fetus due to a toxic substances passing through the placenta. In 1962 MeHg poisoning through the placenta was found for the first time in the world. It used to be considered that poisoning was caused by direct exposure to a toxic substance, and that toxic substances did not pass the placenta. MD had implications in various fields. Namely it also stirred up legal, ethical, and eugenic arguments concerning fetal protection. Also man thought about a man's worth.

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Completion of Mycobacterium leprae genome sequence revealed that there are many pseudogenes and non-coding regions, but rather small numbers of protein-coding genes. This result indicates that M. leprae is a very unique organism, and this future is important to understand the biological nature and/or pathogenicity of M. leprae , which remain unclear. We attempted to find the biological nature of M. leprae by detecting the gene and pseudogene regions transcribed at high level. We detected the genomic regions including pseudogenes and demonstrated that six out of twelve high expression regions were pseudogenes. In addition, its transcription level was changed when M. leprae infects macrophage. RNA was detected from genes, pseudogenes and non-coding regions. The expression levels of these regions were different among patients and a part of them is disappeared just after treatment. These results suggested that RNA derived from pseudogene and non-coding region have some function concerning the infection and/or intracellular parasitism and that the analysis of pseudogene and non-coding region expression pattern of M. leprae is available as a criterion for therapeutic effect and disease type of leprosy, and a prognostic marker.

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Recent advances in the molecular epidemiology of leprosy through genotyping of variable number tandem repeats (VNTRs) and single nucleotide polymorphisms (SNPs) are described. VNTRs with a broad range of diversity are useful genotyping tools for analyzing transmission in community areas, and SNPs and VNTRs with a small degree of variation are favorable for investigating the global transmission of leprosy. We expect that the transmission of leprosy can be fully analyzed by the application of these new methodologies.

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The Ninth meeting of the WHO Technical Advisory Group (TAG) on Leprosy Control was held in Cairo, Egypt on 6th and 7th March 2008. The meeting was chaired by Professor W.C.S. Smith and attended by national leprosy programme managers from Brazil, the Democratic Republic of Congo, Cambodia, Egypt, Iran, India, Nigeria and Thailand. In addition, several experts and members of the Technical Commission of the International Federation of Anti-Leprosy Associations (ILEP) also attended the meeting.

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