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Spasticity is characterized by increased muscle resistance. It is usually associated with muscle weakness or poor motor control. This condition not only reduces activities of daily living (ADLs), but also interferes personal hygiere and causes caregiuer's difficulty. The use of botulinum neurotoxin (BoNT) intramuscular injections is a simple and effective therapy for spasticity. The use of BoNT to treat adult patients with spasticity was first reported in 1989, since then, using the neurotoxin to treat spasticity became popular in some European countries. Now in Japan, BoNT can be used to treat only torticollis, blepharospasm and hemifacial spasm because of the legal limitation on its use. However, clinical research on the use of BoNT in spasticity caused by stroke is presently underway, and an adaptation of the toxin may be available in the near future. This article reviews the characteristics of BoNT and the techniques for injecting this neurotoxin.

Our studies on creation of functional organic compounds and their applications, have focused on three areas, namely, (A) organic chemical studies on VD (vitamin D) analogues, (B) studies on solitary wasp venoms, and (C) studies on functional building blocks for organic synthesis. In the first area, several novel and important vitamin D analogues were synthesized and biologically evaluated, and their high VDR (vitamin D receptor) binding affinities were discussed on the basis of conformational analysis and docking study by Molecular Mechanics Calculation to the LBD (ligand binding domain) of VDR: These compounds include 24,24-difluoro-1 alpha,25-dihydroxy-VD3 (2) (an antimetabolism agent, the first VD analogue having higher potency than the natural hormone (1)), 2 alpha-methyl-1 alpha,25-dihydroxy-VD3 (42b) (the first A-ring-modified VD analogue exhibiting stronger VDR affinity than 1) and its 20-epimer (43b) (a VD analogue having a highest HL-60 cell differentiation inducing activity with a relatively low calcemic effect), and 2 alpha-(omega-hydroxypropyl)-1 alpha,25-dihydroxy-VD3 (exceptionally high calcemic effect). In the second area, we isolated and determined the structure of pompilidotoxins (76, 77), novel peptide neurotoxins in solitary wasp venoms. In the third area, we created furan-fused 3-sulfolene, 4H, 6H-thieno [3,4-c]-furan 5,5-dioxide and pyrrole-fused 3-sulfolene (96), 3,5-dihydro-1H-thieno[3,4-c] pyrrole 2,2-dioxide (125), and studied their inter- and intramolecular Diels-Alder reactions.

The biochemistry, the molecular biology and the biological activity of the eosinophil granule proteins, major basic protein (MBP), eosinophil cationic protein (ECP), eosinophil-derived neurotoxin (EDN) and eosinophil peroxidase (EPO) are reviewed. MBP is present in the core of the eosinophil granule and is toxic to parasite and host cells. ECP and EDN are proteins in the matrix of the granule and share sequence similarity and ribonuclease activity. These two proteins can provoke the Gordon phenomenon in rabbits and are toxic to parasites. EPO consists of two polypeptide and is a toxin for parasite and host cells with or without H2O2. The common characteristics of these proteins are their high isoelectric points and cytotoxic activities.