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Here we report on a patient with schizophrenia who suffered from medication-refractory coprophagia. Although there were few cases in which psychotropic medication was effective against coprophagia, we encountered a patient with schizophrenia in whom coprophagia rapidly disappeared after treatment with perospirone, a novel atypical antipsychotic drug of the serotonin-dopamine antagonist (SDA) type. Perospirone has a uniquely high affinity for serotonin-1A receptors, and it could be speculated that perospirone, as a serotonin-1A receptor agonist combined with SDA, may have greater efficacy for treatment-refractory symptoms of schizophrenia. Thus, perospirone is an agent with possible efficacy for medication-refractory schizophrenia.

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Seasonal variations in the level of total microcystins in water samples collected from Donghu Lake and a fish pond in Wuhan, China, were studied between March 1995 and February 1996 using a protein phosphatase inhibition assay involving a radioactive 32P-labelled substrate. The assay is highly reliable and repeatable, and is probably the most sensitive assay for microcystin detection to date. Results of the survey indicated the presence of microcystins in the water samples, and the concentration of microcystins appeared to be related to the degree of eutrophication and water temperature. There is also a correlative relationship between the quantity of microcystins and the abundance of microcystin-producing cyanobacteria (Anabaena and Oscillatoria) in the water bodies over a year cycle. In the present study, the positive detection of microcystins in water bodies having no signs of algal bloom warns of considerable potential threat of these waters to public health.

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During the summer of 1995, about 20 spot-billed ducks died unnaturally in a pond (Shin-ike) in Nishinomiya, Hyogo Prefecture, Japan. The suspected cause was the sudden appearance of toxic freshwater bloom of cyanobacteria. However, no birds died in a nearby pond (Oo-ike) in which the cyanobacteria was also present. Morphological observation of these cyanobacteria by microscope revealed that they were almost unialgal and were both Microcystis aeruginosa. The lyophilized algal cell powder from Shin-ike contained large amounts of microcystins which showed acute toxicity for mouse, while that from Oo-ike had only a very small amount of microcystin-RR which did not show acute toxicity. Autopsy of one of the birds revealed that the liver was necrotic and severely jaundiced with a dark green color, suggesting the toxicity of the microcystins. These results point to the cause of the unnatural death of spot-billed ducks in Shin-ike as being the sudden appearance of toxic Microcystis aeruginosa. This was due to eutrophication of the pond, following the influx of untreated sewage related to damage from the Great Hanshinn Earthquake of January 1995. This is the first experimental report of toxic cyanobacteria being implicated in the mass death of wild birds in Japan.

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Effects of basic glycoside antibiotic aculeximycin (ACM) on the oxidative phosphorylation of rat-liver mitochondria were examined. ACM was shown to be a potent uncoupler of the oxidative phosphorylation. To cause the same extent of respiration release, higher concentration of ACM was required in phosphate (Pi)-free medium than in Pi medium. During the uncoupling caused by ACM in Pi medium, large amplitude swelling and oxidation of intramitochondrial NAD(P)H occurred, indicating that ACM remarkably enhances permeability of the inner mitochondrial membrane. The Pi uptake via Pi/H+ symporter was shown to play an important, but not essential, role in the uncoupling by ACM, indicating the increase in membrane permeability is mostly due to acceleration of Pi/H+ influx through Pi/H+ symporter activated by ACM. ACM is the first naturally occurring antibiotic, to our knowledge, which activates Pi/H+ symporter. However, since the inhibition of Pi/H+ symporter by N-ethylmaleimide did not completely abolish the uncoupling activity of ACM, and ACM induced the uncoupling even in Pi-free medium, an increase in the membrane permeability for other ions, such as Na+ and K+, due to a different action mechanism has also to be considered. On the other hand, positively charged amine local anesthetics, like dibucaine, prevented the uncoupling activity by ACM in both Pi and Pi-free medium. The uncoupling activity of N-diacetylated ACM lacking free amino groups was ca. 1/120th that of ACM, indicating that positively charged amino groups are important for the uncoupling activity. It is suggested that some specific interactions between positively charged amino groups of ACM and the binding site, which is probably negatively charged, are triggers that affect the permeability of the inner mitochondrial membrane. Amine local anesthetics may mask the negative charge of the binding site, thereby interfering with ACM binding.

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Microcystins are very potent hepatotoxins and strong liver tumor promoters produced by cyanobacteria, and their occurrence has been reported all over the world. They could threaten human health when toxic Microcystis occurs in water supply reservoirs. In this study, we examined the stability of microcystins during photolysis with UV light. The toxins were easily decomposed by UV light at wavelengths around the absorption maxima of the toxins and the decomposition depended on the intensity of the light. The half-life of microcystin LR by 147 microW/cm2 UV irradiation was 10 min, and the toxin was completely decomposed by 2550 microW/cm2 UV after 10 min. When the toxins were irradiated with weaker UV light, isomerization was also observed by a different mechanism from that during photolysis by sunlight and pigment, and several products including three geometrical isomers of the conjugated diene of Adda were detected. Microcystin RR showed almost the same behavior as that of microcystin LR under the same conditions. Since no noxious products were formed in the present study, a water treatment including UV irradiation is very possible for removing microcystins from raw water.

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The effects of cylindrospermopsin isolated from a blue-green alga Umezakia natans on mice were examined morphologically and biochemically. The main target of the phycotoxin was the liver. The thymus, kidneys and heart were also affected. There were four consecutive phases of the pathological changes in the liver. The initial phase was that of inhibition of the protein synthesis, the second phase of membrane proliferation followed, and then the third phase of fat droplet accumulation and finally the phase of cell death. Using globin synthesis in the rabbit reticulocytes system, it was clearly demonstrated that cylindrospermopsin is a potent inhibitor of the protein synthesis. Protein in microsomes from the mouse livers treated by cylindrospermopsin decreased in amount more significantly than that of phospholipid in microsomes. Furthermore, the amount of total P450 was extensively diminished in the toxin treated with hepatic microsomes.

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In 1987 a cyanobacterium (blue-green alga) Umezakia natans was isolated from Lake Mikata, Fukui, Japan, as a new member of the family of Stigonemataceae. The crude extract of U. natans showed hepatotoxicity to mice, from which a toxic compound was isolated. The toxin was identical in all respects to a recently reported hepatotoxin, cylindrospermopsin, isolated from an Australian tropical cyanobacterium Cylindrospermopsis raciborskii. Because cylindrospermopsin causes fatty liver and central necroses in mice and is suspected of being an agent causing human hepatoenteritis, its monitoring in drinking water supplies has been required. So a rapid screening method including four steps, extraction, clean-up, separation, and determination, has been proposed for cylindrospermopsin. A combination of a clean-up using HP-20 and C18-cartridge, and HPLC with photodiode array detector made it possible to establish a screening method for the toxin. The established method was applied to five samples and cylindrospermopsin was traced in one of them.

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The structural characterization of minor components of bacitracin (BC) complex was carried out using a technique of liquid chromatography/mass spectrometry (LC/MS). Satisfactory total ion current chromatogram of BC complex and excellent mass spectra of many components were given by Frit-fast atom bombardment (FAB) LC/MS analytical system, and the structures of 13 minor components could be proposed. The 13 minor components were classified into two groups, bacitracin A (BC-A) related components and bacitracin F (BC-F) related components depending on their common N-terminal moieties. The structures of BC-A related components and BC-F related components were the same as those of BC-A and BC-F, respectively, except that one to three of isoleucine and leucine residues are replaced by valines. The BC-F related components were degradation products of BC-A related components through the same degradation process as that of BC-A.

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By physiochemical analyses and chemical procedures, the structures of a series of basic 16-membered macrolide antibiotics, M-4365, A1, A2, A3, G1, G2 and G3 were elucidated, and it was found that M-4365 A1, G1 and G2 were novel, while M-4365 A2, A3 and G3 were identical with rosamicin, juvenimicins A4 and B1, respectively.

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