A case of systemic lupus erythematosus (SLE) successfully treated with mizoribine (Bredinin)

Mizoribine, a novel immunosuppressive agent developed in Japan, was administered as a monotherapy to a systemic lupus erythematosus (SLE) patient with the clinical symptoms and immunological abnormalities accompanying SLE showing marked improvement. The result of prolonged administration over 22 months in this case showed neither relapse nor side-effects. Reports have been made about mizoribine used concomitantly with steroids in the treatment of SLE; however, there have not been any reports of mizoribine as a monotherapy for SLE being effective. In this case, mizoribine (150 mg/day) was administered without steroids as a monotherapy on a outpatient basis since the patient's condition overall was relatively good and the serious complications of the heart, kidneys, and lungs that accompany SLE were not observed. The results of this treatment showed improvements in alopecia, arthritis, and systemic malaise from about the 4th week after the start of administration, and the clinical symptoms that accompany SLE had completely disappeared in the 8th week. Also, the immunological tests markedly improved. Four months after the start of administration the immunological abnormalities in the anti-DNA antibody, rheumatoid factor, and immune complex were completely corrected. This case showed dramatic improvement in the SLE clinical symptoms and immunological abnormalities with the mizoribine monotherapy as well as the potential for mizoribine monotherapy to maintain a state of remission over the long term.     

On crack closure of precipitation hardened steels in aqueous solution

Fatigue crack propagation tests were carried out in air and in a 3.5 pct NaCl aqueous solution under cathodic potential of −0.85 V (Ag/AgCl) for aged-hardened high strength steel (Ni−Al−Cr−Mo−C steel). the emphasis in the study was placed on the crack closure behavior of age-hardened materials in air and in the NaCl aqueous solution. The degree of crack closure in air was dependent on the behavior of plastic deformation such as inhomogeneous or homogeneous slip under mixed modes I and II. The underaged material containing coherent precipitates with the matrix had a higher crack opening load in air, compared with the overaged steel containing incoherent precipitates with the matrix. The degrec of crack closure of the underaged material in the NaCl aqueous solution was lower than that in air and was similar to that of overaged materials in the NaCl aqueous solution. It was shown that the decreased crack closure level for the underaged material resulted from accelerated fatigue crack growth under mode I due to hydrogen embrittlement in the aqueous solution.     

Viscosity of liquid toluene in the temperature range 25–75°C

New accurate experimental data are presented for the viscosity of liquid toluene. The viscosity was measured relative to the viscosity of liquid water with the aid of an Ubbelohde capillary viscometer. The data cover a temperature range from approximately 25 to 75°C and are represented with high precision by an Arrhenius equation     

Quantitative evaluation of DNA damage caused by atmospheric and room-temperature plasma (ARTP) and other mutagenesis methods using a rapid umu-microplate test protocol for microbial mutation breeding

Mutagenesis is an important technique for microbial mutation breeding. As the source of mutations, DNA damage extent is a key indicator for the effectiveness of mutagenesis. Therefore, a rapid and easy DNA damage quantification method is required for the comparison of mutagenesis effects and development of mutagenesis tools. Here, we used the umu-microplate test system to quantitatively compare the DNA damage strength caused by atmospheric and room-temperature plasma (ARTP) and other traditional mutagenesis methods including:ultraviolet radiation (UV), diethyl sulfate (DES) and 4-nitroquinoline-1-oxide (4-NQO). The test strain of Salmonella typhimurium TA1535/pSK1002 was used to monitor the time-course profile of β-galactosidase activity induced by DNA damage caused by different mutagenesis methods using a microplate reader. The umu-microplate test results showed that ARTP caused higher extent of DNA damage than UV and chemical mutagens, which agrees well with the result obtained by SOS-FACS-based quantification method as reported previously. This umu-microplate test is accessible for broad researchers who are lack of the expensive FACS instruments and allows the quick quantitative evaluation of DNA damage among living cells for different mutagenesis methods in the study of the microbial mutation breeding.     

A 52-week feeding study of genetically modified soybeans in F344 rats

A chronic feeding study to evaluate the safety of the genetically modified glyphosate-tolerant soybeans (GM soybeans) was conducted using rats. F344 DuCrj rats were fed diet containing GM soybeans or Non-GM soybeans at the concentration of 30% in basal diet. Non-GM soybeans were closely related strain of GM soybeans. These two diets were adjusted to an identical nutrient level. In this study, the influence of GM soybeans on rats was compared with that of the Non-GM soybeans, and furthermore, to assess the effect of soybeans themselves, the groups of rats fed GM and Non-GM soybeans were compared with a group fed commercial diet (CE-2). General conditions were observed daily and body weight and food consumption were recorded. At the intermediate examination (26 weeks), and at the termination (52 weeks), animals were subjected to hematology, serum biochemistry, and pathological examination. There were several differences in animal growth, food intake, serum biochemical parameters and histological findings between the rats fed the GM and/or Non-GM soybeans and the rats fed CE-2. However, body weight and food intake were similar for the rats fed the GM and Non-GM soybeans. Gross necropsy findings, hematological and serum biochemical parameters, organ weights, and pathological findings showed no meaningful difference between rats fed the GM and Non-GM soybeans. These results indicate that long-term intake of GM soybeans at the level of 30% in diet has no apparent adverse effect in rats.     

Specific determination of bromate in bread by ion chromatography with ICP-MS

A sensitive method for detecting bromate in bread by ion chromatography with inductively-coupled plasma mass spectrometry (IC/ICP-MS) was developed. Bromate was extracted from bread with water. The clean-up procedure included a 0.2 micron filter, a C18 cartridge for defatting, a silver cartridge to remove halogen anions, a centrifugal ultrafiltration unit to remove proteins, and a cation-exchange cartridge to remove silver ions. A 500 microL sample solution was applied to IC/ICP-MS. The detection limit and the quantitation limit of bromate in the solution were 0.3 ng/mL and 1.0 ng/mL, expressed as HBrO3, respectively, which corresponded to 2 ng/g and 5 ng/g, respectively, in bread. Recovery of bromate was about 90%, and the CV was about 2%. Based on the detection limit in solution and recovery from bread, the detection limit of bromate in bread was estimated to be 2 ng/g.     

Morphological differences and classifications of small spines of puffer fishes

The differences among the small spines of 6 species of puffers have been clarified by means of microscopic observation. Small spines of puffers arise from the basement, which is composed of spines protruding from the surface skin, with roots extending horizontally in all directions in the layer under the surface skin. Using the characteristic shapes of the basement, we have classified the puffer group of "Sansaifugu" (Takifugu flavidus) and "Mefugu" (T. obscurus) as Type I and the group of "Shirosabafugu" (Lagocephalus wheeleri), "Kurosabafugu" (L. gloveri), "Dokusabafugu" (L. lunaris) and "Motosabafugu" (L. spadiceus) as Type II. The number of fore and back roots, including the branches at the ends, further varies in each group. The length and width of each root were measured. As a result, similar species within the group comprising "Sansaifugu" (T. flavidus) and "Mefugu" (T. obscurus) and 4 species of the "Sabafugu" (Lagocephalus) group including "Dokusabafugu" (L. lunaris) have been clearly distinguished. We conclude that examination of the shape of the basement of small spines can be an effective identification index.     

Preparation of monodispersed polymeric microspheres for toner particles by the shirasu porous glass membrane emulsification technique

This investigation describes the experiment directed toward the production of monodispersed toner particles by suspension polymerization. That is, relatively monodispersed poly(styrene-co-divinylbenzene) microspheres containing electrifying additives were successfully prepared by suspension polymerization employing the Shirasu Porous Glass (SPG) membrane emulsification technique. The diameter distribution of the dispersed droplets prepared with an SPG membrane module was fairly narrow, compared with that prepared with a conventional mechanical homogenizer. The effect of Sumiplast Blue S as coloring matter and E-81 as charge control agent on the triboelectric discharging properties of prepared polymeric microspheres was studied. The addition of electrifying additives strongly affected the triboelectric discharging property. It was consequently clarified that a small amount of electrifying additives added raised the electrostatic capacity of polymeric microspheres. However, a further addition reduced the triboelectric discharge of polymeric microspheres. © 1997 John Wiley & Sons, Inc. J Appl Polym Sci 64: 1107–1113, 1997     

Clioquinol Decreases Levels of Phosphorylated,Truncated, and Oligomerized Tau Protein

The neuropathological hallmarks of Alzheimer’s disease (AD) are senile plaques (SPs), which are composed of amyloid β protein (Aβ), and neurofibrillary tangles (NFTs), which consist of highly phosphorylated tau protein. As bio-metal imbalance may be involved in the formation of NFT and SPs, metal regulation may be a direction for AD treatment. Clioquinol (CQ) is a metal-protein attenuating compound with mild chelating effects for Zn²⁺ and Cu²⁺, and CQ can not only detach metals from SPs, but also decrease amyloid aggregation in the brain. Previous studies suggested that Cu²⁺ induces the hyperphosphorylation of tau. However, the effects of CQ on tau were not fully explored. To examine the effects of CQ on tau metabolism, we used a human neuroblastoma cell line, M1C cells, which express wild-type tau protein (4R0N) via tetracycline-off (TetOff) induction. In a morphological study and ATP assay, up to 10 μM CQ had no effect on cell viability; however, 100 μM CQ had cytotoxic effects. CQ decreased accumulation of Cu⁺ in the M1C cells (39.4% of the control), and both total and phosphorylated tau protein. It also decreased the activity of c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (p38 MAPK) (37.3% and 60.7% levels of the control, respectively), which are tau kinases. Of note, activation of protein phosphatase 2A (PP2A), which is a tau phosphatase, was also observed after CQ treatment. Fractionation experiments demonstrated a reduction of oligomeric tau in the tris insoluble, sarkosyl soluble fraction by CQ treatment. CQ also decreased caspase-cleaved tau, which accelerated the aggregation of tau protein. CQ activated autophagy and proteasome pathways, which are considered important for the degradation of tau protein. Although further studies are needed to elucidate the mechanisms responsible for the effects of CQ on tau, CQ may shed light on possible AD therapeutics.