Drug-induced liver injury due to the long-term oral administration of rosuvastatin

A 67-year-old man was admitted to our hospital presenting with a liver injury. He had used several types of oral medication for the prior 2 years, including rosuvastatin calcium for hypertension, hyperlipidemia, and prostatic hypertrophy. His liver dysfunction was noted for the first time in February 2013, and at re-examination in March 2013 he showed exacerbation of the liver dysfunction, he was admitted to our hospital at that time. We stopped all of his oral medications, and his liver function improved steadily. We conducted a drug-induced lymphocyte transformation test (DLST), and the rosuvastatin calcium result was positive. He was diagnosed as having a drug-induced (by rosvastatin calcium) liver injury. He resumed oral medications other than rosuvastatin calcium from the time of discharge, with no exacerbation of liver dysfunction since then. Reports of drug-induced liver injury due to drugs with a long-term oral administration are extremely rare. We discuss the relevant literature herein

Determination of etoposide serum concentrations in small pediatric samples by an improved method of reversed-phase high-performance liquid chromatography.

Several specific assays have been developed for the measurement of etoposide in biological fluids. As large samples are required for high sensitivity, these systems are not appropriate for a pediatric practice. In the present study, however, an improved method for the determination of serum levels of the anticancer drug etoposide was developed, using high-performance liquid chromatography with fixed-wavelength ultraviolet detection. Etoposide was extracted from serum using dichloromethane. The efficiency of extraction from serum was 85.7 +/- 7.7% for etoposide and 81.1 +/- 8.4% for diphenylhydantoin, the internal standard. The serum concentrations of etoposide were measured in 0.2-ml serum samples. The lower limit of detection was 50 ng/ml. Each measurement was completed within 5 min. The linear quantitation range for etoposide was 0.05-50 microg/ml. This assay presents an alternative method for routine measurement of serum levels of etoposide in the pediatric oncology setting.</p

プロポフォールの脳移行における赤血球の役割

取得学位 : 博士（医学）, 学位授与番号 : 医博乙第1464号, 学位授与年月日：平成10年11月4日,学位授与年：199

High-mass star formation in Orion triggered by cloud-cloud collision II, Two merging molecular clouds in NGC2024

We analyzed the NANTEN2 13CO (J=2-1 and 1-0) datasets in NGC 2024. We found that the cloud consists of two velocity components, whereas the cloud shows mostly single-peaked CO profiles. The two components are physically connected to the HII region as evidenced by their close correlation with the dark lanes and the emission nebulosity. The two components show complementary distribution with a displacement of 0.4 pc. Such complementary distribution is typical to colliding clouds discovered in regions of high-mass star formation. We hypothesize that cloud-cloud collision between the two components triggered the formation of the late O stars and early B stars localized within 0.3 pc of the cloud peak. The collision timescale is estimated to be ~ 10^5 yrs from a ratio of the displacement and the relative velocity 3-4 km s-1 corrected for probable projection. The high column density of the colliding cloud 1023 cm-2 is similar to those in the other massive star clusters in RCW 38, Westerlund 2, NGC 3603, and M42, which are likely formed under trigger by cloud-cloud collision. The present results provide an additional piece of evidence favorable to high-mass star formation by a major cloud-cloud collision in Orion.Comment: 24 pages, 10 figures, submitted for publication in PASJ (cloud-cloud collision special issue

FFC Ceramic Water(TM) Enhances Plant Apyrase Activity

The FFC ceramics(TM) from FFC Japan Co., Ltd. are now widely used in the fields of agriculture, fishery and food industry in Japan. Recently the FFC ceramic beads-based technology has been also applied to meet several environmental problems including pollution in sea, lakes and rivers. In this study the FFC ceramic water was tested for effect on plant enzyme, potato apyrase (EC 3.6.1.5; ATP-diphosphohydrolase), which hydrolyses nucleoside triphosphate (NTP) and -diphosphate (NDP) to produce corresponding nucleoside monophosphate (NMP) and inorganic phosphate (Pi). Addition of the FFC ceramic water to the enzyme reaction mixture markedly enhanced ATP-hydrolyzing activity, when used as ATP as substrate. However, the concomitant presence of Ca(2+) chelator, EGTA (O,O'-bis(2-aminoethyl)ethyleneglycol-N,N,N',N'-tetraacetic acid) with the FFC ceramic water, completely abolished the enzyme activation. In fact, exogenous calcium ion such as CaSO4 mimicked the FFC ceramic water. These results indicate that apyrase activation by the FFC ceramic water largely depends on calcium ions. On the other hand, when the FFC ceramic water prepared from "used" ceramics was tested for the apyrase activity, the enhanced effect on apyrase was decreased compared to the FFC ceramic water from "new" ones. This result, consistent with our present data covering concentration of calcium ions and conductivity, indicates that long and/or successive usage of the ceramic beads results in decrease of contents of released minerals, especially calcium ions. The apyrase-based enzyme assay presented here is probably applicable to estimate and quantify the effect of FFC ceramic water.本報は，FFC セラミックス(TM)（㈱エフエフシー・ジャパン）で調製した FFC セラミック水（FFC 水）の植物アピラーゼ（EC 3.6.1.5）の活性に及ぼす直接的な作用について調べたものである．FFC 水はアピラーゼがもつ ATP加水分解活性を促進し，その作用は反応液への添加量に依存した．先の無機元素分析結果から，FFC 水に含まれる主要な塩類はCa(2＋)であることが判明している．そこで，Ca(2＋)キレート剤EGTAを反応液へ加え，その影響について調べたところ，FFC 水による活性化作用は消失することが明らかとなった．また，FFC 水と類似の作用は，硫酸カルシウム，塩化カルシウムまたは硝酸カルシウムの添加で認められ，陰イオンの種類によって明確な違いはなかった．これらの結果から，FFC 水が植物アピラーゼに及ぼす活性化作用の一因は，セラミックスから遊離する Ca(2＋)に依存しているものと推察された．一方，アピラーゼ活性を指標として，使用済のセラミックスから調製した FFC 水の効果について検討したところ，未使用からの水と比べて，カルシウム濃度ならびに活性化作用の顕著な低下が認められた．このことは，継続的な使用によってセラミックスから遊離する塩類，特にカルシウムの溶出量が大きく変わることを意味し，アピラーゼを用いた本検定が，FFC 水の効果を定量的に確かめる方法の一つとして利用できると考えられた．以上，これらの結果を総合して，FFC水の植物酵素への直接的作用，ならびに植物への施用によって効果が現れる耐病性獲得作用との関連について考察した

HopAZ1, a type III effector of Pseudomonas amygdali pv. tabaci, induces a hypersensitive response in tobacco wildfire-resistant Nicotiana tabacum 'N509'

Pseudomonas amygdali pv. tabaci (formerly Pseudomonas syringae pv. tabaci; Pta) is a gram-negative bacterium that causes bacterial wildfire disease in Nicotiana tabacum. The pathogen establishes infections by using a type III secretion system to inject type III effector proteins (T3Es) into cells, thereby interfering with the host & apos;s immune system. To counteract the effectors, plants have evolved disease-resistance genes and mechanisms to induce strong resistance on effector recognition. By screening a series of Pta T3E-deficient mutants, we have identified HopAZ1 as the T3E that induces disease resistance in N. tabacum 'N509'. Inoculation with the Pta increment hopAZ1 mutant did not induce resistance to Pta in N509. We also found that the Pta increment hopAZ1 mutant did not induce a hypersensitive response and promoted severe disease symptoms in N509. Furthermore, a C-terminal truncated HopAZ1 abolished HopAZ1-dependent cell death in N509. These results indicate that HopAZ1 is the avirulence factor that induces resistance to Pta by N509

Liver Sarcoidosis with Unique MRI Images Using Gadolinium Ethoxybenzyl Diethylenetriamine Pentaacetic Acid

Sarcoidosis is a systemic disease characterized by the formation of non-caseating granulomas in multiple organs. In the diagnosis of sarcoidosis, imaging modalities such as ultrasonography, computed tomography (CT) and magnetic resonance imaging (MRI) are useful;however, there are few reports of MRI imaging using gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB) MRI. A 46-year-old Japanese female with suspected pulmonary sarcoidosis was admitted to our hospital because low-density mottles in the liver were observed incidentally by chest CT. The low-density mottles were not enhanced at the arterial phase or portal phase by abdominal CT and MRI, and decreased uptake was observed in the hepatobiliary phase of Gd-EOB MRI. No hematological disorder was observed except for a slight increase of biliary enzymes. The lesion was diagnosed as liver sarcoidosis by the liver biopsy. Since the patient refused steroid therapy, we prescribed ursodeoxycholic acid (UDCA). 600mg/day. The serum levels of biliary enzymes were normalized and the abdominal CT findings gradually improved after the initiation of UDCA medication. Gd-EOB MRI showed unique hypointense areas in the liver at the hepatobiliary phase, which might be useful in the diagnosis of liver sarcoidosis