抗悪性腫瘍薬・ダカルバジンのラットを用いた薬物動態学的モデル解析の基礎的検討

Dacarbazine is a therapeutic agent for melanoma of alkylating anti-tumor agents. In this study, we examined its pharmacokinetic characteristics using experimental animals and investigated using various pharmacokinetic model analysis methods. The pharmacokinetic behavior of the drug can be simulated in the various treatment routes and/or schedules and provide basic information on medical treatment.The pharmacokinetics of dacarbazine followed a 2-compartment pharmacokinetic model, namely some organs being rapidly distributed and some organs taking a long time, resulting in a relatively large volume of distribution. No accumulation of dacarbazine was observed in the body after intravenous administration once daily for 5 days, which is the standard treatment schedule in clinical practice. It shows effective pharmacokinetics as drugs with a concentration-dependent effect.Dacarbazine is usually administered rapidly intravenous bolus or by iv infusion, though it is considered that dacarbazine shows similar pharmacokinetics and is effective even in the extravascular route where rapid absorption, with an absorption rate constant (ka) of about 0.5 min-1 or more, can be obtained.Using the pharmacokinetic modeling technique, it is possible to predict the pharmacokinetics when administered under various conditions, and further to predict the degree of effect onset and the time transition (duration) of the effect. In addition, by proceeding with the study, it is possible to estimate how the pharmacokinetics will change and how the effects of the drug will be affected when combination therapy is given as compared to monotherapy. Similarly, when physiological conditions change, such as age and pathological condition, the outcome of drug therapy is estimated by how the pharmacokinetics and drug effects are affected or hardly affected.論

N-Acetyl-d-Glucosamine-Binding Lectin in Acropora tenuis Attracts Specific Symbiodiniaceae Cell Culture Strains

Many corals establish symbiosis with Symbiodiniaceae cells from surrounding environments, but very few Symbiodiniaceae cells exist in the water column. Given that the N-acetyl-d-glucosamine-binding lectin ActL attracts Symbiodiniaceae cells, we hypothesized that corals must attract Symbiodiniaceae cells using ActL to acquire them. Anti-ActL antibody inhibited acquisition of Symbiodiniaceae cells, and rearing seawater for juvenile Acropora tenuis contained ActL, suggesting that juvenile A. tenuis discharge ActL to attract these cells. Among eight Symbiodiniaceae cultured strains, ActL attracted NBRC102920 (Symbiodinium tridacnidorum) most strongly followed by CS-161 (Symbiodinium tridacnidorum), CCMP2556 (Durusdinium trenchii), and CCMP1633 (Breviolum sp.); however, it did not attract GTP-A6-Sy (Symbiodinium natans), CCMP421 (Effrenium voratum), FKM0207 (Fugacium sp.), and CS-156 (Fugacium sp.). Juvenile polyps of A. tenuis acquired limited Symbiodiniaceae cell strains, and the number of acquired Symbiodiniaceae cells in a polyp also differed from each other. The number of Symbiodiniaceae cells acquired by juvenile polyps of A. tenuis was correlated with the ActL chemotactic activity. Thus, ActL could be used to attract select Symbiodiniaceae cells and help Symbiodiniaceae cell acquisition in juvenile polyps of A. tenuis, facilitating establishment of symbiosis between A. tenuis and Symbiodiniaceae cells

Introduction for Fisheries and Aquatic Biology

Chapter I. Aquatic Environment. Ken FURUYA and Ichiro YASUDA : chapter_1.pdfChapter II. Biology and Ecology of Aqua-Shere. Toyoji KANEKO, Katsumi TSUKAMOTO, Atsushi TSUDA, Yuzuru SUZUKI and Katsufumi SATOH : chapter_2.pdfChapter III. Aquatic Resource and Production. Ichiro AOKI, Kazuo OGAWA, Taku YAMAKAWA and Tomoyoshi YOSHINAGA : chapter_3.pdfChapter IV. Chemistry of Aquatic Organism and Their Utilization. Hiroki ABE, Shugo WATABE, Yoshihiro OCHIAI, Shigeru OKADA, Naoko YOSHIKAWA, Yoshiharu KINOSHITA, Gen KANEKO and Shigeki MATSUNAGA : chapter_4.pdfChapter V. Relation between Aqua-Shere and Human Life. Hisashi KUROKURA, Hirohide MATSUSHIMA, Shingo KUROHAGI, Haruko YAMASHITA, Akinori HINO, Kazumasa IKUTA, Satoquo SEINO, Masahiko ARIJI, Ken FURUYA, Junichiro OKAMOTO and Nobuyuki YAGI : chapter_5.pdfPart of "Introduction for Fisheries and Aquatic Biology

Possible involvement of Tachylectin-2-like lectin from Acropora tenuis in the process of Symbiodinium acquisition

Most reef-building corals in tropical and subtropical areas symbiose with microalgae from the genus Symbiodinium (dinoflagellate) and depend on the photosynthate produced by the microalgae. The majority of corals acquire Symbiodinium from the surrounding environment through horizontal transfer, but the molecular mechanisms involved in the acquisition of Symbiodinium remain unknown. It has been hypothesized that carbohydrate-binding proteins, or lectins, of the host coral recognize cell surface carbohydrates of Symbiodinium in the process of acquiring symbionts. Thus, we examined the molecular mechanisms involving lectins and carbohydrates using model organism Acropora tenuis, a common reef-building coral, and Symbiodinium culture strains. Juvenile polyps acquire more cells of Symbiodinium strain NBRC102920 at 72–96 h of metamorphosis induction than in any other period. Glycosidase treatment of Symbiodinium inhibited the acquisition of Symbiodinium by juvenile coral polyps. The presence of carbohydrates D-galactose, N-acetyl-D-galactosamine, and N-acetyl-D-glucosamine at 10 mM also tended to decrease Symbiodinium acquisition. We isolated two N-acetyl-D-galactosamine binding lectins with apparent molecular masses of 14.6 and 29.0 kDa from A. tenuis, and de novo sequencing and cDNA cloning showed that the 29.0 kDa protein is Tachylectin-2-like lectin (AtTL-2). The anti-Tachylectin-2 antibody is suggested to bind specifically to AtTL-2. The antibody also inhibited binding of AtTL-2 to N-acetyl-D-galactosamine-resin and the acquisition of Symbiodinium by juvenile A. tenuis polyps. Based on these results, AtTL-2 is likely involved in the process of Symbiodinium acquisition

Age Is No Longer a Limit: Two Cases of Hepatectomy in Patients Over 90 Years Old

Hepatocellular carcinoma (HCC) is a common malignant tumor with poor prognosis. The age of patients affected by HCC is considered to be increasing, and several studies have reported significantly higher rates of morbidity and mortality after hepatectomy for HCC in elderly patients. However, other studies have reported that the short- and long-term outcomes of surgery for HCC in elderly patients are similar to those in younger patients. Whether the indications for hepatic resection in elderly patients resemble those in younger patients has thus been questioned. We describe two cases of patients over 90 years old who underwent major hepatectomy for HCC, representing the oldest patients in the world to have done so