脂質過酸化物により劣化させられたチューブリンのGTPase活性に対するSH基還元剤(グルタチオン・システイン)の回復効果

Tubulin, which is a main component of the cytoskeleton, plays various important roles in cellular processes such as axonal transport, ciliary and flagellar movement, cell division, and cell segregation in the form of microtubules. The aim of the present study was to examine the effect of SH reductants on phospholipid peroxides-induced inhibition of tubulin GTPase activity. Lipid peroxides were prepared by photooxidation of lipoid S100 of phospholipid obtained from soybean. Tubulin GTPase activity was most inhibited by lipid photooxidized for 24 hours among ones for 16 and 24 hours. The more the amount of lipid peroxides is added, the more the activity is inhibited. Tubulin GTPase activity was lowered even in the presence of a slight amount of lipid peroxides. This suggests that the presence of a slight amount of lipid peroxides influences cellular functions in vivo. Prepared lipid peroxides was identified as a monohydroperoxide by an electrochemical detection through HPLC and a mass spectrometry. Glutathione and cysteine was used as water soluble reductants. Tubulin GTPase activity deteriorated by lipid peroxides was restored by the addition of water soluble reductants. The results presented above suggest that glutathione and cysteine have a protective effect on cellular aging by the reduction of materials oxidized in vivo

Erlotinib デ induction therapy オ オコナッタ IIIAキ ヒショウサイボウ ハイガン ノ 1シュジュツレイ

［Background ］Erlotinib, epidermal growth factor receptor-tyrosine kinase inhibitor（EGFR-TKI）, is effective for advanced and metastatic non-small cell lung cancer（NSCLC）with EGFR mutation. However, the report of Erlotinib as induction therapy is rare. We report a surgical case of NSCLC with Erlotinib as induction therapy. ［Case ］A４１-years-old man, diagnosed left lung adenocarcinoma with EGFR mutation（exon１９deletion）, was referred to our hospital. CT showed that the tumor was ３５mm in S８ of the left lung and ＃７ lymphnode was swelling markedly（cT２aN２M０ stage ⅢA）. He took Erlotinib（１５０mg／day）for１２weeks at first because of EGFR mutation positive. The evaluation of Erlotinib was partial response in RESIST. He could take radical operation as lower lobe and lingual segment resection, because CT showed bulky ＃７got smaller significantly. There was no postoperative complication. The pathological finding was adenocarcinoma（papillary& acinartype）, PL０, v（＋）, ly（＋）, br（－）, pa（－）, pv（－）, Ef :１b,（ypT１aN２M０stage ⅢA）. He has taken adjuvant therapy（Erlotinib１５０mg／day）for２８weeks. There is no recurrence six months after operation. ［Conclusion ］It is possible that Erlotinib as induction-therapy is very effective in patients with EGFR mutation like this case ; however there is no evidence of EGFR-TKI as induction therapy. It is necessary to validate the effectiveness of Erlotinib as induction therapy

Glucagon-like peptide-1 receptor agonists as an effective therapeutic agent for diabetes mellitus and obesity in patients with schizophrenia under treatment with second-generation antipsychotics

Objectives: Cases of schizophrenia are commonly complicated with obesity and diabetes mellitus partially caused by excessive eating associated with the use of second-generation antipsychotics (SGAs). We aimed to study the efficacy of glucagon-like peptide-1 in patients with schizophrenia under treatment with SGAs. Methods: Diabetic patients with schizophrenia were included if their HbA1c levels increased more than 1% and/or their weight increased more than 3 kg after treatment with SGAs. Patients who developed diabetes after treatment with SGAs were also included. The participants were treated with GLP-1 receptor agonists for one year, and their changes in weight and HbA1c and any adverse events were evaluated. Results: Seven patients were treated with GLP-1 receptor agonists; their mean age was 46.1 yrs old (range; 26 to 59), mean body weight was 85.3 kg (65.5 to 96.8), and mean BMI was 33.8 (27 to 38.7). Five of them showed improvement in their HbA1c levels of 1.2% (0.1 to 3.4, p=0.089) with a weight loss of 3.7 kg (-9.6 to +3.5, p=0.14) on average. The adverse effects observed were all gastrointestinal, but were not severe enough to cause termination of the GLP-1 receptor agonist treatment. The GLP-1 receptor agonist was not effective in one patient, and another patient terminated the treatment in a few months. Conclusions: Although the number of patients studied was small, GLP-1 receptor agonists seem to be effective for treating diabetes and bringing about weight loss in patients with schizophrenia under treatment with SGAs