The chemistry of 1-hydroxyindole derivatives : nucleophilic substitution reactions on indole nucleus

金沢大学大学院自然科学研究科生理活性物質科学金沢大学薬学

Prostaglandin E2 receptor type 2-selective agonist prevents the degeneration of articular cartilage in rabbit knees with traumatic instability

[Introduction]Osteoarthritis (OA) is a common cause of disability in older adults. We have previously reported that an agonist for subtypes EP2 of the prostaglandin E2 receptor (an EP2 agonist) promotes the regeneration of chondral and osteochondral defects. The purpose of the current study is to analyze the effect of this agonist on articular cartilage in a model of traumatic degeneration. [Methods]The model of traumatic degeneration was established through transection of the anterior cruciate ligament and partial resection of the medial meniscus of the rabbits. Rabbits were divided into 5 groups; G-S (sham operation), G-C (no further treatment), G-0, G-80, and G-400 (single intra-articular administration of gelatin hydrogel containing 0, 80, and 400 μg of the specific EP2 agonist, ONO-8815Ly, respectively). Degeneration of the articular cartilage was evaluated at 2 or 12 weeks after the operation. [Results]ONO-8815Ly prevented cartilage degeneration at 2 weeks, which was associated with the inhibition of matrix metalloproteinase-13 (MMP-13) expression. The effect of ONO-8815Ly failed to last, and no effects were observed at 12 weeks after the operation. [Conclusions]Stimulation of prostaglandin E2 (PGE2) via EP2 prevents degeneration of the articular cartilage during the early stages. With a system to deliver it long term, the EP2 agonist could be a new therapeutic tool for OA

Associations between the orexin (hypocretin) receptor 2 gene polymorphism Val308Ile and nicotine dependence in genome-wide and subsequent association studies

Impact of the HCRTR2 gene risk variant on schizotypal personality traits (mean ± SD). (DOC 54 kb

Pituitary Abscess Manifesting as Meningitis and Photophobia Associated With Rathke's Cleft Cyst in a Child -Case Report-

A 12-year-old girl presented with complaints of headache, lethargy, photophobia, and fever. Cerebrospinal fluid examination revealed bacterial meningitis. Magnetic resonance (MR) imaging showed a cystic lesion with peripheral enhancement in the pituitary fossa. The patient underwent transnasal-transsphenoidal surgery (TSS). The diagnosis was pituitary abscess associated with Rathke's cleft cyst. Postoperatively, the patient recovered rapidly. However, recurrence of the pituitary abscess causing meningitis occurred four times and required repeated TSS. She had diabetes insipidus and received hormone replacement. This case requiring repeated emergency surgeries shows that follow-up examinations including MR imaging and pituitary endocrine evaluation are necessary because the rate of recurrence is high in patients with pituitary abscess associated with Rathke's cleft cyst.ArticleNEUROLOGIA MEDICO-CHIRURGICA. 51(6):455-459 (2011)journal articl

A 96-well Plate Assay for CYP3A Induction Using Cryopreserved Human Hepatocytes

Abstract A reliable and practical cytochrome P450 (CYP) 3A induction assay with cryopreserved human hepatocytes in a 96-well format was developed. Various 96-well plates with different basement membrane were evaluated using prototypical inducers, rifampicin, phenytoin, and carbamazepin. Thin-layer (TL) matrigel was found to yield the highest basal and induced levels of CYP3A activity as determined by testosterone 6β-hydroxylation. Concentration-dependent CYP3A induction of μ M rifampicin. Co-treatment of avasimibe or efavirenz with 10 μ M rifampicin was found to reduce CYP3A activities induced by rifampicin lower than that treated rifampicin alone, whereas the phenobarbital and carbamazepine had no effect. From a comparison of induced CYP3A activities and gene expression levels, there were compounds that would cause induction of CYP3A4 mRNA but not activity, presumably due to their inhibitory effect on CYP3A activity. The co-treatment assay of test compound with rifampicin allows us to exclude the false negative results caused by the cytotoxicity and/or the mechanism-based inactivation, when the drug candidate's ability for CYP3A induction is evaluating by the enzyme activity. This 96-well plate assay, which is robust, reproducible and convenient, has demonstrated the paramount applicability to the early drug discovery stage