巻号一覧
133 巻, 8 号
選択された号の論文の10件中1～10を表示しています
- |<
- <
- 1
- >
- >|
総説
-
郡山 恵樹2013 年 133 巻 8 号 p. 843-848
発行日: 2013年
公開日: 2013/08/01
ジャーナル フリーThe retina has been regarded as 'an approachable part of the brain' for investigating central nervous system (CNS). The optic nerve injury is a well-accepted model to study the mechanisms of neural degeneration and/or axonal regeneration after trauma in the CNS. Nitric oxide (NO) is a gaseous messenger molecule biosynthesized from L-arginine and molecular oxygen by NO synthase. Many reports suggest that excess production of NO plays a crucial role in neuronal cell death including in death of retinal ganglion cells (RGCs). In contrast, several lines of evidence indicate that NO can prevent neuronal death. In general, NO mediates neuroprotection through two main signaling pathways: the NO/cyclic guanosine monophosphate (cGMP) pathway and the S-nitrosylation pathway. Especially, whether S-nitrosylation of proteins promotes RGCs survival and its axonal regeneration after injury is unclear. Thus, we focused on the S-nitrosylation-dependent mechanism of RGCs survival and axonal regeneration by NO after nerve injury.
抄録全体を表示PDF形式でダウンロード (418K) -
室山 明子2013 年 133 巻 8 号 p. 849-856
発行日: 2013/08/01
公開日: 2013/08/01
ジャーナル フリーParkinson's disease (PD) is a progressive neurodegenerative disorder characterized by the core symptoms such as bradykinesia, resting tremor, rigidity and postural instability. Currently, pharmacotherapy and surgical approaches for the treatments of PD can only improve the neurological symptoms. Therefore, to search neuroprotective therapies using pharmacological and nonpharmacological approaches could be important to delay the progression of pathogenesis in PD. Coenzyme Q10 (CoQ10) is a component of the electron transport chain as well as an important antioxidant in mitochondrial and lipid membranes. The central role of CoQ10 in two areas implicated in the pathogenesis of PD, mitochondrial dysfunction and oxidative damages, suggest that it may be useful for treatment to slow the progression of PD. The neuroprotective effect of CoQ10 has been reported in several in vivo and in vitro models of neurodegenerative disorders. Although CoQ10 attenuated the toxin-induced reduction of dopamine content and tyrosine hydroxylase-immunoreactive neurons in the striatum of the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model, it is still unknown how this nutrition affects the mitochondrial function. We demonstrated that oral administration of CoQ10 significantly attenuated the loss of dopaminergic nerve terminals induced by MPTP treatment. Furthermore, our experimental data indicate that an inhibition of mitochondrial cytochrome c release is one of the primary targets for CoQ10 and may lead to a potent neuroprotection.
抄録全体を表示PDF形式でダウンロード (884K) -
田畑 英嗣2013 年 133 巻 8 号 p. 857-866
発行日: 2013/08/01
公開日: 2013/08/01
ジャーナル フリーAxial chirality caused by an sp2-sp2 axis at Ar-N(C=O) (a conformational stereogenic axis) in pharmaceutically important seven-membered-ring benzolactams (I) and N-acyl-benzazepines and related nuclei (II) was investigated to verify the importance of the atropisomerism in the biologically active molecules. Anilide derivatives with the seven-membered-ring benzolactams (derivatives of I: 6-8) and the N-benzoyl derivatives of 1,5-benzodiazepines (derivatives of II: 11-ii-14-ii) were successfully synthesized as new, highly potent acyl-CoA:cholesterol acyltransferase inhibitors and the vaptan class of vasopressin receptor ligands, respectively. By freezing the atropisomerism at the scaffold regions, we succeeded in separating and isolating the atropisomers. The biological activities of the atropisomers were examined to reveal that the axial chirality is recognized by the enzyme and receptor when the molecules exert their activity.
抄録全体を表示PDF形式でダウンロード (916K) -
古徳 直之2013 年 133 巻 8 号 p. 867-872
発行日: 2013/08/01
公開日: 2013/08/01
ジャーナル フリーAngiogenesis, the formation of new blood capillaries from preexisting blood vessels, is a vital process in growth of solid tumors and development to malignant stage. This makes angiogenesis a desirable target for cancer treatment. In this work, design and syntheses of structurally simplified analogues of cortistatin A (1), a novel antiangiogenic steroidal alkaloid from Indonesian marine sponge, and their biological activities were investigated. One of the analogues, in which the isoquinoline moiety was appended to the planar tetracyclic core structure, showed potent antiproliferative activity against human umbilical vein endothelial cells (HUVECs) together with high selectivity and also showed in vivo antiangiogenic activity and significant antitumor effect by oral administration.
抄録全体を表示PDF形式でダウンロード (544K) -
石原 康宏2013 年 133 巻 8 号 p. 873-878
発行日: 2013/08/01
公開日: 2013/08/01
ジャーナル フリーQuinones are widely distributed in nature, and some quinone compounds are used as therapeutic agents such as anti-cancer, anti-malarial or anti-bacterial drugs. However, their therapeutic use is limited in some cases because the use of most quinones is accompanied by adverse effects derived from their cytotoxicity, especially for hepatocytes. Two mechanisms have been proposed to explain quinone toxicity: oxidative stress via redox cycle and the arylation/alkylation of intracellular nucleophiles. A drug metabolizing enzyme, cytochrome P450 is closely involved in the hepatotoxicity of therapeutic agents in general, but quinone hepatotoxicity has been considered not to contribute to cytochrome P450 because the structure of quinone is not modified by cytochrome P450 and thus quinone compounds are thought to be metabolized mainly via a conjugation process. However, we have recently shown that quinone hepatotoxicity is enhanced under conditions of cytochrome P450 inhibition, indicating clearly the involvement of cytochrome P450 in quinone hepatotoxicity. Here, we revisit the generally accepted mechanisms of quinone hepatotoxicity and propose the importance of cytochrome P450 systems in quinone-induced hepatotoxicity on the basis of our recent work.
抄録全体を表示PDF形式でダウンロード (407K) -
岡本 典子2013 年 133 巻 8 号 p. 879-887
発行日: 2013/08/01
公開日: 2013/08/01
ジャーナル フリーTandem reactions for efficient construction of nitrogen-containing heterocycles were developed. One-pot platinum(II)-catalyzed synthesis of indoles and isoquinolines has been achieved via isocyanates, which were derived from a Hofmann-type rearrangement of 2-alkynylbenzamides and 2-alkynylbenzylamides using a hypervalent iodine reagent. As an extension of this approach, trans-2,3-dihydro-4-quinolones were synthesized via acid-catalyzed intermolecular [2+2]-cycloaddition of aldehydes and carbamates, which were formed from nucleophilic addition of alcohols to isocyanate intermediates. Direct, efficient syntheses of the benzimidazo[2,1-a]isoquinoline ring system have been achieved with 2-bromoarylaldehydes, terminal alkynes, and 1,2-phenylenediamines by a microwave-accelerated tandem process in which a Sonogashira coupling, 5-endo cyclization, oxidative aromatization, and 6-endo cyclization can be performed in a single synthetic operation.
抄録全体を表示PDF形式でダウンロード (597K) -
渡邊 博志2013 年 133 巻 8 号 p. 889-895
発行日: 2013/08/01
公開日: 2013/08/01
ジャーナル フリーChronic kidney disease (CKD), marked by a progressive loss in renal function, is a leading cause of hemodialysis initiation and cardiovascular disease (CVD). There are currently 13.3 million patients with CKD and 300 thousand patients are currently undergoing hemodialysis in Japan. Therefore, preventing the initiation of dialysis and reducing the risk of cardiovascular death are high-priority issues from the viewpoint of public health and economic implications. Understanding the molecular mechanism responsible for the progression of CKD and cardiovascular damage regarding crosstalk between the kidney and cardiovascular system is an important issue in controlling the pathogenesis of CKD-CVD. However, the mechanisms involved in CKD-CVD are not well understood. This hinders the development of new treatment strategies. We have been investigating the role of protein bound uremic toxins, that are difficult to remove by hemodialysis, on the onset and progression of CKD and CVD. The relationship between their redox properties and the pathogenesis of CKD-CVD was examined. In this review, we focus on two sulfate conjugated uremic toxins, namely, indoxyl sulfate (IS) and p-cresyl sulfate (PCS), and summarize recent studies that provide new insights on the molecular mechanisms responsible for uremic toxin-induced oxidative tissue damage via a cardiovascular-renal connection.
抄録全体を表示PDF形式でダウンロード (613K)
一般論文
-
佐野 知子, 原田 雅史, 菅原 隆光, 伊坂 直紀, 増岡 昭生, 三上 昭廣, 島森 美光, 黒澤 菜穂子2013 年 133 巻 8 号 p. 897-903
発行日: 2013/08/01
公開日: 2013/08/01
ジャーナル フリーAs hospitalized patients in psychiatry departments are often prescribed multiple psychotropics depending on their psychiatric symptoms, psychotropics are considered as important factors potentially associated with a high risk of falls. In this study, we attempted to investigate, from the aspect of drug prescription, to what degree the number and doses of psychotropics must be adjusted in order to reduce risk of falls in hospitalized psychiatric patients. The subjects were 526 patients, consisting of a fall group of 313 patients, who had experienced 1 to 5 falls (510 events) and a control group of 213 patients who had never experienced falls. Multiple logistic regression analysis was performed to determine the correlations between the occurrence of falls and the number and doses of psychotropics. The results showed that the risk of falls increased with increasing number of antipsychotics and anxiolytics/hypnotics prescribed, with the risk increasing, by 3.75-fold with the increase in the dose of chlorpromazine (CP)-equivalents to more than 600 mg, by 2.08-fold when the dose of diazepam (DAP)-equivalents to more than 15 mg, and by 7.80-fold with increase in CP-equivalents to more than 600 mg concomitantly with an increase in DAP-equivalents to more than 15 mg. In addition, a tendency towards increase in the frequency of falls was observed when more than 5 psychotropics were prescribed concomitantly. The above results suggested that the risk of falls may be reduced by appropriately adjusting the number of drugs and the doses of psychotropics used in the treatment of psychiatric disorders.
抄録全体を表示PDF形式でダウンロード (629K) -
小森 浩二, 古前 竜平, 山崎 裕己, 中野 祥子, 三田村 しのぶ, 宮﨑 珠美, 菊田 真穂, 高田 雅弘, 首藤 誠, ...2013 年 133 巻 8 号 p. 905-911
発行日: 2013年
公開日: 2013/08/01
ジャーナル フリーLoxoprofen (Loxonin®), an antipyretic painkiller, was approved as an over-the-counter (OTC) drug (Loxonin®-S) in January 2011. With regard to self-medication using OTC drugs, the information that pharmacists provide to consumers is very important. Although loxoprofen is a very versatile drug and can be used during breastfeeding, information regarding its mammary gland transfer is inadequate. In this study, we established a simple method to evaluate mammary transfer of drugs, and compared loxoprofen's mammary gland transfer with that of aspirin. Loxoprofen 12 mg/kg and aspirin 132 mg/kg was orally administered to mother mice (ddY), and blood and milk samples were collected. Twenty microliters of ethanol was added to the blood and milk samples (10 μL), and the mixture was centrifuged for 15 min (12000 g); the supernatant was analyzed by high-performance liquid chromatography. Since aspirin was immediately metabolized, we analyzed salicylic acid concentrations. Maximum concentration of loxoprofen was observed at around 15 min after its oral administration, with the concentrations in the blood and milk being 2.9 and 0.5 μg/mL, respectively. The drug was metabolized promptly thereafter. In contrast, maximum concentration of salicylic acid was observed at 30 min after aspirin administration, with the concentrations in the blood and milk being 187.2 and 64.4 μg/mL, respectively. These concentrations remained constant from 60 to 120 min. Salicylic acid could be detected 240 min after aspirin administration. Thus, mammary gland transfer of loxoprofen is lower than that of aspirin, suggesting that loxoprofen does not accumulate in milk.
抄録全体を表示PDF形式でダウンロード (533K)
ノート
-
平山 匡彦, 田中 秀和, 鈴木 慎太郎, 井上 広平, 永富 亜紀, 作元 誠司, 北原 敏弘, 宮﨑 長一郎, 吉谷 清光 ...2013 年 133 巻 8 号 p. 913-922
発行日: 2013/08/01
公開日: 2013/08/01
ジャーナル フリーThis study was conducted among 252 inhabitants aged 16 years or older of small remote islands in Gotoh. The survey was conducted in a direct interview format based on a questionnaire. In the interview, the respondents were asked about the statuses of their Internet usage, purchase/use/storage of nonprescription drugs, acquisition of information regarding nonprescription drugs, as well as regulations pertaining to the sale of nonprescription drugs, including the use of postal services. Among the respondents, 7.5% were Internet users, whereas people who had past experiences in purchasing nonprescription drugs through Internet accounted for as few as 0.8% of the total number of respondents; 63.9% of the inhabitants of small remote islands did not use nonprescription drugs, additionally, most inhabitants of small remote islands did not express any need for nonprescription drugs sold through Internet. Further, the findings suggested that a large number of people felt the need for the presence of pharmacists and experts to provide them with explanations and information regarding nonprescription drugs. However, because a large number of these people were unaware of the existence of pharmacists, it is important that in the future, pharmacists should conduct “consultation meetings and briefings regarding medications.” These meeting may be held in a continuous manner in these small remote islands, such that the inhabitants recognize the difference in a pharmacists' profession. It is essential that “family pharmacies/pharmacists” play a central role in promoting the supply, management, and proper use of pharmaceutical products.
抄録全体を表示PDF形式でダウンロード (1387K)
- |<
- <
- 1
- >
- >|