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127 巻, 11 号
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誌上シンポジウム
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大井 一弥2007 年 127 巻 11 号 p. 1765-1766
発行日: 2007/11/01
公開日: 2007/11/01
ジャーナル フリーPDF形式でダウンロード (171K) -
町田 聖治, 増田 和久, 片岡 泰文2007 年 127 巻 11 号 p. 1767-1779
発行日: 2007/11/01
公開日: 2007/11/01
ジャーナル フリーPharmacological support for the appropriate use of drugs is important. To promote such support, it is necessary to be involved in drug therapy from viewpoints different from those of physicians and nurses, using tools unique to pharmacists, pharmacologically discuss individual cases, and investigate the validity of prescriptions by accumulating data. In Chapter 1, digoxin is necessary to monitor therapy very closely. In addition, patients with an impaired renal dysfunction have a predisposition for developing digitalis toxicity. In clinical cases, digoxin and verapamil are often co-administered for heart rate control, and we have observed the serum trough level of beta-methyldigoxin to be elevated due to drug-interaction. We build upon our previous findings and generated a simple index for the adequate administration dosage of beta-methyldigoxin based on variable degrees of renal function and the serum trough level of beta-methyldigoxin. In Chapter 2, to investigate risk factors of postoperative infection following cardiac surgery, we conducted a retrospective analysis of two surgical procedures, off-pump coronary artery bypass grafting (OPCAB) and surgery for valvular heart disease (valve operation). After discussing the analysis results with the respective physicians, the dosing guidelines for cefazolin (CEZ) were changed. We also analyzed the rate of CEZ replacement with other antibiotics after surgery finding that it decreased in both groups for OPCAB and valve operations. From these results, we conclude that, if CEZ is also administered intra-operatively when surgery is prolonged, its administration for two days following surgery is adequate for prophylaxis against postoperative infection.
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佐藤 弘希, 丸山 徹2007 年 127 巻 11 号 p. 1781-1787
発行日: 2007/11/01
公開日: 2007/11/01
ジャーナル フリーA clinical research is not only an important issue for hospital pharmacist but also for community pharmacist because it is necessary to practice high quality pharmaceutical care. It goes without saying that drug and patient's informations are of great importance to investigate the clinical research in community pharmacist. However, the accessibility of latter information is limited to prescription, medication note, medication and care records, interview to the patients for community pharmacist, so far. Therefore, likewise pharmaceutical care, the abilities that find and solve the problems is very important for the clinical research by community pharmacist. In addition, it should consider that it cooperates with the facilities such as the hospital and faculty of university. This paper give a summary account of the usefulness of clinical research on the practice of pharmaceutical care for community pharmacy using our three examples such as, 1)Evaluation of usefulness of population pharmacokinetics analysis results to community pharmacy -effect of smoking and gender difference on olanzapine dosages, 2)Investigation of binding of drugs with natural polymer supplements, 3)Health promotion by primary-care pharmacist -Usefulness of educational activitys for importance of folic acid intake in pregnancy-aged women, which have been worked together with hospital pharmacist, faculty of university, and community resident, respectively.
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片山 歳也2007 年 127 巻 11 号 p. 1789-1795
発行日: 2007/11/01
公開日: 2007/11/01
ジャーナル フリーWith the revisions to the Japanese medical institutions law of April 2006, an improved medical care security system in a medical institution is indispensable. More and more medical institutions are now assigning full-time pharmacists to the task of medical safety. Hospital pharmacy sections are utilizing a valid evaluation system developed by the Japan Council for Quality Health Care. Pharmaceutical specialists who contribute to medical security, such as certified oncology pharmacists and certified infection control pharmacists (CICPha) are much awaited. In addition, the DPC (Diagnosis Procedure Combination) system has now become widespread in Japan, and the call is for pharmaceutical care that can decrease medical costs. It is imperative for health care systems to assure the appropriate use of drugs to decrease medical costs without reducing medical services. CICPha can contribute to the antimicrobial management program, and has also focused on medical care security. Several antimicrobial management programs of broad-spectrum agents, i.e., formulary restriction and prior approval, are gradually being enforced in Japan. The CICPha role is far-reaching, and it should make a concerted effort to prevent the injudicious use of antimicrobial agents resulting in the emergence of drug resistance; this must be handled by infection control doctors and nurses along with microbiological technicians. The CICPha must regulate the appropriate use of these agents, and perform surveillance of antimicrobial use and resistance (AUR). We describe the necessity and evaluation of AUR, and also underscore the necessity of training clinical pharmacists who will contribute to patient safety in days to come.
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大井 一弥2007 年 127 巻 11 号 p. 1797-1799
発行日: 2007/11/01
公開日: 2007/11/01
ジャーナル フリーThere are many clinical problems which are raised but not responded sufficiently, and pharmacy school plays a key role to solve these problems. We introduce the case in which pharmacy school collaborated with hospital about the clinical problem. Many hemodialysis patients experience much physical and mental pain associated with needle insertion before dialysis. To alleviate this, tape-type lidocaine-containing local anesthetic patches (Penles®, Wyeth, Japan) are widely used. However, the efficacy of Penles® in alleviating pain associated with needle insertion is often limited. Hemodialysis patients exhibit a variety of dermatological symptoms, such as pruritus, xerosis, and erythema. These symptoms may affect the transdermal lidocaine absorption. We surveyed the current use of Penles® and evaluated skin conditions in hemodialysis patients. The results revealed that hemodialysis patients had applied Penles® for about 100 minutes, and the electrical capacitance of the skin surface of hemodialysis patients was significantly lower than that of healthy volunteers. In consideration of these results, we investigated a skin hydration method to enhance the absorption of lidocaine with porcine ear skin. In the result, lidocaine concentration increased significantly with skin hydration. Furthermore, this method was examined with hemodialysis patients, and the results revealed that this skin hydration method might be beneficial. This case was carried out by the collaboration between hospital and pharmacy school, and a clinical sense is necessary for such pharmaceutical research.
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廣谷 芳彦2007 年 127 巻 11 号 p. 1801-1804
発行日: 2007/11/01
公開日: 2007/11/01
ジャーナル フリーThe new pharmaceutical education system starts in Japan, those constructions are performed at a lot of universities aiming at the execution of a common examination and the clinical training, and the workshop for directive pharmacists have been held actively since last year. Moreover, various educational lectures, open lectures, and the training lectures for on-site pharmacist's upskilling are carried out. However, a technical training and the lecture for research approach that supports the pharmacist in a pharmaceutical clinical research are little at the chance to learn the research methods. Now, many joint researches with university initiative or a university is performed, and the institution of presentation inexperience at academic society also exists in terms of a regional element, a staff arrangement side, etc, and also when the continuation is difficult, it looks mostly. It is necessary that the teacher of pharmacy school almost arranged in the whole country support positively a clinical research by the nearby pharmacist, and also it seems that a clinical teacher's role is large in the cooperation of pharmacy school and the medical institution. Moreover, in order to elucidate the scientific basis (mechanism) of a problem suggestion in the clinical spot, basic research in a pharmacy school is also required. We always need to advance a pharmaceutical clinical research by considering the basic research by pharmacy school in medical institution, considering clinical research by medical institution in pharmacy school, while cooperating mutually. In this article, I show how to advance pharmaceutical clinical research.
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高村 徳人, 徳永 仁, 帖佐 悦男, 川井 恵一, 藤田 健一, 有森 和彦2007 年 127 巻 11 号 p. 1805-1811
発行日: 2007/11/01
公開日: 2007/11/01
ジャーナル フリーIn pharmacotherapy, to alleviate pains of patients and to provide comforts to patients, pharmacists should improve their pharmaceutical skills of their clinical sense involving pharmaceutical investigational outcomes. Without pharmaceutical skills, pharmacists cannot apply the essence of drug therapies for patients in the most urgent 24 hours treatment. To cope with these drug therapies, we have developed search methods which easily identify the diachronic change of protein binding and the factors in serum (=a new pharmaceutical distribution diagnostic method). This method can speculate diachronic change factors in serum, by monitoring diachronically binding capacities of drug binding sites on human serum albumin (HSA) and α1-acid glycoprotein (AGP) molecules in patient sera (add each site probe to each patient serum, and measure the free level of each probe by using TDX/FLX® analyzer and HPLC detector), and considering the binding capacities and values of HSA, AGP, free fatty acids, bilirubin (Bil) and blood urea nitrogen (BUN) associating with the amounts of uremic toxins laboratory tests. In addition, the diagnostic method could attempt effective administration by using the protein binding displacement of drugs that have a high protein binding capacity and small distribution volume, or high targeting (=the pharmaceutical skill of protein binding displacement). We have practiced pain control of patients with rheumatoid arthritis by the pharmaceutical skill. It is important for pharmacists to master the pharmaceutical skill in pharmacotherapy.
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総説
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竹尾 聰, 高木 教夫, 高木 慶子2007 年 127 巻 11 号 p. 1813-1823
発行日: 2007/11/01
公開日: 2007/11/01
ジャーナル フリーCerebral ischemia causes an irreversible and neurodegenerative disorder that may lead to progressive dementia and global cognitive deterioration. Since the overall process of ischemic brain injuries is extremely complex, treatment with endogenous multifunctional factors would be better choices for preventing complicated ischemic brain injuries. Hepatocyte growth factor, HGF, is a multifunctional cytokine originally identified and purified as a potent mitogen for hepatocyte. The activation of the c-Met/HGF receptor evokes diverse cellular responses, including mitogenic, morphogenic, angiogenic and anti-apoptotic activities in various types of cell. Previous studies showed that HGF and c-Met were expressed in various brain regions under normal conditions and that HGF enhanced the survival of hippocampal and cortical neurons during the aging of cells in culture. The protective effects of HGF on in vivo ischemic brain injuries and their mechanisms have not fully understood. To elucidate therapeutic potencies of HGF for ischemic brain injuries, we examined effects of HGF on ischemia-induced learning and memory dysfunction, neuronal cell death and endothelial cell damage by using the 4-vessel occlusion model and the microsphere embolism model in rats. Our findings suggested that treatment with HGF was capable of protecting hippocampal neurons against ischemia-induced cell death through the prevention of apoptosis-inducing factor translocation to the nucleus. Furthermore, we demonstrated that HGF had the ability to prevent tissue degeneration and improved learning and memory function after cerebral embolism, possibly through prevention of cerebral vessel injuries. As HGF has a potent cerebroprotective effect, it could be a prospective agent for the therapy against complicated ischemic brain diseases.
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岡 希太郎2007 年 127 巻 11 号 p. 1825-1836
発行日: 2007/11/01
公開日: 2007/11/01
ジャーナル フリーWith an increasing number of studies describing the negative correlation of coffee consumption and the risk for type 2 diabetes mellitus, we were compelled to elucidate the nutrients which bring pharmacological effects on risk reduction for diabetes. In this review, the author's interest is focused on chlorogenic and caffeic acids derived from lightly roasted coffee beans, as well as nicotinic acid, volatile Maillard reaction products (vMRPs), and another structurally unknown compound contained in heavily roasted beans. Caffeine is a common compound in both lightly and heavily roasted beans and its anti-inflammatory effects on degenerative diseases such as diabetes mellitus has been reevaluated recently. The prophylactic effects of coffee on diabetes involve pleiotropy of plural components in accordance to the degree of the roasting. A new concept of nutritional blended coffee may be important to optimize the prophylactic effects of coffee on lowering the risk factors of diabetes and delaying the progress of diabetes complications as well.
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水谷 秀樹2007 年 127 巻 11 号 p. 1837-1842
発行日: 2007/11/01
公開日: 2007/11/01
ジャーナル フリーA number of anticancer drugs exert their effect by causing DNA damage and subsequent apoptosis induction. Reactive oxygen species (ROS), such as hydrogen peroxide (H2O2) and super oxide anion (O2-), participate in apoptosis and DNA damage induced by some anticancer drugs, however, the precise mechanism of apoptosis via ROS formation remains to be clarified. I investigated the mechanism of apoptosis and DNA damage induced by anticancer drugs, especially topoisomerase inhibitors, using human cultured cells. TAS-103, a topoisomerase inhibitor, induces apoptosis through DNA cleavage and subsequent H2O2 generation mediated by poly (ADP-ribose) polymerase (PARP) and NAD(P)H oxidase activation. Doxorubicin (DOX), an anthracycline antibiotic and topoisomerase inhibitor, induces apoptosis through direct oxidative DNA damage leading to indirect H2O2 generation mediated by PARP and NAD(P)H oxidase activation. DOX caused site-specific oxidative DNA damage in the presence of copper(II), which may contribute to apoptosis. These findings suggest that ROS formation plays important roles in apoptosis induced by anticancer drugs. Furthermore, these studies may provide an insight into the development of new effective chemotherapeutic drugs.
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田中 将史2007 年 127 巻 11 号 p. 1843-1849
発行日: 2007/11/01
公開日: 2007/11/01
ジャーナル フリーInteraction of apolipoproteins with lipid surfaces plays crucial roles in lipoprotein metabolism and cholesterol homeostasis. In this study, to understand the detailed mechanism by which apolipoprotein (apo) A-I associates with plasma membrane and lipoprotein particles, we investigated the effects of lipid composition and surface curvature on the lipid-apoA-I interactions. ApoA-I binding to lipid particles depends on membrane structure. Fluorescence and 13C-NMR measurements revealed that apoA-I recognizes headgroup separation (hydrated space) between phospholipid molecules and displaces water molecules from the surface when it binds. At the surface monolayers of lipoprotein particles, interpenetration of core triglyceride molecules with phospholipid molecules appears to occur to alter the surface structure. ApoA-I binding to lipid membrane induces an increase in α-helical structure. This α-helix formation generates exothermic heat and promotes apoA-I binding to lipid. However, binding of apoA-I to small emulsions exhibited endothermic heat although apoA-I increases α-helical content. Taken together, these observations suggest that the presence of core triglyceride modifies the highly curved emulsion surface and thereby the thermodynamics of apoA-I binding in a manner that compensates for the exothermic heat generated by α-helix formation.
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一般論文
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Hai TANG, Ning XU, Jin MENG, Chao WANG, Shu-fang NIE, Wei-san PAN原稿種別: Regular Article
2007 年 127 巻 11 号 p. 1851-1862
発行日: 2007/11/01
公開日: 2007/11/01
ジャーナル フリーA novel approach which had foreground of industrialization, surface liquid spraying, was studied in this paper to prepare biodegradable polylactic-co-glycolic acid (PLGA) microspheres for controlled release drug delivery system. To compare with the normal methods, the microspheres prepared by this approach were characterized by particle size distribution and photograph of microscope. The relationship between the particle size and the instrument parameters of novel method was set up for the first time. The central composite design (CCD) was applied to study the main effects and interactions of three instrument factors on preparation of microspheres. The particle size of microspheres was below 200 μm and the shape of microspheres was spherical in nature evidenced by microscope photographs. Vinpocetine was used as the model drug to prepare the vinpocetine PLGA microspheres (VIN-PLGA-MS), and then drug loading, entrapment efficiency, scanning electron microscopy (SEM), Differential Scanning Calorimetry (DSC) and in vitro drug release behavior were examined. The results indicated that the drug loading and entrapment efficiency were increased using the novel method. The drug released slowly more than 30 days. The release behavior was fit for four kinds of kinetic model. The result indicated that release behavior was fitted by Zero-order kinetic model before release 72 hours, and was fitted with First-order kinetic model after release 72 hours. The novel method developed in our paper can give a promising way for industrialization, and the foreground was also proved by the scale-up batch experiment.
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Selvakumar DHANALAKSHMI, Rathinasamy Sheela DEVI, Ramasundaram SRIKUMA ...原稿種別: Regular Article
2007 年 127 巻 11 号 p. 1863-1867
発行日: 2007/11/01
公開日: 2007/11/01
ジャーナル フリーStress is one of the basic factors in the etiology of number of diseases. Cold-stress occurs when the surrounding temperature drops below 18°C, the body may not be able to warm itself, and hence serious cold-related illnesses, permanent tissue damage and death may results. The present study was aimed to investigate the effect of Triphala (Terminalia chebula, Terminalia belerica and Emblica officinalis) against the cold stress-induced alterations in the behavioral and biochemical abnormalities in four different groups (saline control, Triphala, cold-stress and Triphala with cold-stress) of Wistar strain albino rats. In this study cold-stress (8°C for 16 h/d/15 days) was applied and the oxidative stress was assessed by measuring the extent of lipid peroxidation (LPO) and the changes in corticosterone levels. Upon exposure to the cold-stress, a significant (P<0.05) increase in immobilization with decrease in rearing, grooming, and ambulation behavior was seen in open field. Following cold-exposure, significant increase in the LPO and corticosterone levels was observed. Oral administration of Triphala (1 g/kg/animal body weight) for 48 days significantly prevented these cold stress-induced behavioral and biochemical abnormalities in albino rats. The results of this study suggest that Triphala supplementation can be regarded as a protective drug against stress.
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Yu YUN, Peng CHEN, Chun Lan ZHENG, Yong YANG, Wei Gang DUAN, Lei WANG, ...原稿種別: Regular Article
2007 年 127 巻 11 号 p. 1869-1875
発行日: 2007/11/01
公開日: 2007/11/01
ジャーナル フリーThe antiinflammatory effects of the copper-aspirin complex (Cu-Asp) were more potent than that of Asp in rats or mice with fewer classic adverse effects. The aim of this study was to determine the cause by evaluating Cu-Asp selective inhibition on cyclooxygenases (COX). COX-1 inhibition was evaluated based on 6-keto-prostaglandin F1α (6-keto-PGF1α) in an endothelial cell model, and COX-2 inhibition was based on prostaglandin E2 (PGE2) in a macrophage model. Radioimmunoassay (RIA) was applied to determine 6-keto-PGF1α in resting human umbilical vein endothelial cell line (ECV304), and PGE2 in activated macrophages. The results showed that the inhibition of 6-keto-PGF1α yield by Cu-Asp (3 to 0.01 mM) was markedly weaker than that by aspirin (Asp); while the inhibition of PGE2 yield by Cu-Asp (10 to 0.1 mM) was significantly stronger than that by Asp. Based on the inhibition on 6-keto-PGF1α and PGE2, the medium inhibitory concentration (IC50) of Cu-Asp on COX-1 and on COX-2 was 1.03±0.15 mM, and 0.32±0.04 mM, respectively. The selective inhibition index on COX-2, IC50 (COX-1)/IC50 (COX-2), of Cu-Asp was 3.33±0.89, while that of Asp was 0.42±0.12. The results suggest that, unlike Asp, Cu-Asp is a relatively selective inhibitor of COX-2 in the present models; the selectivity of Cu-Asp is about seven-fold greater than that of Asp.
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野村 政孝, 圓尾 奈緒美, 座間味 義人, 高取 真吾, 土井 志真, 川崎 博己2007 年 127 巻 11 号 p. 1877-1882
発行日: 2007/11/01
公開日: 2007/11/01
ジャーナル フリーRoyal jelly (RJ) is known to have abundant nutritional properties and a variety of biological activities. To investigate the effects of RJ on insulin resistance, 10-week-old Otsuka Long-Evans Tokushima Fatty (OLETF) rats, a type 2 diabetic model, were treated for 4 weeks with RJ (10, 30, and 300 mg/kg, p.o.). RJ treatment tended to decrease systolic blood pressure and significantly decreased serum levels of insulin and the Homeostasis Model Assessment ratio, an index of insulin resistance. In isolated and perfused mesenteric vascular beds of OLETF rats, RJ treatment resulted in significant reduction of the sympathetic nerve-mediated vasoconstrictor response to periarterial nerve stimulation (PNS) and potentiation of the calcitonin gene-related peptide (CGRP) nerve-mediated vasodilator response to PNS, compared with that in untreated OLETF rats. However, RJ treatment did not significantly affect norepinephrine-induced vasoconstriction and CGRP-induced vasodilation. These results suggest that RJ could be an effective and functional food to prevent the development of insulin resistance.
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ノート
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田山 剛崇, 三宅 勝志, 長藤 多香美, 郷原 貴子, 森田 修之, 新井 茂昭, 佐藤 英治, 北浦 照明, 木平 健治2007 年 127 巻 11 号 p. 1883-1889
発行日: 2007/11/01
公開日: 2007/11/01
ジャーナル フリーTacrolimus is an immunosuppressive drug that causes glucose intolerance. On the other hand, ciprofloxacin, which is widely used in the treatment of infectious diseases, is known to cause hypoglycemia as a side effect. We investigated the effects of tacrolimus and ciprofloxacin on serum glucose and insulin levels in rats, as well as on insulin secretion and the viability of HIT-T15 cells. The rats received intraperitoneal injections of tacrolimus and/or ciprofloxacin for 1 week, and their arterial blood was sampled after the administration of glucose. HIT-T15 cells were cultured in the presence of tacrolimus and/or ciprofloxacin, and the insulin level in the supernatant was measured. Ciprofloxacin did not show a significant effect on serum glucose and insulin levels after multiple administrations in the rats. In contrast, rats in the tacrolimus treatment group showed low serum insulin and high serum glucose levels. Moreover, the coadministration of ciprofloxacin and tacrolimus resulted in higher glucose levels compared with tacrolimus alone 0.5 h after glucose stimulation. In addition, we observed that the rats administered tacrolimus and/or ciprofloxacin had low body weight and food intake. Tacrolimus caused a dose-dependent decrease in the viability of the HIT-T15 cells. Furthermore, both drugs were highly toxic to HIT-T15 cells. In contrast, tacrolimus alone and coadministration of the drugs resulted in no significant difference in insulin secretion. These results suggest that the cytotoxic effects of ciprofloxacin and tacrolimus cause a decrease in insulin secretion, leading to glucose intolerance.
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菱沼 滋, 齋藤 政樹原稿種別: Note
2007 年 127 巻 11 号 p. 1891-1894
発行日: 2007/11/01
公開日: 2007/11/01
ジャーナル フリーIt is important to clarify developmental mechanisms of desensitization because of their great significance in regulation of cellular responsiveness. We have found that carbachol-induced desensitization to carbachol develops in three successive phases in the presence of extracellular Ca2+ in the smooth muscle of guinea pig taenia caeci: fast desensitization within 15 s, transient resensitization reaching a peak at 1 min and the subsequent re-development of desensitization to terminate resensitization for up to 30 min. In contrast, in the absence of extracellular Ca2+, desensitization develops without resensitization. To further clarify the roles of Ca2+ in the formation of the transient resensitization phase, we examined the developmental process of carbachol-induced desensitization in the absence of extracellular Ca2+, following the induction of desensitization by a 15-s treatment with carbachol in the presence of extracellular Ca2+. Desensitization to carbachol occurred due to pretreatment with 10-4 M carbachol for 15 s in normal physiological solution, and continued pretreatment with carbachol in Ca2+-free solution containing 0.2 mM EGTA induced resensitization followed by the obscure progress of re-desensitization for up to 30 min resulting in a long-lasting phase of resensitization. These results suggest that resensitization is promptly terminated by the Ca2+-dependent development of subsequent desensitization for further regulation of cellular responsiveness via Gq protein-coupled Ca2+-mobilizing receptors against sustained stimuli.
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