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Innovative Approaches for Next-generation Biodrugs Development.
PMID: 26135082 [PubMed - as supplied by publisher] (Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan)
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - July 3, 2015 Category: Drugs & Pharmacology Authors: Tsunoda SI, Ishii-Watabe A Tags: Yakugaku Zasshi Source Type: research

Development of New Biologics through Creation of a Functional Cytokine Mutant.
In this study, tumor necrosis factor (TNF) was used as a model cytokine to create agonist and antagonist activities against two TNF receptors TNFR1 and TNFR2, respectively. We created a phage library expressing mutant TNF, where the amino acids in the binding interface between TNF and TNF receptors were alternately exchanged. Affinity panning was performed at the optimum condition and the bioactivities of these mutant TNFs were analyzed to obtain the objective agonists or antagonists. The pharmacological activity and toxicity of these engineered TNF mutants could indicate their potential use as novel biopharmaceutical agen...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - July 3, 2015 Category: Drugs & Pharmacology Authors: Kamada H Tags: Yakugaku Zasshi Source Type: research

Functionalization of Bispecific Therapeutic Antibodies Based on Protein Engineering.
Abstract   Although antibodies have been used as molecularly targeted agents for difficult-to-treat diseases such as cancers, the high production costs associated with mammalian expression systems continue to be a drawback. In addition, the clinical efficacy of conventional IgG antibodies is limited. Several types of recombinant antibody (e.g. fused with anticancer drugs, multivalent, or multispecific) have been designed in efforts to develop next-generation antibodies with higher functionality. We used protein engineering to construct several anticancer recombinant antibodies by developing bispecific antibodies ...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - July 3, 2015 Category: Drugs & Pharmacology Authors: Asano R, Kumagai I Tags: Yakugaku Zasshi Source Type: research

Nonclinical Evaluation of Next-generation Therapeutic Monoclonal Antibodies.
Abstract   Therapeutic monoclonal antibodies (mAbs) exert their effects via binding to specific target molecules, which is expected to show rare off-target adverse reactions. However, nonclinical evaluation of mAbs is difficult because they often lack reactivity toward orthologous targets in animals. During the nonclinical evaluation of mAbs, not only the target molecules but fragment crystallizable (Fc) receptors, which regulate the immune effector functions and pharmacokinetic properties of mAbs, should be considered. In this review, factors for extrapolating nonclinical study results to clinical settings are d...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - July 3, 2015 Category: Drugs & Pharmacology Authors: Ishii-Watabe A, Tada M, Suzuki T, Kawasaki N Tags: Yakugaku Zasshi Source Type: research

Sugar Chain Construction of Functional Natural Products Using Plant Glucosyltransferases.
Abstract   Plant secondary product glycosyltransferases belong to family 1 of the glycosyltransferase superfamily and mediate the transfer of a glycosyl residue from activated nucleotide sugars to lipophilic small molecules, thus affecting the solubility, stability and pharmacological activities of the sugar-accepting compounds. The biotechnological application of plant glycosyltransferases in glycoside synthesis has attracted attention because enzymatic glycosylation offers several advantages over chemical methods, including (1) avoiding the use of harsh conditions and toxic catalysts, (2) providing strict contr...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - July 3, 2015 Category: Drugs & Pharmacology Authors: Mizukami H Tags: Yakugaku Zasshi Source Type: research

Vacuolar H(+)-ATPase and the Secondary Transporters: Their Identification, Mechanism, Function and Physiological Relevance.
Abstract   Eukaryotic cells possess acidic compartments with pH ranging from 0.1-6.5. Studies in the last couple of decades indicated that the acid pool is established by vacuolar proton ATPase, and is essential for various physiological and pathological processes. I have identified the vacuolar ATPase as well as several secondary transporters which are energetically coupled with vacuolar ATPase. I have also established the protocol for analysis of the structure and function of transporter proteins applicable to essentially all known transporters. In this article, I am going to summarize this study and describe s...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - July 3, 2015 Category: Drugs & Pharmacology Authors: Moriyama Y Tags: Yakugaku Zasshi Source Type: research

Development and Validation of Estimate Equations for Adverse Drug Reactions Using Risk Factors and Subjective Symptoms.
Abstract   The purpose of this study was to develop and validate estimate equations for preventing adverse drug reactions (ADRs). We conducted five case-control studies to identify individual risk factors and subjective symptoms associated with the following five ADRs: drug-induced ischemic heart disease; renal damage; muscle disorder; interstitial pneumonia; and leucopenia. We performed logistic regression analysis and obtained eight regression equations for each ADR. We converted these to ADR estimate equations for predicting the likelihood of ADRs. We randomly selected 50 cases with non-individual ADRs from th...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - July 3, 2015 Category: Drugs & Pharmacology Authors: Suzuki R, Ohtsu F, Goto N Tags: Yakugaku Zasshi Source Type: research

Frontier of gastrointestinal taste and nutrient sensor research: search for potential drug target.
PMID: 26028410 [PubMed - in process] (Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan)
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - June 3, 2015 Category: Drugs & Pharmacology Authors: Takeuchi K, Uneyama H Tags: Yakugaku Zasshi Source Type: research

Role of the sweet taste receptor in glucose metabolism: no sweets for diabetes?
Abstract   Type 2 diabetes is closely associated with our daily diets and has become a global health problem with increasing number of patients. Maintaining energy homeostasis is essentially required for the treatment of diabetes. Energy metabolism starts with taking in a meal. Nutrients including amino acids, fatty acids and glucose in the digest have been shown to act on the neuroendocrine cells in the gastrointestinal (GI) tract, and thereby play important roles in energy homeostasis. Therefore, the GI tract is now recognized as a sensor system for nutrient signals. Taste receptor type 1 member 2 (T1R2) is kno...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - June 3, 2015 Category: Drugs & Pharmacology Authors: Nomura M, Kawahara Y Tags: Yakugaku Zasshi Source Type: research

Free Fatty Acid receptor family: a new therapeutic target for metabolic diseases.
Abstract   Free fatty acids (FFAs) are not only essential nutritional components but they also act as signaling molecules in various physiological processes. A strategy to deorphanize G-protein-coupled receptors (GPCRs) identified a series of receptors for FFAs that play significant roles in nutrition regulation. In this free fatty acid receptor family, FFAR1 (GPR40) and FFAR4 (GPR120) are activated by long-chain FFAs. FFAR1 regulates insulin secretion in pancreatic β-cells, whereas FFAR4 promotes the secretion of glucagon-like peptide-1 (GLP-1) in the intestine, and also acts as a lipid sensor in adipose tissue...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - June 3, 2015 Category: Drugs & Pharmacology Authors: Hirasawa A Tags: Yakugaku Zasshi Source Type: research

Glutamate as a potential protective drug in the gastrointestinal mucosa.
Abstract   Monosodium glutamate (MSG) is known to provide the umami taste in the food. We have recently reported that glutamate has the potential to protect the small intestine against non-steroidal anti-inflammatory drugs (NSAIDs)-induced lesions in rats. In this paper, we examined this protective effect using sodium loxoprofen, one of the NSAIDs frequently used in Asian countries, to determine whether MSG accelerates the healing of loxoprofen-induced small intestinal lesions in rats. Loxoprofen at 60 mg/kg caused hemorrhagic lesions in the small intestine, mainly in the jejunum and ileum. These lesions spontane...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - June 3, 2015 Category: Drugs & Pharmacology Authors: Amagase K, Nakamura E, Kato S, Takeuchi K Tags: Yakugaku Zasshi Source Type: research

New remedy for dry mouth using the gustatory-salivary reflex.
We examined the gustatory-salivary reflex to explore a remedy for dry mouth. We have demonstrated that umami stimulation increases saliva from both minor- and major salivary-glands, and that the effect is longer-lasting than with the other four basic tastes. Stimulating the umami response could therefore be a safe and useful remedy for dry mouth. PMID: 26028414 [PubMed - in process] (Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan)
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - June 3, 2015 Category: Drugs & Pharmacology Authors: Kuriwada-Satoh S, Sasano T Tags: Yakugaku Zasshi Source Type: research

Impact of Taste Sensitivity on Lifestyle-related Diseases.
Abstract   Individual taste sensitivity affects one's eating habits, and could thus play a role in the development of lifestyle-related diseases, such as obesity, hypertension and dyslipidemia. However, only a handful of studies have been conducted to investigate these associations. Therefore, we performed taste sensitivity tests on approximately 250 patients with lifestyle-related diseases who were undergoing outpatient treatment at the Department of Internal Medicine, or received a health check-up in order to examine the associations of individual taste sensitivity with their eating habits and lifestyle-related...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - June 3, 2015 Category: Drugs & Pharmacology Authors: Mizuta E Tags: Yakugaku Zasshi Source Type: research

Bias and confounding: pharmacoepidemiological study using administrative database.
Abstract   The provision of health care frequently creates digitalized data such as hospital-based electronic data, medication prescription records, and claims data collectively termed "administrative database research". The data source and analytical opportunities for study create risks that can lead to misinterpretation or bias the results. This review serves as an introduction to the concept of bias and confounding to help researchers conduct methodologically sound pharmacoepidemiologic research projects using administrative databases. Beyond general considerations for observational study, there are several un...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - June 3, 2015 Category: Drugs & Pharmacology Authors: Nojiri S Tags: Yakugaku Zasshi Source Type: research

Plasma concentrations of anionic uremic toxins in hemodialysis patients and their effects on protein binding of pravastatin.
In this study, we assayed plasma concentrations of three typical anionic UTs, indoxyl sulfate (IS), 3-indoleacetic acid (IA), and 3-carboxy-4-methyl-5-propyl-2-furanpropionic acid (CMPF), in 20 hemodialysis patients and 5 healthy volunteers. Moreover, the effects of these anionic UTs on the binding of pravastatin to human serum albumin (HSA) were also evaluated. CMPF concentrations in the plasma of patients were unchanged before and after dialysis (63.0±6.3 μM and 65.1±6.7 μM, respectively), and these values were about 5-fold greater compared with those in healthy volunteers. Although dialysis decreased the plasma IS c...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - June 3, 2015 Category: Drugs & Pharmacology Authors: Ichimura Y, Takamatsu H, Ideuchi H, Oda M, Takeda K, Saitoh H Tags: Yakugaku Zasshi Source Type: research

Evaluation of Antibiotics for the Treatment of Bacteremia Due to Extended-spectrum β-Lactamase-producing Escherichia coli.
In conclusion, patients at high risk of infection due to ESBL-producing E. coli should be empirically treated with carbapenem antibiotics. In addition, cefmetazole may be a treatment option for patients with ESBL-producing E. coli bacteremia. PMID: 26028418 [PubMed - in process] (Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan)
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - June 3, 2015 Category: Drugs & Pharmacology Authors: Sugawara T, Murakami N, Uetake N, Hiraki K Tags: Yakugaku Zasshi Source Type: research

Effect of food thickener on disintegration and dissolution of magnesium oxide tablets.
Abstract   It has been reported that magnesium oxide tablets are excreted in a non-disintegrated state in the stool of patients when the tablets are administered after being immersed in a food thickener. Therefore we examined whether immersion in a food thickener affects the pharmacological effect in patients taking magnesium oxide tablets, and whether immersion affects its disintegration and solubility. The mean dosage (1705 mg/d) was higher for patients who took tablets after immersion in a food thickener than for those who took non-immersed tablets (1380 mg/d). The disintegration time and dissolution rate of t...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - June 3, 2015 Category: Drugs & Pharmacology Authors: Tomita T, Goto H, Yoshimura Y, Tsubouchi Y, Nakanishi R, Kojima C, Yoneshima M, Yoshida T, Tanaka K, Sumiya K, Kohda Y Tags: Yakugaku Zasshi Source Type: research

Regulatory science on biomarker usage for development and proper use of drugs.
PMID: 25948296 [PubMed - in process] (Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan)
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - May 9, 2015 Category: Drugs & Pharmacology Authors: Saito Y, Tohkin M Tags: Yakugaku Zasshi Source Type: research

Regulatory science for the proper evaluation of biomarkers (overview).
Abstract   New drug development (NDD) for intractable diseases such as cancer and Alzheimer's disease has been challenging in recent years because it is difficult to evaluate the therapeutic efficacy of new drugs and the response of individual patients. Thus biomarkers might be a useful tool to facilitate NDD because they can be used to evaluate accurately drug responses. Biomarkers include proteins, metabolites, and genetic targets; imaging data and can also be used in pre-clinical studies, clinical trials, and post-marketing surveillance. In pre-clinical studies, biomarkers are used as an index of the pharmacol...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - May 9, 2015 Category: Drugs & Pharmacology Authors: Tohkin M, Saito Y Tags: Yakugaku Zasshi Source Type: research

Investigation of Predisposition Biomarkers to Identify Risk Factors for Drug-induced Liver Injury in Humans: Analyses of Endogenous Metabolites in an Animal Model Mimicking Human Responders to APAP-induced Hepatotoxicity.
Abstract   Drug-induced liver injury is a main reason of regulatory action pertaining to drugs, including restrictions to clinical indications and withdrawal from the marketplace. Acetaminophen (APAP) is a commonly used and effective analgesic/antipyretic agent and relatively safe drug even in long-term treatment. However, it is known that APAP at therapeutic doses may cause hepatotoxicity in some individuals. Hence great efforts have been made to identify risk factors for APAP-induced chronic hepatotoxicity. We investigated the contribution of undernourishment to susceptibility to APAP-induced chronic hepatotoxi...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - May 9, 2015 Category: Drugs & Pharmacology Authors: Kobayashi A, Kondo K, Sugai S Tags: Yakugaku Zasshi Source Type: research

Development of mogamulizumab and establishment of an optimal therapy based on genomic biomarkers: from the academic viewpoint.
Abstract   Mogamulizumab (Moga; KW-0761) is a defucosylated humanized anti-CC chemokine receptor 4 (CCR4) antibody engineered to exert potent antibody-dependent cellular cytotoxicity (ADCC). A collaborative investigation with industry in preclinical studies has demonstrated in vitro and in vivo efficacy via ADCC for adult T-cell leukemia/lymphoma (ATLL) and CCR4-positive peripheral T-cell lymphoma (PTCL). In a phase I study, once-weekly administration of mogamulizumab (0.01-1.0 mg/kg) for 4 weeks was well tolerated. In a phase II study of once-weekly mogamulizumab (1.0 mg/kg) for 8 weeks in relapsed/refractory AT...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - May 9, 2015 Category: Drugs & Pharmacology Authors: Iida S, Ishida T, Ueda R Tags: Yakugaku Zasshi Source Type: research

Utilization of Genomic Biomarkers for Post-marketing Safety of Drugs.
Abstract   To prevent adverse drug reactions in the post-marketing phase, therapeutic drug monitoring and various laboratory tests have been used for decades. Recently, data on associations between drug adverse reactions and biomarkers based on "omics" technologies/studies have been increasing. Using genomic biomarkers, patients at high risk for developing side effects can be distinguished before initiating medical treatment, allowing the choice of an appropriate drug/initial dosage regimen. Biomarkers based on proteomics or metabolomics can detect the onset of adverse reactions at an earlier stage than can be ac...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - May 9, 2015 Category: Drugs & Pharmacology Authors: Kaniwa N Tags: Yakugaku Zasshi Source Type: research

Current PMDA Activities for Use of Biomarkers in Drug Evaluation.
This article outlines the regulatory perspective on remaining challenges and current Pharmaceuticals and Medical Devices Agency (PMDA) activities for use of BM in drug evaluation. PMID: 25948301 [PubMed - in process] (Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan)
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - May 9, 2015 Category: Drugs & Pharmacology Authors: Ishiguro A Tags: Yakugaku Zasshi Source Type: research

Frontiers in research of drug transporters aimed at appropriate pain relief by narcotic analgesics.
PMID: 25948302 [PubMed - in process] (Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan)
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - May 9, 2015 Category: Drugs & Pharmacology Authors: Tokuyama S, Kawakami J Tags: Yakugaku Zasshi Source Type: research

Role of Scaffold Proteins in Functional Alteration of Small Intestinal P-glycoprotein by Anti-cancer Drugs.
Abstract   Since there is accumulating evidence to indicate that introduction of early palliative care for cancer patients may improved their quality of life or survival rates, the number of patients receiving pain relief by narcotic analgesics in conjunction with chemotherapy is predicted to increase. Therefore to provide effective combination treatments it is important to evaluate basic evidence regarding drug-drug interactions between anti-cancer drugs and narcotics. We have focused on P-glycoprotein (P-gp), a drug efflux transporter, in small intestine where the absorption process of drugs administered via or...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - May 9, 2015 Category: Drugs & Pharmacology Authors: Kobori T, Harada S, Nakamoto K, Tokuyama S Tags: Yakugaku Zasshi Source Type: research

The blood-brain barrier transport mechanism controlling analgesic effects of opioid drugs in CNS.
Abstract   The transport of opioid analgesics across the blood-brain barrier (BBB) is an important determinant of their therapeutic effects. The human brain is protected by the BBB, which consists of brain capillary endothelial cells linked with tight junctions. It is well established that the polarized expression of numerous transporters and receptors at the brain capillary endothelial cells controls the blood-brain exchange of nutrients, waste products deriving from neurotransmitter substances, and drugs. Morphine is a substrate of P-glycoprotein and the P-glycoprotein-mediated efflux transport at the BBB maint...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - May 9, 2015 Category: Drugs & Pharmacology Authors: Okura T, Higuchi K, Deguchi Y Tags: Yakugaku Zasshi Source Type: research

Altered expression of transporter and analgesic of morphine in neuropathic pain mice.
We examined the reason for the decreased concentration of morphine in the brain in case of neuropathic pain. We discovered increased P-glycoprotein (P-gp) expression in the small intestine, increased expression and activity of UGT2B in the liver, and increased P-gp expression in the brain under conditions of neuropathic pain. In this symposium, we argue that low brain morphine concentration is considered one of the causes of lower sensitivity to morphine in neuropathic pain patients. PMID: 25948305 [PubMed - in process] (Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan)
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - May 9, 2015 Category: Drugs & Pharmacology Authors: Ochiai W, Sugiyama K Tags: Yakugaku Zasshi Source Type: research

Interindividual variation of pharmacokinetic disposition of and clinical responses to opioid analgesics in cancer pain patients.
Abstract   Use of prescription opioids for cancer pain according to the World Health Organization analgesic ladder has been accepted in Japan. Although oxycodone and fentanyl are commonly used as first-line analgesics, a few clinical reports have been published on interindividual variations in their pharmacokinetics and clinical responses in cancer patients. (1) Some factors relating to CYP2D6, CYP3A, ATP-binding cassette sub-family B member 1 (ABCB1), and opioid receptor mu 1 (OPRM1) involve oxycodone pharmacokinetics and sensitivity in humans. The relations between their genetic variations and clinical response...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - May 9, 2015 Category: Drugs & Pharmacology Authors: Naito T, Kawakami J Tags: Yakugaku Zasshi Source Type: research

Imaging in vivo redox metabolism.
PMID: 25948307 [PubMed - in process] (Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan)
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - May 9, 2015 Category: Drugs & Pharmacology Authors: Anzai K, Hyodo F Tags: Yakugaku Zasshi Source Type: research

Radiation therapy and redox imaging.
Abstract   Radiation therapy kills cancer cells in part by flood of free radicals. Radiation ionizes and/or excites water molecules to create highly reactive species, i.e. free radicals and/or reactive oxygen species. Free radical chain reactions oxidize biologically important molecules and thereby disrupt their function. Tissue oxygen and/or redox status, which can influence the course of the free radical chain reaction, can affect the efficacy of radiation therapy. Prior observation of tissue oxygen and/or redox status is helpful for planning a safe and efficient course of radiation therapy. Magnetic resonance-...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - May 9, 2015 Category: Drugs & Pharmacology Authors: Matsumoto K Tags: Yakugaku Zasshi Source Type: research

Redox Molecular Imaging Using ReMI.
Abstract   Tissue redox status is one of the most important parameters to maintain homeostasis in the living body. Numerous redox reactions are involved in metabolic processes, such as energy production in the mitochondrial electron transfer system. A variety of intracellular molecules such as reactive oxygen species, glutathione, thioredoxins, NADPH, flavins, and ascorbic acid may contribute to the overall redox status in tissues. Breakdown of redox balance may lead to oxidative stress and can induce many pathological conditions such as cancer, neurological disorders, and aging. Therefore imaging of tissue redox...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - May 9, 2015 Category: Drugs & Pharmacology Authors: Hyodo F, Ito S, Utsumi H Tags: Yakugaku Zasshi Source Type: research

Development of a new redox molecular imaging method.
Abstract   For indirect tissue observation, electron-spin, Overhauser-enhanced, dynamic nuclear polarization magnetic resonance imaging (DNP-MRI) is a useful technique. However, its sensitivity and resolution are low compared with the clinical MRI apparatus. By switching to electron spin resonance (ESR) excitation, the magnetic field of the NMR detection, field cycle technique, which aims to improve resolution, was proposed. However, the effect of eddy currents or current value was altered unsatisfactorily. A team at Kyushu University proposed a new DNP-MRI technique capable of improving NMR detection field by pr...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - May 9, 2015 Category: Drugs & Pharmacology Authors: Naganuma T, Nakao M, Ichikawa K, Utsumi H Tags: Yakugaku Zasshi Source Type: research

Redox and microglia in the pathophysiology of schizophrenia.
Abstract   Altered antioxidant status has been implicated in schizophrenia. Microglia are major sources of free radicals such as superoxide in the brain, and play crucial roles in various brain diseases. Recent postmortem and imaging studies have indicated microglial activation in the brain of schizophrenia patients. Animal models that express some phenotypes of schizophrenia have revealed the underlying microglial pathology. In addition, minocycline, an antibiotic and the best known inhibitor of microglial activation, has therapeutic efficacy in schizophrenia. We have recently revealed that various antipsychotic...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - May 9, 2015 Category: Drugs & Pharmacology Authors: A Kato T, Hyodo F, Yamato M, Utsumi H, Kanba S Tags: Yakugaku Zasshi Source Type: research

Influence of systemic inflammatory response syndrome on the pharmacokinetics of vancomycin.
This study investigated the effect of SIRS on the pharmacokinetics of VCM by analyzing the predictability of TDM and pharmacokinetic parameters in 31 non-SIRS patients and 52 SIRS patients, with stratification by SIRS score. The mean prediction error (ME) and mean absolute prediction error in SIRS score 2 and 3 patients differed from those in non-SIRS patients. The ME in the score 4 group showed a negative value. In the comparison of pharmacokinetic parameters by SIRS score, a significantly lower CLvcm value was observed at score 4 compared with scores 2 and 3, a higher Vd value was observed at score 4 compared with non-SI...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - May 9, 2015 Category: Drugs & Pharmacology Authors: Irikuchi J, Imai T, Yoshida Y, Orii T Tags: Yakugaku Zasshi Source Type: research

Studies Using Text Mining on the Differences in Learning Effects between the KJ and World Café Method as Learning Strategies.
Abstract   The KJ method (named for developer Jiro Kawakita; also known as affinity diagramming) is widely used in participatory learning as a means to collect and organize information. In addition, the World Café (WC) has recently become popular. However, differences in the information obtained using each method have not been studied comprehensively. To determine the appropriate information selection criteria, we analyzed differences in the information generated by the WC and KJ methods. Two groups engaged in sessions to collect and organize information using either the WC or KJ method and small group discussio...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - May 9, 2015 Category: Drugs & Pharmacology Authors: Yasuhara T, Sone T, Konishi M, Kushihata T, Nishikawa T, Yamamoto Y, Kurio W, Kohno T Tags: Yakugaku Zasshi Source Type: research

Outcomes of a Long-Term Case Review Program during the On-Site Training of Pharmacy Students.
This study sought to determine whether a long-term case review (LTCR) program helped pharmacy students develop their abilities as pharmacists, and how their level of satisfaction changed.  LTCRs were comprised of four elements: self-learning, one-on-one bedside training with advising pharmacists, daily group sessions including three members, and weekly plenary sessions (case conferences). This program conducted on-site training in a hospital for 21 fifth-year students. The students were divided into 7 groups. One member of each group was assigned to a ward for bedside training for three weeks, while other member(s) of th...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - April 28, 2015 Category: Drugs & Pharmacology Authors: Murai Y, Suzuki H, Mori M, Tasaka H, Suzuki N, Shimada M, Sato H, Hirasawa N, Mano N, Tomioka Y Tags: Yakugaku Zasshi Source Type: research

A successful case of a patient undergoing warfarin and S-1 therapy using Internet-based control of home-measured PT-INR.
Abstract   To avoid major bleeding events in warfarin and S-1 combination therapy, PT-INR levels should be monitored frequently to allow for precise adjustments of the warfarin dose and to verify any side effects reported by the patient. We therefore developed a support system where outpatients obtain a home-measured PT-INR value using the CoaguChek(®) system and submit it along with details of any side effects to us via the Internet using their mobile phone. A 59-year-old man was started on warfarin (1.5 mg/day) and S-1 (100 mg/day), a combination preparation of tegafur, gimeracil, and oteracil potassium, to tr...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - April 24, 2015 Category: Drugs & Pharmacology Authors: Yamamura K, Yano K, Hirooka Y, Hirashiki A, Murohara T, Yamada K Tags: Yakugaku Zasshi Source Type: research

New Trend in Metal-based Drug Research.
PMID: 25832832 [PubMed - in process] (Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan)
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - April 5, 2015 Category: Drugs & Pharmacology Authors: Sakurai H, Odani A Tags: Yakugaku Zasshi Source Type: research

Iron, Aluminum, and Lanthanum-based Drugs for Treatment of Hyperphosphatemia.
Abstract   The control of the serum phosphorus (P) level in chronic kidney disease patients is important because elevated serum P levels are associated with progression of vascular calcification and increased mortality in these patients. In 2014, a novel phosphate binder, ferric citrate hydrate (Riona(®)), became available for the treatment of hyperphosphatemia in Japan, the first country to approve this medication. Ferric citrate hydrate, which relies upon the potent phosphate-binding capacity of ferric iron, inhibits P absorption by forming complexes between ferric iron and dietary phosphate in the gut. The ac...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - April 5, 2015 Category: Drugs & Pharmacology Authors: Matsumura K Tags: Yakugaku Zasshi Source Type: research

Application of radioisotopes for theranostics, a combination of diagnostics and therapy.
Abstract   Radioisotopes emit radiation with various characteristics. These characteristics have been used for various applications of radioisotopes in clinical fields. For example, diagnostic nuclear medicine is a technique that uses gamma-emitted radionuclides with high permeability into the body and can visualize changes in physiological and biochemical processes throughout the distributed and interrelated systems of living tissues and organs. Therapeutic nuclear medicine is a technique that uses beta-emitted radionuclides with high radiation damage to the cell and can be used for internal radiation therapy. T...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - April 5, 2015 Category: Drugs & Pharmacology Authors: Saji H Tags: Yakugaku Zasshi Source Type: research

Decorporation agents for internal radioactive contamination.
Abstract   When radionuclides are accidentally ingested or inhaled, blood circulation or tissue/organ deposition of the radionuclides causes systemic or local radiation effects. In such cases, decorporation therapy is used to reduce the health risks due to their intake. Decorporation therapy includes reduction and/or inhibition of absorption from the gastrointestinal tract, isotopic dilution, and the use of diuretics, adsorbents, and chelating agents. For example, penicillamine is recommended as a chelating agent for copper contamination, and diethylene triamine pentaacetic acid is approved for the treatment of i...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - April 5, 2015 Category: Drugs & Pharmacology Authors: Ohmachi Y Tags: Yakugaku Zasshi Source Type: research

Front-line Research of Idiosyncratic Drug Toxicity.
PMID: 25832836 [PubMed - in process] (Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan)
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - April 5, 2015 Category: Drugs & Pharmacology Authors: Yamada H Tags: Yakugaku Zasshi Source Type: research

Recent findings regarding the mechanism of idiosyncratic drug toxicity.
Abstract   Animal experiments cannot predict the probability of idiosyncratic drug toxicity; consequently, an important goal of the pharmaceutical industry is to develop a new methodology for preventing this form of drug reaction. Although the mechanism remains unclear, immune reactions are likely involved in the toxic processes underlying idiosyncratic drug toxicity: the drug is first activated into a chemically reactive metabolite that binds covalently to proteins and then acts as an immunogen. Therefore, screening tests to detect chemically reactive metabolites are conducted early during drug development and t...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - April 5, 2015 Category: Drugs & Pharmacology Authors: Ikeda T Tags: Yakugaku Zasshi Source Type: research

Establishment of Animal Models of Drug-induced Liver Injury and Analysis of Possible Mechanisms.
Abstract   Drug-induced liver injury (DILI) is one of leading causes of attrition during both early and late stages of drug development and postmarketing. DILI is generally classified into the intrinsic and idiosyncratic types. Intrinsic DILI is dose dependent and predictable as exemplified by acetaminophen toxicity. However, the occurrence of idiosyncratic DILI with very low incidence and severe liver damage is difficult to predict because of the complex nature of DILI and poor understanding of its mechanism. In this review, we summarize current knowledge and our accumulated experimental findings on the pathogen...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - April 5, 2015 Category: Drugs & Pharmacology Authors: Oda S, Yokoi T Tags: Yakugaku Zasshi Source Type: research

Predictive genomic markers for severe adverse drug reactions.
Abstract   Severe adverse drug reactions are an important issue to be considered during proper drug usage in postmarketing period. Most severe adverse reactions are idiosyncratic and unrelated to their pharmacological actions via primary targets. Although these reactions were not predictable, recent developments in the field of genomics have revealed closely associated markers responsible for some severe adverse reactions, including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). This review demonstrates genomic biomarkers for SJS/TEN and drug-induced liver injury (DILI) that were found mainl...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - April 5, 2015 Category: Drugs & Pharmacology Authors: Saito Y, Kodama S, Sugiyama E, Nakamura R Tags: Yakugaku Zasshi Source Type: research

Gene Regulation Involved in the Formation of Long-term Memory.
Abstract   My former research focused on silk fibroin gene transcription. The in vivo transcription initiation site of the fibroin gene, which is similar to the site corresponding to the 5'-terminal of mature fibroin mRNA, was determined. By developing a cell-free transcription system prepared from silk glands, it was found that the upstream region of the fibroin gene is responsible for efficient transcription initiation, which has enhancer-like features. More recent research has switched my focus to cellular neurobiology to understand the molecular mechanisms of long-term memory at the level of gene expression i...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - April 5, 2015 Category: Drugs & Pharmacology Authors: Tsuda M Tags: Yakugaku Zasshi Source Type: research

Clinical pharmacology and pharmacoepidemiology for medication safety in clinical settings.
In conclusion, our achievement in accurately assessing these would contribute to medication safety and the appropriate use of medicines in clinical settings. PMID: 25832841 [PubMed - in process] (Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan)
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - April 5, 2015 Category: Drugs & Pharmacology Authors: Kawakami J Tags: Yakugaku Zasshi Source Type: research

Preparation and physicochemical study of the preservation of nanoparticles.
In this study, trisaccharides, tetrasaccharides, and pentasaccharides were added to nanoparticle suspensions, followed by rehydration of the samples, which had been either dried normally or freeze-dried. The particle size after rehydration was measured. In addition, each powder was measured using a powder X-ray diffractometer and thermal analysis device to investigate the correlation between the nanoparticles' aggregation and the crystal form of saccharides. The diameter of the nanoparticles was maintained when it was freeze-dried, while particle aggregation occurred when normally dried samples were used. In addition, crys...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - April 5, 2015 Category: Drugs & Pharmacology Authors: Kamiya S Tags: Yakugaku Zasshi Source Type: research

Analysis of phthalates in aromatic and deodorant aerosol products and evaluation of exposure risk.
Abstract   We established an analytical method for the detection of seven phthalates, dimethyl phthalate, diethyl phthalate (DEP), benzyl butyl phthalate, di-i-butyl phthalate, dibutyl phthalate (DBP), diethylhexyl phthalate (DEHP), and di-n-octhyl phthalate, using an ultra high performance liquid chromatograph equipped with a photodiode array detector. This method is quick, with minimal contamination, and was applied to the analysis of aromatic and deodorant aerosol products. Phthalates were detected in 15 of 52 samples purchased from 1999 to 2012 in Yokohama. Three types of phthalate (DEP, DBP, DEHP) were detec...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - April 5, 2015 Category: Drugs & Pharmacology Authors: Sato Y, Sugaya N, Nakagawa T, Morita M Tags: Yakugaku Zasshi Source Type: research

Elevated serum lithium concentration due to switch from parenteral nutrition alone to parenteral with enteral nutrition.
We report a patient with elevated serum lithium concentration caused by switching from parenteral nutrition alone to parenteral with enteral nutrition. A 73-year-old female inpatient was treated with lithium carbonate 600 mg/d for manic episodes of bipolar disorder. Her serum lithium level was maintained at 0.57-0.79 mEq/L. She was administered total parenteral nutrition owing to difficulty in oral intake. Her diet contained 4.8-5.8 g/d of sodium chloride. After this, parenteral with enteral nutrition was initiated. The total sodium chloride intake decreased from 6.3 to 3.0-4.0 g/d following this change. On day 15 after in...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - April 5, 2015 Category: Drugs & Pharmacology Authors: Goto H, Tomita T, Doki S, Nakanishi R, Kojima C, Yoneshima M, Yoshida T, Tanaka K, Kohda Y Tags: Yakugaku Zasshi Source Type: research