Takenao Koseki

Publications of Takenao Koseki

• A permission system for carbapenem use reduced incidence of drug-resistant bacteria and cost of antimicrobials at a general hospital in Japan.

  Authors: Yoshiaki Ikeda, Takayoshi Mamiya, Hideki Nishiyama, Shiho Narusawa, Takenao Koseki, Akihiro Mouri, Toshitaka Nabeshima

  Nagoya journal of medical science. 02/2012; 74(1-2):93-104.

  Some drug management systems have been established in Japanese hospitals to reduce medical costs and regulate drug usage. Among the many available prescription drugs, antimicrobials should be givenSome drug management systems have been established in Japanese hospitals to reduce medical costs and regulate drug usage. Among the many available prescription drugs, antimicrobials should be given special attention because their inappropriate use often leads to sudden outbreaks of resistant bacteria. As drug specialists, pharmacists should monitor the use of all drugs, particularly antimicrobials. Carbapenems are a class of broad-spectrum antimicrobials that are widely used to treat infections worldwide. However, their inappropriate use has led to an increase in the incidence of drug-resistant bacteria and consequently, medical costs, at hospitals. To reduce inappropriate use and drug resistance, we have established a permission system to control the use of carbapenems at the Japanese Red Cross Nagoya Daiichi Hospital. In this study, we retrospectively evaluated the applicability of the new permission system compared to that of the notification system and the non control system for 14 months each. The two management systems were able to maintain total antibiotic use density and control the outbreak of drug-resistant bacteria (P. aeruginosa, E. coli, and K. pneumoniae). The number of carbapenem prescriptions was decreased dramatically when this permission system was enforced. Compared to the non control system, the cost of antimicrobials was reduced by $757,470 for the 14-month study period using the permission system. These results suggest that our system to control the use of antimicrobials can efficiently suppress the incidence of drug-resistant bacteria and medical costs at hospitals.

• Risk factors for extended-spectrum beta-lactamase-producing Escherichia coli infection in hospitalized patients.

  Authors: Yoshiaki Ikeda, Takayoshi Mamiya, Hideki Nishiyama, Takenao Koseki, Akihiro Mouri, Toshitaka Nabeshima

  Nagoya journal of medical science. 02/2012; 74(1-2):105-14.

  The incidence of nosocomial infection caused by extended-spectrum beta-lactamase (ESBL)-producing bacteria is increasing worldwide. Infections caused by ESBL producers have been associated withThe incidence of nosocomial infection caused by extended-spectrum beta-lactamase (ESBL)-producing bacteria is increasing worldwide. Infections caused by ESBL producers have been associated with severe adverse clinical outcomes that have led to increased mortality, prolonged hospitalization, and rising medical costs. To avoid such adverse events and ineffective treatment, an appropriate use of drugs for infectious diseases is needed. To suppress the emergence and spread of drug-resistant bacteria in hospitals, it is important to be vigilant about ESBL-producing Escherichia coli (E. coli). In this study, we examined and compared seven items in a blood test between patients with ESBL-producing E. coli and non-ESBL-producing E. coli among febrile patients. We examined the levels of serum albumin, hemoglobin, and C-reactive protein (CRP), and the numbers of leucocytes, neutrophils, lymphocytes, and platelets in blood on the day of admission, the screening day during hospitalization, and the day immediately before discharge from the hospital. There were no significant differences in clinical background characteristics between the two groups of patients. In patients with invasive infections caused by ESBL-producing E. coli, serum albumin levels and the number of lymphocytes were significantly lower than those in patients not infected with ESBL producers. These values recovered to their baseline levels on the day of hospital discharge. This retrospective study suggests that serum albumin levels and the number of lymphocytes may serve as risk factors for infection by ESBL-producing E. coli, thereby supporting the appropriate use of antimicrobials in hospitals.

• Galantamine attenuates reinstatement of cue-induced methamphetamine-seeking behavior in mice.

  Authors: Takenao Koseki, Akihiro Mouri, Shizuka Suzuki, Azusa Nakajima, Takayoshi Mamiya, Yijin Yan, Toshitaka Nabeshima

  Addiction biology. 01/2012;

  Methamphetamine (METH) dependence is becoming a serious socioeconomic health problem worldwide. The enhancement of the cholinergic nervous system is expected to greatly alleviate drug dependence. WeMethamphetamine (METH) dependence is becoming a serious socioeconomic health problem worldwide. The enhancement of the cholinergic nervous system is expected to greatly alleviate drug dependence. We investigated the effect of galantamine on the reinstatement of cue-induced METH-seeking behavior using a self-administration experiment. Treatment with galantamine (1 mg/kg, p.o.) 30 minutes before exposure to the cues suppressed the reinstatement of METH-seeking behavior. However, galantamine did not affect the cue-induced reinstatement of food-seeking behavior or locomotor activity. These results suggest that galantamine may be a candidate drug for treating relapses of METH-seeking behavior.

• Dissociable role of tumor necrosis factor alpha gene deletion in methamphetamine self-administration and cue-induced relapsing behavior in mice.

  Authors: Yijin Yan, Atsumi Nitta, Takenao Koseki, Kiyofumi Yamada, Toshitaka Nabeshima

  Psychopharmacology. 12/2011;

  RATIONALE: During the development of addiction, addictive drugs induce transient and long-lasting changes in the brain including expression of endogenous molecules and alteration of morphologicalRATIONALE: During the development of addiction, addictive drugs induce transient and long-lasting changes in the brain including expression of endogenous molecules and alteration of morphological structure. Of the altered endogenous molecules, some facilitate but others slow the development of drug addiction. Previously, we have reported that tumor necrosis factor alpha (TNF-α) is a critical molecule among endogenous anti-addictive modulators using animal models of drug-conditioned place preference and drug discrimination. OBJECTIVES: Does targeted deletion of the TNF-α gene in mice affect methamphetamine (METH) self-administration, motivation to self-administer METH, cue-induced reinstatement of METH-seeking behavior, and food reinforcement or seeking behavior? METHODS: Both METH self-administration and reinstatement of drug-seeking behavior and food self-delivery and food-seeking behavior were measured in TNF-α (-/-) and wild-type mice. RESULTS: There were an upward shift of dose responses to METH self-administration under a fixed ratio schedule of reinforcement and higher breaking points under a progressive ratio schedule of reinforcement in TNF-α knockout (TNF-α (-/-)) mice as compared with wild-type mice. There was no significant difference in cue-induced reinstatement of METH-seeking behavior, food-maintained operant behavior, motivation to natural food, and cue-induced food-seeking behavior between TNF-α (-/-) and wild-type mice. CONCLUSION: TNF-α affects METH self-administration and motivation to self-administer METH but contributes to neither METH-associated cue-induced relapsing behavior nor food reward and food-seeking behavior. TNF-α may be explored for use as a diagnostic biomarker for the early stage of drug addiction.

• Exposure to enriched environments during adolescence prevents abnormal behaviours associated with histone deacetylation in phencyclidine-treated mice.

  Authors: Takenao Koseki, Akihiro Mouri, Takayoshi Mamiya, Yuki Aoyama, Kazuya Toriumi, Shizuka Suzuki, Azusa Nakajima, Takuma Yamada, Taku Nagai, Toshitaka Nabeshima

  The international journal of neuropsychopharmacology / official scientific journal of the Collegium Internationale Neuropsychopharmacologicum (CINP). 11/2011;

  Enriched environments (EEs) during development have been shown to influence adult behaviour. Environmental conditions during childhood may contribute to the onset and/or pathology of schizophrenia;Enriched environments (EEs) during development have been shown to influence adult behaviour. Environmental conditions during childhood may contribute to the onset and/or pathology of schizophrenia; however, it remains unclear whether EE might prevent the development of schizophrenia. Herein, we investigated the effects of EE during adolescence on phencyclidine (PCP)-induced abnormal behaviour, a proposed schizophrenic endophenotype. Male ICR mice (3 wk old) were exposed to an EE for 4 wk and then treated with PCP for 2 wk. The EE potentiated the acute PCP treatment-induced hyperlocomotion in the locomotor test and prevented chronic PCP treatment-induced impairments of social behaviour and recognition memory in the social interaction and novel object recognition tests. It also prevented the PCP-induced decrease of acetylated Lys9 in histone H3-positive cells and increase of the histone deacetylase (HDAC)5 level in the prefrontal cortex. To investigate whether the histone modification during adolescence might be critical for the effect of EE, 3-wk-old mice were first treated with sodium butyrate (SB; an HDAC inhibitor) for 4 wk and then treated with PCP for 2 wk. Chronic SB treatment during adolescence mimicked the effects of EE, including potentiation of hyperlocomotion induced by acute PCP treatment and prevention of social and cognitive impairments, decrease of acetylated Lys9 in histone H3-positive cells and increase of the HDAC5 level in the prefrontal cortex associated with chronic PCP treatment. Our results suggest that EEs prevent PCP-induced abnormal behaviour associated with histone deacetylation. EEs during childhood might prove to be a novel strategy for prophylaxis against schizophrenia.

• The antidepressant-like effects of the 3β-hydroxysteroid dehydrogenase inhibitor trilostane in mice is related to changes in neuroactive steroid and monoamine levels.

  Authors: Julie Espallergues, Takayoshi Mamiya, Monique Vallée, Takenao Koseki, Toshitaka Nabeshima, Jamal Temsamani, Claude Laruelle, Tangui Maurice

  Neuropharmacology. 09/2011; 62(1):492-502.

  In the present study, we analyzed the effects of a systemic treatment with the competitive 3β-hydroxysteroid dehydrogenase (3β-HSD) inhibitor trilostane on: (i) neurosteroid and monoamine levels inIn the present study, we analyzed the effects of a systemic treatment with the competitive 3β-hydroxysteroid dehydrogenase (3β-HSD) inhibitor trilostane on: (i) neurosteroid and monoamine levels in the brain, and (ii) the antidepressant activity of steroids and antidepressants in the forced swimming test (FST). 3β-HSD converts pregnenolone (PREG) into progesterone (PROG) or dehydroepiandrosterone (DHEA) into androstenedione. These neuroactive steroids are known to regulate neurotransmitters effects in the brain, particularly glutamate, γ-aminobutyric acid (GABA) and serotonin (5-HT), with consequences on mood and depression. We previously reported that trilostane showed antidepressant-like properties in the FST and concomitantly regulated plasma adrenocorticotropin (ACTH) and corticosterone levels, markers of the stress-induced hypothalamus-pituitary-adrenal (HPA) axis activation. We here observed that adrenalectomy/castration blocked the trilostane effect, outlining the importance of peripheral steroid levels. Trilostane (25 mg/kg) decreased hippocampus PROG contents and paradoxically increased circulating PROG levels. It also increased PREG levels in the hippocampus and frontal cortex. In the FST, a co-treatment with trilostane facilitated DHEAS (5-20 mg/kg) antidepressant activity, but showed only an additive, not facilitative, effect with PREGS (10-40 mg/kg), PROG (10-40 mg/kg) or allopregnanolone (ALLO, 1-8 mg/kg). Trilostane (25 mg/kg) treatment significantly increased 5-HT and (-)-norepinephrine (NE) turnovers in the hippocampus, an effect likely related to its antidepressant action. In co-administration studies, trilostane further decreased immobility following fluoxetine (30-60 mg/kg), sertraline (20-40 mg/kg) and imipramine (20-40 mg/kg), but not desipramine (20-40 mg/kg), treatments. A significant additive effect was observed for the selective 5-HT reuptake inhibitors (SSRI) at their highest dose. This study confirmed that a systemic administration of trilostane directly affected peripheral and brain levels in neuroactive steroids and monoamine turnover, resulting in antidepressant activity. The drug could be proposed as a co-treatment with SSRI. This article is part of a Special Issue entitled 'Anxiety and Depression'.

• Mouse strain differences in phencyclidine-induced behavioural changes.

  Authors: Akihiro Mouri, Takenao Koseki, Shiho Narusawa, Minae Niwa, Takayoshi Mamiya, Shin-Ichi Kano, Akira Sawa, Toshitaka Nabeshima

  The international journal of neuropsychopharmacology / official scientific journal of the Collegium Internationale Neuropsychopharmacologicum (CINP). 06/2011;

  Administration of phencyclidine (PCP) is acknowledged to generate a model of psychosis in animals. With the identification of genetic susceptibility factors for schizophrenia and bipolar disorder,Administration of phencyclidine (PCP) is acknowledged to generate a model of psychosis in animals. With the identification of genetic susceptibility factors for schizophrenia and bipolar disorder, great efforts have been made to generate genetic animal models for major mental illnesses. As these disorders are multifactorial, comparisons among drug-induced (non-genetic) and genetic models are becoming an important issue in biological psychiatry. A major barrier is that the standard mouse strain used in the generation of genetic models is C57BL/6, whereas almost all studies with PCP-induced models have utilized other strains. To fill this technical gap, we systematically compared the behavioural changes upon PCP administration in different mouse strains, including C57BL/6N, C57BL/6J, ddY, and ICR. We observed strain differences in PCP-induced hyperlocomotion and enhanced immobility in the forced swim test (ddY>C57BL/6N and 6J>ICR). In contrast, there was no strain difference in the impairment of recognition memory in the novel object recognition memory test after withdrawal of chronic PCP administration. This study provides practical guidance for comparing genetic with PCP-induced models of psychosis in C57BL/6. Furthermore, such strain differences may provide a clue to the biological mechanisms underlying PCP-induced endophenotypes possibly relevant to major mental illnesses.

• Genetic animal models of schizophrenia related with the hypothesis of abnormal neurodevelopment.

  Authors: Lingling Lu, Takayoshi Mamiya, Takenao Koseki, Akihiro Mouri, Toshitaka Nabeshima

  Biological & pharmaceutical bulletin. 01/2011; 34(9):1358-63.

  Accumulating evidence supports the existence of an overlap in genetic susceptibility with schizophrenia. Translation of human genetic mutations into animals is one of the most important strategies toAccumulating evidence supports the existence of an overlap in genetic susceptibility with schizophrenia. Translation of human genetic mutations into animals is one of the most important strategies to study the pathogenesis of schizophrenia, identify potential drug targets, and test new medicines for antipsychotic treatment. Recent discoveries of susceptibility genes for schizophrenia make the possibility to develop newer genetic mouse models based on the neurodevelopmental hypotheses of schizophrenia. Although it is not possible to mimic all schizophrenic symptoms by these animal models, the genetic mouse models based on the neurodevelopmental hypothesis are widely developed to reproduce several schizophrenia-like behavioral and biochemical changes in humans. In this mini review, we will discuss the neuropathological and behavioral manifestations of representative genetic mouse models for schizophrenia, associated with the hypothesis of abnormal neurodevelopment.

• [Phencyclidine abuse, dependence, intoxication, and psychosis].

  Authors: Takenao Koseki, Toshitaka Nabeshima

  Nihon rinsho. Japanese journal of clinical medicine. 08/2010; 68(8):1511-5.

  Phencyclidine (PCP), the potent psychotomimetic drug, is an illicit street drug which is used widely among youth in the United States. The popularity of PCP abuser gradually decreased in recentPhencyclidine (PCP), the potent psychotomimetic drug, is an illicit street drug which is used widely among youth in the United States. The popularity of PCP abuser gradually decreased in recent years. However, the PCP abuse is still serious social problem due to its severe intoxication. In the present review, recent progress in our understanding about PCP abuse, dependence, intoxication, psychosis and the diagnosis and treatment was summarized. A long time has passed since the epidemic of PCP abuse, while there are few medical advances for PCP-induced disorder. It is strongly desirable to develop medical approaches to PCP abuse, dependence, intoxication, and psychosis.

• [Drug addiction research using intravenous self-administration procedure in mice].

  Authors: Takenao Koseki, Toshitaka Nabeshima

  Nihon Arukōru Yakubutsu Igakkai zasshi = Japanese journal of alcohol studies & drug dependence. 06/2010; 45(3):147-56.

  A major clinical problem in treating drug abusers or addicts is the high rate of relapse to abuse even long after abstinence. In drug dependence research, drug self-administration displays excellentA major clinical problem in treating drug abusers or addicts is the high rate of relapse to abuse even long after abstinence. In drug dependence research, drug self-administration displays excellent face validity, good construct validity, and appealing predictive validity with respect to drug consumption in humans. Because of the technical feasibility of intravenous drug self-administration, it is limited in mice relative to larger animals. Nevertheless, technical innovations made in the last 10 years have vastly improved the feasibility of long-term studies in mice. In addition, mice with targeted gene mutations, such as transgenic and knockout mice, provide a powerful tool for investigating candidate genes that may be involved in abuse of drugs in humans. Therefore, it is essential for researchers to extend the extinction-reinstatement procedure in mice. However, there are few reports that proven the relationship between genetic factor and relapsing behavior using drug self-administration procedure in mice. Based on recent documented information and our own experiences, in the present review, we described some procedural considerations for the successful establishment of drug self-administration procedure in mice, and then summarized some behavioral characteristics of genetic mouse models under the drug self-administration, and reinstatement procedure.