Frontiers Media S.A.Acta Medica Okayama1663-9812132022Anxiolytic-like effects of hochuekkito in lipopolysaccharide-treated mice involve interleukin-6 inhibition890048ENSoichiroUshioDepartment of Pharmacy, Okayama University HospitalYudaiWadaDepartment of Clinical Pharmacy, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMizukiNakamuraDepartment of Clinical Pharmacy, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesDaikiMatsumotoDepartment of Clinical Pharmacy, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKotaHoshikaDepartment of Clinical Pharmacy, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesShoyaShiromizuDepartment of Pharmacy, Okayama University HospitalNaohiroIwataDepartment of Pharmacy, Okayama University HospitalSatoruEsumiDepartment of Pharmacy, Okayama University HospitalMakotoKajizonoDepartment of Pharmacy, Okayama University HospitalYoshihisaKitamuraDepartment of Pharmacy, Okayama University HospitalToshiakiSendoDepartment of Pharmacy, Okayama University HospitalHochuekkito (HET) is a Kampo medicine used to treat postoperative and post-illness general malaise and decreased motivation. HET is known to regulate immunity and modulate inflammation. However, the precise mechanism and effects of HET on inflammation-induced central nervous system disorders remain unclear. This study aimed to assess the effect of HET on inflammation-induced anxiety-like behavior and the mechanism underlying anxiety-like behavior induced by lipopolysaccharide (LPS). Institute of Cancer Research mice were treated with LPS (300 mu g/kg, intraperitoneally), a bacterial endotoxin, to induce systemic inflammation. The mice were administered HET (1.0 g/kg, orally) once a day for 2 weeks before LPS treatment. The light-dark box test and the hole-board test were performed 24 h after the LPS injection to evaluate the effects of HET on anxiety-like behaviors. Serum samples were obtained at 2, 5, and 24 h after LPS injection, and interleukin-6 (IL-6) levels in serum were measured. Human and mouse macrophage cells (THP-1 and RAW264.7 cells, respectively) were used to investigate the effect of HET on LPS-induced IL-6 secretion. The repeated administration of HET prevented anxiety-like behavior and decreased serum IL-6 levels in LPS-treated mice. HET significantly suppressed LPS-induced IL-6 secretion in RAW264.7 and THP-1 cells. Similarly, glycyrrhizin, one of the chemical constituents of HET, suppressed LPS-induced anxiety-like behaviors. Our study revealed that HET ameliorated LPS-induced anxiety-like behavior and inhibited IL-6 release in vivo and in vitro. Therefore, we postulate that HET may be useful against inflammation-induced anxiety-like behavior.No potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X7622022Retrospective Cohort Study of Clinical Efficacy and Safety of Cefozopran for Treating Febrile Neutropenia during Chemotherapy in Patients with Lung Cancer167172ENTsukasaHigashionnaDepartment of Pharmacy, Okayama University HospitalSoichiroUshioDepartment of Pharmacy, Okayama University HospitalSatoruEsumiDepartment of Pharmacy, Okayama University HospitalKiminakaMurakawaDepartment of Pharmacy, Okayama University HospitalYoshihisaKitamuraDepartment of Pharmacy, Okayama University HospitalToshiakiSendoDepartment of Pharmacy, Okayama University HospitalOriginal Article10.18926/AMO/63410Febrile neutropenia (FN) is a serious side effect in patients undergoing cancer chemotherapy and frequently proves fatal. Since infection control is crucial in the management of FN, the antimicrobial agent cefozopran (CZOP) has been recommended but not approved for routine use in clinical care of FN in Japan. However, few studies of CZOP in the management of FN have used a thrice daily dose schedule. The aim of this study was to retrospectively compare the efficacy and safety of CZOP at a dose of 1 g three times daily to those of cefepime (CFPM) in the treatment of FN in our lung cancer patients. The response rates of the CZOP and CFPM groups were 89.5% (17/19 cases) and 83.0% (39/47 cases), respectively, with no significant difference between the two groups. The median duration of antimicrobial treatment was 6 days (4-10 days) in the CZOP group and 7 days (3-13 days) in the CFPM group, with no significant difference between groups. The incidence rates of adverse events were 21.1% (4/19 cases) in the CZOP group and 19.1% (9/47 cases) in the CFPM group. No adverse events of Grade 3 or higher were observed in either group. The findings of the present study suggest that CZOP administration at a dose of 1 g three times per day as an antimicrobial treatment alternative against FN.No potential conflict of interest relevant to this article was reported.岡山医学会Acta Medica Okayama0030-155813232020薬物相互作用(49―新規経口分子標的薬の相互作用)174179ENYuKinashiDepartment of Pharmacy, Okayama University HospitalSatoruEsumiDepartment of Pharmacy, Okayama University HospitalToshiakiSendoDepartment of Pharmacy, Okayama University HospitalNo potential conflict of interest relevant to this article was reported.MDPIActa Medica Okayama1422-00672032019Region-Specific Neuroprotective Features of Astrocytes against Oxidative Stress Induced by 6-Hydroxydopamine 598ENMasatoAsanumaDepartment of Medical Neurobiology, Okayama University Graduate School of Medical, Dental and Pharmaceutical SciencesNaoOkumura-TorigoeDepartment of Clinical Pharmacy, Okayama University Graduate School of Medical, Dental and Pharmaceutical SciencesIkukoMiyazakiDepartment of Medical Neurobiology, Okayama University Graduate School of Medical, Dental and Pharmaceutical SciencesShinkiMurakamiDepartment of Medical Neurobiology, Okayama University Graduate School of Medical, Dental and Pharmaceutical SciencesYoshihisaKitamuraDepartment of Clinical Pharmacy, Okayama University Graduate School of Medical, Dental and Pharmaceutical SciencesToshiakiSendoDepartment of Clinical Pharmacy, Okayama University Graduate School of Medical, Dental and Pharmaceutical SciencesIn previous studies, we found regional differences in the induction of antioxidative molecules in astrocytes against oxidative stress, postulating that region-specific features of astrocytes lead region-specific vulnerability of neurons. We examined region-specific astrocytic features against dopaminergic neurotoxin 6-hydroxydopamine (6-OHDA) as an oxidative stress using co-culture of mesencephalic neurons and mesencephalic or striatal astrocytes in the present study. The 6-OHDA-induced reduction of mesencephalic dopamine neurons was inhibited by co-culturing with astrocytes. The co-culture of midbrain neurons with striatal astrocytes was more resistant to 6-OHDA than that with mesencephalic astrocytes. Furthermore, glia conditioned medium from 6-OHDA-treated striatal astrocytes showed a greater protective effect on the 6-OHDA-induced neurotoxicity and oxidative stress than that from mesencephalic astrocytes. The cDNA microarray analysis showed that the number of altered genes in both mesencephalic and striatal astrocytes was fewer than that changed in either astrocyte. The 6-OHDA treatment, apparently up-regulated expressions of Nrf2 and some anti-oxidative or Nrf2-regulating phase II, III detoxifying molecules related to glutathione synthesis and export in the striatal astrocytes but not mesencephalic astrocytes. There is a profound regional difference of gene expression in astrocytes induced by 6-OHDA. These results suggest that protective features of astrocytes against oxidative stress are more prominent in striatal astrocytes, possibly by secreting humoral factors in striatal astrocytes.No potential conflict of interest relevant to this article was reported.Nature ResearchActa Medica Okayama2045-23221012020Mirtazapine exerts astrocyte-mediated dopaminergic neuroprotection20698ENRyoKikuokaDepartment of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesIkukoMiyazakiDepartment of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesNatsukiKubotaDepartment of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMegumiMaedaDepartment of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesDaikiKagawaDepartment of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMasaakiMoriyamaDepartment of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesAsukaSatoDepartment of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesShinkiMurakamiDepartment of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYoshihisaKitamuraDepartment of Clinical Pharmacy, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesToshiakiSendoDepartment of Clinical Pharmacy, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMasatoAsanumaDepartment of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMirtazapine, a noradrenergic and specific serotonergic antidepressant (NaSSA), is known to activate serotonin (5-HT) 1A receptor. Our recent study demonstrated that stimulation of astrocytic 5-HT1A receptors promoted astrocyte proliferation and upregulated antioxidative property in astrocytes to protect dopaminergic neurons against oxidative stress. Here, we evaluated the neuroprotective effects of mirtazapine against dopaminergic neurodegeneration in models of Parkinson's disease (PD). Mirtazapine administration attenuated the loss of dopaminergic neurons in the substantia nigra and increased the expression of the antioxidative molecule metallothionein (MT) in the striatal astrocytes of 6-hydroxydopamine (6-OHDA)-injected parkinsonian mice via 5-HT1A receptors. Mirtazapine protected dopaminergic neurons against 6-OHDA-induced neurotoxicity in mesencephalic neuron and striatal astrocyte cocultures, but not in enriched neuronal cultures. Mirtazapine-treated neuron-conditioned medium (Mir-NCM) induced astrocyte proliferation and upregulated MT expression via 5-HT1A receptors on astrocytes. Furthermore, treatment with medium from Mir-NCM-treated astrocytes protected dopaminergic neurons against 6-OHDA neurotoxicity, and these effects were attenuated by treatment with a MT-1/2-specific antibody or 5-HT1A antagonist. Our study suggests that mirtazapine could be an effective disease-modifying drug for PD and highlights that astrocytic 5-HT1A receptors may be a novel target for the treatment of PD.No potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X7462020Delayed Methotrexate Elimination after Administration of a Medium Dose of Methotrexate in a Patient with Genetic Variants Associated with Methotrexate Clearance545550ENYasuhisaTatebeDepartment of Pharmacy, Okayama University HospitalKiichiroKanamitsuDepartment of pediatrics, Okayama University HospitalHirotakaKanzakiDepartment of Pharmacy, Okayama University HospitalHisashiIshidaDepartment of pediatrics, Okayama University HospitalKaoriFujiwaraDepartment of pediatrics, Okayama University HospitalKanaWashioDepartment of pediatrics, Okayama University HospitalYoshihisaKitamuraDepartment of Pharmacy, Okayama University HospitalToshiakiSendoDepartment of Pharmacy, Okayama University HospitalAkiraShimadaDepartment of pediatrics, Okayama University HospitalHirokazuTsukaharaDepartment of pediatrics, Okayama University HospitalCase Report10.18926/AMO/61215Polymorphisms in methotrexate transporter pathways have been associated with methotrexate toxicities and clearance. Recent genome-wide association studies have revealed that the SLCO1B1 T521C variant is associated with methotrexate elimination. We present a case of a pediatric patient with acute lymphoblastic leukemia who suffered from persistently high plasma methotrexate concentrations and acute kidney injuries after the admin-istration of a medium dose of methotrexate. Subsequent genetic analysis showed that he was a carrier of dys-functional genetic variants associated with methotrexate clearance. This case highlights that polymorphisms of methotrexate transporter pathways can adversely affect methotrexate elimination in a clinically significant manner.No potential conflict of interest relevant to this article was reported.岡山医学会Acta Medica Okayama0030-155813222020薬物相互作用(48―体外式膜型人工肺(ECMO)と 薬物の相互作用)102107ENYasumasaOkawaDepartment of Pharmacy, Okayama University HospitalSatoruEsumiDepartment of Pharmacy, Okayama University HospitalToshiakiSendoDepartment of Pharmacy, Okayama University HospitalNo potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X7442020Immobility-reducing Effects of Ketamine during the Forced Swim Test on 5-HT1A Receptor Activity in the Medial Prefrontal Cortex in an Intractable Depression Model301306ENKeiTakahashiDepartment of Clinical Pharmacy, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYoshihisaKitamuraDepartment of Clinical Pharmacy, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesSoichiroUshioDepartment of Clinical Pharmacy, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesToshiakiSendoDepartment of Clinical Pharmacy, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesOriginal Article10.18926/AMO/60368Ketamine has been clinically proven to ameliorate depression, including treatment-resistant depression. The detailed mechanism of action of ketamine in treatment-resistant depression remains unclear. We examined the effects of ketamine on the immobility times of adrenocorticotropic hormone (ACTH)-treated rats during the forced swim test, and we explored the mechanism by which ketamine acts in this model. We investigated the neuroanatomical site of action by microinjecting ketamine into the medial prefrontal cortex of rats. A significant reduction of the rats’ immobility during the forced swim test was observed after the intraperitoneal injection of ketamine in both saline- and ACTH-treated rats. The microinjection of ketamine into the medial prefrontal cortex also decreased immobility during the forced swim test in both saline- and ACTH-treated rats. The immobility-decreasing effect of intraperitoneally injected ketamine was blocked by administering WAY100635, a 5-HT1A receptor antagonist, into the medial prefrontal cortex. These findings contribute to the evidence that ketamine can be useful against treatment-resistant depressive conditions. The immobility-reducing effects of ketamine might be mediated by 5-HT1A receptor activity in the medial prefrontal cortex.No potential conflict of interest relevant to this article was reported.BMCActa Medica Okayama2055-0294612020Development of an appropriate simple suspension method for valganciclovir medication16ENYasuyukiMasaokaDepartment of Pharmacy, Okayama University HospitalYoichiKawasakiDepartment of Pharmacy, Okayama University HospitalRyoKikuokaDepartment of Clinical Pharmacy,Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesAtsushiOgawaDepartment of Pharmacy, Okayama University HospitalSatoruEsumiDepartment of Pharmacy, Okayama University HospitalYudaiWadaDepartment of Clinical Pharmacy,Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesSoichiroUshioDepartment of Pharmacy, Okayama University HospitalYoshihisaKitamuraDepartment of Pharmacy, Okayama University HospitalToshiakiSendoDepartment of Pharmacy, Okayama University HospitalBackground</br>
Valganciclovir (VGC) is essential for preventing cytomegalovirus infections after transplants in adult and pediatric patients. In pediatric patients, VGC tablets have to be pulverized so that they can be delivered via nasogastric tubes. The “simple suspension method” is usually used to suspend tablets in hot water in Japan. However, the optimal suspension conditions and metering methods for preparing VGC suspensions using the simple suspension method are unclear. The purpose of this study was to clarify these issues.</br>
Methods</br>
VGC tablets were suspended in water (initial water temperature: 25 °C or 55 °C) using the simple suspension method. The residual rate of VGC after it had been suspended in hot water was determined using HPLC. In addition, the suspended solution was passed through 6, 8, and 12 Fr. gavage tubes. The VGC concentrations of suspensions produced using different preparation methods were also determined using HPLC.</br>
Results</br>
Cracking the surfaces of VGC tablets and suspending them in water at an initial temperature of 55 °C was effective at dissolving the tablets. The VGC concentration of the suspension remained stable for at least 80 min. Furthermore, the VGC concentration remained stable for 48 h during cold dark storage. Cracking the surfaces of VGC tablets could be a more effective metering method than preparing powder from VGC tablets. In addition, little VGC remained in 6, 8, or 12 Fr. gavage tubes after VGC solution was passed through them.</br>
Conclusion</br>
The amount of VGC should be measured carefully when preparing VGC solutions using the simple suspension method.No potential conflict of interest relevant to this article was reported.岡山医学会Acta Medica Okayama0030-155813212020薬物相互作用(47―全身麻酔薬の薬物相互作用)2933ENYusukeIgawaDepartment of Pharmacy, Okayama University HospitalSatoruEsumiDepartment of Pharmacy, Okayama University HospitalYoshihisaKitamuraDepartment of Pharmacy, Okayama University HospitalToshiakiSendoDepartment of Pharmacy, Okayama University HospitalNo potential conflict of interest relevant to this article was reported.WileyActa Medica Okayama1347-903211132019YES1 activation induces acquired resistance to neratinib in HER2-amplified breast and lung cancers849856ENTatsuakiTakedaDepartment of Clinical Pharmacy, Okayama University Graduate School of Medicine,Dentistry and Pharmaceutical SciencesHiromasaYamamotoDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery,Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKenSuzawaDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery,Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesShutaTomidaCenter for Comprehensive Genomic Medicine, Okayama University HospitalShunsakuMiyauchiDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery,Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKotaArakiDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery,Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKentaroNakataDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery,Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesAkihiroMiuraDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery,Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKeiNambaDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery,Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKazuhikoShienDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery,Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesJunichiSohDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery,Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTadahikoShienDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery,Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYoshihisaKitamuraDepartment of Clinical Pharmacy, Okayama University Graduate School of Medicine,Dentistry and Pharmaceutical SciencesToshiakiSendoDepartment of Clinical Pharmacy, Okayama University Graduate School of Medicine,Dentistry and Pharmaceutical SciencesShinichiToyookaDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery,Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMolecular-targeted therapies directed against human epidermal growth factor receptor 2 (HER2) are evolving for various cancers. Neratinib is an irreversible pan-HER tyrosine kinase inhibitor and has been approved by the FDA as an effective drug for HER2-positive breast cancer. However, acquired resistance of various cancers to molecular-targeted drugs is an issue of clinical concern, and emergence of resistance to neratinib is also considered inevitable. In this study, we established various types of neratinib-resistant cell lines from HER2-amplified breast and lung cancer cell lines using several drug exposure conditions. We analyzed the mechanisms of emergence of the resistance in these cell lines and explored effective strategies to overcome the resistance. Our results revealed that amplification of YES1, which is a member of the SRC family, was amplified in two neratinib-resistant breast cancer cell lines and one lung cancer cell line. Knockdown of YES1 by siRNA and pharmacological inhibition of YES1 by dasatinib restored the sensitivity of the YES1-amplified cell lines to neratinib in vitro. Combined treatment with dasatinib and neratinib inhibited tumor growth in vivo. This combination also induced downregulation of signaling molecules such as HER2, AKT and MAPK. Our current results indicate that YES1 plays an important role in the emergence of resistance to HER2-targeted drugs, and that dasatinib enables such acquired resistance to neratinib to be overcome.No potential conflict of interest relevant to this article was reported.岡山医学会Acta Medica Okayama0030-155813132019薬物相互作用(46―注射薬の配合変化 : 注射薬の物理的・化学的な相互作用)161164ENYosukeMorishitaDepartment of Pharmacy, Okayama University HospitalSatoruEsumiDepartment of Pharmacy, Okayama University HospitalShigekiNishiharaDepartment of Pharmacy, Okayama University HospitalYoshihisaKitamuraDepartment of Pharmacy, Okayama University HospitalToshiakiSendoDepartment of Pharmacy, Okayama University HospitalNo potential conflict of interest relevant to this article was reported.BMJ Publishing GroupActa Medica Okayama2044-60559122019Fall-related mortality trends in older Japanese adults aged >= 65 years: a nationwide observational studye033462ENHideharuHagiyaDepartment of General Internal Medicine, Osaka University HospitalToshihiroKoyamaDepartment of Pharmaceutical Biomedicine, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityYoshitoZamamiDepartment of Clinical Pharmacology and Therapeutics, Tokushima University Graduate SchoolYasuhisaTatebeDepartment of Pharmacy, Okayama University HospitalTomokoFunahashiDepartment of Pharmaceutical Biomedicine, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityKazuakiShinomiyaDepartment of Pharmaceutical Care and Clinical Pharmacy, Faculty of Pharmaceutical Sciences Tokushima Bunri UniversityYoshihisaKitamuraDepartment of Pharmacy, Okayama University HospitalShiroHinotsuDepartment of Biostatistics, Sapporo Medical UniversityToshiakiSendoDepartment of Pharmacy, Okayama University HospitalHiromiRakugiDepartment of General Internal Medicine, Osaka University HospitalMitsunobu R.KanoDepartment of Pharmaceutical Biomedicine, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityOBJECTIVES:<br/>
Fall-related mortality among older adults is a major public health issue, especially for ageing societies. This study aimed to investigate current trends in fall-related mortality in Japan using nationwide population-based data covering 1997-2016.<br/>
DESIGN:<br/>
We analysed fall-related deaths among older persons aged ≥65 years using the data provided by the Japanese Ministry of Health, Labour and Welfare.<br/>
RESULTS:<br/>
The crude and age-standardised mortality rates were calculated per 100 000 persons by stratifying by age (65-74, 75-84 and ≥85 years) and sex. To identify trend changes, a joinpoint regression model was applied by estimating change points and annual percentage change (APC). The total number of fall-related deaths in Japan increased from 5872 in 1997 to 8030 in 2016, of which 78.8% involved persons aged ≥65 years. The younger population (65-74 years) showed continuous and faster-decreasing trends for both men and women. Average APC among men aged ≥75 years did not decrease. Among middle-aged and older women (75-84 and ≥85 years) decreasing trends were observed. Furthermore, the age-adjusted mortality rate of men was approximately twice that of women, and it showed a faster decrease for women.<br/>
CONCLUSIONS:<br/>
Although Japanese healthcare has shown improvement in preventing fall-related deaths over the last two decades, the crude mortality for those aged over 85 years remains high, indicating difficulty in reducing fall-related deaths in the super-aged population. Further investigations to uncover causal factors for falls in older populations are required.No potential conflict of interest relevant to this article was reported.Nature Publishing GroupActa Medica Okayama2045-232292019Place of death trends among patients with dementia in Japan: a population-based observational study 20235ENToshihiroKoyamaDepartment of Pharmaceutical Biomedicine, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityMisatoSasakiDepartment of Pharmaceutical Biomedicine, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityHideharuHagiyaDepartment of General Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityYoshitoZamamiDepartment of Clinical Pharmacology and Therapeutics, Tokushima University Graduate SchoolTomokoFunahashiDepartment of Pharmaceutical Biomedicine, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityAyakoOhshimaDepartment of Pharmaceutical Biomedicine, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityYasuhisaTatebeDepartment of Pharmacy, Okayama University HospitalNaokoMikamiDivision of Pharmacy, Chiba University HospitalKazuakiShinomiyaDepartment of Pharmaceutical Care and Clinical Pharmacy, Faculty of Pharmaceutical Sciences, Tokushima Bunri UniversityYoshihisaKitamuraDepartment of Pharmacy, Okayama University HospitalToshiakiSendoDepartment of Pharmacy, Okayama University HospitalShiroHinotsuDepartment of Biostatistics, Sapporo Medical UniversityMitsunobu R.KanoDepartment of Pharmaceutical Biomedicine, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityDementia is a major public health concern in ageing societies. Although the population of Japan is among the most aged worldwide, long-term trends in the place of death (PoD) among patients with dementia is unknown. In this Japanese nationwide observational study, we analysed trends in PoD using the data of patients with dementia who were aged >= 65 years and died during 1999-2016. Trends in the crude death rates and PoD frequencies were analysed using the Joinpoint regression model. Changes in these trends were assessed using the Joinpoint regression analysis in which significant change points, the annual percentage change (APC) and average APCs (AAPC) in hospitals, homes, or nursing homes were estimated. During 1999-2016, the number of deaths among patients with dementia increased from 3,235 to 23,757 (total: 182,000). A trend analysis revealed increased mortality rates, with an AAPC of 8.2% among men and 9.3% among women. Most patients with dementia died in the hospital, although the prevalence of hospital deaths decreased (AAPC: -1.0%). Moreover, the prevalence of nursing home deaths increased (AAPC: 5.6%), whereas the prevalence of home deaths decreased (AAPC: -5.8%). These findings support a reconsideration of the end-of-life care provided to patients with dementia.No potential conflict of interest relevant to this article was reported.岡山医学会Acta Medica Okayama0030-155812922017薬物相互作用 (39―前立腺がん治療薬と薬物相互作用)131136ENHirotakaKanzakiDepartment of Pharmacy, Okayama University HospitalYutaTanakaDepartment of Pharmacy, Okayama University HospitalAkinoriMaruoDepartment of Pharmacy, Okayama University HospitalShigeki NishiharaDepartment of Pharmacy, Okayama University HospitalYoshihisaKitamuraDepartment of Pharmacy, Okayama University HospitalToshiakiSendoDepartment of Pharmacy, Okayama University HospitalNo potential conflict of interest relevant to this article was reported.SpringerActa Medica Okayama2210-77033762015Exploring autistic-like traits relating to empathic attitude and psychological distress in hospital pharmacists12581266ENYuji HiguchiDepartment of NeuropsychiatryOkayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYosukeUchitomiInnovation Center for Supportive, Palliative and Psychosocial CareNational Cancer CenterMaikoFujimoriCenter for Suicide Prevention, National Institute of Mental HealthNational Center for Neurology and PsychiatryToshihiroKoyamaDepartment of Clinical PharmacyOkayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHitomiKataokaDepartment of Primary Care and Medical EducationOkayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYoshihisaKitamuraDepartment of Clinical PharmacyOkayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesToshiakiSendoDepartment of Clinical PharmacyOkayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMasatoshiInagakiDepartment of NeuropsychiatryOkayama University HospitalBACKGROUND:
Pharmacists are expected to play a key role in modern cancer care. Research suggests that an empathic approach and attitude in medical staff improves the quality of patient care. An empathic attitude and psychological distress are thought to be associated with autistic-like traits, but little is known about such traits.
OBJECTIVE:
In this study, we aimed to clarify the associations among autistic-like traits, empathic attitude in a medical context, and psychological health in hospital pharmacists.
SETTING:
Eligibility criteria for inclusion were certified pharmacists working at hospitals for patient care who returned their questionnaires.
METHOD:
Eight hundred and twenty-three hospital pharmacists completed a number of self-administered questionnaires anonymously by mail.
MAIN OUTCOME MEASURES:
Scores were obtained on the Autism-Spectrum Quotient, the Jefferson Scale of Empathy, the General Health Questionnaire-12, and subscales of the Interpersonal Reactivity Index (Perspective Taking, IRI-Empathic Concern, IRIPersonal Distress). We performed correlation and mediation analyses to confirm that the empathy and general health questionnaires were associated with autism-spectrum quotient scores, and with each IRI subscale.
RESULTS:
Complete responses were obtained from 379 pharmacists comprising 151 males (39.8 %) with a mean age of 37.7 ± 10.8 years (missing data, n = 13) and a median of 11 years after qualification as a pharmacist. Autism-Spectrum Quotient scores were inversely correlated with empathy (r = -0.22, p < 0.001) and positively correlated with general health scores (r = 0.40, p < 0.001). In the models with mediation, the inverse correlation between autism-spectrum quotient and empathy scores was mediated indirectly by IRI-Perspective Taking and IRI-Empathic Concern, and the positive correlation between autism-spectrum quotient and general health was mediated indirectly by IRI-Personal Distress. There were also direct effects, with significant effects of autism-spectrum quotient on empathy and general health scores.
CONCLUSION:
Our findings suggest that autistic-like traits affect both empathic attitude in a medical context and the psychological health of pharmacists. We recommend that to improve empathy in those with high levels of autistic-like traits, we may need to develop specialized interventions, such as improving communication skills training.No potential conflict of interest relevant to this article was reported.岡山医学会Acta Medica Okayama0030-155812912017薬物相互作用 ( 38 - 新規睡眠薬 : ラメルテオン, スボレキサントの相互作用)5357ENKazukoKuboDepartment of Pharmacy, Okayama University HospitalSatoruEsumiDepartment of Pharmacy, Okayama University HospitalYoshihisaKitamuraDepartment of Pharmacy, Okayama University HospitalToshiakiSendoDepartment of Pharmacy, Okayama University HospitalNo potential conflict of interest relevant to this article was reported.岡山医学会Acta Medica Okayama0030-155812832016薬物相互作用(37―新規C型肝炎治療薬の相互作用)231235ENMasashiMiyamotoDepartment of Pharmacy, Okayama University HospitalSatoruEsumiDepartment of Pharmacy, Okayama University HospitalYoshihisaKitamuraDepartment of Pharmacy, Okayama University HospitalToshiakiSendoDepartment of Pharmacy, Okayama University HospitalNo potential conflict of interest relevant to this article was reported.岡山医学会Acta Medica Okayama0030-155812822016薬物相互作用(36―肺癌領域における経口分子標的治療薬)141146ENTsukasaHigashionnaDepartment of Pharmacy, Okayama University HospitalSatoruEsumiDepartment of Pharmacy, Okayama University HospitalYoshihisaKitamuraDepartment of Pharmacy, Okayama University HospitalToshiakiSendoDepartment of Pharmacy, Okayama University HospitalNo potential conflict of interest relevant to this article was reported.岡山医学会Acta Medica Okayama0030-155812812016薬物相互作用 (35―オピオイド鎮痛薬の薬物相互作用)5359ENHikaruSadaMakotoKajizonoYoshihisaKitamuraToshiakiSendoNo potential conflict of interest relevant to this article was reported.岡山医学会Acta Medica Okayama0030-155812732015薬物相互作用 (34―食事と薬の薬物相互作用)245249ENHayatoHinoYoshihisaKitamuraToshiakiSendoNo potential conflict of interest relevant to this article was reported.岡山医学会Acta Medica Okayama0030-155812722015薬物相互作用(33―抗菌薬の薬物相互作用)151154ENKenTasakaNaokoShiraishiYoshihisaKitamuraToshiakiSendoNo potential conflict of interest relevant to this article was reported.日本静脈経腸栄養学会Acta Medica Okayama1344-49802942014粉砕法による経管投与における薬剤量損失に対する簡易懸濁法の有用性についての検討10271033ENYoshitoZamamiToshihiroKoyamaTetsuyaAibaManabuAmanoTetsuakiAndoNaomiKurataHidekiNawaHironoriNakuraYoshihisaKitamuraToshiakiSendo【目的】従来の薬剤経管投与法である粉砕法は薬効の減少につながる薬剤量の損失が指摘されている。そこで粉砕法による薬剤量損失に対する簡易懸濁法の有用性について検討した。
【方法】頻繁に粉砕指示がなされる5種類の薬剤を用いて粉砕・分包による薬物含量減少、薬剤調製時の懸濁性および実際の経管投与を想定した薬物含量について2つの方法を比較した。
【結果】薬剤を粉砕・分包するとそれぞれの薬物含量は減少した。またワーファリン®錠を粉砕して水に溶解すると完全には懸濁せず、小さな塊が生じたが、簡易懸濁法では均一に懸濁した。ワーファリン®錠の経管投与を想定した実験において粉砕法では薬物含量が大幅に減少したが、簡易懸濁法では、ほとんど損失が認められなかった。【結論】簡易懸濁法は粉砕法に比べて薬剤損失の面で有用性が高いことが示唆され、ワーファリン®錠のように安定性が悪い薬剤では特に適正な薬物投与に貢献出来ると考えられる。No potential conflict of interest relevant to this article was reported.岡山医学会Acta Medica Okayama0030-155812712015薬物相互作用 (32―新規経口抗凝固薬における薬物相互作用)5961ENHiromiIdaYoshihisaKitamuraToshiakiSendoNo potential conflict of interest relevant to this article was reported.岡山医学会Acta Medica Okayama0030-155812632014薬物相互作用 (31―乳がんホルモン療法における薬物相互作用)245248ENYasuyukiMasaokaYoshihisaKitamuraToshiakiSendoNo potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X6852014Characteristics of the Runway Model of Intracranial Self-stimulation Behavior and Comparison with Other Motivated Behaviors255262ENSatoruEsumiYoichiKawasakiYutakaGomitaYoshihisaKitamuraToshiakiSendoReview10.18926/AMO/52893Motivation incorporates several psychological aspects that produce reward-related and learning behaviors. Although reward-related behavior is reported to be mediated by the dopaminergic reward pathway, the involvement of dopaminergic systems in motivated behavior has not been fully clarified. Several experimental methodologies for motivational behavior have been reported, but pharmacological characteristics seem to vary among these methodologies. In this review, we attempt to summarize three main concepts:(1) the relationship of dopamine neuron physiology with motivated behavior, (2) the pharmacological characteristics of the runway intracranial self-stimulation model, and (3) the behavioral distinction of disparate motivated behaviors.No potential conflict of interest relevant to this article was reported.Acta Medica Okayama0013-95805252011Therapy for hyperthermia-induced seizures in Scn1a mutant rats10101017ENKeiichiroHayashiSatoshiUeshimaMamoruOuchidaTomojiMashimoTeiichiNishikiToshiakiSendoTadaoSerikawaHidekiMatsuiIoriOhmoriPurpose: Mutations in the SCN1A gene, which encodes the alpha 1 subunit of voltage-gated sodium channels, cause generalized epilepsy with febrile seizures plus (GEFS+) and severe myoclonic epilepsy of infancy (SMEI). N1417H-Scn1a mutant rats are considered to be an animal model of human FS+ or GEFS+. To assess the pharmacologic validity of this model, we compared the efficacies of eight different antiepileptic drugs (AEDs) for the treatment of hyperthermia-induced seizures using N1417H-Scn1a mutant rats.
Methods: AEDs used in this study included valproate, carbamazepine (CBZ), phenobarbital, gabapentin, acetazolamide, diazepam (DZP), topiramate, and potassium bromide (KBr). The effects of these AEDs were evaluated using the hot water model, which is a model of experimental FS. Five-week-old rats were pretreated with each AED and immersed in water at 45 degrees C to induce hyperthermia-induced seizures. The seizure manifestations and video-electroencephalographic recordings were evaluated. Furthermore, the effects of each AED on motor coordination and balance were assessed using the balance-beam test.
Key Findings: KBr significantly reduced seizure durations, and its anticonvulsant effects were comparable to those of DZP. On the other hand, CBZ decreased the seizure threshold. In addition, DZP and not KBr showed significant impairment in motor coordination and balance.
Significance: DZP and KBr showed potent inhibitory effects against hyperthermia-induced seizures in the Scn1a mutant rats, whereas CBZ exhibited adverse effects. These responses to hyperthermia-induced seizures were similar to those in patients with GEFS+ and SMEI. N1417H-Scn1a mutant rats may, therefore, be useful for testing the efficacy of new AEDs against FS in GEFS+ and SMEI patients.No potential conflict of interest relevant to this article was reported.Acta Medica Okayama0918-615835102012Quantitation and Human Monocyte Cytotoxicity of the Polymerization Agent 1-Hydroxycyclohexyl Phenyl Ketone (Irgacure 184) from Three Brands of Aqueous Injection Solution18211825ENKazuhikoYamajiYoichiKawasakiKeiYoshitomeHisashiMatsunagaToshiakiSendoIn this study, levels of the photoinitiator 1-hydroxycyclohexyl phenyl ketone (1-HCHPK) in aqueous injection solutions were analyzed by GC-MS. In our previous studies, photoinitiators such as 2-methyl-4'-(methylthio)-2-morpholinopropiophenone (MTMP) were detected in intravenous (i.v.) injection bag solution, and they were found to be cytotoxic to human monocytes. Therefore, we hypothesized that 1-HCHPK might display similarly cytotoxicity. The purpose of this study was to quantitate the amount of contaminants from plastic containers such as those used for peripheral parenteral nutrition and to determine the cytotoxicity of such extracts on human monocytes. The sample extraction procedure for GC-MS analysis involved a liquid-phase extraction. The solvent was evaporated under a stream of nitrogen at 50 degrees C to yield a residue, which was dissolved in n-hexane and injected into a GC-MS. Normal human peripheral blood mononuclear cells (PBMC), isolated from the buffy coat by centrifugation, were suspended in RPMI 1640 medium supplemented with 10% (v/v) heat-inactivated fetal calf serum. In the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) cell viability assay, cells (1x10(4)) were treated with 1-HCHPK for 24h or 48h at 37 degrees C. From the GC-MS analysis, 6.13-8.32 mu g/mL of 1-HCHPK was found in 20 mL vials of water for injection solution. In the MTT assay, 1-HCHPK decreased cell viability for both the 24h and 48h incubation periods. In conclusion, our findings suggest that 1-HCHPK could promote adverse events in patients. Future studies will clarify the possible health risks of photoinitiator accumulation in human cells.No potential conflict of interest relevant to this article was reported.岡山医学会Acta Medica Okayama0030-155812622014薬物相互作用 (30―慢性疼痛治療薬の相互作用)159163ENAtsushiOgawaYoshihisaKitamuraToshiakiSendoNo potential conflict of interest relevant to this article was reported.岡山医学会Acta Medica Okayama0030-155812612014薬物相互作用(29―ステロイドの薬物相互作用)5963ENYoukoHayashiHidekiNawaYoshihisaKitamuraToshiakiSendoNo potential conflict of interest relevant to this article was reported.岡山医学会Acta Medica Okayama0030-155812532013薬物相互作用 (28―過活動膀胱治療薬の薬物相互作用)259262ENYusukeHarutaYoichiKawasakiYoshihisaKitamuraToshiakiSendoNo potential conflict of interest relevant to this article was reported.岡山医学会Acta Medica Okayama0030-155812532013抗菌薬TDMガイドライン251255ENMasatoshiOkazakiToshiakiSendoNo potential conflict of interest relevant to this article was reported.岡山医学会Acta Medica Okayama0030-155812532013GBR12909の情動行動への影響:脳内自己刺激行動の Runway法を用いた動機付け行動と,抗うつ様行動および依存様行動の区別205209ENSatoruEsumiHidenoriSagaraAkihikoNakamotoYoichiKawasakiYutakaGomitaToshiakiSendoNo potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X6752013Preparation of Enteric-coated Capsules of Beclomethasone Dipropionate for Patients with Intestinal Graft-versus-Host Disease and a Case Study319324ENKiminakaMurakawaTomoakiSatoYoshinobuMaedaYoshihisaKitamuraMitsuneTanimotoToshiakiSendoCase Report10.18926/AMO/51868Graft-versus-host disease (GVHD) is a major concern in transplantation patients. Gut GVHD is accompanied by diarrhea, abdominal pain, and/or melena. Although oral treatment with corticosteroids (CSs) is effective in treating gut GVHD, it can cause adverse reactions that affect the entire body. Topical administration of CSs can be effective in treating diseases in which lesions are limited locally, because adverse reactions can then be alleviated. In this study, we examine and discuss an enteric-coated beclomethasone dipropionate (BDP) capsule (BDP-EC) formulated at Okayama University Hospital. The BDP-EC did not dissolve in solution 1 (pH1.2), and began disintegrating in solution 2 (pH6.8) after 5min, with a mean dissolution rate at 15min of 85%. We then used the capsule to treat a patient who developed gut GVHD after allogeneic hematopoietic stem cell transplantation. Clinically, the frequency of diarrhea decreased after BDP-EC administration. In addition, we were able to decrease the prednisolone equivalent dose. Symptoms associated with adverse reactions to BDP were not observed during the hospitalization period. These findings suggest that the administration of BDP-EC in the early stages of gut GVHD may allow a reduction in the initial doses of systemic CSs.No potential conflict of interest relevant to this article was reported.Acta Medica Okayama0166-43282432013Effect of GBR12909 on affective behavior: Distinguishing motivational behavior from antidepressant-like and addiction-like behavior using the runway model of intracranial self-stimulation313321ENSatoruEsumiHidenoriSagaraAkihikoNakamotoYoichiKawasakiYutakaGomitaToshiakiSendoRationale: It was recently demonstrated that the priming stimulation effect (PSE) in the runway model of intracranial self-stimulation (ICSS) can be used as a model system to study the motivational effects of drugs. However, the characteristics of this navel experimental model have not been fully clarified.
Objective: To elucidate the involvement of dopamine uptake inhibition in motivated behavior and the difference in experimental characteristics between closely related experimental models, we investigated the effects of the dopamine uptake inhibitor GBR12909 in the runway ICSS model, in the forced swimming test (FST), and on conditioned place preference (CPP). In addition, the role of dopamine receptor signaling in the runway model was evaluated using dopamine receptor agonists and antagonists.
Results: GBR12909 dose-dependently increased running speed on the runway and decreased immobility time in the FST without affecting the time spent in the drug-associated compartment in CPP tests. The effect of GBR12909 in the runway model was inhibited by pre-treatment with the dopamine receptor antagonists haloperidol and raclopride. The dopamine receptor agonists SKF38393 and quinpirole dose-dependently decreased running speed.
Conclusions: These results demonstrate that GBR12909 displays motivation-enhancing and antidepressant-like effects without place conditioning effects. In addition, the mechanisms of PSE enhancement in the runway ICSS model are different from those underlying closely associated experimental models and are mediated by increases in dopamine signaling.No potential conflict of interest relevant to this article was reported.岡山医学会Acta Medica Okayama0030-155812522013薬物相互作用(27―がん化学療法における制吐剤の薬物相互作用)163167ENYasukoKurataSatokoFujiwaraMakotoKajizonoMegumuAoyagiYoshihisaKitamuraToshiakiSendoNo potential conflict of interest relevant to this article was reported.岡山医学会Acta Medica Okayama0030-155812512013遺伝子多型と薬剤感受性7778ENSatoshiKurodaToshiakiSendoNo potential conflict of interest relevant to this article was reported.岡山医学会Acta Medica Okayama0030-155812512013薬物相互作用(26―高尿酸血症治療薬の薬物相互作用)7375ENTakashiMakitaYoshihisaKitamuraToshiakiSendoNo potential conflict of interest relevant to this article was reported.岡山医学会Acta Medica Okayama0030-155812432012薬物相互作用 (25―C型肝炎治療薬テラプレビルにおける薬物相互作用)259263ENKazuhikoYamajiToshiakiSendoNo potential conflict of interest relevant to this article was reported.岡山医学会Acta Medica Okayama0030-155812422012薬物相互作用(24―ICUでの注意すべき薬物相互作用)167173ENYusukeNishimiyaToshimitsuKonumaKenTasakaToshiakiSendoNo potential conflict of interest relevant to this article was reported.岡山医学会Acta Medica Okayama0030-155812412012薬物相互作用(23―抗精神病薬の薬物相互作用)7981ENKoheiKitagawaHisashiMatsunagaToshiakiSendoNo potential conflict of interest relevant to this article was reported.岡山医学会Acta Medica Okayama0030-155812332011薬物相互作用(22―オピオイドの薬物相互作用)239241ENRiekoKawashimaHisashiMatsunagaToshiakiSendoNo potential conflict of interest relevant to this article was reported.岡山医学会Acta Medica Okayama0030-155812322011薬物相互作用(21―分子標的薬剤(低分子阻害剤)の 薬物相互作用)147153ENMakotoKajizonoMegumuMaedaSatokoFujiwaraHisashiMatsunagaToshiakiSendoNo potential conflict of interest relevant to this article was reported.岡山医学会Acta Medica Okayama0030-155812312011薬物相互作用(20―経腸栄養剤の薬物相互作用)5962ENKentaroTairaHisashiMatsunagaToshiakiSendoNo potential conflict of interest relevant to this article was reported.岡山医学会Acta Medica Okayama0030-155812232010薬物相互作用(19―パーキンソン病治療薬の薬物相互作用)259264ENSatoruEzumiSatoshiKurodaHisashiMatsunagaToshiakiSendoNo potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X6452010Evaluation of Motivational Effects Induced by Intracranial Self-Stimulation Behavior267275ENHidenoriSagaraToshiakiSendoYutakaGomitaReview10.18926/AMO/40501In the runway model of intracranial self-stimulation (ICSS) experimentation, the experimental animal is timed in running a fixed distance to depress a lever that releases electrical stimulation to an electrode implanted along its medial forebrain bundle. This ICSS has both a reward and a motivational component. Using the runway method and priming stimulation, we designed an experimental method for directly measuring motivation. An assessment of pharmacological agents that are known to influence motivational states was also undertaken. Using the experimental methods that we created, we observed prominent changes in running speed when animals were exposed to methamphetamine and nicotine. According to these data, the runway method employing intracranial self-stimulation behavior may be useful for the evaluation of substances that act on motivation. We review the underlying neuropharmacological and anatomical functions associated with our experimental methods. We hope that this technique will be used to scientifically evaluate the impact of drugs and/or therapeutic interventions on human motivation.No potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X6442010Effects of Imipramine and Lithium on the Suppression of Cell Proliferation in the Dentate Gyrus of the Hippocampus in Adrenocorticotropic Hormone-treated Rats219223ENMahoDoiIkukoMiyazakiTomokoNagamachiKazuakiShinomiyaHisashiMatsunagaToshiakiSendoHiromuKawasakiMasatoAsanumaYutakaGomitaYoshihisaKitamuraOriginal Article10.18926/AMO/40129We examined the influence of chronic adrenocorticotropic hormone (ACTH) treatment on the number of Ki-67-positive cells in the dentate gyrus of the hippocampus in rats. ACTH treatment for 14 days decreased the number of such cells. The administration of imipramine or lithium alone for 14 days had no effect in saline-treated rats. The effect of ACTH was blocked by the administration of imipramine. Furthermore, the coadministration of imipramine and lithium for 14 days significantly increased the number of Ki-67-positive cells in both the saline and ACTH-treated rats. The coadministration of imipramine and lithium normalized the cell proliferation in the dentate gyrus of the hippocampus in rats treated with ACTH.No potential conflict of interest relevant to this article was reported.岡山医学会Acta Medica Okayama0030-155812222010薬物相互作用(18―降圧薬の薬物相互作用)163167ENToshiakiMiyazakiAtsumiNishikoriHisashiMatsunagaToshiakiSendoNo potential conflict of interest relevant to this article was reported.Acta Medica Okayama8932008Chronic coadministration of carbamazepine together with imipramine produces antidepressant-like effects in an ACTH-induced animal model of treatment–resistant depression: Involvement of 5-HT 2A receptors?ENYoshihisaKitamuraKozueAkiyamaKouheiKitagawaKazuhikoShibataHiromuKawasakiKatsuyaSuemaruHiroakiArakiToshiakiSendoYutakaGomita<p>The use of carbamazepine has been reported to be an effective treatment for severe depression. We have already shown that the antidepressant-like effects of tricyclic antidepressants in the rat forced swim test (FST) are blocked by chronic treatment with adrenocorticotropic hormone (ACTH). In the present study, we examined the effect of the chronic administration of carbamazepine on the FST and the wet-dog shakes induced by (+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aiminopropane (DOI), a 5-HT2A receptor agonist, in ACTH-treated rats. Chronic administration of carbamazepine did not affect the duration of immobility in saline-treated and ACTH-treated rats. The reduction of immobility, induced by chronic administration of imipramine, was blocked by treatment with ACTH. When carbamazepine was administered concurrently with imipramine, we observed a significant decrease in immobility in rats treated with ACTH. Chronic ACTH treatment increased the number of the wet-dog shakes induced by DOI. This effect of ACTH was significantly increased by the coadministration of carbamazepine and imipramine. These results suggest that the use of carbamazepine together with tricyclic antidepressants had the effect of reducing immobility time in the FST in a tricyclic antidepressant-treatment-resistant depressive model induced by chronic ACTH treatment. </p>
No potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X6242008Motivational Effects of Nicotine as Measured by the Runway Method Using Priming Stimulation of Intracranial Self-stimulation Behavior227233ENHidenoriSagaraYoshihisaKitamuraSatoruEsumiToshiakiSendoHiroakiArakiYutakaGomitaOriginal Article10.18926/AMO/30940<p>It is well known that priming stimulation promotes the motivational effects of intracranial self-stimulation(ICSS) behavior. An experimental methodology using the runway method could separately study the reward and motivational effects of ICSS behavior. In the present study, we examined the motivational effect of nicotine as measured by the runway method using priming stimulation of ICSS behavior. Electrodes were implanted chronically into the medial forebrain bundle (MFB) in rats. A lever for stimulation of the MFB was set on the opposite side of the start box in the apparatus, and rats were trained to get a reward stimulation (50-200 microA, 0.2 ms, 60 Hz) of MFB when the goal lever was pressed. After the rats were trained to press the lever, a priming stimulation of the MFB was performed. After receiving the priming stimulation, rats were placed at the start box of the runway apparatus, and the running time duration until the goal lever was pressed was measured. Subcutaneous injection of nicotine at a dose of 0.2mg/kg produced an increase in running speed to obtain the reward stimulation, and priming stimulation facilitated the motivational effect to obtain the electrical brain stimulation reward in the rats. These results suggest that nicotine significantly enhanced the motivational effect on ICSS behavior as determined using the runway method. The runway method using priming stimulation of ICSS behavior may become the new experimental methodology with which to measure the motivational effect of some drugs.</p>No potential conflict of interest relevant to this article was reported.岡山医学会Acta Medica Okayama0030-155812212010薬物相互作用(17―脂質異常症治療薬の相互作用)7376ENYoichiKawasakiHisashiMatsunagaToshiakiSendoNo potential conflict of interest relevant to this article was reported.岡山医学会Acta Medica Okayama0030-155812132009薬物相互作用(16―抗真菌薬の薬物相互作用)209213ENSatoshiKurodaHidekoIsozakiHisashiMatsunagaToshiakiSendoNo potential conflict of interest relevant to this article was reported.岡山医学会Acta Medica Okayama0030-155812122009造影剤腎症の発現機序解明による予防薬の探索研究99103ENToshiakiSendoNo potential conflict of interest relevant to this article was reported.岡山医学会Acta Medica Okayama0030-155812112009薬物相互作用 (15―H(2)ブロッカー・プロトンポンプインヒビターの薬物相互作用)4951ENHidekiNawaToshiakiSendoNo potential conflict of interest relevant to this article was reported.岡山医学会Acta Medica Okayama0030-155812032008薬物相互作用 (14-糖尿病治療薬の薬物相互作用)347350ENRisaKatsubeToshiakiSendoNo potential conflict of interest relevant to this article was reported.岡山医学会Acta Medica Okayama0030155812022008薬物相互作用 (13―下剤の薬物相互作用)223226ENHidekoYokohariMasatoshiOkazakiToshiakiSendoNo potential conflict of interest relevant to this article was reported.岡山医学会Acta Medica Okayama0030155811932008薬物相互作用 (11―抗がん剤の薬物相互作用)319322ENHisashiMatsunagaToshiakiSendoNo potential conflict of interest relevant to this article was reported.岡山医学会Acta Medica Okayama0030155811922007薬物相互作用 (10―免疫抑制薬の薬物相互作用)199203ENTomoakiSatoSatoshiUeshimaToshiakiSendoNo potential conflict of interest relevant to this article was reported.岡山医学会Acta Medica Okayama0030155811922007III 外来化学療法における薬剤師の役割181186ENSatokoFujiwaraToshiakiSendoNo potential conflict of interest relevant to this article was reported.岡山医学会Acta Medica Okayama0030155811912007薬物相互作用 (9―喫煙と薬の相互作用)8385ENHidenoriSagaraYoshihisaKitamuraToshiakiSendoYutakaGomitaNo potential conflict of interest relevant to this article was reported.岡山医学会Acta Medica Okayama0030155812012008薬物相互作用(12―ベンゾジアゼピン系睡眠薬の薬物相互作用)9194ENKazuakiShinomiyaYoshihisaKitamuraSatoshiUeshimaTomoakiSatohToshiakiSendoNo potential conflict of interest relevant to this article was reported.