著者
Daisuke Furushima Hiroshi Yamada Michiko Kido Yuko Ohno
出版者
The Pharmaceutical Society of Japan
雑誌
Biological and Pharmaceutical Bulletin (ISSN:09186158)
巻号頁・発行日
vol.41, no.3, pp.409-418, 2018-03-01 (Released:2018-03-01)
参考文献数
40
被引用文献数
2

Improvement in patient waiting time in dispensing pharmacies is an important element for patient and pharmacists. The One-Dose Package (ODP) of medicines was implemented in Japan to support medicine adherence among elderly patients; however, it also contributed to increase in patient waiting times. Given the projected increase in ODP patients in the near future owing to rapid population aging, development of improved strategies is a key imperative. We conducted a cross-sectional survey at a single dispensing pharmacy to clarify the impact of ODP on patient waiting time. Further, we propose an improvement strategy developed with use of a discrete event simulation (DES) model. A total of 673 patients received pharmacy services during the study period. A two-fold difference in mean waiting time was observed between ODP and non-ODP patients (22.6 and 11.2 min, respectively). The DES model was constructed with input parameters estimated from observed data. Introduction of fully automated ODP (A-ODP) system was projected to reduce the waiting time for ODP patient by 0.5 times (from 23.1 to 11.5 min). Furthermore, assuming that 40% of non-ODP patients would transfer to ODP, the waiting time was predicted to increase to 56.8 min; however, introduction of the A-ODP system decreased the waiting time to 20.4 min. Our findings indicate that ODP is one of the elements that increases the waiting time and that it might become longer in the future. Introduction of the A-ODP system may be an effective strategy to improve waiting time.
著者
Sveinbjörn Gizurarson
出版者
The Pharmaceutical Society of Japan
雑誌
Biological and Pharmaceutical Bulletin (ISSN:09186158)
巻号頁・発行日
vol.38, no.4, pp.497-506, 2015-04-01 (Released:2015-04-01)
参考文献数
89
被引用文献数
19 76

Nasal mucociliary clearance is one of the most important factors affecting nasal delivery of drugs and vaccines. This is also the most important physiological defense mechanism inside the nasal cavity. It removes inhaled (and delivered) particles, microbes and substances trapped in the mucus. Almost all inhaled particles are trapped in the mucus carpet and transported with a rate of 8–10 mm/h toward the pharynx. This transport is conducted by the ciliated cells, which contain about 100–250 motile cellular appendages called cilia, 0.3 µm wide and 5 µm in length that beat about 1000 times every minute or 12–15 Hz. For efficient mucociliary clearance, the interaction between the cilia and the nasal mucus needs to be well structured, where the mucus layer is a tri-layer: an upper gel layer that floats on the lower, more aqueous solution, called the periciliary liquid layer and a third layer of surfactants between these two main layers. Pharmacokinetic calculations of the mucociliary clearance show that this mechanism may account for a substantial difference in bioavailability following nasal delivery. If the formulation irritates the nasal mucosa, this mechanism will cause the irritant to be rapidly diluted, followed by increased clearance, and swallowed. The result is a much shorter duration inside the nasal cavity and therefore less nasal bioavailability.
著者
Akihiro Sonoda Yoshitaka Iwashita Yukina Takada Ryu Hamazono Kazuhisa Ishida Hiroshi Imamura
出版者
The Pharmaceutical Society of Japan
雑誌
Biological and Pharmaceutical Bulletin (ISSN:09186158)
巻号頁・発行日
vol.45, no.6, pp.763-769, 2022-06-01 (Released:2022-06-01)
参考文献数
31
被引用文献数
1

An administration plan for vancomycin (VCM) in bedridden elderly patients has not been established. This retrospective study aimed to evaluate the prediction accuracy of the area under the concentration–time curve (AUC) of VCM by the Bayesian approach using creatinine-based equations of estimated kidney function in such patients. Kidney function was estimated using the Japanese equation of estimated glomerular filtration rate (eGFR) and the Cockcroft–Gault equation of estimated creatinine clearance (eCCr). eCCr (serum creatinine (SCr) + 0.2) was calculated by substituting the SCr level +0.2 mg/dL into the Cockcroft–Gault equation. For eGFR/0.789, eGFR, eCCr, and eCCr (SCr + 0.2), the AUC values were calculated by the Bayesian approach using the therapeutic drug monitoring (TDM) software, BMs-Pod (ver 8.06) and denoted as AUCeGFR/0.789, AUCeGFR, AUCeCCr, and AUCeCCr (SCr + 0.2) respectively. The reference AUC (AUCREF) was calculated by applying VCM’s peak and trough steady-state concentrations to first-order pharmacokinetic equations. The medians (range) of AUCeGFR/0.789/AUCREF, AUCeGFR/AUCREF, AUCeCCr/AUCREF, and AUCeCCr (SCr + 0.2)/AUCREF were 0.88 (0.74–0.93), 0.90 (0.79–1.04), 0.92 (0.81–1.07), and 1.00 (0.88–1.11), respectively. Moreover, the percentage of patients within 10% of the AUCREF, defined as |Bayesian-estimated AUC − AUCREF| < AUCREF × 0.1, was the highest (86%) in AUCeCCr (SCr + 0.2). These results suggest that the Bayesian approach using eCCr (SCr + 0.2) has the highest prediction accuracy for the AUCREF in bedridden elderly patients. Although further studies are required with more accurate determination methods of the CCr and AUC, our findings highlight the potential of eCCr (SCr + 0.2) for estimating VCM’s AUC by the Bayesian approach in such patients.
著者
JaeHo Lee SeungJun Lee ByungMan Lee KyungBaeg Roh DeokHoon Park EunSun Jung
出版者
公益社団法人日本薬学会
雑誌
Biological and Pharmaceutical Bulletin (ISSN:09186158)
巻号頁・発行日
pp.b15-00305, (Released:2015-07-15)
参考文献数
14
被引用文献数
5

For screening of skin-whitening ingredients that modulate inhibition of melanogenesis, tyrosinase promoter-based assay using a 3D spheroid culture technique is a beneficial tool to improve the accuracy of raw material screening in cosmetics through mimicking of the in vivo microenvironment. Although the advantages of high-throughput screening (HTS) are widely known, there has been little focus on specific cell-based promoter assays for HTS in identifying skin-whitening ingredients that inhibit accumulation of melanin. The aim of this study was therefore to develop a large-scale compatible assay through pTyr-EGFP, an enhanced green fluorescent protein (EGFP)-based tyrosinase-specific promoter, to seek potential melanogenesis inhibitors for cosmetic use. Herein, a stably transfected human melanoma cell line expressing EGFP under the control of a 2.2-kb fragment derived from the tyrosinase gene was generated. Spontaneous induction of the tyrosinase promoter by 3D spheroid culture resulted in increased expression of EGFP, providing a significant correlation with the tyrosinase mRNA level, and subsequent inhibition of tyrosinase activity. Importantly, the pTyr-EGFP system provided successful tracking of the changes in the live image and real-time monitoring. Thus tyrosinase promoter-based fluorescent assay using a 3D spheroid culture can be useful as a screening system for exploring the efficiency of anti-melanogenesis ingredients.
著者
Alia Badawi Mai El Halawany Randa Latif
出版者
The Pharmaceutical Society of Japan
雑誌
Biological and Pharmaceutical Bulletin (ISSN:09186158)
巻号頁・発行日
vol.43, no.2, pp.284-288, 2020-02-01 (Released:2020-02-01)
参考文献数
22
被引用文献数
5

Thiamine hydrochloride has been suggested as a natural, safe yet effective alternative for chemical insect repellents. However, there is a demand for a reassessment of the minimum required dose that is sufficient to perform a topical repellency on the human skin. Therefore, the purpose of the current work is to establish a dose–response curve from which the effective dose (ED) is calculated. A series of increasing concentrations of thiamine hydrochloride were applied to the forearm of adult volunteers, the number of bites was counted and the percent repellency calculated accordingly. Data of percent repellency were converted to probit values which were plotted against log doses. A linear relation was obtained from the dose–response curve with an r2 = 0.958. Statistical validation of the equation was tested through linear regression analysis, where the slope and intercept were found significant from zero. No significant difference was shown between observed and expected responses (p > 0.05). ED 50 and 99.9% were computed from the linear equation and found to be 4.57 and 344 mg, respectively. This finding can be supported by future works in which a proper formulation of thiamine hydrochloride in the respective doses would be presented. One can get prolonged safe protection against insect bites.
著者
Aina Fukuda Souichi Nakashima Yoshimi Oda Kaneyasu Nishimura Hidekazu Kawashima Hiroyuki Kimura Takashi Ohgita Eri Kawashita Keiichi Ishihara Aoi Hanaki Mizuki Okazaki Erika Matsuda Yui Tanaka Seikou Nakamura Takahiro Matsumoto Satoshi Akiba Hiroyuki Saito Hisashi Matsuda Kazuyuki Takata
出版者
The Pharmaceutical Society of Japan
雑誌
Biological and Pharmaceutical Bulletin (ISSN:09186158)
巻号頁・発行日
vol.46, no.2, pp.320-333, 2023-02-01 (Released:2023-02-01)
参考文献数
69

Alzheimer’s disease (AD) is a progressive neurodegenerative disease characterized by dementia. The most characteristic pathological changes in AD brain include extracellular amyloid-β (Aβ) accumulation and neuronal loss. Particularly, cholinergic neurons in the nucleus basalis of Meynert are some of the first neuronal groups to degenerate; accumulating evidence suggests that Aβ oligomers are the primary form of neurotoxicity. Bacopa monniera is a traditional Indian memory enhancer whose extract has shown neuroprotective and Aβ-reducing effects. In this study, we explored the low molecular weight compounds from B. monniera extracts with an affinity to Aβ aggregates, including its oligomers, using Aβ oligomer-conjugated beads and identified plantainoside B. Plantainoside B exhibited evident neuroprotective effects by preventing Aβ attachment on the cell surface of human induced pluripotent stem cell (hiPSC)-derived cholinergic neurons. Moreover, it attenuated memory impairment in mice that received intrahippocampal Aβ injections. Furthermore, radioisotope experiments revealed that plantainoside B has affinity to Aβ aggregates including its oligomers and brain tissue from a mouse model of Aβ pathology. In addition, plantainoside B could delay the Aβ aggregation rate. Accordingly, plantainoside B may exert neuroprotective effects by binding to Aβ oligomers, thus interrupting the binding of Aβ oligomers to the cell surface. This suggests its potential application as a theranostics in AD, simultaneously diagnostic and therapeutic drugs.
著者
Shizen Inoue Kaneyasu Nishimura Serina Gima Mai Nakano Kazuyuki Takata
出版者
The Pharmaceutical Society of Japan
雑誌
Biological and Pharmaceutical Bulletin (ISSN:09186158)
巻号頁・発行日
vol.46, no.3, pp.517-522, 2023-03-01 (Released:2023-03-01)
参考文献数
20
被引用文献数
2

Parkinson’s disease (PD) is an age-related disorder with selective dopaminergic (DA) neuronal degeneration in the substantia nigra pars compacta. The presence of mainly α-synuclein-composed Lewy bodies in DA neurons is among the disease hallmarks in the brain of patients with PD. Human induced pluripotent stem cells (hiPSCs) are powerful tools to investigate PD pathophysiology and understand its molecular and cellular mechanisms better. In this study, we generated an α-synuclein-null hiPSC line introducing a nonsense mutation in the α-synuclein-encoding SNCA alleles using clustered regularly interspaced short palindromic repeats CRISPR-associated protein 9 (CRISPR-Cas9)-mediated gene editing. Our Western blotting analysis revealed the lack of α-synuclein protein expression in SNCA knockout hiPSC-derived cells. In addition, SNCA knockout hiPSCs retained healthy cell morphology, undifferentiated marker gene (e.g., NANOG, POU5F1, and SOX2) expression, and differentiation ability (based on the marker gene expression levels of the three germ layers). Finally, SNCA knockout hiPSC-derived DA neurons exhibited reduced vulnerability to the DA neurotoxin, 1-methyl-4-phenylpyridinium. In conclusion, the SNCA knockout hiPSC line we generated would provide a useful experimental tool for studying the physiological and pathological role of α-synuclein in PD.
著者
Seiryo Ogata Shingo Ito Takeshi Masuda Sumio Ohtsuki
出版者
The Pharmaceutical Society of Japan
雑誌
Biological and Pharmaceutical Bulletin (ISSN:09186158)
巻号頁・発行日
vol.45, no.6, pp.751-756, 2022-06-01 (Released:2022-06-01)
参考文献数
32
被引用文献数
1

Circadian rhythms influence the transport function of the blood–brain barrier (BBB) and peripheral organs. However, the influence of circadian rhythms on protein expression in the BBB remains to be completely elucidated. Therefore, we aimed to investigate diurnal changes in protein expression in the mouse BBB using quantitative proteomics. Quantitative proteomics showed that the expression of 67, 10, and 20 proteins in the isolated mouse brain capillary fraction changed significantly at zeitgeber time (ZT) 6, 12, and 18, respectively, compared to ZT0. Among them, the levels of 44 proteins were significantly increased at ZT6 and then returned to the same level as ZT0 at ZT12 and ZT18. Gene ontology analysis indicated that the proteins significantly increased at ZT6 were majorly related to translation. The brain capillary endothelial cell-selective proteins sepiapterin reductase and vascular endothelial growth factor receptor 2 showed diurnal variation. In contrast, the expression of ABC transporters, SLC transporters, and receptors associated with receptor-mediated transcytosis, and tight junction proteins did not change within a day. The present findings demonstrated that protein expression related to transport function and physical barrier at the BBB was maintained throughout the day, although the proteins involved in some biological processes exhibited diurnal variation at the BBB.
著者
Kayoko Matsubara Kazuaki Matsumoto Yuta Yokoyama Erika Watanabe Yuki Enoki Akari Shigemi Kazuro Ikawa Hideyuki Terazono Norifumi Morikawa Tamao Ohshige Yasuo Takeda
出版者
The Pharmaceutical Society of Japan
雑誌
Biological and Pharmaceutical Bulletin (ISSN:09186158)
巻号頁・発行日
vol.44, no.5, pp.732-736, 2021-05-01 (Released:2021-05-01)
参考文献数
27
被引用文献数
3

Ampicillin-sulbactam is a first-line therapy for pneumonia and is mainly excreted by the kidney. It is important to optimize the dose and dosing interval of ampicillin-sulbactam because in patients with decreased renal function and low skeletal muscle mass, such as the elderly, excess drug may burden renal function. In this study, we evaluated indices of renal function and optimized the dose and dosing interval of ampicillin-sulbactam based on pharmacokinetics (PK) and pharmacodynamics theory in elderly patients. The serum concentrations of ampicillin and sulbactam were measured by HPLC, and PK parameters were calculated. Correlations between the clearance of ampicillin or sulbactam and renal function were evaluated, and dosing optimization was calculated based on PK parameters. The PK parameters of ampicillin were CL = 6.5 ± 4.0 L/h, Vd = 19.3 ± 0.2 L, Ke = 0.4 ± 0.2, and t1/2 = 2.7 ± 1.6 h. The most correlated renal function index was estimated glomerular filtration rate (eGFRcys-c) calculated by serum cystatin-c (r = 0.7374, correlation formula; CL of ampicillin = 0.1937 × eGFRcys-c−0.6726). Based on this formula, we calculated the clearance of ampicillin and developed dosing regimens for the elderly. Serum cystatin-c concentration is an ideal index to optimize ampicillin-sulbactam antimicrobial therapy in elderly patients with pneumonia.
著者
Tomohiro Yamaguchi
出版者
The Pharmaceutical Society of Japan
雑誌
Biological and Pharmaceutical Bulletin (ISSN:09186158)
巻号頁・発行日
vol.33, no.3, pp.342-345, 2010-03-01 (Released:2010-03-01)
参考文献数
32
被引用文献数
24 27

The surfaces of lipid droplets (LDs) constitute major sites of regulated accumulation and degradation of lipid in cells, and hence play important roles in lipid homeostasis of the whole body. CGI-58 (also called α/β hydrolase domain-containing protein 5 (ABHD5)) is a member of the α/β-hydrolase family of proteins and is a product of the causal gene of Chanarin–Dorfman syndrome (CDS), which is characterized by excessive storage of triacylglycerol (TG) in various tissues. CGI-58 is distributed predominantly on the surface of LDs and plays a crucial role in TG degradation in cells. In the process of lipolysis, CGI-58 coordinates with several proteins, including perilipin, a member of the PAT family of proteins, and adipose triglyceride lipase (ATGL), a putative rate-limiting enzyme for TG degradation in adipocytes. Besides its role in adipocytes, CGI-58 is involved in lipid degradation in various tissues, including those of skin and liver. This review focuses on the functions and protein interactions of CGI-58 on the surface of LDs in the regulation of fat mobilization in cells.
著者
Annie Shirwaikar Arun Shirwaikar Kuppusamy Rajendran Isaac Sam Raj Punitha
出版者
公益社団法人日本薬学会
雑誌
Biological and Pharmaceutical Bulletin (ISSN:09186158)
巻号頁・発行日
vol.29, no.9, pp.1906-1910, 2006 (Released:2006-09-01)
参考文献数
39
被引用文献数
85 221

Berberine is a benzyl tetra isoquinoline alkaloid which is widely used as an antimicrobial and an antidiarrhoeal. As berberine containing plants are virtually used in all forms of traditional medicine, our study aimed to examine the antioxidant activity of berberine using 2,2-diphenyl 1-picrylhydrazyl (DPPH) radical scavenging, nitric oxide scavenging, lipid peroxidation, superoxide scavenging, iron chelating activity and 2,2-azino bis(3-ethylbenzothiazoline-6-sulfonate) (ABTS) radical scavenging methods. The IC50 values for all the models were calculated by regression analysis. In all the models tested, berberine showed its ability to scavenge the free radicals in a concentration dependent manner. The present study thereby justifies the therapeutic potential of berberine.
著者
Hideyuki Katsura Yukio Suga Anna Kubo Hayato Sugimura Kaname Kumatani Kazunobu Haruki Miwa Yonezawa Ayaka Narita Rei Ishijima Hiroaki Ikesue Hitomi Toi Naoko Takata
出版者
The Pharmaceutical Society of Japan
雑誌
Biological and Pharmaceutical Bulletin (ISSN:09186158)
巻号頁・発行日
vol.47, no.1, pp.98-103, 2024-01-01 (Released:2024-01-01)
参考文献数
20

Hypomagnesemia commonly occurs as a side effect of panitumumab treatment. In severe cases, temporary discontinuation or dose reduction of panitumumab may be necessary. Proton pump inhibitors (PPIs) are reportedly potential risk factors for hypomagnesemia. We conducted a multicenter study to assess the impact of PPIs on the risk of grade 3–4 hypomagnesemia in patients with metastatic colorectal cancer (mCRC) receiving panitumumab. We adjusted for potential bias using a propensity score-matched analysis and retrospectively reviewed the medical records of patients. Hypomagnesemia severity was graded according to the Common Terminology Criteria for Adverse Events, version 5.0. A total of 165 patients were enrolled in this study. The incidence of grade 3–4 hypomagnesemia was significantly higher in the PPI group than in the non-PPI group, both before (20.0% [30/60] vs. 8.0% [8/105], p = 0.026) and after propensity score matching (16.2% [6/37] vs. 0% [0/37], p = 0.025). In the propensity score-matched cohort, the risk of grade 3–4 hypomagnesemia was significantly higher in the PPI group (odds ratio, 2.19; 95% confidence interval, 1.69–2.84; p = 0.025). These findings suggest that concomitant use of PPIs significantly increases the risk of grade 3–4 hypomagnesemia in patients with mCRC receiving panitumumab. Therefore, close monitoring of these patients is imperative.
著者
Hayahide Ooi Yuki Asai Yoshiki Koriyama Masaaki Takahashi
出版者
The Pharmaceutical Society of Japan
雑誌
Biological and Pharmaceutical Bulletin (ISSN:09186158)
巻号頁・発行日
vol.46, no.12, pp.1731-1736, 2023-12-01 (Released:2023-12-01)
参考文献数
20

The albumin–bilirubin (ALBI) score is an index of hepatic functional reserve and is calculated from serum albumin and total bilirubin levels. However, the relationship between ceftriaxone (CTRX)-induced liver injury and ALBI score remains unknown. Therefore, we aimed to elucidate the risk of CTRX-induced liver injury based on the ALBI scores and CTRX dosage. This was a single-center, retrospective, case-control study of 490 patients and the primary outcome was CTRX-induced liver injury. We performed a COX regression analysis using age ≥75 years, male sex, alanine aminotransferase levels, ALBI score, and CTRX dosage regimen (4 ≥2 or 1 g/d) as explanatory factors. We also performed 1 : 1 propensity score matching between non-liver injury and liver injury groups. The incidence of liver injury was 10.0% (49/490). In COX regression analysis, CTRX 4 g/d was an independent risk factor for liver injury (95% coefficient interval: 1.05–6.96, p = 0.04). Meanwhile, ALBI score ≥−1.61 was an independent factor for liver injury (95% coefficient interval: 1.03–3.22, p = 0.04) with the explanatory factor of ≥2 and 1 g/d. The Kaplan–Meier curve indicated that the cumulative risk for CTRX-induced liver injury was significantly higher in the ALBI score ≥−1.61 group than in the ALBI score <−1.61 group before propensity score matching (p = 0.032); however, no significant differences were observed after propensity score matching (p = 0.791). These findings suggest that in patients treated with CTRX with ALBI score ≥−1.61, frequent liver function monitoring should be considered.
著者
Masami Yamada Yumi Jimaru Sari Torii Naoko Mitsuba Kazushige Takahashi
出版者
The Pharmaceutical Society of Japan
雑誌
Biological and Pharmaceutical Bulletin (ISSN:09186158)
巻号頁・発行日
vol.46, no.12, pp.1826-1831, 2023-12-01 (Released:2023-12-01)
参考文献数
23

Naldemedine is indicated for the treatment of opioid-induced constipation (OIC), but reports on its efficacy in preventing OIC are few. Therefore, we retrospectively investigated factors affecting the efficacy of concurrent prescription of naldemedine on OIC. Outpatients with cancer who were started on oxycodone 10 mg/d were included in the study. The eligible patients were classified by their physicians into the following three groups: Group A used regular laxatives before the introduction of oxycodone and initiated naldemedine treatment simultaneously with oxycodone administration, Group B did not take laxatives before the introduction of oxycodone and started naldemedine simultaneously with oxycodone administration, and Group C had been administering regular laxatives before the introduction of oxycodone and were not prescribed naldemedine simultaneously with oxycodone treatment. The Support Team Assessment Schedule Japanese edition score for constipation, frequency of defecation, Bristol Stool Form Scale, sense of incomplete rectal evacuation, and development or worsening of straining to pass bowel movements were compared among the three groups before and after oxycodone administration. In Group B, there was significant worsening of the four parameters except for the sense of incomplete rectal evacuation, whereas Groups A and C did not present any changes. In logistic regression analysis, body weight ≥51.8 kg was a factor significantly decreasing the preventive effect of naldemedine on OIC, and regular use of laxatives was a factor significantly increasing the preventive effect of naldemedine on OIC. Thus, the initiation of naldemedine should be considered depending on the body weight and regular laxative use.
著者
Yuichi Sakashita Kenji Abe Nobuyuki Katagiri Toshie Kambe Toshiaki Saitoh Iku Utsunomiya Yoshie Horiguchi Kyoji Taguchi
出版者
The Pharmaceutical Society of Japan
雑誌
Biological and Pharmaceutical Bulletin (ISSN:09186158)
巻号頁・発行日
vol.38, no.1, pp.134-138, 2015-01-01 (Released:2015-01-01)
参考文献数
34
被引用文献数
13 40

Psilocin (3-[2-(dimethylamino)ethyl]-1H-indol-4-ol) is a hallucinogenic component of the Mexican mushroom Psilocybe mexicana and a skeletal serotonin (5-HT) analogue. Psilocin is the active metabolite of psilocybin (3-[2-(dimethylamino)ethyl]-1H-indol-4-yl dihydrogen phosphate). In the present study, we examined the effects of systemically administered psilocin on extracellular dopamine and 5-HT concentrations in the ventral tegmental area (VTA), nucleus accumbens, and medial prefrontal cortex of the dopaminergic pathway in awake rats using in vivo microdialysis. Intraperitoneal administration of psilocin (5, 10 mg/kg) significantly increased extracellular dopamine levels in the nucleus accumbens. Psilocin did not affect the extracellular 5-HT level in the nucleus accumbens. Conversely, systemic administration of psilocin (10 mg/kg) significantly increased extracellular 5-HT levels in the medial prefrontal cortex of rats, but dopamine was decreased in this region. However, neither extracellular dopamine nor 5-HT levels in the VTA were altered by administration of psilocin. Behaviorally, psilocin significantly increased the number of head twitches. Thus, psilocin affects the dopaminergic system in the nucleus accumbens. In the serotonergic system, psilocin contribute to a crucial effect in the medial prefrontal cortex. The present data suggest that psilocin increased both the extracellular dopamine and 5-HT concentrations in the mesoaccumbens and/or mesocortical pathway.
著者
Meiyu Zhang Taro Miura Shunsuke Suzuki Masako Chiyotanda Sachiko Tanaka Kentaro Sugiyama Hisashi Kawashima Toshihiko Hirano
出版者
The Pharmaceutical Society of Japan
雑誌
Biological and Pharmaceutical Bulletin (ISSN:09186158)
巻号頁・発行日
vol.44, no.1, pp.7-17, 2021-01-01 (Released:2021-01-01)
参考文献数
40
被引用文献数
3 4

Vitamin K2 is suggested to have a suppressive effect on the peripheral blood mononuclear cells (PBMCs) of pediatric atopic dermatitis patients. We examined the molecular targets of vitamin K2 to suppress proliferation and cytokine production in T-cell mitogen-activated PBMCs of atopic dermatitis patients from the viewpoint of mitogen-activated protein kinase signaling molecules. The study population included 16 pediatric vitamin K2 patients and 21 healthy subjects. The effect of vitamin K2 on concanavalin A-activated PBMC proliferation was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and cell counting assays. T-helper (Th)1/Th2/Th17 cytokine profiles in plasma and PBMC-culture supernatants were analyzed by a cytometric beads array assay. Mitogen-activated protein kinase signaling molecules in concanavalin A-activated PBMCs were examined by enzyme-linked immunosorbent assay (ELISA) assays. At 10–100 µM, vitamin K2 significantly suppressed the proliferation of mitogen-activated PBMCs derived from atopic dermatitis patients and healthy subjects (p < 0.05). The interleukin (IL)-10 concentrations in plasma and the PBMC culture supernatants of atopic dermatitis patients were significantly higher than those of healthy subjects (p < 0.05). The IL-2 concentrations in the culture supernatants of atopic dermatitis PBMCs were significantly lower than those of healthy PBMCs (p < 0.05). Vitamin K2 significantly inhibited the IL-17A, IL-10, and tumor necrosis factor α (TNF-α) production (p < 0.05), and increased the IL-2 production (p < 0.01) in the culture supernatant of atopic dermatitis PBMCs. At 10–100 µM, vitamin K2 markedly decreased the of Mek1, extracellular signal-regulated kinases (ERK)1/2 mitogen-activated protein kinase, and SAPK/c-Jun N-terminal kinase (JNK) expression in atopic dermatitis PBMCs (p < 0.05). Vitamin K2 is suggested to attenuate activated T-cell immunity in atopic dermatitis patients through the inhibition of mitogen-activated protein kinase-Mek1-ERK1/2 and SAPK/JNK signaling pathways.
著者
Hidenori Ando Sherif E. Emam Yoshino Kawaguchi Taro Shimizu Yu Ishima Kiyoshi Eshima Tatsuhiro Ishida
出版者
The Pharmaceutical Society of Japan
雑誌
Biological and Pharmaceutical Bulletin (ISSN:09186158)
巻号頁・発行日
vol.44, no.6, pp.844-852, 2021-06-01 (Released:2021-06-01)
参考文献数
45
被引用文献数
10

Acidic extracellular pH (pHe) is characteristic of the tumor microenvironment. Several reports suggest that increasing pHe improves the response of immune checkpoint inhibitors in murine models. To increase pHe, either sodium bicarbonate (NaHCO3) or citric acid/potassium-sodium citrate (KNa-cit) was chronically administered to mice. It is hypothesized that bicarbonate ions (HCO3−), produced from these alkalinizing agents in vivo, increased pHe in the tumor, and excess HCO3− eliminated into urine increased urinary pH values. However, there is little published information on the effect of changing serum HCO3− concentrations, urinary HCO3− concentrations and urinary pH values on the therapeutic outcomes of immunotherapy. In this study, we report that oral administration of either NaHCO3 or KNa-cit increased responses to anti-programmed cell death-1 (PD-1) antibody, an immune checkpoint inhibitor, in a murine B16 melanoma model. In addition, we report that daily oral administration of an alkalinizing agent increased blood HCO3− concentrations, corresponding to increasing the tumor pHe. Serum HCO3− concentrations also correlated with urinary HCO3− concentrations and urinary pH values. There was a clear relationship between urinary pH values and the antitumor effects of immunotherapy with anti-PD-1 antibody. Our results imply that blood HCO3− concentrations, corresponding to tumor pHe and urinary pH values, may be important factors that predict the clinical outcomes of an immunotherapeutic agent, when combined with alkalinizing agents such as NaHCO3 and KNa-cit.
著者
Kenshi Ohbori Makiko Fujiwara Akihiro Ohishi Kentaro Nishida Yoshinobu Uozumi Kazuki Nagasawa
出版者
The Pharmaceutical Society of Japan
雑誌
Biological and Pharmaceutical Bulletin (ISSN:09186158)
巻号頁・発行日
vol.40, no.7, pp.1071-1077, 2017-07-01 (Released:2017-07-01)
参考文献数
38
被引用文献数
3 13

The number of patients with colitis has been increasing year by year. Recently, intestinal inflammation, as one of the factors for its onset, has been demonstrated to be induced by P2X7 receptor-mediated activation of colonic immune cells such as mast cells. Activation of P2X7 receptor (P2X7R) is known to be inhibited by divalent metal cations such as magnesium, but whether or not magnesium administration prevents/relieves colitis is unknown so far. Here, we report that oral (per os (p.o.)) administration of MgCl2 and ingestion of commercially available magnesium-rich mineral hard water relieves dextran sulfate sodium (DSS)-induced colitis in mice. Colitis was induced through ingestion of a 3% (w/v) DSS solution ad libitum for 10 d. Brilliant blue G (BBG, a P2X7R antagonist), MgCl2 or magnesium-rich mineral hard water was administered p.o. to mice via gastric intubation once a day or ad libitum from a day before DSS administration for 11 times or 11 d, respectively. DSS-treated mice exhibited a low disease activity index, a short colon and a high histological score compared to in control mice. As BBG (250 mg/kg, p.o.), administration of a MgCl2 solution (100 or 500 mg/kg, p.o.) and ad libitum ingestion of the magnesium-rich mineral hard water (212 ppm as magnesium) partially, but significantly, attenuated the severity of colitis by decreasing the accumulation of P2X7R-immunopositive mast cells in the colon. Therefore, prophylactic p.o. administration/ingestion of magnesium is considered to be partially effective to protect mice against DSS-induced colitis by inhibiting P2X7R-mediated activation/accumulation of colonic mast cells.
著者
Kakuyou Ogawa Michiho Ito
出版者
The Pharmaceutical Society of Japan
雑誌
Biological and Pharmaceutical Bulletin (ISSN:09186158)
巻号頁・発行日
vol.39, no.9, pp.1559-1563, 2016-09-01 (Released:2016-09-01)
参考文献数
18
被引用文献数
8 12

Inhalation of scent compounds with phenylpropanoidal structures, such as trans-cinnamaldehyde, is expected to increase the appetite. The scent of curry powder is well known for its appetite-enhancing effect on humans. In this work, we show that the appetite of mice after inhalation of curry powder essential oil or benzylacetone showed a similar increase. The components of curry oil, trans-cinnamaldehyde, trans-anethole, and eugenol, each showed appetite-enhancing effects; therefore, these three scent compounds may be the active compounds in curry powder oil.
著者
Hiroaki Takemoto Jun Takahashi Sumiko Hyuga Hiroshi Odaguchi Nahoko Uchiyama Takuro Maruyama Tadatoshi Yamashita Masashi Hyuga Naohiro Oshima Yoshiaki Amakura Takashi Hakamatsuka Yukihiro Goda Toshihiko Hanawa Yoshinori Kobayashi
出版者
The Pharmaceutical Society of Japan
雑誌
Biological and Pharmaceutical Bulletin (ISSN:09186158)
巻号頁・発行日
vol.41, no.2, pp.247-253, 2018-02-01 (Released:2018-02-01)
参考文献数
33
被引用文献数
17

Ephedrine alkaloids-free Ephedra Herb extract (EFE) has been developed to eliminate the adverse effects caused by ephedrine alkaloid-induced sympathetic hyperactivation. Previously, we reported that EFE possesses analgesic, anti-influenza, and cancer metastatic inhibitory effects at comparable levels to that of Ephedra Herb extract (EHE). However, it has not yet been demonstrated that EFE is free from the known side effects of EHE, such as excitation, insomnia, and arrhythmias. In this study, the incidence of these adverse effects was compared between mice administered EHE and those administered EFE. Increased locomotor activity in an open-field test, reduced immobility times in a forced swim test, and reduced sleep times in a pentobarbital-induced sleep test were observed in EHE-treated mice, when compared to the corresponding values in vehicle-treated mice. In contrast, EFE had no obvious effects in these tests. In electrocardiograms, atrial fibrillation (i.e., irregular heart rhythm, absence of P waves, and appearance of f waves) was observed in the EHE-treated mice. It was suggested that this atrial fibrillation was induced by stimulation of adrenaline β1 receptors, but not by hypokalemia. However, EFE did not affect cardiac electrophysiology. These results suggest that the abovementioned side effects are caused by ephedrine alkaloids in EHE, and that EFE is free from these adverse effects, such as excitation, insomnia, and arrhythmias. Thus, EFE is a promising new botanical drug with few adverse effects.