著者
Yusuke Watanabe Yuji Ikegaya
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.40, no.7, pp.1111-1115, 2017-07-01 (Released:2017-07-01)
参考文献数
28
被引用文献数
6

Caffeine promotes memory consolidation. Memory consolidation is thought to depend at least in part on hippocampal sharp waves (SWs). In the present study, we investigated the effect of bath-application of caffeine in spontaneously occurring SWs in mouse acute hippocampal slices. Caffeine induced an about 100% increase in the event frequency of SWs at concentrations of 60 and 200 µM. The effect of caffeine was reversible after washout of caffeine and was mimicked by an adenosine A1 receptor antagonist, but not by an A2A receptor antagonist. Caffeine increased SWs even in dentate-CA3 mini-slices without the CA2 regions, in which adenosine A1 receptors are abundantly expressed in the hippocampus. Thus, caffeine facilitates SWs by inhibiting adenosine A1 receptors in the hippocampal CA3 region or the dentate gyrus.
著者
Kazuma Higashisaka Kazuya Nagano Yasuo Yoshioka Yasuo Tsutsumi
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.40, no.3, pp.243-248, 2017-03-01 (Released:2017-03-01)
参考文献数
61
被引用文献数
25

In the past decade, nanotechnology has advanced rapidly, and many products containing nanoparticles are now an important part of our daily lives. Despite our increasing exposure to nanoparticles, however, information regarding the absorption, distribution, metabolism, excretion, and toxicity of nanoparticles remains limited. In this review, we introduce our group’s ongoing research into the biological effects and toxicities of nanoparticles, which we broadly refer to as “nano-safety research.” In addition to determining the biological effects of nanoparticles and elucidating the underlying mechanisms of those effects, we are also exploring the associations among the physicochemical properties and kinetics of nanoparticles. Furthermore, we are currently developing a battery of biomarkers that we hope will be used to predict the biological effects of nanoparticles during the early stages of development. Our research provides valuable basic information on the safety of nanoparticles. We hope that this information will be used for the development of better assessments of nanoparticles safety and for the creation of more appropriate regulations to ensure not only the safety but also the sustainability of nanotechnology.
著者
Hideharu Maruta Naoyuki Okita Ryoko Takasawa Fumiaki Uchiumi Tsutomu Hatano Sei-ichi Tanuma
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.30, no.3, pp.447-450, 2007 (Released:2007-03-01)
参考文献数
34
被引用文献数
9 26

The formation of ATP produced from poly(ADP-ribose) [(ADP-R)n] has been suggested to be required to repair damaged DNA. Here we investigate whether this ATP is involved in DNA replication processes during DNA repair. Poly(ADP-ribosyl)ated mid-S phase cell nuclei, which were isolated from synchronized HeLa S3 cells followed by the treatment with a DNA damaging agent, N-methyl-N′-nitro-N-nitrosoguanidine (MNNG), were revealed to retain DNA replication synthesizing activity during preincubation for de-poly(ADP-ribosyl)ation only in the presence of pyrophosphate (PPi) before DNA synthesis was started by adding 3 mM ATP. This DNA replication activity was not maintained in the presence of a potent and specific inhibitor of poly(ADP-ribose) glycohydrolase (PARG), Oenothein B (Oen B) during the preincubation with PPi. In the preincubation with PPi, μM orders of ATP was produced from (ADP-R)n. These results point to an important function of ATP generated from (ADP-R)n in nuclei for the maintenance of replication apparatus during DNA repair.
著者
Sat Byul Park Kyu-Nam Kim Eunju Sung Suk Young Lee Ho Cheol Shin
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.b15-00623, (Released:2016-02-25)
参考文献数
25
被引用文献数
11

Chronic Fatigue (CF) is a common reason for consulting a physician due to affecting quality of life, but only a few effective treatments are available. The aim of this study was to examine the effectiveness of subcutaneous injection of the human placental extract (HPE) on medically indescribable cases of CF and safety in a randomized, double-blind, placebo-controlled clinical trial. A total of seventy eight subjects with CF were randomly assigned to either a HPE group or a placebo group. Subjects in the HPE group were treated with HPE three times a week subcutaneously for 6 weeks, whereas those in the placebo group with normal saline. Then, the Fatigue Severity Scale (FSS), Visual Analog Scale (VAS) and Multidimensional Fatigue Inventory (MFI) were measured in both CF group and chronic fatigue syndrome (CFS) and idiopathic chronic fatigue (ICF) subgroup. The FSS, VAS and MFI score at baseline were not different between the HPE and placebo group in total subjects with CF. In CFS group, the FSS (p= 0.0242), VAS (p =0.0009) and MFI (p= 0.0159) scores measured at the end of the study period decreased more in the HPE group than in the placebo group when compared with those at the baseline. There were no significant differences between the HPE group and placebo group in the mean change from baseline in FSS, VAS, and MFI in subjects with ICF during the study period. The subcutaneous injection of HPE was effective in the improvement of CFS.
著者
Ryota Tanaka Yuko Morinaga Motoshi Iwao Ryosuke Tatsuta Takehiro Hashimoto Kazufumi Hiramatsu Hiroki Itoh
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.10, pp.1365-1370, 2023-10-01 (Released:2023-10-01)
参考文献数
31

Several cases of severe hyponatremia induced by linezolid (LZD) were reported. However, severe infections could also cause hyponatremia by increasing vasopressin secretion. To prove that hyponatremia is associated with LZD rather than infection, we compared the incidence and risk of developing hyponatremia between patients receiving LZD and those receiving vancomycin (VCM). A retrospective, single-center, observational cohort study was conducted in patients aged 18 years or older who received intravenous LZD or VCM for 7 d or longer. Hyponatremia was defined as serum sodium level lower than 134 mEq/L and more than 5% decrease from baseline after treatment initiation. The incidence and risk of developing hyponatremia were analyzed between LZD and VCM groups using chi-square test. Four hundred and fifty patients who satisfied the selection criteria were divided into LZD (n = 97) and VCM groups (n = 353). Significant differences in patient characteristics between LZD and VCM groups were observed before propensity score matching, but no significant differences were found after matching. LZD group showed a significantly higher incidence and risk of developing hyponatremia compared to VCM group both before (LZD: 16.5%, VCM: 5.4%; p < 0.001, odds ratio 3.472 [95% confidence interval (CI) 1.711–7.048]) and after (LZD: 17.8%, VCM: 5.5%; p = 0.020, odds ratio 3.738 [95% CI 1.157–12.076]) propensity score matching. In conclusion, propensity score analyses suggest that the risk of hyponatremia associated with LZD is approximately 3.7-fold higher than that associated with VCM, regardless of patient background.
著者
Shiori Tomita Fumiko Sekiguchi Maho Tsubota Atsufumi Kawabata
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.9, pp.1343-1346, 2023-09-01 (Released:2023-09-01)
参考文献数
22

Cav3.2 channels belong to the T-type calcium channel (T-channel) family, i.e., low voltage-activated calcium channels, and are abundantly expressed in the nociceptors, playing a principal role in the development of pathological pain. The channel activity of Cav3.2 is suppressed by zinc under physiological conditions. We thus tested whether dietary zinc deficiency would cause Cav3.2-dependent nociceptive hypersensitivity in mice. In the mice fed with zinc deficient diet for 2 weeks, plasma zinc levels declined by more than half, and mechanical allodynia developed. The dietary zinc deficiency-induced allodynia was restored by T-channel inhibitors or by Cav3.2 gene silencing. These data demonstrate that zinc deficiency induces Cav3.2-dependent nociceptive hypersensitivity in mice, thereby suggesting that pain experienced by patients with diseases accompanied by zinc deficiency (e.g., chronic kidney disease) might involve the increased Cav3.2 activity.
著者
Takaki Kamiya Daiki Hira Ryo Nakajima Kazuha Shinoda Atsuko Motomochi Aya Morikochi Yoshito Ikeda Tetsuichiro Isono Michiya Akabane Satoshi Ueshima Mikio Kakumoto Shinji Imai Shin-ya Morita Tomohiro Terada
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.7, pp.907-913, 2023-07-01 (Released:2023-07-01)
参考文献数
31
被引用文献数
1

Tramadol is metabolized by CYP2D6 to an active metabolite, which in turn acts as an analgesic. This study aimed to investigate the impact of CYP2D6 genotype on the analgesic effect of tramadol in clinical practice. A retrospective cohort study was performed in patients treated with tramadol for postoperative pain after arthroscopic surgery for rotator cuff injury during April 2017–March 2019. The impact of CYP2D6 genotypes on the analgesic effects was assessed by the numeric rating scale (NRS) pain scoring and analyzed by the Mann–Whitney U test. Stepwise multiple linear regression analysis was performed to identify predictive factors for the area under the time-NRS curve (NRS-AUC), which was calculated using the linear trapezoidal method. Among the 85 enrolled Japanese patients, the number of phenotypes with CYP2D6 normal metabolizer (NM) and intermediate metabolizer (IM) was n = 69 (81.1%) and n = 16 (18.9%), respectively. The NRS and NRS-AUC in the IM group were significantly higher than those in the NM group until Day 7 (p < 0.05). The multiple linear regression analysis indicated that the CYP2D6 polymorphism was a prediction factor of the high NRS-AUC levels in Days 0–7 (β = 9.52, 95% CI 1.30–17.7). In IM patients, the analgesic effect of tramadol was significantly reduced one week after orthopedic surgery in clinical practice. Therefore, dose escalation of tramadol or the use of alternative analgesic medications can be recommended for IM patients.
著者
Taisuke Konno Hiroyuki Suzuki Hitoshi Nakamura Yuriko Murai
出版者
The Pharmaceutical Society of Japan
雑誌
Biological and Pharmaceutical Bulletin (ISSN:09186158)
巻号頁・発行日
pp.b22-00050, (Released:2022-06-29)
参考文献数
15

In veterinary medicine, various drugs are used on a daily basis. Using inappropriate medications poses health hazards to companion animals and humans; thus, assessing adverse events in veterinary medicine has great social significance but remains an untapped area of research. In this study, to promote the appropriate use of veterinary drugs and clarify common pharmaceutical issues in Japanese veterinary medicine, we analyzed information in the Veterinary Drug Side Effects Database (National Veterinary Assay Laboratory of the Ministry of Agriculture, Forestry and Fisheries, Japan). We found that the number of reports has been increasing annually, including those on high-risk drugs, molecular-targeted drugs, and antibody-based drugs. The details of the reports were similar to those from the United States, including the misadministration of veterinary drugs to humans, improper drug management, and re-administering drugs with a history of side effects. Furthermore, 46.50% of all reports mentioned the administration of one or more drugs, with the highest number of concomitant drugs being 10. In addition, 37.78% of all reports described the use of drugs in manners deviating from the intended use indicated in the package insert. Therefore, to avoid adverse events, pharmacists may have to be involved in dispensing and aseptically preparing veterinary medicines and providing drug information and medication guidance. To optimize pharmacotherapy for ill companion animals, "veterinary pharmacy" and "veterinary medicine pharmacy" must be developed in line with clinical situations in Japan, while considering knowledge from countries that are advanced in terms of veterinary medicine.
著者
Fan Zhang Mu-rong Liu Hai-tong Wan
出版者
The Pharmaceutical Society of Japan
雑誌
Biological and Pharmaceutical Bulletin (ISSN:09186158)
巻号頁・発行日
vol.37, no.3, pp.335-339, 2014-03-01 (Released:2014-03-01)
参考文献数
72
被引用文献数
63 99

PEGylation changes the physical and chemical properties of the biomedical molecule, such as its conformation, electrostatic binding, and hydrophobicity, and results in an improvement in the pharmacokinetic behavior of the drug, while it also causes some disadvantages of which cannot be neglected. The available data manifests that polyethylene glycol (PEG) itself shows potential risk, such as immunogenicity of the PEG and PEG-containing vacuoles in cells observed with PEGylated biologicals. Decreased activity and heterogeneity are also the negative aspects of PEGylation. The unfavorable impacts which are brought by the PEGylation are described here with examples of modified therapeutic proteins on the market and used in the clinical trials.
著者
Ryota Tanaka Daiki Eto Koji Goto Yoshifumi Ohchi Norihisa Yasuda Yosuke Suzuki Ryosuke Tatsuta Takaaki Kitano Hiroki Itoh
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.737-741, 2021-05-01 (Released:2021-05-01)
参考文献数
18
被引用文献数
5

For intensive care unit (ICU) patients, injectable voriconazole (VRCZ) is difficult to use because the patients often develop acute kidney injury. Since many ICU patients have consciousness disturbance, oral ingestion of tablet formulation is also difficult, and administration of a suspension via enteral feeding tube is required when using VRCZ. In this study, we investigated the in vitro adsorption property of oral VRCZ to feeding tube and performed pharmacokinetic analysis of VRCZ prepared by powdering and simple suspension for ICU patients. VRCZ was tube-administered to five ICU patients at a loading dose of 300 mg and plasma VRCZ concentrations before and at 1, 2, 4, 8, 12 h after the first dose were measured using HPLC. Pharmacokinetic parameters were calculated by non-compartmental model analysis. The recovery rate of VRCZ after infusion of the suspension through feeding tube was 89.8 ± 8.3%, but the cumulative rates after the first and second re-infusion were 102.7 ± 20.7 and 99.3 ± 10.3%, respectively, suggesting almost no residual drug in the tube after re-infusion. Metabolic phenotype was extensive metabolizer (EM) in two patients and intermediate metabolizer (IM) in three patients. The values of total clearance (CLtot/F) calculated by moment analysis were 0.51 and 0.55 L/h/kg in two EM patients, and 0.09, 0.29 and 0.31 L/h/kg in three IM patients. The CLtot/F was apparently lower in IM patients compared to EM. In conclusion, powdered and suspended VRCZ administered via enteral feeding tube showed pharmacokinetics depending on CYP2C19 gene polymorphism, similar to that observed in usual oral administration.
著者
Kosuke Kusamori
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.8, pp.1029-1036, 2021-08-01 (Released:2021-08-01)
参考文献数
70
被引用文献数
2

Cell-based therapy for disease treatment involves the transplantation of cells obtained either from self or others into relevant patients. While cells constituting the body tissues maintain homeostasis by performing remarkable functions through complicated cell–cell interactions, transplanted cells, which are generally cultured as a monolayer, are unable to recapitulate similar interactions in vivo. The regulation of cell–cell interactions can immensely increase the function and therapeutic effect of transplanted cells. This review aims to summarize the methods of regulating cell–cell interactions that could significantly increase the therapeutic effects of transplanted cells. The first method involves the generation of multicellular spheroids by three-dimensional cell culture. Spheroid formation greatly improved the survival and therapeutic effects of insulin-secreting cells in diabetic mice after transplantation. Moreover, mixed multicellular spheroids, composed of insulin-secreting cells and aorta endothelial cells or fibroblasts, were found to significantly improve insulin secretion. Secondly, adhesamine derivatives, which are low-molecular-weight compounds that accelerate cell adhesion and avoid anoikis and anchorage-dependent apoptosis, have been used to improve the survival of bone marrow-derived cells and significantly enhanced the therapeutic effects in a diabetic mouse model of delayed wound healing. Finally, the avidin-biotin complex method, a cell surface modification method, has been applied to endow tumor-homing mesenchymal stem cells with anti-tumor ability by modifying them with doxorubicin-encapsulated liposomes. The modified cells showed excellent effectiveness in cell-based cancer-targeting therapy. The discussed methods can be useful tools for advanced cell-based therapy, promising future clinical applications.
著者
Kazuyuki Niki Maki Yasui Maika Iguchi Tomomi Isono Hiroto Kageyama Mikiko Ueda
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.2, pp.279-282, 2021-02-01 (Released:2021-02-01)
参考文献数
16
被引用文献数
1

Taking bitter-tasting drugs can be stressful for children who have underdeveloped swallowing skills and do not understand the meaning of medication. Furthermore, the senses of vision and smell are known to majorly influence taste. This pilot study was aimed at determining the effect of visual stimulation by immersive virtual reality (iVR) on taste and the safety of this approach for developing a new method to assist children with taking medication. Ten subjects participated in this study, and their mean (standard deviation (S.D.)) age was 21.8 (0.8) years. The subjects tasted the bitter aqueous solution (quinine 0.00375%) while viewing two different VR images (strawberry sponge cake and orange juice) alternately and received sensory tests immediately after the tasting and again 30 s later. In addition, nausea was assessed 30 s after tasting for each VR image. The primary endpoint was the difference in sensory test scores immediately after the tasting and 30 s later, between the two images. There were no significant differences in the sensory test scores between the placebo and either strawberry sponge cake or orange juice immediately after tasting. However, 30 s after tasting, the scores changed significantly to a tendency to perceive sweetness from the strawberry sponge cake and orange juice images compared with the placebo. No subject experienced nausea. Therefore, the findings of this study suggest that displaying images of sweet foods by using iVR to stimulate visual perception could safely reduce the sense of bitterness.
著者
Yoshitaka Saito Kazuki Uchiyama Tatsuhiko Sakamoto Kosei Kubota Hiromitsu Oki Miwako Iwai Yoh Takekuma Yoshito Komatsu Mitsuru Sugawara
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.3, pp.293-297, 2021-03-01 (Released:2021-03-01)
参考文献数
15
被引用文献数
2

Chemotherapy regimen management is one of the most important oncology pharmacy practices, because chemotherapy is conducted according to the registered regimens. In this study, we evaluated the pharmaceutical practice that assumes the initial confirmation of chemotherapy regimens and the quality of practice sharing between oncology-specialized and non-specialized pharmacists in regimen management committee. Pharmacists initially confirmed the applied regimen prescribed by physicians regarding chemotherapeutic agents and prophylactic supportive care medicines. Following confirmation, the regimens were reviewed by the Hokkaido University Hospital Regimen Management Committee. A total of 233 regimens were reviewed by the committee over three years. In total, 110 pharmaceutical inquiries were conducted, 45% of inquiries were concerning chemotherapeutic agents, of which approximately half were regarding supportive care medicines. Most inquiries were regarding premedication, followed by those on administration time, solvent of infusion medicines, and dosage. Correction was performed for 84.5% of inquiries. There was no significant difference in inquiry rates between practice and trial regimens. We have entrusted the first basic regimen review according to the checklist, creation of the chemotherapy plan document, and registry of the adopted regimens in the ordering system from oncology-certified pharmacists to non-certified pharmacists. Basic regimen review was well conducted by a non-certified pharmacist, and a more advanced review was additionally performed by certified pharmacists. In conclusion, we demonstrated the utility of pharmaceutical confirmation in a chemotherapeutic regimen review, suitable review coverage, and quality practice sharing between oncology-certified and non-certified pharmacists, which is one of the recommended methods in chemotherapy regimen review.
著者
Shungo Imai Kenji Momo Hitoshi Kashiwagi Takayuki Miyai Mitsuru Sugawara Yoh Takekuma
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.10, pp.1519-1525, 2020-10-01 (Released:2020-10-01)
参考文献数
37
被引用文献数
7

The anti-inflammatory agent colchicine may cause toxic effects such as rhabdomyolysis, pancytopenia, and acute respiratory distress syndrome in cases of overdose and when patients have renal or liver impairment. As colchicine is a substrate for CYP3A4 and P-glycoprotein (P-gp), drug–drug interactions are important factors that cause fatal colchicine-related side effects. Thus, we conducted a nation-wide survey to determine the status of inappropriate colchicine prescriptions in Japan. Patients prescribed the regular use of colchicine from April 2014 to March 2017 were identified using the Japanese large health insurance claims database. As the primary endpoint, we evaluated the concomitant prescription proportions of strong CYP3A4 and/or P-gp inhibitors classified as “contraindications for co-administration” with colchicine in patients with renal or liver impairment. We defined these cases as “inappropriate colchicine prescriptions.” Additionally, factors affecting inappropriate colchicine prescriptions were analyzed. Among the 3302 enrolled patients, 43 (1.30%) were inappropriately prescribed colchicine. Of these 43 patients, 11 had baseline renal and/or liver impairment. By multiple regression analysis, the primary diseases “gout” and “Behçet’s disease” were extracted as independent factors for inappropriate colchicine prescriptions with odds ratios of 0.40 (95% confidence interval: 0.19–0.84) and 4.93 (95% confidence interval: 2.12–11.5), respectively. We found that approximately 1% of patients had important colchicine interactions. Particularly, Behçet’s disease was a risk factor for inappropriate prescriptions, with approximately 25% of patients showing renal and/or liver impairment (classified as “contraindications for co-administration”). These findings may be useful for medical professionals who prescribe colchicine therapy.
著者
Takumi Matsuzaki Masao Nakamura Takehide Nogita Atsushi Sato
出版者
The Pharmaceutical Society of Japan
雑誌
Biological and Pharmaceutical Bulletin (ISSN:09186158)
巻号頁・発行日
vol.42, no.6, pp.989-995, 2019-06-01 (Released:2019-06-01)
参考文献数
19
被引用文献数
20

An Intact form of lactoferrin (LF) is known to be absorbed from the small intestine and transported into the blood circulation. We reevaluated the cellular uptake and release of LF using an enterocyte model of human small intestinal cells derived from the Caco-2 cell line. In contrast to a previous report, we observed that intact bovine LF was taken up into seven and 21 d-cultured Caco-2 cells and successfully released back into the culture medium, even though the human intestinal LF receptor, intelectin-1, was not immunochemically detectable. Similar observations were made for human LF and its derivatives (the N-terminal half of LF designated N-lobe and Fc fusions). These observations regarding the uptake and release of intact LF in Caco-2 cells were consistent with in vivo observations. Therefore, we propose that the uptake and release of intact LF by Caco-2 cells should be assessed as a potential in vitro model of in vivo LF absorption in human intestines.
著者
Toshiro Niwa Toshifumi Shiraga Akira Takagi
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.28, no.9, pp.1805-1808, 2005 (Released:2005-09-01)
参考文献数
50
被引用文献数
82 185

The effects of five antifungal drugs, fluconazole, itraconazole, micafungin, miconazole, and voriconazole, on cytochrome P450 (CYP) 2C9-mediated tolbutamide hydroxylation, CYP2C19-mediated S-mephenytoin 4′-hydroxylation, and CYP3A4-mediated nifedipine oxidation activities in human liver microsomes were compared. In addition, the effects of preincubation were estimated to investigate the mechanism-based inhibition. The IC50 value against tolbutamide hydroxylation was the lowest for miconazole (2.0 μM), followed by voriconazole (8.4 μM) and fluconazole (30.3 μM). Similarly, the IC50 value against S-mephenytoin 4′-hydroxylation was the lowest for miconazole (0.33 μM), followed by voriconazole (8.7 μM) and fluconazole (12.3 μM). On the other hand, micafungin at a concentration of 10 or 25 μM neither inhibited nor stimulated tolbutamide hydroxylation and S-mephenytoin 4′-hydroxylation, and the IC50 values for itraconazole against these were greater than 10 μM. These results suggest that miconazole is the strongest inhibitor of CYP2C9 and CYP2C19, followed by voriconazole and fluconazole, whereas micafungin would not cause clinically significant interactions with other drugs that are metabolized by CYP2C9 or CYP2C19 via the inhibition of metabolism. The IC50 value of voriconazole against nifedipine oxidation was comparable with that of fluconazole and micafungin and higher than that of itraconazole and miconazole. The stimulation of the inhibition of CYP2C9-, CYP2C19-, or CYP3A4-mediated reactions by 15-min preincubation was not observed for any of the antifungal drugs, suggesting that these drugs are not mechanism-based inhibitors.
著者
Jong-Ho Koh Kyung-Mi Kim Jin-Man Kim Jae-Chul Song Hyung-Joo Suh
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.26, no.5, pp.691-694, 2003 (Released:2003-05-01)
参考文献数
24
被引用文献数
29 53

This study was conducted to investigate the chemical component of the hot water (HW) fraction of mycelia of Cordyceps sinensis and its antifatigue and antistress effect against a stimulus in vivo using rats and mice. The growth of mycelia reached a maximum level of 31.6 g/l after 120 h of incubation. The main chemical composition of the HW fraction of mycelia of C. sinensis was found to be carbohydrate (78.9%) with 5% moisture. The swimming endurance capacity of mice orally administered with the HW fraction (150 and 300 mg/kg/d, respectively) was significantly prolonged from 75 to 90 min with a lessening of fatigue. When the HW fraction (150 mg/kg/d) was given to rats for 8 d including a 48 h stress period, the weight changes of the adrenal gland, spleen, thymus, and thyroid, which is an index of stress, were suppressed. The HW fraction also significantly inhibited the increase in total cholesterol and the decrease in alkaline phosphatase levels as biochemical parameters of immobilization stress in rats.
著者
Ghazi Mohamed Eisa Hussein Hisashi Matsuda Seikou Nakamura Makoto Hamao Toshihito Akiyama Kouhei Tamura Masayuki Yoshikawa
出版者
The Pharmaceutical Society of Japan
雑誌
Biological and Pharmaceutical Bulletin (ISSN:09186158)
巻号頁・発行日
vol.34, no.12, pp.1849-1855, 2011-12-01 (Released:2011-12-01)
参考文献数
26
被引用文献数
39 52

We previously investigated the effects of an aqueous extract of maté (mate) tea, made from the leaves of Ilex paraguariensis, on the diabesity and metabolic syndrome features in a mouse model. Mate induced significant decreases in body weight (BW), body mass index, and food intake (FI). In this study, to verify the mode of action of mate on FI and consequently on BW, we examined the anorexic effects of mate on the appetite and satiety markers glucagon-like peptide 1 (GLP-1) and leptin in high-fat diet-fed ddY mice. GLP-1 is a peptide signal generated by the gastrointestinal tract, which regulates appetite and influences BW, whereas leptin is an afferent signal from the periphery to the brain in a homeostatic feedback loop that regulates adipose tissue mass, thus leading to decreased appetite and FI and increased energy expenditure. Chronic administration of mate (50, 100 mg/kg) for 3 weeks significantly reduced FI, BW, and ameliorated blood fats, liver fats, and adipose tissue. Mate induced significant increases in GLP-1 levels and leptin levels compared with the control. Acute administration of major constituents of mate showed significant increases in GLP-1 levels by dicaffeoyl quinic acids and matesaponins, and significant induction of satiety by caffeoyl quinic acids and caffeine in ddY mice. These findings suggest that mate may induce anorexic effects by direct induction of satiety and by stimulation of GLP-1 secretion and modulation of serum leptin levels.
著者
Takashi MaruYama Hiroyuki Yamakoshi Yoshiharu Iwabuchi Hiroyuki Shibata
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.6, pp.756-763, 2023-06-01 (Released:2023-06-01)
参考文献数
59
被引用文献数
1

Curcumin has long been recognized for its anti-inflammatory properties. An antitumor effect has been recently reported in curcumin and clinical trials are being conducted. However, a large amount of required intake to obtain the antitumor effect of curcumin has been regarded as a problem. Therefore, curcumin analogs have been created by many researchers to enhance the effects of curcumin. We have synthesized >50 curcumin analogs and revealed greater growth suppression of various tumor cells with mono-carbonyl analogs than curcumin. Mechanistically, mono-carbonyl analogs inhibited transcriptional activity (e.g., nuclear factor kappa B, signal transducer, and activator of transcription 3) or activated caspase-3. Additionally, mono-carbonyl analogs of curcumin control tumor cell metabolism. Herein, we summarize the current knowledge about mono-carbonyl curcumin analogs and discuss their potential clinical applications.
著者
Ryo Iketani Shinobu Imai
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.4, pp.592-598, 2023-04-01 (Released:2023-04-01)
参考文献数
17
被引用文献数
1

In April 2014, sodium-glucose cotransporter 2 inhibitor (SGLT-2i) was introduced in Japan. In May 2015, the prescription limitation for SGLT-2i was lifted. Subsequently, SGLT-2i was shown to reduce cardiovascular events in patients with type 2 diabetes mellitus (T2DM). SGLT-2i prescription is expected to increase and consequently affect the prescription trends for other antidiabetic agents. Therefore, we evaluated the trends for antidiabetic agent prescriptions in Japan from April 2012 to March 2020. In this study, a dynamic cohort consisting of patients with T2DM derived from the Japan Medical Data Center health insurance database and with at least one antidiabetic agent prescription was investigated. The prescription rates were calculated monthly (/1000 person-months) for each class of antidiabetic agent. The eligible cohort comprised 34333 patients. The prescription rate for dipeptidyl peptidase-4 inhibitor increased from 424.0 in April 2012 to 656.3 in May 2015, and slightly decreased to 635.4 in March 2020. The prescription rate for biguanide consistently increased from 347.2 in April 2012 to 500.1 in March 2020. The prescription rate for sulfonylurea consistently decreased from 393.8 in April 2012 to 172.5 in March 2020. The prescription rate for SGLT-2i consistently increased from 4.1 in April 2014 to 363.1 in March 2020. SGLT-2i prescription increased and may affect the prescription trends for dipeptidyl peptidase-4 inhibitor and sulfonylurea after May 2015, when the prescription limitation for SGLT-2i was lifted. Biguanide prescriptions increased regardless of the introduction of SGLT-2i. The treatment of T2DM in Japan is clearly changing, with a focus on SGLT-2i and biguanide.