著者
Hyun-Kyung Chang Mal-Soon Shin Hye-Young Yang Jin-Woo Lee Young-Sick Kim Myoung-Hwa Lee Jullia Kim Khae-Hawn Kim Chang-Ju Kim
出版者
The Pharmaceutical Society of Japan
雑誌
Biological and Pharmaceutical Bulletin (ISSN:09186158)
巻号頁・発行日
vol.29, no.8, pp.1597-1602, 2006 (Released:2006-08-01)
参考文献数
41
被引用文献数
83 100

Prostate cancer is one of the most common non-skin cancers in men. Amygdalin is one of the nitrilosides, natural cyanide-containing substances abundant in the seeds of plants of the prunasin family that have been used to treat cancers and relieve pain. In particular, D-amygdalin (D-mandelonitrile-β-D-gentiobioside) is known to exhibit selective killing effect on cancer cells. Apoptosis, programmed cell death, is an important mechanism in cancer treatment. In the present study, we prepared the aqueous extract of the amygdalin from Armeniacae semen and investigated whether this extract induces apoptotic cell death in human DU145 and LNCaP prostate cancer cells. In the present results, DU145 and LNCaP cells treated with amygdalin exhibited several morphological characteristics of apoptosis. Treatment with amygdalin increased expression of Bax, a pro-apoptotic protein, decreased expression of Bcl-2, an anti-apoptotic protein, and increased caspase-3 enzyme activity in DU145 and LNCaP prostate cancer cells. Here, we have shown that amygdalin induces apoptotic cell death in human DU145 and LNCaP prostate cancer cells by caspase-3 activation through down-regulation of Bcl-2 and up-regulation of Bax. The present study reveals that amygdalin may offer a valuable option for the treatment of prostate cancers.
著者
Satoshi Yamaori Yoshimi Okushima Kazufumi Masuda Mika Kushihara Takashi Katsu Shizuo Narimatsu Ikuo Yamamoto Kazuhito Watanabe
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.36, no.7, pp.1197-1203, 2013-07-01 (Released:2013-07-01)
参考文献数
39
被引用文献数
2 11

Our recent work has shown that cannabidiol (CBD) exhibits the most potent direct inhibition of human cytochrome P450 1A1 (CYP1A1) among the CYP enzymes examined. However, the mechanism underlying this CBD inhibition remains to be clarified. Thus, to elucidate the structural requirements for the potent inhibition by CBD, the effects of CBD and its structurally related compounds on CYP1A1 activity were investigated with recombinant human CYP1A1. Olivetol, which corresponds to the pentylresorcinol moiety of CBD, inhibited the 7-ethoxyresorufin O-deethylase activity of CYP1A1; its inhibitory effect (IC50=13.8 µM) was less potent than that of CBD (IC50=0.355 µM). In contrast, d-limonene, which corresponds to the terpene moiety of CBD, only slightly inhibited CYP1A1 activity. CBD-2′-monomethyl ether (CBDM) and CBD-2′,6′-dimethyl ether inhibited CYP1A1 activity with IC50 values of 4.07 and 23.0 µM, respectively, indicating that their inhibitory effects attenuated depending on the level of methylation on the free phenolic hydroxyl groups in the pentylresorcinol moiety of CBD. Cannabidivarin inhibited CYP1A1 activity, although its inhibitory potency (IC50=1.85 µM) was lower than that of CBD. The inhibitory effects of Δ9-tetrahydrocannabinol and cannabielsoin (IC50s ≈10 µM), which contain a free phenolic hydroxyl group and are structurally constrained, were less potent than that of CBDM, which contains a free phenolic hydroxyl group and is rotatable between pentylresorcinol and terpene moieties. These results suggest that the pentylresorcinol structure in CBD may have structurally important roles in direct CYP1A1 inhibition, although the whole structure of CBD is required for overall inhibition.
著者
藤田 貢 洪 卿秀 伊東 八重 三沢 悟 竹内 尚人 仮家 公夫 西室 悟司
出版者
The Pharmaceutical Society of Japan
雑誌
Biological and Pharmaceutical Bulletin (ISSN:09186158)
巻号頁・発行日
vol.18, no.9, pp.1194-1196, 1995-09-15 (Released:2008-04-10)
参考文献数
11
被引用文献数
47 57

Intraduodenal administration of nattokinase (NK) at a dose of 80mg/kg, resulted in the degradation of fibrinogen in plasma suggesting transport of NK across the intestinal tract in normal rats. The action of NK on the cleavage of fibrinogen in the plasma from blood samples drawn at intervals after intraduodenal administration of the enzyme was investigated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and Western blotting analysis with an anti-fibrinogen γ chain antibody. The 270 kDa fragment carrying antigenic sites for the binding of the anti-fibrinogen γ chain antibody appeared within 0.5h and was then degraded gradually to a 105kDa fragment via a 200 kDa fragment. This suggests that fibrinogen was degraded to a 105 kDa fragment via several intermediates (270 and 200kDa). In parallel with the degradation process, plasma recalcification times were remarkably prolonged. NK was also detected in the plasma from blood samples drawn 3 and 5 h after administration of the enzyme by SDS-PAGE and Western blotting analysis with an anti-NK antibody. The results indicate that NK is absorbed from the rat intestinal tract and that NK cleaves fibrinogen in plasma after intraduodenal administration of the enzyme.
著者
Tomoharu Kuboyama Chihiro Tohda Katsuko Komatsu
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.6, pp.892-897, 2014-06-01 (Released:2014-06-01)
参考文献数
60
被引用文献数
16 59

Neurodegenerative diseases commonly induce irreversible destruction of central nervous system (CNS) neuronal networks, resulting in permanent functional impairments. Effective medications against neurodegenerative diseases are currently lacking. Ashwagandha (roots of Withania somnifera Dunal) is used in traditional Indian medicine (Ayurveda) for general debility, consumption, nervous exhaustion, insomnia, and loss of memory. In this review, we summarize various effects and mechanisms of Ashwagandha extracts and related compounds on in vitro and in vivo models of neurodegenerative diseases such as Alzheimer’s disease and spinal cord injury.
著者
Maaged Akiel Jawaher Alsughayyir Ahmed M. Basudan Hassan S. Alamri Ayed Dera Tlili Barhoumi Abdullah M. Al Subayyil Yasser S. Basmaeil Fahad M. Aldakheel Raid Alakeel Hazem K. Ghneim Yazeed A. Al-Sheikh Yasser Alraey Saeed Asiri Mohammad A. Alfhili
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.372-378, 2021-03-01 (Released:2021-03-01)
参考文献数
33

The prevalence of cancer-associated anemia (CIA) is high, and the mechanisms governing its development remain poorly understood. Eryptosis, the suicidal cell death of red blood cells (RBCs), may account for CIA as it is triggered by clinically approved chemotherapeutics including cisplatin and paclitaxel. Physcion (PSN), an anthraquinone extracted from rhubarb and other plants, has shown great promise as an anticancer agent. However, the potential toxicity of PSN to RBCs remains elusive. RBCs were isolated from heparinized blood, and incubated with 10–100 µM of PSN for 24 h at 37 °C. Hemolysis was photometrically calculated from hemoglobin concentration in the medium at 405 nm, while flow cytometry was employed to investigate cardinal markers of eryptosis. Phosphatidylserine (PS) exposure was detected by Annexin-V-fluorescein isothiocyanate (FITC), intracellular calcium by Fluo4/AM, cellular volume from forward scatter (FSC), and oxidative stress by 2′,7′-dichlorodihydrofluorescein diacetate (H2DCFDA). PSN induced overt hemolysis at 50 and 100 µM which was not mediated through calcium influx, protein kinase C, casein kinase 1α, or receptor-interacting protein 1. Moreover, PSN caused significant increase in Annexin-V-FITC and Fluo4 fluorescence with no appreciable influence on FSC or DCF values. Accordingly, PSN stimulates premature eryptosis characterized by PS externalization and intracellular calcium overload without cell shrinkage or oxidative damage. In conclusion, this report shows, for the first time, that PSN is cytotoxic to RBCs by inducing hemolysis and programmed cell death which may limit its success as a chemotherapeutic agent.
著者
Kiyoko Kaneko Yasuo Aoyagi Tomoko Fukuuchi Katsunori Inazawa Noriko Yamaoka
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.5, pp.709-721, 2014-05-01 (Released:2014-05-01)
参考文献数
42
被引用文献数
11 68

Purines are natural substances found in all of the body’s cells and in virtually all foods. In humans, purines are metabolized to uric acid, which serves as an antioxidant and helps to prevent damage caused by active oxygen species. A continuous supply of uric acid is important for protecting human blood vessels. However, frequent and high intake of purine-rich foods reportedly enhances serum uric acid levels, which results in gout and could be a risk factor for cardiovascular disease, kidney disease, and metabolic syndrome. In Japan, the daily intake of dietary purines is recommended to be less than 400 mg to prevent gout and hyperuricemia. We have established an HPLC method for purine analysis and determined purines in a total of 270 foodstuffs. A relatively small number of foods contained concentrated amounts of purines. For the most part, purine-rich foods are also energy-rich foods, and include animal meats, fish meats, organs such as the liver and fish milt, and yeast. When the ratio of the four purine bases (adenine, guanine, hypoxanthine, and xanthine) was compared, two groups of foods were identified: one that contained mainly adenine and guanine and one that contained mainly hypoxanthine. For patients with gout and hyperuricemia, the amount of total purines and the types of purines consumed, particularly hypoxanthine, are important considerations. In this context, the data from our analysis provide a purine content reference, and thereby clinicians and patients could utilize that reference in nutritional therapy for gout and hyperuricemia.
著者
Shin Nakao Keiichi Kojima Yuki Sudo
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.10, pp.1357-1363, 2021-10-01 (Released:2021-10-01)
参考文献数
51

In life science research, methods to control biological activities with stimuli such as light, heat, pressure and chemicals have been widely utilized to understand their molecular mechanisms. The knowledge obtained by those methods has built a basis for the development of medicinal products. Among those various stimuli, light has the advantage of a high spatiotemporal resolution that allows for the precise control of biological activities. Photoactive membrane protein rhodopsins from microorganisms (called microbial rhodopsins) absorb visible light and that light absorption triggers the trans–cis photoisomerization of the chromophore retinal, leading to various functions such as ion pumps, ion channels, transcriptional regulators and enzymes. In addition to their biological significance, microbial rhodopsins are widely utilized as fundamental molecular tools for optogenetics, a method to control biological activities by light. In this review, we briefly introduce the molecular basis of representative rhodopsin molecules and their applications for optogenetics. Based on those examples, we discuss the high potential of rhodopsin-based optogenetics tools for basic and clinical research in pharmaceutical sciences.
著者
Lucia Renee Ruhaak Jenny Felth Pernilla Christina Karlsson Joseph James Rafter Robert Verpoorte Lars Bohlin
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.5, pp.774-778, 2011-05-01 (Released:2011-05-01)
参考文献数
35
被引用文献数
23 63

Cyclooxygenase enzymes (COX-1 and COX-2) catalyse the production of prostaglandins from arachidonic acid. Prostaglandins are important mediators in the inflammatory process and their production can be reduced by COX-inhibitors. Endocannabinoids, endogenous analogues of the plant derived cannabinoids, occur normally in the human body. The Endocannabinoids are structurally similar to arachidonic acid and have been suggested to interfere with the inflammatory process. They have also been shown to inhibit cancer cell proliferation. Anti-inflammatory effects of cannabinoids and endocannabinoids have been observed, however the mode of action is not yet clarified. Anti-inflammatory activity (i.e., inhibition of COX-2) is proposed to play an important role in the development of colon cancer, which makes this subject interesting to study further. In the present work, the six cannabinoids tetrahydrocannabinol (Δ9-THC), tetrahydrocannabinolic acid (Δ9-THC-A), cannabidiol (CBD), cannabidiolic acid (CBDA), cannabigerol (CBG) and cannabigerolic acid (CBGA), isolated from Cannabis sativa, were evaluated for their effects on prostaglandin production. For this purpose an in vitro enzyme based COX-1/COX-2 inhibition assay and a cell based prostaglandin production radioimmunoassay were used. Cannabinoids inhibited cyclooxygenase enzyme activity with IC50 values ranging from 1.7·10−3 to 2.0·10−4 M.
著者
Eriko Uchida Yoshitaka Kondo Akiko Amano Shingo Aizawa Takayuki Hanamura Hitoshi Aoki Kenichi Nagamine Takeshi Koizumi Naoki Maruyama Akihito Ishigami
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.11, pp.1744-1747, 2011-11-01 (Released:2011-11-01)
参考文献数
20
被引用文献数
7 12

It has been suggested that some food components, such as bioflavonoids, affect the bioavailability of ascorbic acid in humans. Since little is known in Japan about the effective intake of this dietary requirement, we tested young Japanese males after the ingestion of commercial ascorbic acid or acerola (Malpighia emarginata DC.) juice to compare the quantities absorbed and excreted. Healthy Japanese subjects received a single oral dose of ascorbic acid solution (50, 100, 200 or 500 mg) and received distilled water as a reference at intervals of 14 d or longer. All subjects were collected blood and urine until 6 h after ingestion and evaluated for time-dependent changes in plasma and urinary ascorbic acid levels. Predictably, the area under the curve (AUC) values in plasma and urine after ingestion increased dose-dependently. Next, each subject received diluted acerola juice containing 50 mg ascorbic acid. Likewise, their plasma and urinary ascorbic acid concentrations were measured. In plasma, the AUC value of ascorbic acid after ingestion of acerola juice tended to be higher than that from ascorbic acid alone. In contrast, the urinary excretion of ascorbic acid at 1, 2 and 5 h after ingestion of acerola juice were significantly less than that of ascorbic acid. These results indicate that some component of acerola juice favorably affected the absorption and excretion of ascorbic acid.
著者
Toshinori Hirai Ryosuke Yamaga Motoki Kei Keiko Hosohata Toshimasa Itoh
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.11, pp.1742-1748, 2020-11-01 (Released:2020-11-01)
参考文献数
34

Although hypokalemia is an adverse effect of Yokukansan preparation, especially in geriatric patients, its association with age is unclear. We investigated whether age is a risk factor for hypokalemia. This single-center retrospective cohort study, conducted at Tokyo Women’s Medical University, Medical Center East between June 2015 and May 2019, included patients who received the Yokukansan preparation. The primary outcome was hypokalemia (serum potassium level: < 3.0 mEq/L). A multivariate Cox proportional hazard model was used to determine risk factors, hazard ratio (HR) and 95% confidence interval (95% CI). The cut-off age was also examined. Of 665 patients (median age: 78 years; interquartile range: 68–84 years), 55 (8.3%) developed hypokalemia associated with Yokukansan preparation. Risk factors for hypokalemia were age (HR: 1.013, 95% CI: 1.006–1.021, p < 0.001), dementia (HR: 0.500, 95% CI: 0.357–0.682, p < 0.001), serum albumin level (HR: 0.754, 95% CI: 0.669–0.850, p < 0.001), and daily Yokukansan preparation dose ≥ 7.5 g (HR: 1.446, 95% CI: 1.144–1.850, p = 0.002). The cut-off ages were >75 and >80 years but not 65 years and >70 years. Clinicians should assess risk factors and monitor serum potassium levels to avoid hypokalemia associated with the Yokukansan preparation.
著者
Hiroyuki Koide
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.1-6, 2021-01-01 (Released:2021-01-01)
参考文献数
47
被引用文献数
2

Protein affinity reagents are widely used for basic research, diagnostics, and disease therapy. Antibodies and their fragments are known as the most common protein affinity reagents. They specifically and strongly bind to target molecules and inhibit their functions. Thus, antibody drugs have increased in the recent two decades for disease therapy, such as cancer. These strong protein–protein interactions are composed of a nexus of multiple weak interactions. Synthetic polymers that bind to target molecules have been developed by the imitation of protein–protein interactions. These polymers show nanomolar affinity for the target and neutralize their functions; thus, they are of significant interest as a cost-effective protein affinity reagent. We have been developing synthetic polymer nanoparticles (NPs) that bind to target peptides and proteins by the inclusion of several functional monomers, such as charged and hydrophobic monomers. In this review, the focus is on the design of synthetic polymer NPs that bind to target molecules for disease therapy. We succeeded in neutralization of toxic peptides and signaling proteins both in vitro and in vivo. Additionally, linear polymers were modified on a lipid nanoparticle surface to improve polymer biodistribution. Our recent findings should provide useful information for the development of abiotic protein affinity reagents.
著者
Shigeo Shinoda Takahiko Aoyama Yukio Aoyama Sachiko Tomioka Yoshiaki Matsumoto Yoko Ohe
出版者
The Pharmaceutical Society of Japan
雑誌
Biological and Pharmaceutical Bulletin (ISSN:09186158)
巻号頁・発行日
vol.30, no.1, pp.157-161, 2007 (Released:2007-01-01)
参考文献数
27
被引用文献数
31 34

Acetaminophen (APAP) is a popular analgesic. In the present study, we characterized the pharmacokinetics and pharmacodynamics of APAP in the Japanese. Five healthy volunteers were administered 1000 mg of APAP orally. Five patients with chronic pain were administered the optimal oral dose of APAP ranging from 600 to 1000 mg to allow for an adequate analgesic effect. Plasma APAP and APAP metabolite concentrations were measured in the volunteers, plasma APAP concentrations and pain scores using a visual analog scale were measured in the patients with chronic pain. Patient data were fitted to a first-order absorption one-compartment model with delayed effects accounted for by an effect compartment. A sigmoid Emax model was used as the pharmacodynamic model. Acetaminophen-cysteine metabolites, which are conjugates of the toxic metabolite N-acetyl-p-benzoquinone-imine, were detected in the plasma at levels lower than 0.2 μg/ml, but no side effects were observed. The pharmacokinetic and pharmacodynamic parameter (mean±S.D.) estimates were as follows: clearance, 18.7±4.7 l/h; distribution volume, 30.9±6.8 l; absorption rate constant, 2.4±1.3 h−1; rate constant for the elimination of APAP from the effect compartment, 1.3±0.5 h−1; maximum pain relief score, 4.6±2.2 units; effect compartment concentration at 50% maximum, 2.0±1.2 μg/ml; and sigmoid factor, 1.3±0.7. These results suggest that these parameters can be used to determine an effective APAP dosage regimen for Japanese patients with chronic pain.
著者
Yohei Kawano Maho Katsuyama Masashi Nagata Maki Obana Satoshi Nakamatsu Ayano Mori Namiki Sakamoto Yasunari Mano Kenichi Negishi Shuji Shimada Takao Aoyama
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.238-244, 2021-02-01 (Released:2021-02-01)
参考文献数
28

Mirtazapine (MTZ) is a noradrenergic and specific serotonergic antidepressant. MTZ is reportedly associated with an increased risk of bleeding. However, the underlying mechanism remains unclear. In this study, we investigated the antiplatelet effect of MTZ in mice via light transmission aggregometry to elucidate the mechanism of MTZ-induced bleeding. The results of the ex vivo study showed that the oral administration of MTZ (20 or 100 mg/kg) significantly suppressed platelet aggregation mediated by the synergic interaction of 5-hydroxytryptamine (5-HT) and adrenaline. Additionally, MTZ significantly suppressed platelet aggregation, mediated by the synergic interaction of ADP and 5-HT or adrenaline. Similar results were obtained in vitro, under the condition of 5-HT- and adrenaline-induced platelet aggregation. Overall, the results suggest that MTZ exerts antiplatelet effect by co-blocking 5-HT2A and α2-adrenergic receptors on platelets and suppresses platelet aggregation mediated by ADP, increased by either 5-HT or adrenaline. Thus, a detailed monitoring of bleeding is recommended for patients taking MTZ.
著者
Junkichi Kanda Nobuo Izumo Yoshiko Kobayashi Kenji Onodera Taketoshi Shimakura Noriaki Yamamoto Hideaki E. Takahashi Hiroyuki Wakabayashi
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.11, pp.1934-1940, 2017-11-01 (Released:2017-11-01)
参考文献数
35
被引用文献数
1 16

Long-term treatment with antiepileptic drugs (AEDs) is accompanied by reduced bone mass that is associated with an increased risk of bone fractures. Although phenytoin has been reported to adversely influence bone metabolism, little is known pertaining to more recent AEDs. The aim of this study was to evaluate the effects of gabapentin or levetiracetam on bone strength, bone mass, and bone turnover in rats. Male Sprague-Dawley rats were orally administered phenytoin (20 mg/kg), gabapentin (30 or 150 mg/kg), or levetiracetam (50 or 200 mg/kg) daily for 12 weeks. Bone histomorphometric analysis of the tibia was performed and femoral bone strength was evaluated using a three-point bending method. Bone mineral density (BMD) of the femur and tibia was measured using quantitative computed tomography. Administration of phenytoin significantly decreased bone strength and BMD, which was associated with enhanced bone resorption. In contrast, treatment with gabapentin (150 mg/kg) significantly decreased bone volume and increased trabecular separation, as shown by bone histomorphometric analysis. Moreover, the bone formation parameters, osteoid volume and mineralizing surface, decreased after gabapentin treatment, whereas the bone resorption parameters, osteoclast surface and number, increased. Levetiracetam treatment did not affect bone strength, bone mass, and bone turnover. Our data suggested that gabapentin induced the rarefaction of cancellous bone, which was associated with decreased bone formation and enhanced bone resorption, and may affect bone strength and BMD after chronic exposure. To prevent the risk of bone fractures, patients prescribed a long-term administration of gabapentin should be regularly monitored for changes in bone mass.
著者
Yağız Anıl Çiçek David C. Luther Jessica A. Kretzmann Vincent M. Rotello
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.3, pp.304-311, 2019-03-01 (Released:2019-03-01)
参考文献数
83
被引用文献数
2

Clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) technology has revolutionized therapeutic gene editing by providing researchers with a new method to study and cure diseases previously considered untreatable. While the full range and power of CRISPR technology for therapeutics is being elucidated through in vitro studies, translation to in vivo studies is slow. To date there is no totally effective delivery strategy to carry CRISPR components to the target site in vivo. The complexity of in vivo delivery is furthered by the number of potential delivery methods, the different forms in which CRISPR can be delivered as a therapeutic, and the disease target and tissue type in question. There are major challenges and limitations to delivery strategies, and it is imperative that future directions are guided by well-conducted studies that consider the full effect these variables have on the eventual outcome. In this review we will discuss the advances of the latest in vivo CRISPR/Cas9 delivery strategies and highlight the challenges yet to be overcome.
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

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
Kazuo Yamada Atsushi Watanabe Haruo Takeshita Atsushi Fujita Noriko Miyake Naomichi Matsumoto Ken-ichi Matsumoto
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.9, pp.1596-1599, 2019-09-01 (Released:2019-09-01)
参考文献数
15
被引用文献数
4 5

Joint hypermobility syndrome (JHS) (also termed hypermobility type Ehlers–Danlos syndrome, hEDS) is a heritable connective tissue disorder that is characterized by generalized joint hypermobility, chronic pain, fatigue, and minor skin changes. Initially, it was reported that there is a small subset of patients with JHS/hEDS who have haploinsufficiency of tenascin-X (TNX). However, the relationship between TNXB and JHS/hEDS has not been reported at all afterwards. EDS was reclassified into thirteen types in 2017, and the causative gene of JHS/hEDS remained to be identified. Therefore, in this study in order to determine whether JHS/hEDS can be diagnosed by the concentrations of serum form of TNX (sTNX), we measured the concentrations of sTNX in 17 JHS/hEDS patients. The sTNX concentrations in half of the JHS/hEDS patients were significantly lower than those in healthy individuals. No mutations, insertions or deletions were detected in the TNX exon sequence of the JHS/hEDS patients except for one in patient. That patient has a heterozygous mutation. A correlation between sTNX concentration and mutation of the TNXB genomic sequence was not found in the JHS/hEDS patients. These results indicate that the decrease in sTNX concentration could be used as a risk factor for JHS/hEDS.
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
4

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
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 25

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
85 167

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.