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
Harumi Okuyama Yoichi Fujii Atsushi Ikemoto
出版者
The Pharmaceutical Society of Japan
雑誌
Journal of Health Science (ISSN:13449702)
巻号頁・発行日
vol.46, no.3, pp.157-177, 2000-06-01 (Released:2008-04-14)
参考文献数
183
被引用文献数
16 25

Classic lipid nutrition for the prevention of chronic, elderly-onset diseases was apparently established before 1960, assuming that hypercholesterolemia is the major risk factor and that raising the polyunsaturated/saturated (P/S) ratio of dietary fatty acids is hypocholesterolemic. However, the hypocholesterolemic effect of linoleic acid (LA) was found to be transient. Furthermore, hypercholesterolemia itself is unlikely to be a serious risk factor for diseases in the elderly because serum cholesterol level is positively correlated with longevity. Instead, a high n-6/n-3 ratio of dietary fatty acids was found to increase thrombotic tendency, decrease peripheral blood flow and lead to persistent inflammation, which was proposed to be the major risk factor for atherosclerosis and related diseases. Based on animal experiments and epidemiological studies, we recommend a reduction in the intake of LA from a current value of >6 en% to half, and a reduced n-6/n-3 ratio from the current value of >4 to 2. Simply decreasing LA intake would produce the recommended n-6 and n-3 fatty acid balance in Japan due to the typical Japanese diet, but both decreasing the intake of LA and increasing that of n-3 fatty acids, particularly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), is necessary in Western industrialized countries for the effective prevention of atherosclerosis and related diseases, as well as of apoplexy, allergic hyper-reactivity and cancers typical in Western populations.
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
Toshihiko Ishizaka Sachie Okada Emi Tokuyama Junji Mukai Takahiro Uchida
出版者
The Pharmaceutical Society of Japan
雑誌
Chemical and Pharmaceutical Bulletin (ISSN:00092363)
巻号頁・発行日
vol.56, no.10, pp.1395-1399, 2008-10-01 (Released:2008-10-01)
参考文献数
18
被引用文献数
9 9

The aim of the study was to suppress the bitterness and improve the palatability of pediatric prednisolone powder (PP) by the addition of simple sucrose syrup (SS) and various beverages and foods. Bitterness suppression was evaluated using the human gustatory sensory test. The suppression of the bitterness and improvement of palatability of PP by addition of SS solutions was investigated using standard taste substances: sucrose for sweetness, tartaric acid for sourness, and sodium chloride as saltiness. Dilution with SS solutions of up to 50% (w/w) was successful in bitterness-suppression and improvement of palatability, but at 80% (w/w) SS, the palatability of the diluted solution was reduced. The kinematic viscosities of SS solutions were therefore evaluated using the Uberorde viscosity meter, to see whether the high viscosity of the more concentrated solutions was responsible for the reduced palatability. The kinematic viscosity of the 80% SS was 16.60 mm2/s. Judging from above information, the palatability might become worse when the kinematic viscosity of syrup exceeded 15 mm2/s. Finally, the ability of various beverages and foods with low viscosity to suppress the bitterness and improve the palatability of PP were examined. The additions of orange juice or a carbonated lemon drink to simple syrup solution were most effective in suppressing bitterness and improving palatability of PP.
著者
Kounosuke Oisaki
出版者
The Pharmaceutical Society of Japan
雑誌
Chemical and Pharmaceutical Bulletin (ISSN:00092363)
巻号頁・発行日
vol.66, no.10, pp.907-919, 2018-10-01 (Released:2018-10-01)
参考文献数
40
被引用文献数
1

To conduct organic synthesis in the field of pharmaceutical science, methodologies that can easily and quickly supply compounds with high drug-likeness are highly desirable. Based on the original catalyst design concept “Radical-Conjugated Redox Catalysis (RCRC)” established during my research, various C(sp3)–H functionalizations and protein modifications have been developed, taking advantage of the high reactivity and chemoselectivity of the single-electron transfer process. This review focuses on the eight-year research efforts by my collaborators and me, from conception to results.
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
Md Mahadi Hassan Ahmed Fouad Abdelwahab Mohammed Khaled M. Elamin Hari Prasad Devkota Yoshitaka Ohno Keiichi Motoyama Taishi Higashi Teruko Imai
出版者
The Pharmaceutical Society of Japan
雑誌
Chemical and Pharmaceutical Bulletin (ISSN:00092363)
巻号頁・発行日
vol.68, no.11, pp.1117-1120, 2020-11-01 (Released:2020-11-01)
参考文献数
7

Zerumbone is a multifunctional compound which shows various biological activities, such as antitumor activity, anti-inflammatory activity, antiulcer activity, etc. However, to use Zerumbone as functional foods or medicines, its pharmaceutical properties such as solubility should be improved. In the present study, we prepared its inclusion complexes with various cyclodextrin (CyD) derivatives, and evaluated their solubility, release profile of the drug and cytotoxic activity. Among 11 CyDs, sulfobutylether (SBE)-β-CyD showed the highest solubilizing effect for Zerumbone. Phase solubility diagrams of SBE-β-CyD/Zerumbone in 10% methanol solution showed AL type, and the stability constant was 756 M−1. SBE-β-CyD also formed the solid complex with Zerumbone by kneading for 90 min. Importantly, the dissolution rate of Zerumbone was improved by complexation with SBE-β- and hydroxypropyl (HP)-β-CyDs, and its supersaturation was maintained for several hours. The solubilizing effects by SBE-β-CyD was greater than that of HP-β-CyD. Moreover, SBE-β-CyD/Zerumbone complex also retained the cytotoxic activity of Zerumbone. These results suggest that CyDs, especially SBE-β-CyD, were useful to improve the solubility of Zerumbone.
著者
Kouichi Yoshizaki Hari Prasad Devkota Hiroharu Fujino Shoji Yahara
出版者
The Pharmaceutical Society of Japan
雑誌
Chemical and Pharmaceutical Bulletin (ISSN:00092363)
巻号頁・発行日
vol.61, no.3, pp.344-350, 2013-03-01 (Released:2013-03-01)
参考文献数
24
被引用文献数
9 12

A new dammarane-type triterpenoid saponin, chikusetsusaponin VII (1), and nineteen known triterpenoid saponins, ginsenoside Rb1 (2), ginsenoside Rb3 (3), ginsenoside Rc (4), ginsenoside Rd (5), ginsenoside Re (6), ginsenoside Rg1 (7), ginsenoside Rg2 (8), ginsenoside Rh1 (9), notoginsenoside R1 (10), notoginsenoside R2 (11), notoginsenoside Fe (12), chikusetsusaponin IVa (13), chikusetsusaponin IV (14), chikusetsusaponin V (15), chikusetsusaponin VI (16), chikusetsusaponin FK6 (17), gypenoside XVII (18), 28-desglucosylchikusetsusaponin IV (19), and zingibroside R1 (20), were isolated from rhizomes, taproots, and lateral roots of Panax japonicus C. A. Meyer, so-called “Satsuma-ninjin,” grown in southern Miyazaki Prefecture, Japan. The structure of new chikusetsusaponin VII was elucidated on the basis of spectral and physicochemical evidence. Although the chemical composition of the rhizome was found to be similar to that of the “Chikusetsu-ninjin,” the saponin composition of lateral root of “Satsuma-ninjin” was found to be close to that of lateral root of P. ginseng. The total yield of oleanolic acid saponins of the taproot was less than that of rhizome, but the total yield of dammarane-type saponins of the taproot was found to be similar to that of rhizome.
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
Xiaolu FENG Jincai LU Hailiang XIN Lei ZHANG Yuliang WANG Kexuan TANG
出版者
The Pharmaceutical Society of Japan
雑誌
YAKUGAKU ZASSHI (ISSN:00316903)
巻号頁・発行日
vol.131, no.3, pp.423-429, 2011-03-01 (Released:2011-03-01)
参考文献数
25
被引用文献数
19 21

The aim of this study was to ascertain the anti-arthritic active fraction of Capparis spinosa L. (Capparidaceae) fruits and its chemical constituents. The adjuvant arthritic rat model was developed to evaluate the anti-arthritic effects of different fractions of ethanol extraction from C. spinosa L. The fraction eluted by ethanol-water (50:50, v/v) had the most significant anti-arthritic activity. The chemical constituents of this fraction were therefore studied; seven known compounds were isolated and identified as: (1) P-hydroxy benzoic acid; (2) 5-(hydroxymethyl) furfural; (3) bis (5-formylfurfuryl) ether; (4) daucosterol; (5) α-D-fructofuranosides methyl; (6) uracil; and (7) stachydrine.
著者
Yujiro Kameyama Maki Matsuhama Chie Mizumaru Rieko Saito Tsuyoshi Ando Seiko Miyazaki
出版者
The Pharmaceutical Society of Japan
雑誌
Chemical and Pharmaceutical Bulletin (ISSN:00092363)
巻号頁・発行日
vol.67, no.12, pp.1301-1313, 2019-12-01 (Released:2019-12-01)
参考文献数
60
被引用文献数
2

A pharmacopoeia’s core mission is to protect public health by creating and making available public standards to help ensure the quality of drugs. In recent years, pharmacopoeias around the world have harmonized their standards in the present context of globalized drug supply chains and markets. For example, the Pharmacopoeial Discussion Group has worked to harmonize excipient monographs and general chapters. In addition, the International Meeting of World Pharmacopoeias has been held by the WHO to discuss information exchange and international collaboration, among other topics. To contribute further to the protection of public health in the globalized drug market, we conducted a comparative study of the pharmacopoeias in Japan, Europe, and the United States. We aimed to examine current differences among the Japanese Pharmacopoeia, the European Pharmacopoeia, and the United States Pharmacopeia–National Formulary and to identify areas that require further collaboration among the three pharmacopoeias. In this study, we analyzed monographs and general chapters listed in the three pharmacopoeias. We identified the features of the monographs and general chapters listed in each pharmacopoeia, as well as differences across the pharmacopoeias. Moreover, on the basis of our findings, we suggest standards that require further collaboration among the pharmacopoeias in certain preferred areas. The comparison data produced by this study are expected to be used to develop strategies for future revisions of pharmacopoeias around the world.
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
Khem Raj Joshi Hari Prasad Devkota Takashi Watanabe Shoji Yahara
出版者
The Pharmaceutical Society of Japan
雑誌
Chemical and Pharmaceutical Bulletin (ISSN:00092363)
巻号頁・発行日
vol.62, no.2, pp.191-195, 2014-02-01 (Released:2014-02-01)
参考文献数
24
被引用文献数
4 5

Three new glycosides: thotneoside A (quercetin 3-O-(6″-O-phenylacetyl)-β-D-galactopyranoside) (1), thotneoside B (quercetin 3-O-(6″-O-phenylacetyl)-β-D-glucopyranoside) (2) and thotneoside C (3-methyl-2-butenoic acid 1-O-β-D-glucopyranoside) (3), together with nine known compounds; quercetin (4), quercetin 3-O-β-D-galactopyranoside (5), quercetin 3-O-(6″-O-galloyl)-β-D-galactopyranoside (6), quercetin 3-O-β-D-galacturonopyranoside (7), quercetin 3-O-β-D-glucuronopyranoside (8), quercetin 3-O-α-L-rhamnopyranoside (9), rutin (10), quercetin 3-O-α-L-arabinopyranoside (11) and 2,4,6-trihydroxyacetophenone 2-O-β-D-glucopyranoside (12) have been isolated from the shade dried leaves of Aconogonon molle, commonly known as “Thotne″ in Nepal. The structures were elucidated on the basis of chemical and spectroscopic methods. All of these compounds were isolated for the first time from A. molle and their in vitro antioxidant activity was evaluated by 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging assay. Quercetin (4) and its glycosides (1–2, 5–11) showed potent free radical scavenging activity.
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.