著者

Tetsuya Suzuki Takuya Goda Hiroyuki Kamiya

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.9, pp.1489-1493, 2018-09-01 (Released:2018-09-01)

参考文献数

32

被引用文献数

2 4

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The duration of transgene expression from plasmid DNAs is important for gene therapy with nonviral vectors. In the present study, various cytosine-phosphate-guanine (CpG)-free and CpG-containing transcription regulatory sequences were introduced into plasmid DNAs with a CpG-free backbone. The transgenes encoding mouse secreted alkaline phosphatase and Gaussia princeps luciferase, which are both apparently non-immunogenic, were used as reporters. The plasmid DNAs were injected by the hydrodynamics-based method, and the expression was monitored for 28 d. All transcription regulatory sequences achieved long-term expression, with different expression levels depending on the sequences themselves. These results suggested that durable transgene expression at the proper level can be achieved with plasmid DNAs containing the CpG-free backbone.

著者

Hiroshi Ueda Chikako Yamazaki Masatoshi Yamazaki

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.25, no.9, pp.1197-1202, 2002 (Released:2002-09-01)

参考文献数

24

被引用文献数

169 207

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Oral administration of the perilla leaf extract (PLE) to mice inhibits inflammation, allergic response, and tumor necrosis factor-α production. We also found that PLE suppressed the tumor necrosis factor-α (TNF-α) production in vitro. Using the inhibitory activity of TNF-α production in vitro as the index for isolation, we searched the active constituents from PLE and isolated luteolin, rosmarinic acid and caffeic acid as active components. Among the isolated compounds, only luteolin showed in vivo activity: inhibition of serum tumor necrosis factor-α production, inhibition of arachidonic acid-induced ear edema, inhibition of 12-O-tetradecanoylphorbol-13-acetate-induced ear edema and inhibition of oxazolone-induced allergic edema. These results suggest that luteolin is a genuinely active constituent which is accountable for the oral effects of perilla.

著者

Magie Melanie Kapojos Delfly Booby Abdjul Hiroyuki Yamazaki Akiho Yagi Ryuji Uchida

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.9, pp.903-906, 2020-09-01 (Released:2020-09-01)

参考文献数

14

被引用文献数

1

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Bioassay screening using Indonesian plants, such as traditional foods (vegetables, spices, and tea) and folk medicinal herbs, identified eight protein tyrosine phosphatase (PTP) 1B inhibitory and two antibacterial plants. The leaves of Syzygium polyanthum (Wight) Walp. were examined in more detail to define PTP1B inhibitory components, resulting in the isolation of a new active acylbenzene (1) along with four related congeners of 1 (2–5) and four oleanane triterpenes (6–9). The structure of 1 was elucidated as 12-oxo-12-(2,3,5-trihydroxy-4-methylphenyl)dodecanoic acid based on its spectroscopic data. The acylbenzenes 1 and 3–5 inhibited PTP1B activity with IC50 values ranging between 9.5 and 14 µM, whereas the triterpenes 7–9 also suppressed this activity with IC50 values of 3.3–5.7 µM.

著者

Michiaki Okuda Yuki Fujita Hachiro Sugimoto

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.10, pp.1694-1706, 2019-10-01 (Released:2019-10-01)

参考文献数

135

被引用文献数

2 12

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Alzheimer’s disease (AD) is the most common form of dementia and its prevention and treatment is a worldwide issue. Many natural components considered to be effective against AD have been identified. However, almost all clinical trials of these components for AD reported inconclusive results. We thought that multiple factors such as amyloid β (Aβ) and tau progressed the pathology of AD and that a therapeutic effect would be obtained by using multiple active ingredients with different effects. Thus, in this study, we treated ferulic acid (FA), phosphatidylserine (PS) and curcumin (Cur) in combination or alone to APPswe/PS1dE9 transgenic mice and evaluated cognitive function by Y-maze test. Consequently, only the three-ingredient group exhibited a significant improvement in cognitive function compared to the control group. In addition, we determined the amounts of Aβ, brain-derived neurotrophic factor (BDNF), interleukin (IL)-1β, acetylcholine and phosphorylated tau in the mouse brains after the treatment. In the two-ingredient (FA and PS) group, a significant decrease in IL-1β and an increasing trend in acetylcholine were observed. In the Cur group, significant decreases in Aβ and phosphorylated tau and an increasing trend in BDNF were observed. In the three-ingredient group, all of them were observed. These results indicate that the intake of multiple active ingredients with different mechanisms of action for the prevention and treatment of AD.

著者

Hiroshi Arakawa Natsumi Amezawa Yu Kawakatsu Ikumi Tamai

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.1792-1798, 2020-11-01 (Released:2020-11-01)

参考文献数

42

被引用文献数

10

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Xanthine and hypoxanthine are intermediate metabolites of uric acid and a source of reactive oxidative species (ROS) by xanthine oxidoreductase (XOR), suggesting that facilitating their elimination is beneficial. Since they are reabsorbed in renal proximal tubules, we investigated their reabsorption mechanism by focusing on the renal uric acid transporters URAT1 and GLUT9, and examined the effect of clinically used URAT1 inhibitor on their renal clearance when their plasma concentration is increased by XOR inhibitor. Uptake study for [3H]xanthine and [3H]hypoxanthine was performed using URAT1- and GLUT9-expressing Xenopus oocytes. Transcellular transport study for [3H]xanthine was carried out using Madin–Darby canine kidney (MDCK)II cells co-expressing URAT1 and GLUT9. In in vivo pharmacokinetic study, renal clearance of xanthine was estimated based on plasma concentration and urinary recovery. Uptake by URAT1- and GLUT9-expressing oocytes demonstrated that xanthine is a substrate of URAT1 and GLUT9, while hypoxanthine is not. Transcellular transport of xanthine in MDCKII cells co-expressing URAT1 and GLUT9 was significantly higher than those in mock cells and cells expressing URAT1 or GLUT9 alone. Furthermore, dotinurad, a URAT1 inhibitor, increased renal clearance of xanthine in rats treated with topiroxostat to inhibit XOR. It was suggested that xanthine is reabsorbed in the same manner as uric acid through URAT1 and GLUT9, while hypoxanthine is not. Accordingly, it is expected that treatment with XOR and URAT1 inhibitors will effectively decrease purine pools in the body and prevent cell injury due to ROS generated during XOR-mediated reactions.

著者

本橋 範子 西川 晴美 森 五彦

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.39, no.1, pp.142-145, 1991-01-25 (Released:2008-03-31)

参考文献数

26

被引用文献数

3 5

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The inhibitory effects of sulfur compounds, namely cysteine and α-mercaptopropionylglycine (α-MPG) (thiol type), and N-methyl-3-mercaptoimidazole (MMI), 6-propylthiouracil (PTU) and ergothioneine (ESH) (thione type) on melanin formation reaction by tyrosinase, in the presence of tyrosine as a substrate, were assessed. Tyrosine oxidation was monitored both by radioassay using L-[3, 5-3H]tyrosine, L-[2, 6-3H]tyrosine and L-[carboxyl-14C]tyrosine as substrates, and by spectrometry to quantitate the dopachrome formed from L-tyrosine. The rated compounds, ranked as to inhibitory effect in descending order are : cysteine ≃α-MPG>MMI>PTU>ESH. Cysteine and α-MPG, both noncyclic thiol compounds, formed a 3, 4-dihydroxyphenylalanine (dopa) conjugate to inhibit melanin formation when added at low concentrations. At high concentrations, they inctivated the enzyme by interacting with tyrosinase. In MMI, PTU and ESH of heterocyclic thione structure, dopa conjugate formation was more inhibitory than tyrosinase inactivation on melanin formation.

著者

Ghazi Hussein Hirozo Goto Shinobu Oda Ushio Sankawa Kinzo Matsumoto Hiroshi Watanabe

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.4, pp.684-688, 2006 (Released:2006-04-01)

参考文献数

37

被引用文献数

43 73

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We investigated the effects of a dietary astaxanthin (ASX-O) on oxidative parameters in spontaneously hypertensive rats (SHR), by determination of the level of nitric oxide (NO) end products nitrite/nitrate (NO2−/NO3−) and lipid peroxidation in ASX-O-treated SHR. Oral administration of the ASX-O significantly reduced the plasma level of NO2−/NO3− compared to the control vehicle (p<0.05). The lipid peroxidation level, however, was reduced in both ASX-O- and olive oil-treated groups. We also analyzed the post-treatment effects of ASX-O on the vascular tissues by examining the changes in the aorta and coronary arteries and arterioles. The dietary ASX-O showed significant reduction in the elastin bands in the rat aorta (p<0.05). It also significantly decreased the [wall : lumen] aerial ratio of the coronary arteries. These results suggest that ASX-O can modulate the oxidative condition and may improve vascular elastin and arterial wall thickness in hypertension.

著者

Rui Niu Yue Chen Yufang Xiang Ying Liu Jiadong Guo Bianling Feng

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.1476-1480, 2020-10-01 (Released:2020-10-01)

参考文献数

30

被引用文献数

2

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Various sources of information are available for identifying and evaluating adverse drug reactions (ADRs). However, some studies only used the ADR data from spontaneous reporting databases to evaluate the safety of post-marketing drugs. This study was performed to identify an appropriate method for evaluating the safety of post-marketing drugs by comparing the frequencies of ADRs among three datasets: randomized controlled trials, published case reports, and spontaneous reports. Taking ADR data for fluorouracil as an example, we collected the three types of data and extracted their ADR information. All listed ADRs were sorted by frequency from high to low, and the top five ADRs were chosen from each dataset. We assigned an index value of 1.0 to the frequency of one specific ADR (diarrhea) and then calculated the index values of the other ADRs relative to diarrhea. Ten different ADRs were mentioned in the top five ADRs of the three datasets, and only diarrhea and nausea/vomiting were included in all three datasets. The rank orders of the top five ADRs varied among the three datasets. Nausea and vomiting was the most frequent ADR in all three datasets; the remaining ADRs differed among the datasets. There were significant differences in the recording of ADRs and the frequency distributions among the three datasets. A comprehensive and reliable safety profile for post-marketing drugs should not be based on any one source. Spontaneous reports from monitoring institutions provided the most ADR data. Randomized controlled trials and case reports published in the literature can supplement the results from spontaneous reports.

著者

Nobuhiko Hoshi Tetsushi Hirano Takuya Omotehara Junko Tokumoto Yuria Umemura Youhei Mantani Takashi Tanida Katsuhiko Warita Yoshiaki Tabuchi Toshifumi Yokoyama Hiroshi Kitagawa

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.9, pp.1439-1443, 2014-09-01 (Released:2014-09-01)

参考文献数

12

被引用文献数

15 56

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Neonicotinoids, which were developed in the 1990 s as an insecticide having selective toxicity, were later found to cause reproductive abnormalities in experimental animals. In Japan there is an attempt to preserve endangered animals, including the Japanese crested ibis, and there is a question of whether neonicotinoids affect the reproduction of this bird, since they are used in its habitat. Hence, we investigated whether the daily oral administration of the neonicotinoid clothianidin (CTD) has any deleterious effects on the reproductive function of mature male only or both young male and female quails as experimental animals. Vacuolization and the number of germ cells having fragmented DNA in seminiferous tubules, as well as the number and size of vacuoles in hepatocytes, increased dose-dependently. The ovaries showed abnormal histology in the granulosa cells, which produce progesterone. There were significant differences in egg-laying rates and embryo weights between the groups. Glutathione Peroxidase 4 (GPx4) and Manganese Superoxide Dismutase (Mn-SOD), which protect the organism from oxidative damage, showed a dose-dependent decrease. Thus, it is possible neonicotinoids affect the bird’s reproductive system through oxidative stress, reflecting an imbalance between the production of reactive oxygen species (ROS) and a biological system’s ability to readily detoxify the reactive intermediates or easily repair the resulting damage. Responding to our study, Sado Island has since succeeded in breeding Japanese crested ibis in the wild without the use of neonicotinoids.

著者

Mayako Uchida Yasuhiro Mori Kenta Akiba Moena Miyasaka Tatsuya Hirano Hiroaki Ikesue Yuki Yamaguchi Aoi Takano Nami Maegawa Yoshimitsu Shimomura Keiko Hosohata Nobuyuki Muroi Takayuki Ishikawa Tohru Hashida Tsutomu Nakamura

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.1577-1582, 2020-10-01 (Released:2020-10-01)

参考文献数

26

被引用文献数

2

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Bendamustine plays an especially important role as a treatment for non-Hodgkin lymphoma (NHL). However, patients administered bendamustine alone or in combination with rituximab (BR) may experience drug-associated skin toxicities that can profoundly impact their health-related QOL through both physical discomfort and psychological distress. Moreover, worsening skin symptoms may lead to dose reduction or termination in the management of cancer chemotherapy. We retrospectively investigated patient backgrounds and pretreatment characteristics from medical records of NHL patients treated with bendamustine alone or BR therapy and identified predictive factors for skin toxicities at the start of chemotherapy. Patients were eligible for the study if they were 20 years older, diagnosed with NHL, and received bendamustine alone or BR therapy at the Department of Hematology, Kobe City Medical Center General Hospital, between April 1, 2011, and March 31, 2018. This study included 95 patients with newly diagnosed or refractory or relapsed NHL. Multivariate stepwise logistic regression analysis with backward selection revealed that baseline non-prior chemotherapy (odds ratio (OR), 15.72; 95% confidence interval (CI), 4.24–83.13, p < 0.001) was a significant factor influencing the occurrence of skin toxicity. Our results demonstrated that non-prior chemotherapy was a significant risk factor for skin toxicities in patients with NHL receiving bendamustine alone or BR therapy. No patient experience serious side effects of grade 3 or higher and that bendamustine is very useful as a first-line treatment.

著者

Takanori Mei Hiroshi Noguchi Kimitaka Suetsugu Yu Hisadome Keizo Kaku Yasuhiro Okabe Satohiro Masuda Masafumi Nakamura

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.1600-1603, 2020-10-01 (Released:2020-10-01)

参考文献数

16

被引用文献数

3

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Vonoprazan fumarate (vonoprazan) is a new kind of acid suppressant with potent acid inhibitory effects. Therefore, it has been administered to kidney transplant recipients for treatment or prophylaxis of steroid ulcers, refractory peptic ulcers, and gastroesophageal reflux disease. Because tacrolimus, which is a well-established immunosuppressant for kidney transplantation, and vonoprazan share the CYP3A4 system for metabolism, drug interactions are anticipated upon simultaneous administration. We retrospectively analyzed 52 kidney transplant recipients who were converted from rabeprazole, which has a small effect on the tacrolimus trough blood concentration (C0), to vonoprazan between August 2016 and July 2019. We compared the tacrolimus C0/tacrolimus dose (C0/D) before and after conversion and serum liver enzymes, serum total bilirubin, and the estimated glomerular filtration rate (eGFR). As a result, mean tacrolimus C0/D before and after conversion was 1.98 ± 1.02 and 2.19 ± 1.15 (ng/mL)/(mg/d), respectively, (p < 0.001). Additionally, mean aspartate transaminase (AST) before and after conversion was 18.6 ± 4.2 and 19.6 ± 5.2 IU/L, respectively, (p = 0.037). Mean alanine transaminase (ALT) before and after conversion was 15.8 ± 5.5 and 17.6 ± 7.1 IU/L, respectively, (p = 0.007). Mean eGFR before and after conversion was 50.6 ± 14.4 and 51.4 ± 14.7 mL/min/1.73 m2, respectively (p = 0.021). Mean AST, ALT, and eGFR were slightly but significantly elevated within normal ranges after conversion. In conclusion, our study suggests that the mean tacrolimus C0/D was elevated significantly by converting from rabeprazole to vonoprazan, but it had little clinical significance. Vonoprazan can be administered safely to kidney transplant recipients receiving tacrolimus.

著者

Miko Kondo Shunsaku Nakagawa Satoru Orii Kotaro Itohara Mitsuhiro Sugimoto Tomohiro Omura Yuki Sato Satoshi Imai Atsushi Yonezawa Takayuki Nakagawa Kazuo Matsubara

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.1463-1468, 2020-10-01 (Released:2020-10-01)

参考文献数

34

被引用文献数

1

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Vancomycin is a glycopeptide antibiotic used for the treatment of Gram-positive infections. For adult patients, treatment with vancomycin requires effective therapeutic drug-monitoring (TDM) to achieve clinical outcomes and reduce the incidence of adverse effects. However, it remains still unclear whether the TDM with vancomycin is beneficial in yielding better clinical outcomes in pediatrics. The objective of our study was to evaluate whether the clinical response to treatment was associated with initial trough concentrations of vancomycin in pediatric patients. A retrospective observation study of 60 patients (age: 1 month–15 years) who had completed and qualified for analysis was conducted at Kyoto University Hospital. The response to treatment was assessed by the time to resolution of fever and time to 50% decline in C-reactive protein (CRP). In addition, we explored whether vancomycin trough level was associated with the baseline characteristics. Trend analysis showed that there were significant correlations between vancomycin trough level and age, body weight, estimated glomerular filtration rate, and serum albumin levels. The time to resolution of fever of the patients with higher initial trough level (≥ 5 µg/mL) was significantly lower than that of the patients with lower trough level (< 5 µg/mL). The higher vancomycin concentration tended to be associated with the shorter time to 50% decline in CRP. The findings suggest that initial trough concentration is important in achieving better outcomes with vancomycin treatment in pediatrics.

著者

Yasuhiro Abe Eiichi Yamamoto Hiroyuki Yoshida Akiko Usui Naomi Tomita Hitomi Kanno Sayaka Masada Hidetomo Yokoo Genichiro Tsuji Nahoko Uchiyama Takashi Hakamatsuka Yosuke Demizu Ken-ichi Izutsu Yukihiro Goda Haruhiro Okuda

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

pp.c20-00431, (Released:2020-08-08)

参考文献数

28

被引用文献数

20

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The purpose of this study was to elucidate the effect of high-temperature storage on the stability of ranitidine, specifically with respect to the potential formation of N-nitrosodimethylamine (NDMA), which is classified as a probable human carcinogen. Commercially available ranitidine reagent powders and formulations were stored under various conditions, and subjected to LC-MS/MS analysis. When ranitidine tablets from two different brands (designated as tablet A and tablet B) were stored under accelerated condition (40°C with 75% relative humidity), following the drug stability guidelines issued by the International Conference on Harmonisation (ICH-Q1A), for up to 8 weeks, the amount of NDMA in them substantially increased from 0.19 to 116 ppm and from 2.89 to 18 ppm, respectively. The formation of NDMA that exceeded the acceptable daily intake limit (0.32 ppm) at the temperature used under accelerated storage conditions clearly highlights the risk of NDMA formation in ranitidine formulations when extrapolated to storage under ambient conditions. A forced-degradation study under the stress condition (60°C for 1 week) strongly suggested that environmental factors such as moisture and oxygen are involved in the formation of NDMA in ranitidine formulations. Storage of ranitidine tablets and reagent powders at the high temperatures also increased the amount of nitrite, which is considered one of the factors influencing NDMA formation. These data indicate the necessity of controlling/monitoring stability-related factors, in addition to controlling impurities during the manufacturing process, in order to mitigate nitrosamine-related health risks of certain pharmaceuticals.

著者

Shoko Yamamoto Kisaburo Deguchi Masamichi Onuma Noriaki Numata Yasuo Sakai

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.39, no.3, pp.428-434, 2016-03-01 (Released:2016-03-01)

参考文献数

27

被引用文献数

18 53

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Collagen tripeptide (CTP) is a collagen hydrolysate containing a high concentration of tripeptides with a Gly-X-Y sequence, such as Gly-Pro-Hyp. To test the effects of this preparation, we compared the absorption of peptides in humans after ingestion of a tripeptide fraction of CTP (CTP-100), a CTP preparation containing ca. 50% Gly-X-Y tripeptides (CTP-50), and a collagen peptide that did not contain tripeptides (CP). The postprandial levels of Gly-Pro-Hyp and Pro-Hyp in the plasma increased in those subjects who ingested CTP-100 and CTP-50, and were higher with greater Gly-Pro-Hyp ingestion. This demonstrated that collagen hydrolysates were efficiently absorbed when the collagen was ingested in the tripeptide form. Gly-Pro-Hyp and Pro-Hyp were also found in the urine after ingestion of CTP-100 or CTP-50. Similar to the results for the plasma concentration, the urinary excretion of Gly-Pro-Hyp and Pro-Hyp was also dependent on the amount of Gly-Pro-Hyp ingested. This indicates that ingested Gly-Pro-Hyp and generated Pro-Hyp were relatively stable in the body and were transported to the urine in the peptide form. The concentration of Hyp-Gly in the plasma was low after the ingestion of CP and CTP-100 but higher after the ingestion of CTP-50. Overall, our results suggest that tripeptides derived from collagen are absorbed efficiently by the body.

著者

Akiko Iwata Koei Satoh Mitsuhiro Murata Mikio Hikata Takao Hayakawa Teruhide Yamaguchi

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.26, no.8, pp.1065-1069, 2003 (Released:2003-08-01)

参考文献数

24

被引用文献数

14 17

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To enhance the sensitivity of virus detection by polymerase chain reaction (PCR) and reverse-transcriptional (RT)-PCR, we developed a novel virus-concentration method using sulfonated (SO-) magnetic beads in the presence of divalent cations. In the presence of either Zn2+ or Cu2+ ions, we showed that SO-magnetic beads were able to concentrate non-enveloped model viruses, such as porcine parvovirus (PPV) and poliovirus, which were not concentrated by polyethyleneimine (PEI)-magnetic beads.1) Using the SO-magnetic beads, the sensitivity of virus genome detection by PCR or RT-PCR can be enhanced. Therefore, an efficient virus concentration method using either SO-magnetic beads or PEI-magnetic beads enhances the sensitivity of virus detection by PCR or RT-PCR.

著者

Hyun Lim Kun Ho Son Hyeun Wook Chang KiHwan Bae Sam Sik Kang Hyun Pyo Kim

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.31, no.11, pp.2063-2067, 2008-11-01 (Released:2008-11-01)

参考文献数

36

被引用文献数

46 93

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In order to identify the active anti-inflammatory ingredient(s) in Cirsium chanroenicum (Compositae), its methanol extract and several solvent fractions were prepared; the methanol extract and the ethylacetate fraction inhibited cyclooxygenase-2 (COX-2)-mediated prostaglandin E2 (PGE2) and 5-lipoxygenase (5-LOX)-mediated leukotriene (LT) production in lipopolysaccharide-treated RAW 264.7 cells and A23187-treated rat basophilic leukemia (RBL-1) cells, respectively. Further bioactivity-guided fractionation of the ethylacetate fraction using column chromatography led to the isolation of pectolinarigenin (5,7-dihydroxy-4′,6-dimethoxyflavone), along with pectolinarin [pectolinarigenin 7-rhamnosyl-(1→6)-glucoside]. Pectolinarigenin strongly inhibited COX-2-mediated PGE2 and 5-LOX-mediated LT production at >1 μM, indicating that it is a dual inhibitor of COX-2/5-LOX. However, pectolinarigenin did not affect COX-2 expression or nuclear transcription factor (NF-κB) activation. In addition, in vivo studies demonstrated that oral administration of these two compounds at 20—100 mg/kg resulted in similar inhibitory activities against several animal models of inflammation/allergy: arachidonic acid-induced mouse ear edema, carrageenan-induced mouse paw edema and passive cutaneous anaphylaxis. All of these results suggest that pectolinarigenin and pectolinarin possess anti-inflammatory activity and that they may inhibit eicosanoid formation in inflammatory lesions. These activities certainly contribute to the anti-inflammatory mechanism of C. chanroenicum.

著者

Sakura Nakatani Keisuke Maeda Junji Akagi Misato Ichigi Marina Murakami Yoshihiko Harada Sara Utsumi Masaki Fukunaga Yuki Narita Yuki Kondo Yoichi Ishitsuka Tetsumi Irie Daisuke Kadowaki Sumio Hirata

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.8, pp.1350-1357, 2019-08-01 (Released:2019-08-01)

参考文献数

30

被引用文献数

1 7

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Creatinine (Cr) levels are strongly affected by muscle mass, and the estimated glomerular filtration rate (eGFR), a measure based on serum creatinine (SCr), is often overestimated in patients with sarcopenia. To evaluate the coefficient of determination (R2) between eGFR and the actual measured value, we performed a linear regression analysis of a modified GFR (mGFR: measured Cr clearance × 0.715) and various renal function estimates adjusted for muscle mass in 19 patients with sarcopenia. The eGFR values based on SCr (eGFRcr) were higher than those based on mGFR, although a high R2 (0.704; p < 0.001) was found between these values. There was no deviation between eGFR based on serum cystatin C (eGFRcys) and mGFR, although the R2 value 0.691 was equivalent to that of eGFRcr. In the equation used to calculate eGFRcr not adjusted for body surface area (mL/min), muscle mass parameters obtained from bioelectrical impedance analysis were used instead of actual body weight to recalculate the eGFRcr. The R2 between this eGFRcr and mGFR did not improve, although there was less deviation. However, assuming that all patients were female by using female coefficients for all patients, the R2 between eGFRcr-fcc (eGFRcr with female coefficient correction) and mGFR improved and was the highest (0.808) on substitution of appendicular skeletal muscle mass. The correlation between eGFRcr-fcc and mGFR improved over eGFRcys when muscle mass was substituted for body weight in the equation used to estimate eGFR in patients with sarcopenia and sex differences were removed.

著者

Kensuke Yagi Keiichi Goto Fumio Nanjo

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.57, no.11, pp.1284-1288, 2009-11-01 (Released:2009-11-01)

参考文献数

21

被引用文献数

17 25

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The polyphenolic composition of Camellia irrawadiensis, which is a closely related species of Camellia sinensis (cultivated tea), was investigated. The most predominant polyphenol, a kind of ellagitannin, was isolated from leaves of C. irrawadiensis. Its structure was established as 1,2-di-O-galloyl-4,6-O-(S)-hexahydroxydiphenoyl-β-D-glucose (2) on the basis of spectral and chemical evidence. Moreover, the polyphenols [catechins, strictinin (1), compound 2, theogallin, and gallic acid] and two methylxanthines (theobromine and caffeine) in leaves of C. irrawadiensis were determined by HPLC-Photodiode array detector analysis, and were compared to those in C. sinensis and Camellia taliensis. Total catechin content in C. irrawadiensis was lower than that in C. sinensis and C. taliensis. Theobromine content in C. irrawadiensis was higher than that in C. sinensis and C. taliensis. The content of 2 in C. irrawadiensis was 8.4% of dry leaf weight and comprised approximately 60% of the total polyphenols detected, while the compound was not detected in C. sinensis and was reported to be 2.4% in C. taliensis.

著者

Yoko Kado Masayuki Tsujimoto Shin-ichi Fuchida Akira Okano Mayumi Hatsuse Satoshi Murakami Hikofumi Sugii Kumi Ueda Yuki Toda Tetsuya Minegaki Kohshi Nishiguchi Yuichi Muraki Chihiro Shimazaki Eishi Ashihara

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.8, pp.1253-1258, 2020-08-01 (Released:2020-08-01)

参考文献数

19

被引用文献数

1

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Long-term combination treatment with lenalidomide and low-dose dexamethasone is important to achieve a curative effect in patients with multiple myeloma (MM). In this study, the plasma concentration of lenalidomide was measured at 3 h after oral administration, when the drug is in the elimination phase and can be easily measured in outpatients, to identify factors that may lead to the discontinuation of this combination therapy. Patients were assigned to continuation or discontinuation of therapy groups, and the baseline characteristics of patients, lenalidomide concentration, and concentration/dose (C/D) ratios reflecting oral clearance were compared between the two groups. The efficacy and severity of adverse events were also compared. The results showed that patients who discontinued or modified treatment had low plasma concentrations of lenalidomide and C/D ratios, indicating high oral clearance of lenalidomide. The estimated creatinine clearance rate was negatively correlated with the C/D ratio. The plasma concentrations of lenalidomide were independent from kidney function and differed significantly among patients. Taken together, the results indicate that low plasma concentrations of lenalidomide and low C/D ratios may lead to discontinuation of combination therapy in patients with MM. This suggests that early measurement of lenalidomide plasma continuation would help to prevent discontinuation of therapy or a delay in modifying the dose of lenalidomide.

著者

Mayako Uchida Yuki Yamaguchi Syuhei Hosomi Hiroaki Ikesue Yasuhiro Mori Nami Maegawa Aoi Takano Yuki Sato Keiko Hosohata Nobuyuki Muroi Keisuke Tomii Tohru Hashida Tsutomu Nakamura

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.8, pp.1235-1240, 2020-08-01 (Released:2020-08-01)

参考文献数

42

被引用文献数

3

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We retrospectively obtained data of patient background and pretreatment characteristics from medical records and identified the predictive factors of febrile neutropenia (FN) in patients with non-small cell lung cancer (NSCLC) treated with docetaxel alone or in combination with the anti-vascular endothelial growth factor (VEGF) antibody bevacizumab. Patients were eligible for inclusion in the study if they were 20 years or older, diagnosed with NSCLC, and received docetaxel monotherapy alone or in combination with bevacizumab at the Department of Respiratory Medicine, Kobe City Medical Center General Hospital, between July 1, 2011, and March 31, 2018. Eighty-one patients with recurrent or advanced NSCLC were included. Multivariate stepwise logistic regression analysis with backward selection revealed that lower baseline Eastern Cooperative Oncology Group performance status (ECOG-PS) scores of 1 and 2 (odds ratio (OR), 5.098; 95% confidence interval (CI), 1.045–24.879, p = 0.021) and baseline platelet count below 18.8 × 104/µL (OR, 3.861; 95% CI, 1.211–12.311, p = 0.022) were significant factors influencing the FN occurrence rate. Our results demonstrated that ECOG-PS 1–2 and lower baseline platelet count were significant risk factors of FN in patients with NSCLC receiving docetaxel-based chemotherapy. Moreover, the combination of anti-VEGF antibodies and docetaxel might be associated with increased FN frequency. Despite the limitations of this study including its retrospective design, single-center site, and small sample size, baseline ECOG-PS score and platelet count may be regarded as important indices to identify patients for prophylactic granulocyte-colony stimulating factor (G-CSF) treatment before docetaxel-based chemotherapy.