著者

KITAGAWA Shuji SUGAYA Yoshio

出版者

公益社団法人日本薬学会

雑誌

Biological & pharmaceutical bulletin (ISSN:09186158)

巻号頁・発行日

vol.19, no.2, pp.268-273, 1996-02-15

参考文献数

34

被引用文献数

4 1

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Characteristics of transport of an oral aminocephalosporin, cefroxadine, in rabbit small intestinal brush border membrane vesicles were examined. Uptake rate of cefroxadine was saturable in the presence of an inward H<SUP>+</SUP> gradient, and kinetic parameters were similar to those of cephradine. However, the uptake rate was almost linear with the concentration in the absence of an inward H<SUP>+</SUP> gradient up to 5mM. Overshoot phenomenon was observed in the presence of an inward H<SUP>+</SUP> gradient at 37°C, but it disappeared with decrease of temperature. The Arrhenius plot of uptake rate constant showed a break point at approximately 30°C. Cefroxadine uptake was optimum in the vicinity of pH 5.5 at 37°C, but the dependence on extravesicular pH disappeared at 15°C. The uptake of cefroxadine in the presence of an inward H<SUP>+</SUP> gradient was markedly inhibited by other aminocephalosporins such as cephalexin, but the inhibition was only slight in the absence of an inward H<SUP>+</SUP> gradient. Alkyl alcohols such as n-hexyl alcohol also inhibited H<SUP>+</SUP>-coupled uptake of cefroxadine at the concentration range at which the alcohols increased the membrane fluidity, and overshoot phenomenon diminished, suggesting that H<SUP>+</SUP>-coupled transport of cefroxadine is sensitive to the alcohol-induced increase in membrane fluidity. On the other hand, the alcohols rather stimulated its uptake in the absence of an H<SUP>+</SUP> gradient.

著者

Masaki Takigawa Hirofumi Masutomi Yuki Kishimoto Yoshitomo Shimazaki Yoshitomo Hamano Yoshitaka Kondo Tomio Arai Jaewon Lee Toshihiro Ishii Yoshiko Mori 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.40, no.7, pp.975-983, 2017-07-01 (Released:2017-07-01)

参考文献数

21

被引用文献数

1 8

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Vancomycin hydrochloride (VCM) is a glycopeptide antibiotic that is commonly used against methicillin-resistant, Gram-positive cocci despite the nephrotoxic side effects. VCM-induced nephrotoxicity has been reported in 5–28% of recipient patients. Therefore, renal failure induced by VCM has become an important clinical problem. However, the exceedingly complex mechanism of VCM-induced nephrotoxicity is not fully understood. Therefore, this study was designed to clarify time-dependent alterations of VCM-induced nephrotoxicity in mice as a step toward decreasing the risks of kidney injury associated with VCM therapy. VCM was injected intraperitoneally into mice at a dose of 400 mg/kg body weight at 24-h intervals for 3, 5, 7, and 14 d. At 24 h after the last injection, we examined histopathological alterations of the kidney as well as blood biochemistry. VCM administration resulted in a decrease of body weight and increase of kidney weight. Histological examination revealed renal damage such as dilated proximal tubules with occasional casts and interstitial fibrosis in VCM-treated mice. Furthermore, immunohistochemical staining with anti-CD10 and anti-single-stranded DNA antibodies highlighted damaged renal proximal tubules with marked dilatation as well as numerous apoptotic cells as early as day 4 of VCM-treatment. The severity of symptoms progressed until day 15. These results suggest that VCM-induced renal damage and incipient renal failure begin soon after the start of treatment and progressively worsen. This is the first report describing the time-dependence of VCM-induced nephrotoxicity in mice and depicting a model that clarifies the mechanisms of this tissue damage.

著者

木村 正康 / 柳 誠治 今野 泰生 野島 浩史 木村 郁子 Ikuko KIMURA

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.3, pp.407-410, 1995-03-15 (Released:2008-04-10)

参考文献数

8

被引用文献数

5 11

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β-Eudesmol, a sesquiterpenoid alcohol contained in Atractylodes lancea, potentiates succinylcholine (SuCh)-induced neuromuscular blockade. The potentiating effect is greater in diabetic muscles than in normal ones. As a ligand for affinity chromatography to study the potentiating mechanism, we designed and synthesized newly β-eudesmol-related cyclohexylidene derivatives (2-(3-hydroxy-3-methylbutyl) cyclohexylidene ; KTE-13, 2-(3-hydroxy-3-methylbutyl)-4-cyclohexylidene carboxylic acid ; KTE-32 and 4-tert-butoxycarbonyl-2-(3-hydroxy-3-methylbutyl) cyclohexylidene ; KTE-33). We examined the potentiating effects of those compounds in phrenic nerve-diaphragm muscle preparations of normal and alloxan-diabetic mice. KTE-33 (100μM) potentiated more greatly SuCh-induced neuromuscular blockade in diabetic muscles than in normal ones (the potentiating ratios in normal and diabetic muscles were 6.7 and 10.6, respectively), while KTE-13 (100 μM) and -32 (200 μM) potentiated weakly. These results suggest that the ester group in KTE-33 rather than a carboxyl group in KTE-32 is important in inducing the potentiation of SuCh-induced neuromuscular blockade in diabetic state.

著者

Pattama Wongsirisin Sirikan Limpakan Yamada Supachai Yodkeeree Wanisa Punfa Pornngarm Limtrakul

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.360-367, 2018-03-01 (Released:2018-03-01)

参考文献数

26

被引用文献数

8

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Acquired resistance is a major reason for poor clinical outcomes in cancer chemotherapy patients. The aim of this study was to determine the sensitivity to anticancer drugs and to identify the alterations of DNA repair and drug transporter in a model of primary culture obtained from pre- and post-platinum-based anticancer treatments in nine Thai gastric cancer patients. Ex vivo sensitivity to anti-cancer drugs (cisplatin, oxaliplatin, 5-fluorouracil (5-FU) and irinotecan) was analysed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The expression of the drug transporter (multidrug resistance-associated protein 1 (MRP1), P-glycoprotein (P-gp)) and DNA repair (X-ray cross-complementing gene 1 (XRCC1) and excision repair cross-complementing 1 (ERCC1)) were examined by RT-PCR. The IC50 to cisplatin and oxaliplatin of the cells obtained from gastric cancer patients after clinical drug treatments were administered to five patients (55.5%) revealed a significant increase when compared with prior treatments. The basal expression values of XRCC1, ERCC1 and MRP1 obtained from the treated patients were in correlation with those of IC50. Ex vivo platinum drug treatment of the primary culture obtained from naïve patients over seven days also revealed a significant increase in MRP1 (7/9), XRCC1 (4/9) and ERCC1 (4/9). These observations have also been observed in the KATOIII cell line. Clinical treatment by platinum-based anti-cancer drug can develop acquired drug resistance in Thai gastric cancer patients through upregulation in the expression of drug transporter MRP1 and DNA repair XRCC1 and ERCC1. In cell culture model, cisplatin-resistant gastric cancer cell line KATOIII/diamminedichloroplatinum (KATOIII/DDP) significantly increased the expression level of these genes when compared to its parental cells (KATOIII).

著者

Koichi Murano Hirofumi Ogino Tomofumi Okuno Tomohiro Arakawa Hitoshi Ueno

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.1, pp.92-98, 2018-01-01 (Released:2018-01-01)

参考文献数

43

被引用文献数

12

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The role of supplementary selenium on the induction of insulin resistance and oxidative stress in a diabetic mouse model was investigated in NSY mice on a high fat diet (HFD) and administered seleno-L-methionine (SeMet)-containing water for 12 weeks. Significant increases in oral glucose tolerance-tested (OGTT), insulin tolerance-tested, and non-fasting blood glucose levels were observed in mice on a HFD, as well as the significant increases in OGTT and non-fasting plasma insulin levels. Mice on a HFD had decreased plasma adiponectin levels and increased free fatty acid (FFA) levels. Supplementary SeMet significantly augmented OGTT blood glucose levels in mice on a HFD and plasma FFA levels in mice on a normal diet. The mRNA levels of six selenoproteins were measured, and glutathione peroxidase (GPx) 1 and selenoprotein P (SelP) were selected as candidates that may be associated with insulin resistance or oxidative stress in the liver. Hepatic GPx1 expression was elevated in mice on a HFD and SeMet supplementation, and SelP expression increased in mice on a HFD. Histopathological observations in hepatic tissues showed hypertrophy of parenchymal cells and significant expression of 4-hydroxy-2-nonenal in mice on a HFD, indicating lipid accumulation and oxidative stress induction. Hepatic protein tyrosine phosphatase activity also increased by a HFD. These results suggest that hepatic lipid accumulation in NSY mice on a HFD promoted oxidative stress and hepatic SelP expression, and supplementary SeMet induced hepatic GPx1 expression.

著者

Yutaro Obara Kuniaki Ishii

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.1, pp.20-23, 2018-01-01 (Released:2018-01-01)

参考文献数

13

被引用文献数

7

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We recently found that 10.5% of sporadic Parkinson’s disease (PD) patients lacked one copy of the midnolin (MIDN) gene. In addition, gene knock-down/out of MIDN caused down-regulation of parkin E3 ubiquitin ligase, indicating MIDN to be a novel PD-risk factor or causative gene. In this study, we performed RNA-sequencing and transcriptome analysis of Midn wild-type and knockout cells. Midn positively or negatively regulated the expression of a wide variety of genes, including causative familial PD genes, such as α-synuclein, parkin, and EIF4G1. However, EIF4G1 protein levels were not altered by the reduction of its mRNA by Midn loss, as seen that parkin protein levels were correlated to the mRNA down-regulation. Taken together, these findings indicate that MIDN regulates the expression of a wide variety of genes, including multiple PD-causative genes and is associated with PD onset.

著者

Takahiro Hayashi Saori Ikehata Haruna Matsuzaki Kimio Yasuda Toshiyasu Makihara Akihiko Futamura Yuki Arakawa Rika Kuki Kumiko Fukuura Hiroshi Takahashi Naoharu Mori Takashi Higashiguchi Shigeki Yamada

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.37, no.12, pp.1860-1865, 2014-12-01 (Released:2014-12-01)

参考文献数

25

被引用文献数

3 7

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Morphine, oxycodone, and fentanyl are commonly used to control cancer pain. Because these drugs have differences in receptor affinity or pharmacokinetic parameters, changing the opioid formulation may result in an unexpected outcome, depending on the patient’s condition. This study investigated whether low serum protein levels influence the effectiveness of opioid rotation by determining the impact of serum albumin levels on the analgesic effect before and after opioid rotation from morphine or oxycodone to fentanyl in cancer patients. The patients were classified into 3 groups according to their serum albumin levels before opioid rotation: group 1, <2.5 g/dL; group 2, from 2.5 g/dL to <3.0 g/dL; and group 3, ≥3.0 g/dL. There was no significant change in the percentage of patients with good pain control after rotation in group 1 or group 2; however, the percentage of patients with good pain control increased significantly in group 3. When the percentage of patients whose numerical rating scale scores increased, were unchanged, or decreased after rotation were compared, a significant difference in the percentage of those showing improvement was noted among the 3 groups and between groups 1 and 3. These findings suggest that monitoring serum albumin levels during fentanyl therapy is useful for pain management, and that the effectiveness of opioid rotation to fentanyl in patients with serum albumin levels of <2.5 g/dL should be carefully evaluated after rotation.

著者

Yusuke Kono Hitomi Jinzai Yota Kotera Takuya Fujita

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.b17-00563, (Released:2017-09-30)

参考文献数

48

被引用文献数

10

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The present study aimed to investigate the effect of particle size (100 and 500 nm), surface charge (cationic, neutral and anionic) and polyethylene glycol (PEG) modification of magnetic liposomes on their interaction with the human intestinal epithelial cell line, Caco-2. The cellular associated amount of all the magnetic liposomes was significantly increased by the presence of a magnetic field. The highest association and internalization into Caco-2 cells was observed with magnetic cationic liposomes. Moreover, small magnetic liposomes were more efficiently associated and taken up into the cells, than large ones. In contrast, PEG modification significantly attenuated the enhancing effect of the magnetic field on the cellular association of magnetic liposomes. We also found that magnetic cationic liposomes had the highest retention properties to Caco-2 cells. Moreover, the retention of large magnetic liposomes to the cells was much longer than that of small ones. In addition, magnetic cationic and neutral liposomes had relatively high stability in Caco-2 cells, whereas magnetic anionic liposomes rapidly degraded. These results indicate that the physicochemical properties and PEG modification of magnetic liposomes greatly influences their intestinal epithelial transport.

著者

Ryo Iketani Yohei Kawasaki Hiroshi Yamada

出版者

公益社団法人日本薬学会

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.40, no.11, pp.1976-1982, 2017-11-01 (Released:2017-11-01)

参考文献数

43

被引用文献数

12

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We performed a systematic review and Bayesian network meta-analysis to determine atypical antipsychotics that are effective and safe for the treatment of psychosis in Parkinson’s disease (PD). We conducted a comprehensive literature search using PubMed/MEDLINE, Cochrane Library, and Japana Centra Revuo Medicina (Ichu-shi Web). We used randomized controlled trials evaluating the utility of atypical antipsychotics for the treatment of psychosis in PD using the Brief Psychiatric Rating Scale (BPRS) and the Unified PD rating Scale parts III (UPDRS-III) as the endpoints. Posterior distributions of mean differences between each treatment and placebo were estimated using Bayesian network meta-analysis. The distributions describing each treatment effect were expressed as means (95% credible intervals). Ten trials involving any two treatment arms using clozapine (64 subjects in four trials), olanzapine (99 subjects in three trials), quetiapine (79 subjects in five trials), risperidone (five subjects in one trial), or placebo (156 subjects in seven trials) were finally included in the present study. Pooled estimates of each posterior distribution based on the BPRS were as follows: clozapine, −2.0 (−6.7 to 2.7); olanzapine, 0.5 (−2.3 to 3.4); quetiapine, 0.3 (−3.9 to 4.5); and risperidone, −4.7 (−57.4 to 53.3). Based on the UPDRS-III, the pooled estimates were clozapine, 0.7 (−3.8 to 4.3); olanzapine, 2.8 (0.8 to 5.1); quetiapine, 3.3 (−0.7 to 5.8); and risperidone, 4.5 (−57.7 to 63.4). Although clozapine had an effective and relatively safe profile, all atypical antipsychotics included in the present study may be unsafe, as they may worsen motor function when compared to placebo.

著者

Yoshinori Ochiai Kunio Itoh Eiichi Sakurai Mayuko Adachi Yorihisa Tanaka

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.12, pp.2362-2366, 2006 (Released:2006-12-01)

参考文献数

24

被引用文献数

11 22

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The substrate selectivity of monoamine oxidase A (MAO-A), monoamine oxidase B (MAO-B), diamine oxidase (DAO), and semicarbazide-sensitive amine oxidase (SSAO) was investigated in the absence of chemical inhibitors using the COS-1 cells expressed with respective amine oxidase. Serotonin (5-hydroxytryptamine), 1-methylhistamine, and histamine were preferentially oxidized by MAO-A, SSAO, and DAO, respectively, at a low substrate concentration. In contrast, benzylamine, tyramine, and β-phenylethylamine served as substrates for all of MAO-A, MAO-B, and SSAO. Each amine oxidase showed broad substrate selectivity at a high substrate concentration. The cross-inhibition was remarkable in MAO-A and MAO-B, especially in MAO-A, but not in SSAO and DAO. A study of the substrate selectivity of amine oxidases should include consideration of the effects of substrate concentration and specific chemical inhibitors.

著者

Charith UB Wijerathne Hee-Seon Park Hye-Yun Jeong Ji-Won Song Og-Sung Moon Young-Won Seo Young-Suk Won Hwa-Young Son Jong-Hwan Lim Sung-Hum Yeon Hyo-Jung Kwun

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.b17-00468, (Released:2017-09-22)

参考文献数

46

被引用文献数

24

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Quisqualis indica (QI) has been used for treating disorders such as stomach pain, constipation, and digestion problem. This study was aimed to evaluate the therapeutic efficacy of QI extract on treating benign prostatic hyperplasia (BPH) in LNCaP human prostate cancer cell line and a testosterone-induced BPH rat model. LNCaP cells were treated with QI plus testosterone propionate (TP), and androgen receptor (AR) and prostate specific antigen (PSA) expression levels were assessed by Western blotting. To induce BPH, the rats were subjected to a daily subcutaneous injection of TP (3 mg/kg) for 4 wk. The rats in treatment group were orally gavaged with QI (150mg/kg) together with the TP injection. In-vitro studies showed that TP-induced increases in AR and PSA expression in LNCaP cells were reduced by QI treatment. In BPH-model rats, the prostate weight, testosterone in serum, DHT concentration and 5α-reductase mRNA expression in prostate tissue were significantly reduced following the treatment with QI. TP-induced prostatic hyperplasia and the expression of proliferating cell nuclear antigen (PCNA) and cyclin D1 were significantly attenuated in QI-treated rats. In addition, QI induced apoptosis by up-regulating caspase-3 and -9 activity and decreasing the B-cell lymphoma 2 (Bcl-2)/Bcl-2-associated X protein (Bax) ratio in prostate tissues of BPH rats. Further investigation showed that TP-induced activation of AKT and glycogen synthase kinase 3β (GSK3β) was reduced by QI administration. Therefore, our findings suggest that QI attenuates the BPH state in rats through anti-proliferative and pro-apoptotic activities and might be useful in the clinical treatment of BPH.

著者

Akihiko Ikoma

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.8, pp.1235-1240, 2013-08-01 (Released:2013-08-01)

参考文献数

70

被引用文献数

8 20

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The unique physiological features of histamine-sensitive C-fibers and spinothalamic tract neurons support the hypothesis of itch specific pathway, whereas subsequent studies on cowhage-induced itch have provided evidence against it, suggesting the presence of multiple neural pathways for itch. Not only peripheral pruritogens but also spinal neural receptors are involved in the control of itch, and will be the target of treatment. Itch sensitization in chronic pruritus is another crucial factor that needs to be considered in the treatment. Neuropathic itch is the type of itch that occurs when nerve fibers are damaged or injured and spontaneous firing of nerves takes place, and plays a major role in itch accompanying some pathological conditions such as herpes zoster. The complexity of itch is due to the broad range of mediators involved and the large variety of neural mechanisms behind.

著者

津島 己幸 真岡 孝至 勝山 政明 小塚 睦夫 松野 隆男 徳田 春邦 西野 輔翼 岩島 昭夫

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.18, no.2, pp.227-233, 1995-02-15 (Released:2008-04-10)

参考文献数

26

被引用文献数

43 77

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As a screening study for anti-tumor promoters, 51 carotenoids with diverse structures were examined for their inhibitory effects on the Epstein-Barr virus activation activity of 12-O-tetradecanoylphorbol-13-acetate (TPA) in Raji cells. The results showed that most of the carotenoids exhibited inhibitory activity, and in general, no cytotoxicity on Raji cells was observed in the assay. Among the carotenoids, β-cryptoxanthin, lutein, and lactucaxanthin showed the strongest inhibitory activity, superior to the well known anti-tumor promoter, β-carotene. Heteroxanthin, peridinin, and halocynthiaxanthin showed cytotoxicity at the high concentration (1000 molar ratio per TPA), but indicated a strong inhibitory effect at the lower concentrations, which were only weakly toxic (500 and 100 molar ratios). Based on these results, the essential moiety for the activity of carotenoids was considered to be the 3-hydroxy-ε-end group.

著者

Hitomi Ozawa Atsushi Imaizumi Yoshihiko Sumi Tadashi Hashimoto Masashi Kanai Yuji Makino Takanori Tsuda Nobuaki Takahashi Hideaki Kakeya

出版者

公益社団法人日本薬学会

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.40, no.9, pp.1515-1524, 2017-09-01 (Released:2017-09-01)

参考文献数

50

被引用文献数

35

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Curcumin, a polyphenol derived from the rhizome of the naturally occurring plant Curcuma longa, has various pharmacological actions such as antioxidant and anti-inflammatory effects. In this paper, we evaluated the role of its internal metabolite, curcumin β-D-glucuronide (curcumin monoglucuronide, CMG), by investigating curcumin kinetics and metabolism in the blood. Firstly, we orally administered highly bioavailable curcumin to rats to elucidate its kinetics, and observed not only the free-form of curcumin, but also, curcumin in a conjugated form, within the portal vein. We confirmed that curcumin is conjugated when it passes through the intestinal wall. CMG, one of the metabolites, was then orally administered to rats. Despite its high aqueous solubility compared to free-form curcumin, it was not well absorbed. In addition, CMG was injected intravenously into rats in order to assess its metabolic behavior in the blood. Interestingly, high levels of free-form curcumin, thought to be sufficiently high to be pharmacologically active, were observed. The in vivo antitumor effects of CMG following intravenous injection were then evaluated in tumor-bearing mice with the HCT116 human colon cancer cell line. The tumor volume within the CMG group was significantly less than that of the control group. Moreover, there was no significant loss of body weight in the CMG group compared to the control group. These results suggest that CMG could be used as an anticancer agent without the serious side effects that most anticancer agents have.

著者

Mitsuyoshi Okita Yuki Yayoshi Kousuke Ohara Akio Negishi Hayato Akimoto Naoko Inoue Sachihiko Numajiri Shigeru Ohshima Seiichi Honma Shinji Oshima Daisuke Kobayashi

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.b17-00340, (Released:2017-08-04)

参考文献数

21

被引用文献数

3

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Kakkonto (KK), a traditional Japanese Kampo formulation for cold and flu, is generally sold as an over-the-counter (OTC) pharmaceuticals used for self-medication. Kampo formulations should be used according to the Sho-symptoms of Kampo medicine. These symptoms refer to the subjective symptoms themselves. Although with OTC pharmaceuticals, this is often not the case. We surveyed the relationship of agreement of Sho with the benefit feeling rate (BFR) of patients who took KK (n = 555), cold remedies with KK (CK, n = 315), and general cold remedies (GC, n = 539) using internet research. BFR of a faster recovery was greater in participants who took the medication early and who had confidence in their physical strength in all treatment groups. BFR was significantly higher in the GC group than in the KK group for patients with headache, runny nose, blocked nose, sneezing, and cough. BFR was also significantly higher in the GC group than in the CK group for headache (males) and cough (females). BFR was the highest in the KK group for stiff shoulders. All cold remedies were more effective when taken early, and the larger the number of Sho that a patient had, the greater the BFR increased. Therefore, a cold remedy is expected to be most effective when there are many cold symptoms and when it is taken at an early stage of the common cold.

著者

Mina Thon Toru Hosoi Chanbora Chea Koichiro Ozawa

出版者

公益社団法人日本薬学会

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.40, no.8, pp.1161-1164, 2017-08-01 (Released:2017-08-01)

参考文献数

37

被引用文献数

6

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The lack of response to leptin’s actions in the brain, “leptin resistance,” is one of the main causes of the pathogenesis of obesity. However, although high-fat diets affect sensitivity to leptin, the underlying mechanisms of leptin resistance are still an enigma. Here we examined the effect of excess saturated fatty acids (SFAs) on leptin signaling in human neuronal cells. Palmitate, the principle source of SFAs in diet, induced leptin resistance in a human neuroblastoma cell line stably transfected with the Ob-Rb leptin receptor (SH-SY5Y-ObRb). We next investigated the function of stearoyl-CoA desaturase-1 (SCD1), an enzyme which converts SFAs into monounsaturated fatty acids (MUFAs), on leptin-induced signaling. We found that reduction of SCD1 activity, through SCD1 inhibition and knockdown, impairs leptin-induced signal transducer and activator of transcription 3 (STAT3) phosphorylation in human neuronal cells. Our findings suggested that SCD1 plays a key role in the pathophysiology of leptin resistance in neuronal cells associated with obesity.

著者

Ryota Tanaka Yuhki Sato Koji Goto Norihisa Yasuda Yoshifumi Ohchi Yosuke Suzuki Tamio Ueno Kentaro Ito Tetsuya Kaneko Shusaku Kurogi Ko Nonoshita Hiroki Itoh

出版者

公益社団法人日本薬学会

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.40, no.8, pp.1226-1231, 2017-08-01 (Released:2017-08-01)

参考文献数

28

被引用文献数

6

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Doripenem (DRPM) is a broad-spectrum antibacterial agent often used as empirical therapy for critically ill patients, although there is a lack of studies validating the recommended dosage regimen for patients admitted to intensive care unit (ICU), based on pharmacokinetic (PK)/pharmacodynamic (PD) index. In this study, we estimated the free time above minimum inhibitory concentration (fT>MIC (%)) of DRPM using population PK analysis of 12 patients in ICU, and evaluated the validity of the dosage regimen stratified by creatinine clearance. Using a 2-compartment population PK model reported previously, the mean total clearance or distribution volume of DRPM estimated by Bayesian estimation was significantly lower or higher than that of based on population PK model. The estimated fT>MIC (%) of the recommended standard (normal renal function: 0.5 g every 8 h, moderate: 0.25 g every 8 h, severe renal impairment: 0.25 g every 12 h) and higher doses (normal: 1.0 g every 8 h, moderate: 0.5 g every 8 h, severe: 0.25 g every 8 h) against MICs of 0.5, 1 and 2 µg/mL exceeded 40% in all patients. When stratified by creatinine clearance, the PK/PD breakpoints estimated by Monte Carlo simulation in three grades of renal function tended to be higher than the previously reported PK/PD breakpoints for patients with urinary tract infection, an infection of lesser severity than ICU patients. These results suggest that the dosage regimen stratified by renal function derived from Japanese package insert may be sufficient to achieve effective treatment in ICU patients.

著者

Renata Grespan Marcia Paludo Henrique de Paula Lemos Carmem Patrícia Barbosa Ciomar Aparecida Bersani-Amado Marcia Machado de Oliveira Dalalio Roberto Kenji Nakamura Cuman

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.35, no.10, pp.1818-1820, 2012-10-01 (Released:2012-10-01)

参考文献数

11

被引用文献数

8 37

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This study was designed to test the efficacy of eugenol, a compound obtained from the essential oil of cloves (Syzygium aromaticum) in collagen-induced arthritis (CIA), a well characterized murine model of rheumatoid arthritis. Macroscopic clinical evidence of CIA manifests first as periarticular erythema and edema in the hind paws. Treatment with eugenol starting at the onset of arthritis (day 25) ameliorated these clinical signs of CIA. Furthermore, eugenol inhibited mononuclear cell infiltration into the knee joints of arthritic mice and also lowered the levels of cytokines (tumor necrosis factor (TNF)-α, interferon (IFN)-γ and tumor growth factor (TGF)-β) within the ankle joints. Eugenol treatment did not affect the in vitro cell viability as assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Therefore, eugenol ameliorates experimental arthritis and could be useful as a beneficial supplement in treating human arthritis.

著者

Zheng Zhihui Yang Yi Shao Huayi Liu Zongying Lu Xinhua Xu Yanni He Xiaobo Jiang Wei Jiang Qin Zhao Baohua Zhang Hua Li Zhuorong Si Shuyi

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.34, no.10, pp.1631-1634, 2011

被引用文献数

6

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In our previous study, two synthetic thiophenes such as IMB-05 and IMB-15 were found as peroxisome proliferator-activated receptor gamma (PPARγ) agonists and exhibited beneficial effects on glucose tolerance of diabetic mice <i>in vivo</i>. In the present study, their effect on the transactivity of other nuclear receptors was further investigated. IMB-05 and IMB-15 could not only activated PPARγ but also efficiently activate PPARα in GAL4-hPPARα/γ (ligand binding domain (LBD)) chimeric receptor assay and PPAR response element (PPRE)-luc reporter gene assay with EC₅₀ values of 1.8—5.2 μ<small>M</small>, whereas no activity was observed in other nuclear receptor assays. In addition, the maximal efficacy of IMB-05 and IMB-15 in activating PPARα/γ was approximately 30% of that observed with Wy14643 and rosiglitazone. These data indicate that the two thiophene derivatives are novel class of partial PPARα/γ dual agonists, which may be the mechanism underlying their regulatory effects on glucose homeostasis.

著者

Joan Manjuh Tankam Michiho Ito

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.10, pp.1608-1614, 2013-10-01 (Released:2013-10-01)

参考文献数

44

被引用文献数

6 34

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The aromatherapeutical potential of Piper guineense essential oil was investigated in mice via inhalation administration, and the active compounds were identified. An open field test and light/dark transition test were used to evaluate the sedative and anxiolytic activities of this essential oil, respectively. P. guineense essential oil showed significant sedative activity at an effective dose of 4.0×10−5 mg per cage compared to the control group. It also showed potent anxiolytic effect at a dose of 4.0×10−6 mg per cage. The main compounds of P. guineense essential oil were linalool (41.8%) and 3,5-dimethoxytoluene (10.9%). These two main compounds were shown to play a major role in the sedative activity of P. guineense essential oil. These results suggest that inhalation of P. guineense essential oil might induce a mild tranquilizing effect.