著者

Satoko Notomi Mineaki Kitamura Kosei Yamaguchi Maya Komine Kenji Sawase Tomoya Nishino Satoshi Funakoshi

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.46, no.2, pp.286-291, 2023-02-01 (Released:2023-02-01)

参考文献数

38

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Anorexia is a common symptom in older patients undergoing hemodialysis (HD) and has become a serious problem in dialysis facilities with the aging of patients. Polypharmacy, defined as the prescription of several medications, is known to cause drug-induced anorexia. Although polypharmacy is also common in older patients undergoing HD, only a few studies have examined the association between anorexia and polypharmacy. This study used the Simplified Nutritional Appetite Questionnaire for Japanese Elderly (SNAQ-JE) to evaluate patients’ appetite, and examined its association with medications. This cross-sectional study included 233 patients (aged ≥65 years) who underwent HD in October 2021. Among the 233 patients (median age, 73.0 [interquartile range (IQR), 69.0–80.5] years; men, 57.3%; median dialysis vintage, 62.0 [IQR, 30.0–122.0] months), 116 and 117 were classified into the poor (SNAQ-JE total score ≤14) and good (>14) appetite groups, respectively. Although the total number of medications prescribed was not significantly different between the two groups (p = 0.12), the number of antihypertensive drugs was significantly lower (p = 0.03), and that of sleeping medications was significantly higher (p = 0.002) in the poor appetite group. Multivariable logistic regression analysis showed that the number of sleeping medications was associated with poor appetite (odds ratio, 2.08; 95% confidence interval, 1.32–3.27; p < 0.001). The findings suggest that the number of sleeping medications is an important contributing factor to poor appetite in older patients undergoing HD. A proper and regular review of prescriptions may be necessary to improve anorexia.

著者

Risako Morishita Miki Shimada Minami Nagao Shin Shimizu Noriyasu Kamei Mariko Takeda-Morishita

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.46, no.2, pp.343-347, 2023-02-01 (Released:2023-02-01)

参考文献数

14

被引用文献数

1

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Owing to their unique physicochemical properties and diverse biological effects, ultrafine bubbles (UFBs) have recently been expected to be utilized for industrial and biological purposes. Thus, this study investigated the biological safety of UFBs in water for living beings in drinking the water with a view to future use in health sciences. In this study, we used H2-filled UFBs (NanoGAS®) that can hold hydrogen in the aqueous phase for a long time. Mice were randomly assigned to one of three groups: those receiving NanoGAS® water, reverse osmosis water, or natural mineral water, and they ingested it ad libitum for one month or three months. As a result, subchronic drinking of NanoGAS® water does not affect either the common blood biochemical parameters or the health of the organs and mucosal membranes. Our results, for the first time, scientifically demonstrated the biological safety of H2-filled UFBs water for subchronic oral consumption.

著者

Mamiko Kai Kazutaka Hayashi Ippei Kaida Hatsumi Aki Magobei Yamamoto

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.12, pp.1608-1613, 2002 (Released:2002-12-01)

参考文献数

33

被引用文献数

10 13

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The aims of this study were to examine the enhancing effects of aloe-emodin anthrone (AEA) on the colonic membrane permeability of water-soluble and poorly permeable compounds and to clarify the mechanism of the permeation-enhancing activity of AEA. The permeation-enhancing activity of AEA was estimated from changes in the permeability coefficient of 5(6)-carboxyfluorescein (CF) in rat colonic mucosa using a Ussing-type chamber. Various inhibitors were used to investigate the mechanism of action of AEA. The structural change in the membrane and the cytotoxicity of AEA in the intestinal mucosa were evaluated by measuring the electrical resistance of the membrane (Rm) and lactate dehydrogenase (LDH) activity, respectively. AEA significantly increased the permeation of CF in a dose-dependent manner. The enhanced permeability was significantly suppressed by a histamine H1 receptor antagonist, pyrilamine, and a mast cell stabilizer, ketotifen, but not by a histamine H2 receptor antagonist, cimetidine. The enhancing effect was also inhibited by an inhibitor of protein kinase C (PKC). Potential difference and short-circuit current values decreased, while Rm values remained constant throughout the experiment. The addition of AEA to the mucosal solution decreased Rm to 30%, but then remained constant. LDH activity with AEA was not significantly different from that of the control. In conclusion, AEA is a candidate for effective absorption enhancers without damage of the membrane and cytotoxicity. We propose that AEA stimulates mast cells within the colonic mucosa to release histamine, which probably bind to the H1 receptor. The intracellular PKC route activated by H1 receptor activation enhances the permeability of water-soluble and poorly permeable drugs via opening of tight junctions in rat colonic membrane.

著者

Sangchai Yingsakmongkon Daisei Miyamoto Nongluk Sriwilaijaroen Kimie Fujita Kosai Matsumoto Wipawee Jampangern Hiroaki Hiramatsu Chao-Tan Guo Toshihiko Sawada Tadanobu Takahashi Kazuya Hidari Takashi Suzuki Morihiro Ito Yasuhiko Ito Yasuo Suzuki

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.3, pp.511-515, 2008-03-01 (Released:2008-03-01)

参考文献数

30

被引用文献数

42 46

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Using a plaque reduction assay, treatment of human influenza A viruses with the fruit-juice concentrate of Japanese plum (Prunus mume SIEB. et ZUCC) showed strong in vitro anti-influenza activity against human influenza A viruses before viral adsorption, but not after viral adsorption, with 50% inhibitory concentration (IC50) values against A/PR/8/34 (H1N1) virus, A/Aichi/2/68 (H3N2) virus and A/Memphis/1/71 (H3N2) virus of 6.35±0.17, 2.84±1.98 and 0.53±0.10 μg/ml, respectively. The plum-juice concentrate exhibited hemagglutination activity toward guinea pig erythrocytes. Its hemagglutination activity was inhibited by the monosaccharide N-acetylneuraminic acid and a sialoglycoprotein (fetuin), but not by the other tested monosaccharides (mannose, galactose, glucose and N-acetylglucosamine), suggesting the presence of a lectin-like molecule(s) in the Japanese plum-juice concentrate. Our findings suggest that the fruit-juice concentrate of Japanese plum may prevent and reduce infection with human influenza A virus, possibly via inhibition of viral hemagglutinin attachment to host cell surfaces by its lectin-like activity.

著者

Shinobu Nakanishi Kanna Kurihara Mitsuhiro Denda

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.1591-1594, 2020-10-01 (Released:2020-10-01)

参考文献数

18

被引用文献数

1 1

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Japanese cedar (Cryptomeria japonica) pollen allergen Cry j1 increases the intracellular calcium concentration in human keratinocytes, and also impairs the epidermal barrier function. Here, we show that reduced glutathione (GSH) blocks both thrombin activation and the Cry j1-induced intracellular calcium elevation in cultured human keratinocytes, and also prevents the Cry j1-induced decrease of barrier function in ex vivo human skin.

著者

Kousuke Nishikiori Kentaro Tanaka Takashi Ozawa Yoshihiro Uesawa

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.46, no.1, pp.19-25, 2023-01-01 (Released:2023-01-01)

参考文献数

29

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Various factors affect the prognosis of dialysis patients. Analysis of the drugs used and clinical and demographic characteristics of the patient at the time of dialysis initiation is a useful means of estimating prognosis. In this study, we investigated the drugs used by dialysis patients during the induction phase of dialysis and performed a detailed analysis of variables predictive of prognosis. Patients who underwent dialysis between June 1998 and January 2019 and died during this period were included in the study (n = 118). The induction phase of dialysis was defined as the first month after dialysis began. Dialysis duration was defined as the time between dialysis initiation and death. A univariate regression analysis was performed, with dialysis duration as the objective variable and the drugs used during the induction phase of dialysis, blood laboratory values, age at start of dialysis, sex, body height, body weight, medical history and cause of death as the explanatory variables. In addition, multiple logistic regression analysis with stepwise variable selection of significant factors was performed to determine the factors related to dialysis duration. Antihypertensives, hemoglobin (Hb), and age at start of dialysis were found to have significant effects on dialysis duration. It was posited that antihypertensives prolong dialysis duration, thereby improving life expectancy. The regression model developed allowed estimation of prognosis based on the drugs used during the induction phase of dialysis and patient characteristics. These findings may be used to improve drug adherence in dialysis patients and guide physicians in their treatment.

著者

Keisuke Ikegami Megumi Saito Shungo Imai Hayato Kizaki Osamu Yasumuro Ryohkan Funakoshi Satoko Hori

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.46, no.1, pp.95-101, 2023-01-01 (Released:2023-01-01)

参考文献数

15

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To prevent denosumab-induced hypocalcemia in patients with renal dysfunction, combination therapy with 1α,25-dihydroxy-vitamin D3 (active vitamin D) is recommended. We previously developed a risk prediction model for hypocalcemia in patients with cholecalciferol/calcium (natural vitamin D). However, the prescription status and the risk factors of patients with active vitamin D have not been identified, so we designed this retrospective observational study using a large practice database covering June 2013 to May 2020 to analyze prescription status and risk factors. Patients were classified according to vitamin D type. After that, factors associated with development of hypocalcemia in patients with active vitamin D were explored. Univariate analysis was conducted to compare patient backgrounds between the hypocalcemia and non-hypocalcemia groups. Receiver operating characteristic analysis was conducted to evaluate the predictive potential of the extracted factors. Of the 33442 patients who received denosumab, 22347 and 3560 patients were co-administered natural and active vitamin D, respectively. Patients with active vitamin D had significantly lower renal function (estimated glomerular filtration rate (eGFR) median: 74.0 vs. 69.7 mL/min/1.73 m2), but some patients (23.6%) with sufficient renal function (eGFR ≥90) were also receiving active vitamin D. Of the 3560 patients with active vitamin D, non-hypocalcemia (n = 166) and hypocalcemia (n = 17) groups who met the study criteria were analyzed. Renal function was lower in the hypocalcemia group, and alkaline phosphatase gave the best discrimination. High aspartate aminotransferase (AST), renal dysfunction, high alkaline phosphatase (ALP), and low hemoglobin may be significant factors in risk prediction for hypocalcemia in patients with active vitamin D.

著者

Kei Nakayama Mari Kondo Tomoko Okuno Nurhanani Razali Hiroshi Hasegawa

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

pp.b22-00842, (Released:2022-12-27)

参考文献数

29

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Immune suppression in elderly individuals is one of the most important hygienic problems in aged societies. The primary immune organ thymus is histologically and functionally reduced by aging, which is known as thymic involution. The thymus is also involuted by nutritional deficiency, which frequently occurs in elderly individuals. However, there is no information on the thymic changes caused by nutritional deficiency with aging. Therefore, this study was conducted to examine the histological and molecular responses of the thymus to nutritional deficiency in young and aged mice. The thymic size was significantly smaller in 16- or 18-week-old aged mice than in 7-week-old young mice. Dietary restriction for 48 h reduced the thymic size in young mice, but not in aged mice. Immunostaining with anti-keratin 5 antibody revealed that the integrity of the corticomedullary boundary was maintained in the aged thymus, whereas dietary restriction induced its disorganization in both young and aged thymus. The numbers of IgG-positive cells were increased upon dietary restriction in aged, but not in young, thymus. Dietary restriction, but not aging, upregulated the mRNA levels of Th2-related Il5, Il6, and Il10, whereas aging increased that of Th1-related Ifng. The dietary restriction–induced upregulation of prostanoid-synthesizing enzymes was clearly observed in the young thymus but attenuated in the aged thymus. Thus, nutritional deficiency and aging cause an involuted thymus with different properties. Moreover, the thymus in aged mice does not show further reduction in size by nutritional deficiency but still responds differently compared with that in young mice.

著者

Byoung-Seob Ko Soo Bong Choi Seong Kyu Park Jin Sun Jang Yeong Eun Kim Sunmin Park

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.28, no.8, pp.1431-1437, 2005 (Released:2005-08-01)

参考文献数

30

被引用文献数

123 140

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Our preliminary study demonstrated that 70% ethanol Cortidis Rhizoma extracts (CR) had a hypoglycemic action in diabetic animal models. We determined whether CR fractions acted as anti-diabetic agent, and a subsequent investigation of the action mechanism of the major compound, berberine ([C20H18NO4]+), was carried out in vitro. The 20, 40 and 60% methanol fractions from the XAD-4 column contained the most insulin sensitizing activities in 3T3-L1 adipocytes. The common major peak in these fractions was berberine. Treatment with 50 μM berberine plus differentiation inducers significantly reduced triglyceride accumulation by decreased differentiation of 3T3-L1 fibroblasts to adipocytes and triglyceride synthesis. Significant insulin sensitizing activity was observed in 3T3-L1 adipocytes which were given 50 μM berberine plus 0.2 nM insulin to reach a glucose uptake level increased by 10 nM of insulin alone. This was associated with increased glucose transporter-4 translocation into the plasma membrane via enhancing insulin signaling pathways and the insulin receptor substrate-1-phosphoinositide 3 Kinase-Akt. Berberine also increased glucose-stimulated insulin secretion and proliferation in Min6 cells via an enhanced insulin/insulin-like growth factor-1 signaling cascade. Data suggested that berberine can act as an effective insulin sensitizing and insulinotropic agent. Therefore, berberine can be used as anti-diabetic agent for obese diabetic patients.

著者

Young A Lee Eun Ju Cho Takako Yokozawa

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.6, pp.1265-1269, 2008-06-01 (Released:2008-06-01)

参考文献数

41

被引用文献数

44 55

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8-Hydroxy-2′-deoxyguanosine (8-OHdG), one of the most abundant oxidative DNA adducts, is used as an indicator of oxidative DNA damage associated with aging. Among homologs of the silent information regulator (Sir), sirtuin 1 (SIRT1) is suggested as a regulator of the apoptotic response to DNA damage. Since it has been suggested that the aging process can be delayed by the attenuation of oxidative damage such as DNA damage or SIRT1 modulation, we focused on the protective effect against cellular oxidative damage of persimmon peel, a proanthocyanidin-rich food, in relation to its level of polymerization. We confirmed that 8-OHdG expression in TIG-1 human fibroblasts was increased by treatment with 300 μM H2O2 for 2 h. On the other hand, the nuclear SIRT1 level was decreased in H2O2-treated as compared with non-pretreated cells. However, pretreatments with polymers and oligomers led to a decrease in 8-OHdG and elevation in nuclear SIRT1 expression in a concentration-dependent manner. In particular, oligomers exerted a stronger effect. The present study supports the protective potential of proanthocyanidin from persimmon peel against oxidative damage under the aging process, and suggests that the polymerization of proanthocyanidin plays an important role in retarding aging in a cellular senescence model.

著者

Yasuhiro Tsuji

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.9, pp.1174-1183, 2021-09-01 (Released:2021-09-01)

参考文献数

79

被引用文献数

1

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Therapeutic drug monitoring and target concentration intervention based on population pharmacokinetic and pharmacodynamic models has been strongly recommended for anti-methicillin-resistant Staphylococcus aureus (MRSA) agents in order to provide appropriate antimicrobial chemotherapy to each individual patient, and pharmacokinetic and pharmacodynamic analyses in hospitalized patients have been actively conducted, as evidenced with vancomycin. Teicoplanin, daptomycin, and linezolid have been the most studied antibiotics, using population pharmacokinetics of patients with MRSA. Infections caused by MRSA have higher severity and fatality rates than other antimicrobial-susceptible infections. Therefore, many medical facilities have been implementing infection control programs based on antimicrobial stewardship to prevent nosocomial infections and drug-resistant strains. Studies detailing pharmacometrics for these antibiotics have been reported to elucidate the pharmacokinetic and pharmacodynamic properties, to determine significant factors influencing variabilities between individuals, and to develop target concentration interventions and dosing regimens for adults, the elderly, patients with renal insufficiency including those on continuous renal replacement therapies, patients with low body weight, obese patients, and pediatric patients. This review presents the details of our recent research on the optimal dosing design of antimicrobial agents for the treatment of MRSA infection based on hospital pharmacometrics. In addition, the prospect of using modeling and simulation has shown major advantages in supporting dosing regimen selection.

著者

Yasuharu Kashiwagura Shinya Uchida Shimako Tanaka Hiroshi Watanabe Masahiro Masuzawa Tadanori Sasaki Noriyuki Namiki

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.4, pp.666-670, 2014-04-01 (Released:2014-04-01)

参考文献数

12

被引用文献数

5 11

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This study aimed to elucidate the clinical efficacy and pharmacokinetics of levothyroxine (LT4) suppository, thus, we examined the pharmacokinetics of thyroxine (T4) after the administration of the suppository in thyroidectomized rats and examined dose and the levels of free T4 (FT4) in patients with hypothyroidism receiving suppositories. Thyroidectomized rats were administered with LT4 solution and LT4 suppository (30 µg/kg), and plasma T4 concentrations were measured using LC/MS. The AUC0–168 of T4 after rectal administration of the LT4 suppository was 64% lower than these values after oral administration. To evaluate clinical effect of LT4 suppository, we enrolled 6 Japanese patients with hypothyroidism (2 men and 4 women; age, 68.2±13.5 years) who were administered LT4 suppository at Kameda Medical Center from 2007 to 2013 in this case series. The FT4 level during the administration of suppositories was significantly lower than that during the administration of tablets (0.657±0.183 ng/dL vs. 1.25±0.51 ng/dL, p=0.034). The FT4/dose ratio for the suppository was significantly 44% lower than that for the tablet (p=0.020). In conclusion, although the bioavailability of LT4 is lower after administration of the suppository than after the oral formulation, it was suggested that T4 levels can be maintained in patients with hypothyroidism by administering LT4 suppositories at a dose 1.8 times higher than that of the tablet. Thus, the administration of LT4 suppository can be an alternative for treatment with oral medication in clinical practice.

著者

Azliza Mad Anuar Akira Minami Hiroshi Matsushita Kanako Ogino Kosei Fujita Hatsune Nakao Shota Kimura Vikineswary Sabaratnam Kaoru Umehara Yuuki Kurebayashi Tadanobu Takahashi Hiroaki Kanazawa Akihiko Wakatsuki Takashi Suzuki Hideyuki Takeuchi

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.45, no.10, pp.1438-1443, 2022-10-01 (Released:2022-10-01)

参考文献数

59

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Estrogen deficiency during menopause causes a variety of neurological symptoms, including depression. The edible Lion’s Mane mushroom, Hericium erinaceus (Bull.: Fr.) Pers. (HE), is a medicinal mushroom that has the potential for a neuroprotective effect and ameliorating neurological diseases, such as depression, anxiety, and neurodegenerative diseases. HE contains phytoestrogens, including daidzein and genistein. However, the ameliorating effect of HE on menopausal symptoms is not well understood. Here we investigated the impact of methanol extract of the HE fruiting body on depressive-like behavior in postmenopausal model rats. The activation of estrogen receptor alpha (ERα) causes body weight loss and uterine weight gain. Body weight gain and uterine weight loss by estrogen deficiency in ovariectomized (OVX) rats were reversed with 17β-estradiol (E2) but not with HE. Thus, the phytoestrogens in HE may hardly activate ERα. Estrogen receptor beta (ERβ) is expressed in the brain, and activation of ERβ ameliorates menopausal depressive symptoms. Notably, depressive-like behavior in OVX rats evaluated in forced swim test was reduced by administration of not only E2 but also HE for 92 d. Long-term activation of ERα increases the risk of breast and uterine cancers. HE, therefore, may be effective in treating menopausal depression without the risk of carcinogenesis caused by ERα activation.

著者

Eunjin Shin Kyeong-Mi Choi Hwan-Soo Yoo Chong-Kil Lee Bang Yeon Hwang Mi Kyeong Lee

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.33, no.9, pp.1610-1614, 2010-09-01 (Released:2010-09-01)

参考文献数

25

被引用文献数

56 66

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In the course of screening anti-adipogenic activity of natural products employing the preadipocyte cell line, 3T3-L1 as an in vitro assay system, the EtOAc fraction of the stem barks of Fraxinus rhynchophylla DENCE (Oleaceae) showed significant inhibitory activity on adipocyte differentiation as assessed by measuring fat accumulation using Oil Red O staining. Activity-guided fractionation led to the isolation of six coumarins such as esculetin (1), scopoletin (2), fraxetin (3), fraxidin (4) esculin (5) and fraxin (6). Among the six coumarins isolated, esculetin (1) showed the most potent inhibitory activity on adipocyte differentiation, followed by fraxetin (3). Further studies with interval treatment demonstrated that esculetin (1) exerted inhibitory activity on adipocyte differentiation when treated within 2 d (days 0—2) after differentiation induction. We further investigated the effect of esculetin (1) on peroxisome proliferator activated receptor γ (PPARγ), one of the early adipogenic transcription factors. Esculetin (1) significantly blocked the induction of PPARγ protein expression and inhibited adipocyte differentiation induced by troglitazone, a PPARγ agonist. Taken together, these results suggest that esculetin (1), an active compound from F. rhynchophylla, inhibited early stage of adipogenic differentiation, in part, via inhibition of PPARγ-dependent pathway.

著者

Kentaro Nakanishi Keiichi Hiramoto Eisuke F Sato Kazuya Ooi

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.75-81, 2021-01-01 (Released:2021-01-01)

参考文献数

43

被引用文献数

4 7

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Several studies have been conducted to explore the anticancer effects of vitamin C (VC). However, the effect of high-dose VC administration on melanoma is still unknown. Therefore, in this study, we investigated the effects of high-dose VC (4 g/kg) on the invasion and proliferation of melanoma cells in various organs of mice. B16 melanoma cells (1 × 106 cells/100 µL) were intravenously injected into the tails of female mice, and VC solution (4 g/kg) was orally administered once a day for 14 d. On the 15th day, samples from the liver, lungs, jejunum, and ovaries were collected and analyzed for invasion and proliferation of melanoma cells. Oral VC administration decreased the number of dihydroxyphenylalanine (DOPA)-positive cells and gp100-positive melanoma cells in the ovaries and suppressed the invasion and proliferation of melanoma. Compared to melanoma-administered mice, macrophage inflammatory protein-2 levels and number of neutrophils were increased in the VC + melanoma-administered mice. Furthermore, the concentrations of VC, iron, and hydrogen peroxide, and the number of terminal deoxynucleotidyl transferase mediated deoxyuridine triphosphate nick end labeling (TUNEL)-positive cells were significantly increased in the ovaries of VC + melanoma-administered mice compared to those of melanoma-administered mice. These results suggest that VC can reduce the invasion and proliferation of melanoma cells in the ovaries, and neutrophils in the ovaries play an important role in achieving this melanoma-suppressive effect.

著者

Miyuki Yuda Shin Aizawa Isao Tsuboi Yoko Hirabayashi Tomonori Harada Hirotsugu Hino Shuichi Hirai

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.45, no.11, pp.1602-1608, 2022-11-01 (Released:2022-11-01)

参考文献数

28

被引用文献数

3

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Lipopolysaccharide (LPS) treatment induced hemophagocytic lymphohistiocytosis in senescence-accelerated mice (SAMP1/TA-1), but not in senescence-resistant control mice (SAMR1). SAMP1/TA-1 treated with LPS exhibited functional impairment of the hematopoietic microenvironment, which disrupted the dynamics of hematopoiesis. Macrophages are a major component of the bone marrow (BM) hematopoietic microenvironment, which regulates hematopoiesis. Qualitative and quantitative changes in activated macrophages in LPS-treated SAMP1/TA-1 are thought to contribute to the functional deterioration of the hematopoietic microenvironment. Thus, we examined the polarization of pro-inflammatory (M1) and anti-inflammatory (M2) macrophages, and the dynamics of macrophage production in the BM of SAMP1/TA-1 and SAMR1 after LPS treatment. After LPS treatment, the proportions of M1 and M2 macrophages and the numbers of macrophage progenitor (CFU-M) cells increased in both SAMP1/TA-1 and SAMR1. However, compared to the SAMR1, the increase in the M1 macrophage proportion was prolonged, and the increase in the M2 macrophage proportion was delayed. The increase in the number of CFU-M cells was prolonged in SAMP1/TA-1 after LPS treatment. In addition, the levels of transcripts encoding an M1 macrophage-inducing cytokine (interferon-γ) and macrophage colony-stimulating factor were markedly increased, and the increases in the levels of transcripts encoding M2 macrophage-inducing cytokines (interleukin (IL)-4, IL-10, and IL-13) were delayed in SAMP1/TA-1 when compared to SAMR1. Our results suggest that LPS treatment led to the severely imbalanced polarization of activated M1/M2 macrophages accompanied by a prolonged increase in macrophage production in the BM of SAMP1/TA-1, which led to the impairment of the hematopoietic microenvironment, and disrupted the dynamics of hematopoiesis.

著者

Masamichi Inoue Kyosuke Muta Ahmed Fouad Abdelwahab Mohammed Risako Onodera Taishi Higashi Kenta Ouchi Mitsuharu Ueda Yukio Ando Hidetoshi Arima Hirofumi Jono Keiichi Motoyama

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.45, no.11, pp.1660-1668, 2022-11-01 (Released:2022-11-01)

参考文献数

37

被引用文献数

4

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Hereditary amyloidgenic transthyretin (ATTR) amyloidosis is caused by a genetic point-mutated transthyretin such as TTR Val30Met (TTR V30M), since it forms protein aggregates called amyloid resulting in the tissue accumulation and functional disorders. In particular, ATTR produced by retinal pigment epithelial cells often causes ATTR ocular amyloidosis, which elicits deterioration of ocular function and ultimately blindness. Therefore, development of novel therapeutic agents is urgently needed. Genome-editing technology using Clustered Regularly Interspaced Short Palindromic Repeats-CRISPR associated proteins (CRISPR-Cas9) system is expected to be a therapeutic approach to treat genetic diseases, such as ATTR amyloidosis caused by a point mutation in TTR gene. Previously, we reported that glucuronylglucosyl-β-cyclodextrin conjugated with a polyamidoamine dendrimer (CDE) had excellent gene transfer ability and that underlying dendrimer inhibited TTR aggregation. Conversely, folate receptors are known to be highly expressed in retina; thus, folate has potential as a retinal target ligand. In this study, we prepared a novel folate-modified CDE (FP-CDE) and investigated its potential as a carrier for the retinal delivery of TTR-CRISPR plasmid DNA (pDNA). The results suggested that FP-CDE/TTR-CRISPR pDNA could be taken up by retinal pigment epithelial cells via folate receptors, exhibited TTR V30M amyloid inhibitory effect, and suppressed TTR production via the genome editing effect (knockout of TTR gene). Thus, FP-CDE may be useful as a novel therapeutic TTR-CRISPR pDNA carrier in the treatment of ATTR ocular amyloidosis.

著者

山尾 忠直 中上 博秋 古濱 和久 小野寺 威 黒崎 勇二 中山 太二 木村 聰城郎

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.17, no.5, pp.691-695, 1994-05-15 (Released:2008-04-10)

参考文献数

16

被引用文献数

6 6

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The pharmacokinetics of tolbutamide (TB) following intravenous and oral administration was compared between normal rats and rats with experimentally-induced obstructive jaundice (OJ). The plasma concentration-time curve of i.v. administered TB was lower in rats with OJ, in comparison with normal rats. The result of the pharmacokinetic analysis showed no change in the elimination rate constant, but a significant increase in the volume of distribution in the OJ state. The increase in the volume of distribution of TB could be explained by the decreased protein binding in plasma. In the case of oral administration, the elevation of the plasma concentration was slow and the plasma concentration profile was remarkably low in rats with OJ. The rate of TB disappearance from the small-intestinal lumen was delayed in the OJ state, and its marked accumulation in the tissues of the small intestine and the liver was observed. This retarded uptake by the small-intestinal mucosa and subsequent pre-systemic accumulation might, at least in part, be the reason for the slow appearance in the systemic plasma in the OJ state.

著者

Ayako Tamaki Hidetoshi Hayashi Hironori Nakajima Takemasa Takii Daichi Katagiri Keiji Miyazawa Kunitaka Hirose Kikuo Onozaki

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.27, no.3, pp.407-410, 2004 (Released:2004-03-01)

参考文献数

32

被引用文献数

45 51

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Rheumatoid arthritis (RA) is characterized by proliferation of synoviocytes that produce proinflammatory cytokines, which is implicated in the pathogenesis of the disease. Among the cytokines, IL-1 is the critical mediator of the disease. When human fibroblast-like synoviocytes line, MH7A, was treated with 3-methylcholanthrene (3-MC), a polycyclic aromatic hydrocarbon (PAH), mRNA of IL-1β was up-regulated. MH7A cells express functional aryl hydrocarbon receptor (AhR) as shown by 3-MC-inducible CYP1A1 mRNA expression. The effect of 3-MC was inhibited by α-napthoflavone, an AhR antagonist, indicating that the effect of 3-MC is mediated via AhR. Benzo[a]pyrene (B[a]P) and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) also up-regulated mRNA level of IL-1β in the cells via AhR. As PAHs are much contained in cigarette smoke, these findings provide the possible basis for epidemiological studies indicating a strong association between heavy cigarette smoking and outcome of RA.

著者

Takashi Ito Yuuki Hanahata Keita Kine Shigeru Murakami Stephen W. Schaffer

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.10, pp.1561-1566, 2018-10-01 (Released:2018-10-01)

参考文献数

29

被引用文献数

9 12

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Dietary taurine deficiency results in dilated cardiomyopathy in cats while in mice taurine deficiency produced by knocking out the taurine transporter (TauT) gene leads to a reduction in cardiac function with advancing age. The present study elucidated the involvement of cardiac fibrosis in the aging-dependent cardiac disorder of the TauT-knockout (TauTKO) mouse. Old (18–24-month-old) TauTKO mice, but not young (3–5-month-old) mice, exhibit cardiac fibrosis. Transcriptome microarray analysis revealed an increase in pro-fibrotic genes, such as S100A4, ACTA2 and CTGF, in both young and old TauTKO hearts. Based on transcriptome-pathway analysis the genes involved in “organization of extracellular matrix,” such as LGALS3, are enriched in old TauTKO hearts compared to old wild-type hearts, suggesting the contribution of these genes to fibrosis. In conclusion, taurine depletion predisposes the heart to fibrosis, which leads to cardiac fibrosis upon aging.