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Journal of Pharmacological Sciences

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https://www.readbyqxmd.com/read/27884451/cholesterol-lowering-pattern-affects-the-progression-of-atherosclerosis-in-apolipoprotein-e-deficient-mice
#1
Yusuke Masuda, Shinji Yamaguchi, Tomohiro Nishizawa
Although the importance of LDL cholesterol lowering is widely recognized, the impact of the cholesterol-lowering pattern on the atherosclerosis remains unclear. Here, we used cholestyramine in apolipoprotein E deficient mice in two different regimens to induce a see-saw shaped or a sustained cholesterol reduction, with the trough of cholesterol comparable. After 12 weeks-treatment, a sustained cholesterol reduction exhibited a smaller atherosclerotic area. Moreover, we observed a correlation between the area under the curve of plasma cholesterol and the atherosclerotic area...
November 10, 2016: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/27889414/changes-in-glucose-induced-plasma-active-glucagon-like-peptide-1-levels-by-co-administration-of-sodium-glucose-cotransporter-inhibitors-with-dipeptidyl-peptidase-4-inhibitors-in-rodents
#2
Takahiro Oguma, Chiaki Kuriyama, Keiko Nakayama, Yasuaki Matsushita, Kumiko Hikida, Minoru Tsuda-Tsukimoto, Akira Saito, Kenji Arakawa, Kiichiro Ueta, Masabumi Minami, Masaharu Shiotani
We investigated whether structurally different sodium-glucose cotransporter (SGLT) 2 inhibitors, when co-administered with dipeptidyl peptidase-4 (DPP4) inhibitors, could enhance glucagon-like peptide-1 (GLP-1) secretion during oral glucose tolerance tests (OGTTs) in rodents. Three different SGLT inhibitors-1-(β-d-Glucopyranosyl)-4-chloro-3-[5-(6-fluoro-2-pyridyl)-2-thienylmethyl]benzene (GTB), TA-1887, and canagliflozin-were examined to assess the effect of chemical structure. Oral treatment with GTB plus a DPP4 inhibitor enhanced glucose-induced plasma active GLP-1 (aGLP-1) elevation and suppressed glucose excursions in both normal and diabetic rodents...
October 28, 2016: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/27802908/high-dose-dextromethorphan-produces-myelinoid-bodies-in-the-hippocampus-of-rats
#3
Hai-Quyen Tran, Yoon Hee Chung, Eun-Joo Shin, Won Ki Kim, Jae-Chul Lee, Ji Hoon Jeong, Myung Bok Wie, Choon-Gon Jang, Kiyofumi Yamada, Toshitaka Nabeshima, Hyoung-Chun Kim
Dextromethorphan (DM) administered at supra-antitussive doses produce psychotoxic and neurotoxic effects in humans. We administered DM (80 mg/kg) to rats intraperitoneally to determine the ultrastructural change induced by DM, because intraperitoneal route is sensitive for the behavioral responses. Treatment with DM resulted in mitochondrial dysfunction and formation of myelinoid bodies in the hippocampus. MK-801 [(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine maleate] attenuated DM-induced cytosolic oxidative burdens...
October 8, 2016: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/27743814/salubrinal-improves-mechanical-properties-of-the-femur-in-osteogenesis-imperfecta-mice
#4
Shinya Takigawa, Brian Frondorf, Shengzhi Liu, Yang Liu, Baiyan Li, Akihiro Sudo, Joseph M Wallace, Hiroki Yokota, Kazunori Hamamura
Salubrinal is an agent that reduces the stress to the endoplasmic reticulum by inhibiting de-phosphorylation of eukaryotic translation initiation factor 2 alpha (eIF2α). We and others have previously shown that the elevated phosphorylation of eIF2α stimulates bone formation and attenuates bone resorption. In this study, we applied salubrinal to a mouse model of osteogenesis imperfecta (Oim), and examined whether it would improve Oim's mechanical property. We conducted in vitro experiments using RAW264.7 pre-osteoclasts and bone marrow derived cells (BMDCs), and performed in vivo administration of salubrinal to Oim (+/-) mice...
October 1, 2016: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/27773435/a-serine-protease-inhibitor-attenuates-aldosterone-induced-kidney-injuries-via-the-suppression-of-plasmin-activity
#5
Yutaka Kakizoe, Yoshikazu Miyasato, Tomoaki Onoue, Terumasa Nakagawa, Manabu Hayata, Kohei Uchimura, Jun Morinaga, Teruhiko Mizumoto, Masataka Adachi, Taku Miyoshi, Yoshiki Sakai, Kimio Tomita, Masashi Mukoyama, Kenichiro Kitamura
Emerging evidence has suggested that aldosterone has direct deleterious effects on the kidney independently of its hemodynamic effects. However, the detailed mechanisms of these direct effects remain to be elucidated. We have previously reported that camostat mesilate (CM), a synthetic serine protease inhibitor, attenuated kidney injuries in Dahl salt-sensitive rats, remnant kidney rats, and unilateral ureteral obstruction rats, suggesting that some serine proteases would be involved in the pathogenesis of kidney injuries...
September 30, 2016: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/27733273/gomisin-n-ameliorates-lipopolysaccharide-induced-depressive-like-behaviors-by-attenuating-inflammation-in-the-hypothalamic-paraventricular-nucleus-and-central-nucleus-of-the-amygdala-in-mice
#6
Ryota Araki, Yosuke Hiraki, Shoji Nishida, Yuka Inatomi, Takeshi Yabe
Emotional impairments such as depressive symptoms often develop in patients with sustained and systemic immune activation. The objective of this study is to investigate the effect of gomisin N, a dibenzocyclooctadiene lignan isolated from the dried fruits of Schisandra chinensis (Turcz.) Baill., which exhibited inhibitory effects of the bacterial endotoxin lipopolysaccharide (LPS)-induced NO production in a screening assay, on inflammation-induced depressive symptoms. We examined the effects of gomisin N on inflammation induced by LPS in murine microglial BV-2 cells and on LPS-induced behavioral changes in mice...
September 28, 2016: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/27707649/rosmarinic-acid-inhibits-inflammation-and-angiogenesis-of-hepatocellular-carcinoma-by-suppression-of-nf-%C3%AE%C2%BAb-signaling-in-h22-tumor-bearing-mice
#7
Wen Cao, Chao Hu, Lingling Wu, Liba Xu, Weizhe Jiang
The aim of this study was to explore the anti-tumor effect and therapeutic potential of rosmarinic acid (RA) in the treatment of hepatocellular carcinoma (HCC). RA at 75, 150 and 300 mg/kg was given to H22 tumor-bearing mice by intragastric administration once daily for 10 consecutive days. Levels of inflammatory and angiogenic factors, including interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), vascular endothelial growth factor (VEGF), and transforming growth factor-β (TGF-β) were measured by enzyme linked immunosorbent assays (ELISA)...
September 14, 2016: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/27681370/myelin-related-gene-silencing-mediated-by-lpa1-rho-rock-signaling-is-correlated-to-acetylation-of-nf%C3%AE%C2%BAb-in-s16-schwann-cells
#8
Ryoko Tsukahara, Hiroshi Ueda
Lysophosphatidic acid (LPA) initiates demyelination following peripheral nerve injury, which causes neuropathic pain. Our previous in vivo and ex vivo studies using mice have demonstrated that LPA-induced demyelination of spinal dorsal roots is attributed by the LPA1-type receptor-mediated down-regulation of myelin-related molecules, such as MBP and MPZ. In this study using S16 mature-type Schwann cells, we found that LPA-induced down-regulation of myelin-related genes is attributed by the activation of LPA1 receptor, Rho kinase, and p300, leading to an acetylation of NFκB, which down-regulates the transcription of Sox10, MBP and MPZ genes...
September 12, 2016: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/27865709/defective-splicing-of-the-background-k-channel-k2p5-1-by-the-pre-mrna-splicing-inhibitor-pladienolide-b-in-lectin-activated-mouse-splenic-cd4-t-cells
#9
Kazutaka Tagishi, Ayaka Shimizu, Kyoko Endo, Hiroaki Kito, Satomi Niwa, Masanori Fujii, Susumu Ohya
The two-pore domain K(+) channel K2P5.1 has been implicated in the pathogenesis of autoimmune diseases. We investigated the changes in K2P5.1 activity caused by a defect in normal pre-mRNA splicing in concanavalin A-activated mouse splenic CD4(+) T cells. The pre-mRNA splicing inhibitor, pladienolide B (1 μM) markedly decreased full-length K2P5.1 transcription in activated CD4(+) T cells, resulting in the disappearance of K2P5.1 activity and an imbalance in Th17 and Treg cytokines. These results suggest that the defect in K2P5...
November 2016: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/27842970/dentin-hypersensitivity-like-tooth-pain-seen-in-patients-receiving-steroid-therapy-an-exploratory-study
#10
Noriaki Shoji, Yu Endo, Masahiro Iikubo, Tomonori Ishii, Hideo Harigae, Jun Aida, Maya Sakamoto, Takashi Sasano
To ascertain whether steroid therapy evokes dentin hypersensitivity (DH)-like tooth pain, we performed a study based on compelling evidence from patients receiving steroid therapy. An exploratory study was conducted using a questionnaire for 220 patients prescribed steroids who attended the Department of Hematology and Rheumatology of Tohoku University Hospital. Group comparisons between patients with and without steroid pulse therapy were analysed by statistical means. In this study, any DH-like tooth pain that commenced subsequent to steroid treatment was defined as steroid-derived (SD) tooth pain...
November 2016: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/27840063/curcumin-protects-human-adipose-derived-mesenchymal-stem-cells-against-oxidative-stress-induced-inhibition-of-osteogenesis
#11
Nan Wang, Feng Wang, Youshui Gao, Peipei Yin, Chenhao Pan, Wei Liu, Zubin Zhou, Jiaxiang Wang
The detrimental effects of oxidative stress on the skeletal system have been documented, and understanding the mechanisms is important to design a therapeutic strategy. As an antioxidant and anti-inflammatory agent, the active ingredient of turmeric curcumin has been used as medication for numerous complications including bone loss. However, it is unclear if curcumin could influence the osteogenic potential of mesenchymal stem cells (MSCs), particularly in oxidative injuries. Here we demonstrate that curcumin treatment protects cell death caused by hydrogen peroxide (H2O2) exposure in human adipose-derived MSCs in vitro...
November 2016: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/27816547/overexpression-of-na-ca-2-exchanger-1-display-enhanced-relaxation-in-the-gastric-fundus
#12
Yasuyuki Fujimoto, Satomi Hayashi, Yasu-Taka Azuma, Kazunori Mukai, Kazuhiro Nishiyama, Satomi Kita, Ai Morioka, Hidemitsu Nakajima, Takahiro Iwamoto, Tadayoshi Takeuchi
In gastric smooth muscles, the released Ca(2+) activates the contractile proteins and Ca(2+) taken up from the cytosol cause relaxation. The Na(+)/Ca(2+) exchanger (NCX) is an antiporter membrane protein that controls Ca(2+) influx and efflux across the membrane. However, the possible relation of NCX in gastric fundus motility is largely unknown. Here, we investigated electric field stimulation (EFS)-induced relaxations in the circular muscles of the gastric fundus in smooth muscle-specific NCX1 transgenic mice (Tg)...
November 2016: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/27567475/lat1-acts-as-a-crucial-transporter-of-amino-acids-in-human-thymic-carcinoma-cells
#13
Keitaro Hayashi, Promsuk Jutabha, Sumiko Maeda, Yothaisong Supak, Motoshi Ouchi, Hitoshi Endou, Tomoe Fujita, Masayuki Chida, Naohiko Anzai
L-type amino acid transporter 1 (LAT1, SLC7A5) incorporates essential amino acids into cells. Recent studies have shown that LAT1 is a predominant transporter in various human cancers. However, the function of LAT1 in thymic carcinoma remains unknown. Here we demonstrate that LAT1 is a critical transporter for human thymic carcinoma cells. LAT1 was strongly expressed in human thymic carcinoma tissues. LAT1-specific inhibitor significantly suppressed leucine uptake and growth of Ty82 human thymic carcinoma cell lines, suggesting that thymic carcinoma takes advantage of LAT1 as a quality transporter and that LAT1-specific inhibitor might be clinically beneficial in therapy for thymic carcinoma...
November 2016: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/27426917/store-operated-ca-2-entry-soce-contributes-to-angiotensin-ii-induced-cardiac-fibrosis-in-cardiac-fibroblasts
#14
Boyu Zhang, Jianmin Jiang, Zhongbao Yue, Shenglan Liu, Yunzi Ma, Na Yu, Ying Gao, Shuya Sun, Shaorui Chen, Peiqing Liu
Store-operated Ca(2+) entry (SOCE) is an important mechanism of extracellular Ca(2+) entry into cells. It has been proved that SOCE is involved in many pathologic and physiological processes. Two key participants of SOCE, stromal interaction molecule1 (STIM1) and Orai1, have been identified. But their function in cardiac fibroblasts remains elusive. In present study, our findings suggested the expression of STIM1 and Orai1 were increased followed by angiotensin II (Ang II) stimulation in vivo and in vitro...
November 2016: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/27818011/human-grin2b-variants-in-neurodevelopmental-disorders
#15
REVIEW
Chun Hu, Wenjuan Chen, Scott J Myers, Hongjie Yuan, Stephen F Traynelis
The development of whole exome/genome sequencing technologies has given rise to an unprecedented volume of data linking patient genomic variability to brain disorder phenotypes. A surprising number of variants have been found in the N-methyl-d-aspartate receptor (NMDAR) gene family, with the GRIN2B gene encoding the GluN2B subunit being implicated in many cases of neurodevelopmental disorders, which are psychiatric conditions originating in childhood and include language, motor, and learning disorders, autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD), developmental delay, epilepsy, and schizophrenia...
October 2016: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/27671351/dipotassium-n-stearoyltyrosinate-ameliorated-pathological-injuries-in%C3%A2-triple-transgenic-mouse-model-of-alzheimer-s-disease
#16
Sha Liu, Shuang-Qi Tang, Heng-Jing Cui, Sha Yin, Ming Yin, Hong Zhao, Ling-Hua Meng, Ze-Jian Wang, Yang Lu
Recently, anandamide (AEA) analogues have been well recognized for its potent neuroprotective effects in counteracting the deterioration of Alzheimer's disease (AD) brains through multiple pathological processes. In our previous studies, dipotassium N-stearoyltyrosinate (NSTK), an AEA analogue synthesized by our laboratory was reported to exert significant efficacy through multiple interventions. Within this study, the amyloid precursor protein (APP)SWE/presenilin-1 (PS1)M146V/TauP301L mouse (3×Tg-AD) model was used to explore further the neuroprotective effects of NSTK and its underlying mechanisms...
September 2016: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/27666018/effect-of-naftopidil-on-brain-noradrenaline-induced-decrease-in-arginine-vasopressin-secretion-in-rats
#17
Masaki Yamamoto, Takahiro Shimizu, Shogo Shimizu, Youichirou Higashi, Kumiko Nakamura, Mikiya Fujieda, Motoaki Saito
Naftopidil, an α1-adrenoceptor antagonist, has been shown to inhibit nocturnal polyuria in patients with lower urinary tract symptom. However, it remains unclear how naftopidil decreases nocturnal urine production. Here, we investigated the effects of naftopidil on arginine-vasopressin (AVP) plasma level and urine production and osmolality in rats centrally administered with noradrenaline (NA). NA (3 or 30 μg/kg) was administered into the left ventricle (i.c.v.) of male Wistar rats 3 h after naftopidil pretreatment (10 or 30 mg/kg, i...
September 2016: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/27666017/cardiac-dpp-4-inhibition-by-saxagliptin-ameliorates-isoproterenol-induced-myocardial-remodeling-and-cardiac-diastolic-dysfunction-in-rats
#18
Junichi Ikeda, Naoya Kimoto, Tetsuya Kitayama, Shunji Kunori
Saxagliptin, a potent and selective DPP-4 inhibitor, is characterized by its slow dissociation from DPP-4 and its long half-life and is expected to have a potent tissue membrane-bound DPP-4-inhibitory effect in various tissues. In the present study, we examined the effects of saxagliptin on in situ cardiac DPP-4 activity. We also examined the effects of saxagliptin on isoproterenol-induced the changes in the early stage such as, myocardial remodeling and cardiac diastolic dysfunction. Male SD rats treated with isoproterenol (1 mg/kg/day via osmotic pump) received vehicle or saxagliptin (17...
September 2016: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/27665370/estrogenic-compound-attenuates-angiotensin-ii-induced-vascular-smooth-muscle-cell-proliferation-through-interaction-between-lkb1-and-estrogen-receptor-%C3%AE
#19
Sun Ae Kim, Kyung Young Lee, Jae-Ryong Kim, Hyoung Chul Choi
The prevalence rate of cardiovascular disease is higher for males than females, and estradiol (E2) induces AMP-activated protein kinase (AMPK) activation, which is known to regulate proliferation of VSMC. We identified the estrogenic properties of nordihydroguaiaretic acid (NDGA, a lignan phytoestrogen) that inhibit VSMC proliferation and explored the underlying mechanisms. Both the phosphorylation and expression of LKB1 were increased by NDGA. In addition, NDGA significantly attenuated angiotensin II (Ang II)-induced VSMC proliferation...
September 2016: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/27654219/protective-effects-of-the-selective-alpha1a-adrenoceptor-antagonist-silodosin-against-cyclophosphamide-induced-cystitis-in-rats
#20
Nanxi Liu, Shogo Shimizu, Takahiro Shimizu, Kumiko Nakamura, Masaki Yamamoto, Youichirou Higashi, Motoaki Saito
We investigated the protective effects of a selective α1A-adrenoceptor antagonist, silodosin (Silod) on urinary bladder function in cyclophosphamide (CYP)-induced cystitis rats, with and without desensitization of the capsaicin (CAP)-sensitive afferent nerve pathway. Male Wistar rats (310-400 g) were pretreated with Silod (0, 100, or 300 μg/kg/day, p.o.) for 1 week before cystometry, and were administered either CYP (150 mg/kg, i.p.) or saline 2 days before the experiment. In another experiment, the rats were treated with CAP (125 mg/kg, s...
September 2016: Journal of Pharmacological Sciences
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