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Journal of Pharmacological Sciences

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https://www.readbyqxmd.com/read/28694090/milnacipran-affects-mouse-impulsive-aggressive-and-depressive-like-behaviors-in-a-distinct-dose-dependent-manner
#1
Iku Tsutsui-Kimura, Yu Ohmura, Takayuki Yoshida, Mitsuhiro Yoshioka
Serotonin/noradrenaline reuptake inhibitors (SNRIs) are widely used for the treatment for major depressive disorder, but these drugs induce several side effects including increased aggression and impulsivity, which are risk factors for substance abuse, criminal involvement, and suicide. To address this issue, milnacipran (0, 3, 10, or 30 mg/kg), an SNRI and antidepressant, was intraperitoneally administered to mice prior to the 3-choice serial reaction time task, resident-intruder test, and forced swimming test to measure impulsive, aggressive, and depressive-like behaviors, respectively...
June 27, 2017: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/28689962/astaxanthin-analogs-adonixanthin-and-lycopene-activate-nrf2-to-prevent-light-induced-photoreceptor-degeneration
#2
Yuki Inoue, Masamitsu Shimazawa, Ryota Nagano, Yoshiki Kuse, Kei Takahashi, Kazuhiro Tsuruma, Masahiro Hayashi, Takashi Ishibashi, Takashi Maoka, Hideaki Hara
Carotenoids, in particular astaxanthin, possess potent antioxidant capabilities. Astaxanthin also induces NF-E2-related factor 2 (Nrf2), which plays a major regulatory role in the antioxidative response. However, little is known whether the carotenoid, by-products of astaxanthin, activate Nrf2. Toward this end, we screened eight astaxanthin analogs for Nrf2 activation in murine photoreceptor cell line, 661 W, by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). In addition, we monitored cell death in 661 W cells pretreated with astaxanthin analogs or only pretreated for 6 h with astaxanthin analogs and then exposed to light...
June 21, 2017: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/28669596/role-of-microglia-in-mechanical-allodynia-in-the-anterior-cingulate-cortex
#3
Keisuke Miyamoto, Kazuhiko Kume, Masahiro Ohsawa
Plastic changes that increase nociceptive transmission are observed in several brain regions under conditions of chronic pain. Synaptic plasticity in the anterior cingulate cortex (ACC) is particularly associated with neuropathic pain. Glial cells are considered candidates for the modulation of neural plastic changes in the central nervous system. In this study, we aimed to investigate the role of ACC glial cells in the development of neuropathic pain. First, we examined the expression of glial cells in the ACC of nerve-ligated mice...
June 21, 2017: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/28689961/pregabalin-reduces-cisplatin-induced-mechanical-allodynia-in-rats
#4
Yoshihiro Seto, Miyuki Takase, Yasuhiro Tsuji, Hideto To
Although cisplatin (CDDP) is a key drug in cancer chemotherapy, CDDP-induced peripheral neuropathy is a dose-limiting factor. We previously reported that CDDP-induced peripheral neuropathy, which progressed from allodynia to hypoalgesia, was ameliorated by the administration of CDDP to rats at a specific time. However, mechanical allodynia cannot be prevented therapeutically. Pregabalin (PGN) is used to suppress neuropathic pain from herpes zoster and diabetes. Therefore, we investigated the effects of PGN on CDDP-induced mechanical allodynia in rats...
June 20, 2017: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/28673635/chymase-inhibitor-prevents-the-development-and-progression-of%C3%A2-non-alcoholic-steatohepatitis-in-rats-fed-a-high-fat-and-high-cholesterol-diet
#5
Yuta Miyaoka, Denan Jin, Keitaro Tashiro, Koji Komeda, Shinsuke Masubuchi, Fumitoshi Hirokawa, Michihiro Hayashi, Shinji Takai, Kazuhisa Uchiyama
The effect of the chymase inhibitor TY-51469 on the development and progression of non-alcoholic steatohepatitis (NASH) was evaluated in rats fed a high-fat and high-cholesterol (HFC) diet. To evaluate the preventive effect of TY-51469 on the development of NASH, stroke-prone spontaneously hypertensive rat 5 (SHRSP5)/Dmcr rats were fed either a normal or HFC diet for 8 weeks, and concurrently administered either placebo or TY-51469 (1 mg/kg per day). To evaluate the effect of TY-51469 on the survival rate, TY-51469 was administered either concurrently with HFC diet (pretreated group) or 8 weeks after HFC diet at which point NASH had developed (posttreated group)...
June 20, 2017: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/28669597/local-intra-articular-injection-of-resveratrol-delays-cartilage-degeneration-in-c57bl-6-mice-by-inducing-autophagy-via-ampk-mtor-pathway
#6
Na Qin, Liwei Wei, Wuyin Li, Wei Yang, Litao Cai, Zhuang Qian, Shufang Wu
Autophagy is an essential cellular homeostasis mechanism that was found to be compromised in aging and osteoarthritis (OA) cartilage. Previous studies showed that resveratrol can effectively regulate autophagy in other cells. The purpose of this study was to determine whether the chondroprotective effect of resveratrol was related to chondrocyte autophagy and to elucidate underlying mechanisms. OA model was induced by destabilization of the medial meniscus (DMM) in 10-week-old male mice. OA mice were treated with resveratrol with/without 3-MA for 8 weeks beginning 4 weeks after surgery...
June 15, 2017: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/28648299/the-intra-articular-injection-of-rankl-binding-peptides-inhibits-cartilage-degeneration-in-a-murine-model-of-osteoarthritis
#7
Md Zahirul Haque Bhuyan, Yukihiko Tamura, Eri Sone, Yuki Yoshinari, Chizuko Maeda, Mariko Takahashi, Yasuhiko Tabata, Ramachandran Murali, Yoshihiro Waki, Kazuhiro Aoki
We recently found that the receptor activator of NF-κB ligand (RANKL)-binding peptide, OP3-4 stimulated the differentiation of both chondrocytes and osteoblasts. OP3-4 is also shown to inhibit cartilage degeneration. To clarify whether the peptide can inhibit cartilage degeneration without stimulating bone formation, we first performed a proliferation assay using C3H10T1/2 (the murine mesenchymal stem cell line), which is the common origin of both chondrocytes and osteoblasts. The RANKL-binding peptides, OP3-4 and W9, promoted cellular proliferation at 24 and 48 h, respectively...
June 13, 2017: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/28651800/cellular-mechanisms-underlying-the-inhibitory-effect-of-flufenamic-acid-on-chloride-secretion-in-human-intestinal-epithelial-cells
#8
Pawin Pongkorpsakol, Chantapol Yimnual, Varanuj Chatsudthipong, Vatcharin Rukachaisirikul, Chatchai Muanprasat
Intestinal Cl(-) secretion is involved in the pathogenesis of secretory diarrheas including cholera. We recently demonstrated that flufenamic acid (FFA) suppressed Vibriocholerae El Tor variant-induced intestinal fluid secretion via mechanisms involving AMPK activation and NF-κB-suppression. The present study aimed to investigate the effect of FFA on transepithelial Cl(-) secretion in human intestinal epithelial (T84) cells. FFA inhibited cAMP-dependent Cl(-) secretion in T84 cell monolayers with IC50 of ∼8 μM...
June 10, 2017: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/28647281/serotonergic-modulation-of-nicotine-induced-kinetic-tremor-in-mice
#9
Naofumi Kunisawa, Higor A Iha, Yuji Nomura, Misaki Onishi, Nami Matsubara, Saki Shimizu, Yukihiro Ohno
We previously demonstrated that nicotine elicited kinetic tremor by elevating the neural activity of the inferior olive via α7 nicotinic acetylcholine (nACh) receptors. Since α7 nACh receptors reportedly facilitate synaptic monoamine release, we explored the role of 5-HT receptors in induction and/or modulation of nicotine tremor. Treatment of mice with nicotine induced kinetic tremor that normally appeared during movement. The 5-HT1A agonist, 8-hydroxydipropylaminotetraline (8-OH-DPAT), significantly enhanced nicotine-induced tremor and the action of 8-OH-DPAT was antagonized by WAY-100135 (5-HT1A antagonist)...
June 9, 2017: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/28645489/effects-of-hypnotic-bromovalerylurea-on-microglial-bv2-cells
#10
Shun Kawasaki, Naoki Abe, Fumito Ohtake, Afsana Islam, Mohammed Emamussalehin Choudhury, Ryo Utsunomiya, Satoshi Kikuchi, Tasuku Nishihara, Jun Kuwabara, Hajime Yano, Yuji Watanabe, Mayuki Aibiki, Toshihiro Yorozuya, Junya Tanaka
An old sedative and hypnotic bromovalerylurea (BU) has anti-inflammatory effects. BU suppressed nitric oxide (NO) release and proinflammatory cytokine expression by lipopolysaccharide (LPS)-treated BV2 cells, a murine microglial cell line. However, BU did not inhibit LPS-induced nuclear translocation of nuclear factor-κB and subsequent transcription. BU suppressed LPS-induced phosphorylation of signal transducer and activator of transcription 1 (STAT1) and expression of interferon regulatory factor 1 (IRF1)...
June 8, 2017: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/28648300/the-effects-of-2-3-dimercapto-1-propanesulfonic-acid-dmps-and-meso-2-3-dimercaptosuccinic-acid-dmsa-on-the-nephrotoxicity-in-the-mouse-during-repeated-cisplatin-cddp-treatments
#11
Y Yajima, M Kawaguchi, M Yoshikawa, M Okubo, E Tsukagoshi, K Sato, A Katakura
Previously, we reported that specific lower dose of sodium 2,3-dimercapto-1-propanesulfonic acid (DMPS) which is an antidote to heavy metal intoxication, inversely enhanced cisplatin (CDDP)-induced antitumor activity to S-180 cell-bearing mouse. This activity was only weak with meso-2,3-dimercaptosuccinic acid (DMSA), however. This study investigated the effects of lower doses of DMPS or DMSA on the nephrotoxicity and kinetics of CDDP. Kidney and blood isolated from female mice which received CDDP with or without DMPS or DMSA once daily for 4 days were provided for measuring levels of blood urea nitrogen (BUN) and transporter proteins (OCT2: organic cation transporter; MATE1: multidrug and toxin extrusion) mRNA, and CDDP-originated platinum, and TUNEL staining of renal tubular cells...
June 3, 2017: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/28619445/effects-of-kallidinogenase-on-retinal-edema-and-size-of-non-perfused-areas-in-mice-with-retinal-vein-occlusion
#12
Anri Nishinaka, Shinichiro Fuma, Yuki Inoue, Masamitsu Shimazawa, Hideaki Hara
Kallidinogenase has been used to treat retinal vein occlusion (RVO) in patients, although there are no evidences on the effects of kallidinogenase on the retinal edema and the non-perfused areas in eyes with a RVO. We have established a murine RVO model with retinal edema and non-perfused areas. The purpose of this study was to evaluate the effects of kallidinogenase on the retinal edema and size of the non-perfused areas in the mouse RVO model. We evaluated the thickness of the retinal layers and size of the non-perfused areas, and the blood flow by laser speckle flowgraphy in RVO model...
May 27, 2017: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/28615142/overexpression-of-kcnj2-in-induced-pluripotent-stem-cell-derived-cardiomyocytes-for-the-assessment-of-qt-prolonging-drugs
#13
Min Li, Yasunari Kanda, Takashi Ashihara, Tetsuo Sasano, Yuji Nakai, Masami Kodama, Erina Hayashi, Yuko Sekino, Tetsushi Furukawa, Junko Kurokawa
Human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes hold great potentials to predict pro-arrhythmic risks in preclinical cardiac safety screening, although the hiPSC cardiomyocytes exhibit rather immature functional and structural characteristics, including spontaneous activity. Our physiological characterization and mathematical simulation showed that low expression of the inward-rectifier potassium (IK1) channel is a determinant of spontaneous activity. To understand impact of the low IK1 expression on the pharmacological properties, we tested if transduction of hiPSC-derived cardiomyocytes with KCNJ2, which encodes the IK1 channel, alters pharmacological response to cardiac repolarization processes...
May 27, 2017: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/28602541/connexin-43-enhances-bax-activation-via-jnk-activation-in-sunitinib-induced-apoptosis-in-mesothelioma-cells
#14
Miaki Uzu, Hiromi Sato, Ayaka Shimizu, Yukihiro Shibata, Koichi Ueno, Akihiro Hisaka
The constituent protein of gap junctions, connexin (Cx), interacts with various proteins via its C-terminus region, including kinases, cell-adhesion proteins, and a pro-apoptotic protein, Bax. This molecular interaction may affect expression and functioning of the interacting proteins and modulate the cellular physiology. In our previous work, Cx43 was found to interact directly with Bax and in the presence of sunitinib, lead to the Bax-mediated apoptosis in mesothelioma cells. In this study, we investigated the mechanism of how Cx43 promotes Bax-mediated apoptosis using the same cell line...
May 27, 2017: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/28552584/physiological-functions-of-the-cholinergic-system-in-immune-cells
#15
REVIEW
Takeshi Fujii, Masato Mashimo, Yasuhiro Moriwaki, Hidemi Misawa, Shiro Ono, Kazuhide Horiguchi, Koichiro Kawashima
T and B cells, macrophages and dendritic cells (DCs) all express most of the components necessary for a functional cholinergic system. This includes choline acetyltransferase (ChAT), muscarinic and nicotinic acetylcholine (ACh) receptors (mAChRs and nAChRs, respectively) and acetylcholinesterase (AChE). Immunological activation of T cells up-regulates cholinergic activity, including ChAT and AChE expression. Moreover, toll-like receptor agonists induce ChAT expression in DCs and macrophages, suggesting cholinergic involvement in the regulation of immune function...
May 2017: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/28532624/tyrphostin-ag-related-compounds-attenuate-h2o2-induced-trpm2-dependent-and-independent-cellular-responses
#16
Shinichiro Yamamoto, Takahiro Toda, Ryo Yonezawa, Takaharu Negoro, Shunichi Shimizu
PURPOSE: TRPM2 is a Ca(2+)-permeable channel that is activated by H2O2. TRPM2-mediated Ca(2+) signaling has been implicated in the aggravation of inflammatory diseases. Therefore, the development of TRPM2 inhibitors to prevent the aggravation of these diseases is expected. We recently reported that some Tyrphostin AG-related compounds inhibited the H2O2-induced activation of TRPM2 by scavenging the intracellular hydroxyl radical. In the present study, we examined the effects of AG-related compounds on H2O2-induced cellular responses in human monocytic U937 cells, which functionally express TRPM2...
May 2017: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/28522217/celastrol-inhibits-chondrosarcoma-proliferation-migration-and-invasion-through-suppression-cip2a-c-myc-signaling-pathway
#17
Jinhui Wu, Muchen Ding, Ningfang Mao, Yungang Wu, Chao Wang, Jiabin Yuan, Xiong Miao, Jingfeng Li, Zhicai Shi
Chondrosarcomas (CS) is the second most frequent tumors of cartilage origin. A small compound extracted from Thunder God Vine (Tripterygium wilfordii Hook. F.) called celastrol can directly bound CIP2A protein and effectively inhibit cell proliferation and induce apoptosis in several cancer cells. However, little knowledge is concern about the important role of CIP2A in CS patients and the therapeutic value of celastrol on CS. Our results showed that CIP2A and c-MYC were verified to be oncoproteins by detecting their mRNA and protein expression in 10 human CS tissues by qRT-PCR and Western blots...
May 2017: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/28506595/plumbagin-suppresses-the-migration-and-invasion-of-glioma-cells-via-downregulation-of-mmp-2-9-expression-and-inaction-of-pi3k-akt-signaling-pathway-in%C3%A2-vitro
#18
Guanghui Chen, Yan Yue, Jun Qin, Xinping Xiao, Qing Ren, Bin Xiao
Plumbagin is a natural naphthoquinone constituent isolated from the roots of medicinal plant Plumbago zeylanica L., and has demonstrated anti-proliferative and anti-invasion activities in various cancer cells. However, its effect on the migration and invasion of glioma cells has not been elucidated. Therefore, human glioma U87 and U251 cells were treated with plumbagin at 1.0 and 2.0 μM for 24 h, and cell migration and invasion were assessed with scratch wound healing and invasion assays. The results showed that plumbagin significantly inhibited the migration and invasion of U87 and U251 cells, suppressed the activity and expression of MMP-2/-9, and inhibited the nuclear translocation of transcription factors Sp1 in the U87 and U251 cells...
May 2017: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/28499726/inhibitory-effect-of-donepezil-on-bradykinin-induced-increase-in-the-intracellular-calcium-concentration-in-cultured-cortical-astrocytes
#19
Kouki Makitani, Shota Nakagawa, Yasuhiko Izumi, Akinori Akaike, Toshiaki Kume
Donepezil is a potent and selective acetylcholinesterase inhibitor developed for the treatment of Alzheimer's disease. In the present study, we investigated the responses of astrocytes to bradykinin, an inflammatory mediator, and the effect of donepezil on these responses using cultured cortical astrocytes. Bradykinin induced a transient increase of intracellular calcium concentration ([Ca(2+)]i) in cultured astrocytes. Bradykinin-induced [Ca(2+)]i increase was inhibited by the exposure to thapsigargin, which depletes Ca(2+) stores on endoplasmic reticulum, but not by the exclusion of extracellular Ca(2+)...
May 2017: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/28479222/effects-of-a-spleen-tyrosine-kinase-inhibitor-on-progression-of-the-lupus-nephritis-in-mice
#20
Maki Kitai, Noboru Fukuda, Takahiro Ueno, Morito Endo, Takashi Maruyama, Masanori Abe, Kazuyoshi Okada, Masayoshi Soma, Koichi Matsumoto
The Fc receptors (FcR) have pivotal roles in the pathogenesis of the autoimmune glomerulonephritis. We therefore investigated the effects of a Syk inhibitor on the progression of lupus nephritis and SH3 domain binding protein 2 and p38MAP kinase signalings in mice. NZB/W F1 mice, a model of lupus nephritis, received a Syk inhibitor R406. Western blotting and immunohistochemistry revealed that R406 treatment significantly delayed the appearance of proteinuria, histologically improved their glomerulosclerosis and inhibited the increased the expression of MCP-1 and TGF-β1 mRNAs and the nephrin and podocin proteins in the kidney...
May 2017: Journal of Pharmacological Sciences
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