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Pharmacology

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https://www.readbyqxmd.com/read/28743115/cerebrospinal-fluid-levels-of-14-3-3-gamma-what-does-it-tell-us-about-sporadic-creutzfeldt-jakob-disease
#1
Christian Humpel, Thomas Benke
Clinical diagnosis of Creutzfeldt-Jakob disease (CJD) can be supported by the analysis of Tau and 14-3-3 in the cerebrospinal fluid (CSF). In this short report, we report about a retrospective analysis performed on 2,296 routinely collected CSF samples, and 44 samples with a ratio of phosphoTau181/Tau <0.075 were selected. Analysis was performed with a novel 14-3-3 gamma CircuLex Elisa. We show that control levels were around 6,000 AU/mL and samples from Alzheimer patients were not different from those collected from healthy controls...
July 26, 2017: Pharmacology
https://www.readbyqxmd.com/read/28743107/a-prozone-like-effect-influences-the-efficacy-of-the-monoclonal-antibody-abt-700-against-the-hepatocyte-growth-factor-receptor
#2
Kedar S Vaidya, Anatol Oleksijew, Lora A Tucker, William N Pappano, Mark G Anderson, Christine M Grinnell, Qian Zhang, Sarah J Heighton, Michael J Mitten, Sasmita Mishra, Joann P Palma, Jieyi Wang, Edward B Reilly, Erwin R Boghaert
ABT-700 is a therapeutic antibody against the hepatocyte growth factor receptor (MET). At doses or regimens that lead to exposures exceeding optimum in vivo, the efficacy of ABT-700 is unexpectedly reduced. We hypothesized that this reduction in efficacy was due to a "prozone-like" effect in vivo. A prozone-like effect, which is a reduction in efficacy beyond optimum exposure, is caused due a mechanism similar to the generation of false negative flocculation tests by excessive antibody titres. In vitro, we demonstrate that at higher ABT-700 concentrations, this "prozone-like" effect is mediated by a progressive conversion from bivalent to ineffective monovalent binding of the antibody...
July 26, 2017: Pharmacology
https://www.readbyqxmd.com/read/28728159/oxamate-enhances-the-anti-inflammatory-and-insulin-sensitizing-effects-of-metformin-in-diabetic-mice
#3
Mu-Chao Wu, Wei-Ran Ye, Yi-Jia Zheng, Shan-Shan Zhang
Metformin (MET) is the first-line drug for treating type 2 diabetes mellitus (T2DM). However, MET increases blood lactate levels in patients with T2DM. Lactate possesses proinflammatory properties and causes insulin resistance (IR). Oxamate (OXA), a lactate dehydrogenase inhibitor, can decrease tissue lactate production and blood lactate levels. This study was conducted to examine the effects of the combination of OXA and MET on inflammation, and IR in diabetic db/db mice. Supplementation of OXA to MET led to lowered tissue lactate production and serum lactate levels compared to MET alone, accompanied with further decreased tissue and blood levels of pro-inflammatory cytokines, along with better insulin sensitivity, beta-cell mass, and glycemic control in diabetic db/db mice...
July 21, 2017: Pharmacology
https://www.readbyqxmd.com/read/28728150/fisher-discrimination-of-metabolic-changes-in-rats-treated-with-aspirin-and-ibuprofen
#4
Jing Zhang, Huanchun Song, Shuying Jiang, Zhibin Chen, Shuhua Tong, Feiyan Lin, Congcong Wen, Xiuhua Zhang, Lufeng Hu
BACKGROUND: Aspirin and ibuprofen are the most frequently prescribed non-steroidal anti-inflammatory drugs in the world. However, both are associated with a variety of toxicities. We applied serum metabonomics and Fisher discrimination for the early diagnosis of its toxic reaction in order to help diagnose these toxicities. METHODS: A total of 45 rats were randomly divided into Control group, Aspirin group, and Ibuprofen groups. The experiment groups were given intragastric aspirin (15 mg/kg) or ibuprofen (15 mg/kg) for 3 weeks...
July 21, 2017: Pharmacology
https://www.readbyqxmd.com/read/28723688/trigonelline-inhibits-inflammation-and-protects-%C3%AE-cells-to-prevent-fetal-growth-restriction-during-pregnancy-in-a-mouse-model-of-diabetes
#5
Ji-Yin Zhou, Xiao-Huang Du, Zuo Zhang, Gui-Sheng Qian
BACKGROUND: As an active component from traditional Chinese medicine, trigonelline has a protective effect on diabetes. This study evaluated the protective effects of trigonelline on diabetic mice during pregnancy. METHODS: Diabetes was induced in female mice by intraperitoneal injection for continuous 5-day of 40 mg/kg/day streptozotocin. Female mice were divided into 4 groups after they were allowed to mate with normal male mice: nondiabetic, nondiabetic treated with trigonelline (70 mg/kg) for 18 days, diabetic, and diabetic treated with trigonelline (70 mg/kg)...
July 20, 2017: Pharmacology
https://www.readbyqxmd.com/read/28715803/antinociceptive-effects-of-isosakuranetin-in-a-rat-model-of-peripheral-neuropathy
#6
Shushan Jia, Yong Zhang, Jingui Yu
Chronic pain remains a challenging clinical reality, yet currently available analgesics are insufficient to meet clinical needs. Increasing attention has been paid to bioactive compounds from natural plants, which may be efficacious against pain. This study examined the antinociceptive effects of isosakuranetin, a plant-derived transient receptor potential melastatin 3 blocker, in a rat model of peripheral neuropathy. Adult male Sprague-Dawley rats were first allowed to go through the chronic constriction injury surgery to develop neuropathic pain...
July 18, 2017: Pharmacology
https://www.readbyqxmd.com/read/28704834/gper-mediates-functional-endothelial-aging-in-renal-arteries
#7
Matthias R Meyer, Thomas Rosemann, Matthias Barton, Eric R Prossnitz
Aging is associated with impaired renal artery function, which is partly characterized by arterial stiffening and a reduced vasodilatory capacity due to excessive generation of reactive oxygen species by NADPH oxidases (Nox). The abundance and activity of Nox depends on basal activity of the heptahelical transmembrane receptor GPER; however, whether GPER contributes to age-dependent functional changes in renal arteries is unknown. This study investigated the effect of aging and Nox activity on renal artery tone in wild-type and GPER-deficient (Gper-/-) mice (4 and 24 months old)...
July 14, 2017: Pharmacology
https://www.readbyqxmd.com/read/28668949/naringin-reverses-neurobehavioral-and-biochemical-alterations-in-intracerebroventricular-collagenase-induced-intracerebral-hemorrhage-in-rats
#8
Navdeep Singh, Yashika Bansal, Ranjana Bhandari, Lovish Marwaha, Raghunath Singh, Kanwaljit Chopra, Anurag Kuhad
Intracerebral hemorrhage (ICH) contributes to 10-15% of all strokes and is a high risk factor for morbidity and mortality as compared to other subtypes of stroke, that is, cerebral ischemia and subarachnoid hemorrhage. Oxidative stress (OS)-induced neuroinflammation and neuronal cell death contribute towards the hallmarks of ICH. Spared antioxidant levels, increased inflammatory cytokines and free radicals in ICH lead to neuronal death and exaggerate the hallmarks of ICH. Intracerebroventricular (ICV) collagenase (COL-induced neuronal cell damage and cognitive deficits form a widely recognized experimental model for ICH...
July 1, 2017: Pharmacology
https://www.readbyqxmd.com/read/28641304/hyperemesis-gravidarum-a-review-of-recent-literature
#9
Viktoriya London, Stephanie Grube, David M Sherer, Ovadia Abulafia
BACKGROUND: In the United States, hyperemesis gravidarum is the most common cause of hospitalization during the first half of pregnancy and is second only to preterm labor for hospitalizations in pregnancy overall. In approximately 0.3-3% of pregnancies, hyperemesis gravidarum is prevalent and this percentage varies on account of different diagnostic criteria and ethnic variation in study populations. Despite extensive research in this field, the mechanism of the disease is largely unknown...
June 23, 2017: Pharmacology
https://www.readbyqxmd.com/read/28641287/chrysophanol-suppressed-glutamate-induced-hippocampal-neuronal-cell-death-via-regulation-of-dynamin-related-protein-1-dependent-mitochondrial-fission
#10
Unbin Chae, Ju-Sik Min, Hyun Hee Leem, Hyun-Shik Lee, Hong Jun Lee, Sang-Rae Lee, Dong-Seok Lee
Chrysophanic acid, or chrysophanol, is an anthraquinone found in Rheum palmatum, which was used in the preparation of oriental medicine in ancient China. The hippocampus plays a major role in controlling the activities of the short- and long-term memory. It is one of the major regions affected by excessive cell death in Alzheimer's disease. Therefore, neuronal cell-death modulation in the hippocampus is important for maintaining neuronal function. We investigated chrysophanol's effects on glutamate-induced hippocampal neuronal cell death...
June 23, 2017: Pharmacology
https://www.readbyqxmd.com/read/28637045/effects-of-injection-of-gamma-aminobutyric-acid-agonists-into-the-nucleus-accumbens-on-naloxone-induced-morphine-withdrawal
#11
Betilay Topkara, Hasan R Yananli, Eren Sakallı, Mahluga Jafarova Demirkapu
AIMS: This study was to investigate the effects of local administration of gamma-aminobutyric acid (GABA) agonists into the nucleus accumbens (NAc) on naloxone-induced morphine withdrawal symptoms. METHODS: Bilateral guide cannulas were stereotaxically implanted in the shell or core regions of the NAc of Sprague-Dawley rats. After a recovery period, 3 morphine pellets, each consisting of 75 mg morphine base, were placed subcutaneously on the first and third days of the study with the rats under mild ether anaesthesia...
June 22, 2017: Pharmacology
https://www.readbyqxmd.com/read/28637041/the-effects-of-fungicides-on-human-3%C3%AE-hydroxysteroid-dehydrogenase-1-and-aromatase-in-human-placental-cell-line-jeg-3
#12
Shuyan Cao, Leping Ye, Ying Wu, Baiping Mao, Lanlan Chen, Xiudi Wang, Ping Huang, Ying Su, Ren-Shan Ge
Placenta secretes a large amount of progesterone and estradiol, which are critical for maintaining pregnancy. In human placenta, 3β-hydroxysteroid dehydrogenase 1 (HSD3B1) catalyzes pregnenolone to form progesterone, and aromatase (CYP19A1) catalyzes testosterone into estradiol. Fungicides display antifungal activities and are widely used to prevent fungal infections in agricultural plants. These chemicals include azoles, such as tebuconazole (TEB), triadimefon (TRI), and vinclozolin (VCZ) or organotins, such as tributyltin (TBT) and tetrabutyltin (TTBT)...
June 22, 2017: Pharmacology
https://www.readbyqxmd.com/read/28637049/protecting-oligodendrocytes-by-targeting-non-glutamate-receptors-as-a-new-therapeutic-strategy-for-ischemic-stroke
#13
Pan Luo, Dong Liu, Lianjun Guo
Ischemic stroke has many devastating effects within the brain. At the cellular level, excitotoxicity has been a popular pharmacological target for therapeutics. To date, many clinical trials have been performed with drugs that target excitatory neurotransmitter receptors, such as NMDA receptor agonists. The results, however, have been lackluster. Most efforts to understand the impacts of excitotoxicity on the brain have focused primarily on neurons, and to a lesser degree, on gliocytes as cellular targets. Recent evidence suggests that oligodendrocytes (OLGs), the myelin-forming cells in the central nervous system, are damaged by ischemia in a manner completely different from that in neurons...
June 21, 2017: Pharmacology
https://www.readbyqxmd.com/read/28614821/thromboxane-formation-assay-to-identify-high-on-treatment-platelet-reactivity-to-aspirin
#14
Annemarie Mohring, Kerstin Piayda, Lisa Dannenberg, Saif Zako, Theresa Schneider, Kirsten Bartkowski, Bodo Levkau, Tobias Zeus, Malte Kelm, Thomas Hohlfeld, Amin Polzin
Platelet inhibition by aspirin is indispensable in the secondary prevention of cardiovascular events. Nevertheless, impaired aspirin antiplatelet effects (high on-treatment platelet reactivity [HTPR]) are frequent. This is associated with an enhanced risk of cardiovascular events. The current gold standard to evaluate platelet hyper-reactivity despite aspirin intake is the light-transmittance aggregometry (LTA). However, pharmacologically, the most specific test is the measurement of arachidonic acid (AA)-induced thromboxane (TX) B2 formation...
June 15, 2017: Pharmacology
https://www.readbyqxmd.com/read/28554169/neohesperidin-exerts-lipid-regulating-effects-in-vitro-and-in-vivo-via-fibroblast-growth-factor-21-and-amp-activated-protein-kinase-sirtuin-type-1-peroxisome-proliferator-activated-receptor-gamma-coactivator-1%C3%AE-signaling-axis
#15
Haoshu Wu, Yunxi Liu, Xiaobing Chen, Difeng Zhu, Jian Ma, Youyou Yan, Meimei Si, Xian Li, Chongde Sun, Bo Yang, Qiaojun He, Kunsong Chen
The purpose of this study is to prove the lipid-regulating effects of neohesperidin (NHP) and explore the potential mechanisms related to fibroblast growth factor 21 (FGF21) and AMP-activated protein kinase (AMPK). Free fatty acids (FFAs)-induced lipid-accumulated HepG2 cells, acutely egg yolk-induced dyslipidemia and chronically diet-induced obese (DIO) model mice were treated with NHP. Biochemical analyses were carried out to determine the lipid profiles. Western blotting and real-time PCR were employed to analyze FGF21, AMPK and the related proteins or mRNA expressions...
May 30, 2017: Pharmacology
https://www.readbyqxmd.com/read/28521325/effect-of-high-salt-diet-on-age-related-high-blood-pressure-and-hypothalamic-redox-signaling
#16
Bilgen Basgut, Melissa A Whidden, Nataliya Kirichenko, Mary Woods, Benedek Erdos, Philip J Scarpace, Nihal Tümer
AIM: The aim of this study was to investigate the effect of a high salt (HS) diet on age-related changes in blood pressure (BP) and the possible role played by regulatory central mechanisms. METHODS: Young (5 months) and old (27 months) male Fischer 344 × Brown Norway (F344/BN) rats were fed standard chow or 8% HS diet for 12 days. BP and heart rate (HR) were measured by telemetry. RESULTS: Mean arterial BP (MAP) was significantly elevated in old rats during the day and night when compared with young animals...
May 19, 2017: Pharmacology
https://www.readbyqxmd.com/read/28501872/a-mechanism-study-underlying-the-protective-effects-of-cyclosporine-a-on-lung-ischemia-reperfusion-injury
#17
Jian''an Li, Zhongya Yan, Qianjin Fang
AIM: This study is aimed at validating the hypothesis that administration of cyclosporine-A (CsA) would be protective in lung ischemia-reperfusion (I/R) injury and in exploring the underlying mechanism. METHODS: Rabbits were divided into 4 groups: the control, sham operation, I/R, and I/R with CsA treatment. Flow cytometry was used to measure the mitochondrial membrane potential. Laser scanning confocal microscope was used to analyze mitochondrion permeability transition pore (MPTP)...
2017: Pharmacology
https://www.readbyqxmd.com/read/28494454/acceleration-of-apoptosis-by-extracellular-basic-ph-in-a-3d-human-skin-equivalent-system
#18
Gunhyuk Park, Dal-Seok Oh, Yong-Ung Kim, Moon Ki Park
Previously, we have shown that extracellular basic pH plays a significant role in both the direct and indirect regulation of cellular processes in a wound; this in turn affects the wound-healing process. Several studies have demonstrated the importance of apoptosis modulation in the wound-healing process, especially in removing inflammatory cells and in inhibiting scar formation. However, the effects of extracellular basic pH on wound healing-related skin damage are yet to be examined. Therefore, we investigated the induction of accelerated apoptosis by extracellular basic pH in skin...
2017: Pharmacology
https://www.readbyqxmd.com/read/28494448/effects-of-cyp2c19-variants-on-fluoxetine-metabolism-in-vitro
#19
Ping Fang, Jia-Yang He, Ai-Xia Han, Tian Lan, Da-Peng Dai, Jian-Ping Cai, Guo-Xin Hu
AIMS: CYP2C19 is an important member of the cytochrome P450 enzyme superfamily. We recently identified 31 CYP2C19 alleles in the Han Chinese population. The aim of this study was to assess the catalytic activities of these allelic isoforms and their effects on the metabolism of fluoxetine in vitro. METHODS: The wild-type and 30 CYP2C19 variants were expressed in insect cells and each variant was characterized using fluoxetine as the substrate. Reactions were performed at 37°C with 20-1,000 µmol/L substrate for 30 min...
2017: Pharmacology
https://www.readbyqxmd.com/read/28486232/osthole-a-coumadin-analog-from-cnidium-monnieri-l-cusson-ameliorates-nucleus-pulposus-induced-radicular-inflammatory-pain-by-inhibiting-the-activation-of-extracellular-signal-regulated-kinase-in-rats
#20
Hai-Xuan Wu, Yi-Min Wang, Hui Xu, Ming Wei, Qiu-Lan He, Mei-Na Li, Lai-Bao Sun, Ming-Hui Cao
AIM: This study was aimed at assessing the role of extracellular signal regulated kinase (ERK) in mechanical allodynia resulting from lumbar disc herniation (LDH) and exploring the osthole's anti-nociceptive effect on ERK activation. METHODS: Radicular pain was generated by applying nucleus pulposus (NP) to the L5 dorsal root ganglion (DRG). Allodynia was measured using Von Frey filaments to calculate the mechanical pain threshold. Phosphorylated ERK and total ERK protein in the lumbar spinal dorsal horn was detected by using the Western blot technique...
2017: Pharmacology
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