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https://www.readbyqxmd.com/read/28351019/online-microdialysis-ultra-performance-liquid-chromatography-mass-spectrometry-method-for-comparative-pharmacokinetic-investigation-on-iridoids-from-gardenia-jasminoides-ellis-in-rats-with-different-progressions-of-type-2-diabetic-complications
#1
Xueju Zhang, Lu Wang, Zhong Zheng, Zifeng Pi, Zhiqiang Liu, Fengrui Song
Iridoid glycosides consist the main bioactive constituents of Gardenia jasminoides Ellis (G. jasminoides), which is used alone or in combination with other medicine herbs for treatment of diabetes mellitus in China. This paper investigated for the first time comparative pharmacokinetics (PKs) of four unbound iridoids (including genipin, geniposide, gardenoside and geniposidic acid) in rat blood between healthy and type 2 diabetic groups with different disease progressions (9 or 13 weeks). Online microdialysis-ultra performance liquid chromatography-mass spectrometry (MD- UPLC-MS/MS) method was used after oral administration of iridoid extracts obtained from the fruits of G...
March 21, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/28350999/discovery-of-novel-1-2-3-4-tetrahydrobenzo-4-5-thieno-2-3-c-pyridine-derivatives-as-potent-and-selective-cyp17-inhibitors
#2
Mingliang Wang, Yanjia Fang, Shoulai Gu, Fangfang Chen, Zhengjiang Zhu, Xun Sun, Jidong Zhu
The inhibition of CYP17 to block androgen biosynthesis is a well validated strategy for the treatment of prostate cancer. Herein we reported the design, synthesis and structure-activity relationship (SAR) study for a series of novel 1,2,3,4- tetrahydrobenzo[4,5]thieno[2,3-c]pyridine derivatives. Some analogs demonstrated a potent inhibition to both rat and human CYP17 protein and reduced testosterone production in human H295R cell line. Some analogs also showed high selectivity against other CYP enzymes such as 3A4, 1A2, 2C9, 2C19 and 2D6, which may limit side effects due to drug-drug interactions...
March 21, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28350969/mechanisms-of-spontaneous-pacing-sa-nodal-cells-neonatal-cardiomyocytes-and-human-stem-cell-derived-cardiomyocytes
#3
Martin Morad, Xiaohua Zhang
The sino-atrial node is the primary site from which the mammalian heart is paced, but the mechanisms underlying the pacemaking still remain clouded. It is generally believed that the hyperpolarization-activated current I<sub><i>f</i></sub>, encoded by Hyperpolarization-activated cyclic nucleotide-gated (HCN) genes, contributes significantly to pacing, which in tandem with inward current generated by efflux of Ca<sup>2+</sup> via the Na<sup>+</sup>-Ca<sup>2+</sup> exchanger (NCX), resulting from the released Ca<sup>2+</sup>, mediates the diastolic depolarization...
March 28, 2017: Canadian Journal of Physiology and Pharmacology
https://www.readbyqxmd.com/read/28350967/molecular-hydrogen-potentiates-beneficial-anti-infarct-effect-of-hypoxic-postconditioning-in-isolated-rat-hearts-novel-cardioprotective-intervention
#4
Marek Zálešák, Branislav Kura, Ján Graban, Veronika Ledvényiová-Farkašová, Jan Slezak, Tatiana Ravingerova
Generation of free radicals through incomplete reduction of oxygen during ischemia/ reperfusion is well-described. On the other hand, molecular hydrogen (H<sub>2</sub>) reduces oxidative stress due to its ability to react with strong oxidants and easily penetrate cells by diffusion, without disturbing metabolic redox reactions. This study was designed to explore cardioprotective potential of hypoxic postconditioning (HpostC) against ischemia/reperfusion (30-min global I/120-min R) in isolated rat hearts using oxygen-free Krebs-Henseleit buffer (KHB)...
March 28, 2017: Canadian Journal of Physiology and Pharmacology
https://www.readbyqxmd.com/read/28350885/glutamate-dependent-ectodomain-shedding-of-neuregulin-1-type-ii-precursors-in-rat-forebrain-neurons
#5
Yuriko Iwakura, Ran Wang, Naoko Inamura, Kazuaki Araki, Shigeki Higashiyama, Nobuyuki Takei, Hiroyuki Nawa
The neurotrophic factor neuregulin 1 (NRG1) regulates neuronal development, glial differentiation, and excitatory synapse maturation. NRG1 is synthesized as a membrane-anchored precursor and is then liberated by proteolytic processing or exocytosis. Mature NRG1 then binds to its receptors expressed by neighboring neurons or glial cells. However, the molecular mechanisms that govern this process in the nervous system are not defined in detail. Here we prepared neuron-enriched and glia-enriched cultures from embryonic rat neocortex to investigate the role of neurotransmitters that regulate the liberation/release of NRG1 from the membrane of neurons or glial cells...
2017: PloS One
https://www.readbyqxmd.com/read/28350848/reduction-of-oxidative-nitrosative-stress-underlies-anticataract-effect-of-topically-applied-tocotrienol-in-streptozotocin-induced-diabetic-rats
#6
Nurul Alimah Abdul Nasir, Renu Agarwal, Siti Hamimah Sheikh Abdul Kadir, Sushil Vasudevan, Minaketan Tripathy, Igor Iezhitsa, Aqil Mohammad Daher, Mohd Ikraam Ibrahim, Nafeeza Mohd Ismail
Cataract, a leading cause of blindness, is of special concern in diabetics as it occurs at earlier onset. Polyol accumulation and increased oxidative-nitrosative stress in cataractogenesis are associated with NFκB activation, iNOS expression, ATP depletion, loss of ATPase functions, calpain activation and proteolysis of soluble to insoluble proteins. Tocotrienol was previously shown to reduce lens oxidative stress and inhibit cataractogenesis in galactose-fed rats. In current study, we investigated anticataract effects of topical tocotrienol and possible mechanisms involved in streptozotocin-induced diabetic rats...
2017: PloS One
https://www.readbyqxmd.com/read/28350842/combination-of-mesenchymal-stem-cell-injection-with-icariin-for-the-treatment-of-diabetes-associated-erectile-dysfunction
#7
Xiyou Wang, Chuanhai Liu, Yong Xu, Ping Chen, Yue Shen, Yansheng Xu, Yubo Zhao, Weihao Chen, Xinyu Zhang, Yun Ouyang, Yi Wang, Changliang Xie, Maojun Zhou, Cuilong Liu
The present study was aimed to examine whether icariin, a traditional Chinese medicine, could improve therapeutic effects of adipose derived mesenchymal stem cells (ADSCs) for diabetes-associated erectile dysfunction (DMED). DMED were induced in rats by intraperitoneal injection of streptozotocin and confirmed by erectile function measurement. Then, rats of diabetic ED were randomly divided to receive the treatment of saline, ADSCs, icariin or ADSCs combined with icariin respectively. Compared with the treatment by ADSCs or icariin alone, intracavernosum injection of ADSCs combined with the following daily gastric gavage of icariin significantly augmented the value of ICP and ICP/MAP (p<0...
2017: PloS One
https://www.readbyqxmd.com/read/28350818/effects-and-mechanisms-of-auricular-electroacupuncture-on-gastric-hypersensitivity-in-a-rodent-model-of-functional-dyspepsia
#8
Jingzhu Zhou, Shiying Li, Yinping Wang, Yong Lei, Robert D Foreman, Jieyun Yin, Jiande D Z Chen
BACKGROUND: Functional dyspepsia (FD) is a common functional gastrointestinal disease, and abdominal pain is one of the main symptoms. The aim of this study was to explore the effects and mechanisms of auricular electro-acupuncture (AEA) on gastric hypersensitivity in a rodent model of FD. METHODS: Ten-day-old pups were gavaged with 0.2 ml of 0.1% iodoacetamide daily for 6 days. AEA at the "stomach" point with different parameters or sham-EA was performed on 8-week-old animals...
2017: PloS One
https://www.readbyqxmd.com/read/28350760/involvement-of-hsp70-and-ho-1-in-the-protective-effects-of-raloxifene-on-multiple-organ-dysfunction-syndrome-by-endotoxemia-in-ovariectomized-rats
#9
Hsin-Hsueh Shen, Shieh-Yang Huang, Pao-Yun Cheng, Yen-Ju Chu, Shu-Ying Chen, Kwok-Keung Lam, Yen-Mei Lee
OBJECTIVE: Accumulating evidence demonstrates that raloxifene, a selective estrogen receptor modulator, possesses anti-inflammatory action. This study evaluates the preventive effects of long-term treatment of raloxifene on acute inflammation and multiple organ dysfunction syndrome (MODS) in ovariectomized (OVX) rats with endotoxemia and its underlying mechanism of action. METHODS: Adult female rats were OVX bilaterally to induce estrogen insufficiency. OVX rats were administered with raloxifene (1 mg/kg, gavage, once daily) for 8 weeks, beginning 1 week after surgery, followed by induction of sepsis via intravenous infusion of lipopolysaccharides (LPS; 30 mg/kg) for 4 hours...
March 27, 2017: Menopause: the Journal of the North American Menopause Society
https://www.readbyqxmd.com/read/28350536/anti-inflammatory-effects-and-anti-oxidant-capacity-of-myrathius-arboreus-cecropiaceae-in-experimental-models
#10
Oluwafemi Gabriel Oluwole, Olufunmilayo Ologe, Akinyinka Alabi, Ganiyu Tunde Yusuf, Solomon Umukoro
BACKGROUND: Inflammation is involved in various diseases; search for safe treatments is warranted. Anti-inflammatory effects of ethanol extract of Myrathius arboreus (EEMa) were studied in carrageenan-induced model, formaldehyde sub-acute-induced model, and in 48 h lipopolysaccharide-induced air pouch model of inflammation. EEMa membrane-stabilizing activities and anti-oxidant capacity were determined in vitro. METHODS: In the carrageenan model EEMa (125, 250, or 500 mg/kg), indomethacin (5 mg/kg), or vehicle 3 mL/kg was administered orally in rats (n=5)...
March 28, 2017: Journal of Basic and Clinical Physiology and Pharmacology
https://www.readbyqxmd.com/read/28346885/plasma-and-brain-pharmacokinetics-of-ganoderic-acid-a-in-rats-determined-by-a-developed-uflc-ms-ms-method
#11
Fang-Rui Cao, Bing-Xin Xiao, Li-Sha Wang, Xue Tao, Ming-Zhu Yan, Rui-Le Pan, Yong-Hong Liao, Xin-Min Liu, Qi Chang
Ganoderic acid A (GAA), an active triterpenoid of the traditional Chinese herbal medicine Lingzhi, has been reported to exhibit antinociceptive, antioxidative, and anti-cancer activities. The present study aims to establish a sensitive and rapid UPLC-MS/MS method for studying the plasma and brain pharmacokinetics of GAA in rats. The analytes were separated on a C18 column eluted with a gradient mobile phase consisting of acetonitrile and 0.1% aqueous formic acid at 0.3mL/min. The eluate was monitored by a mass detector using an MRM (m/z, 515...
March 11, 2017: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
https://www.readbyqxmd.com/read/28346882/determination-of-prodrug-treosulfan-and-its-biologically-active-monoepoxide-in-rat-plasma-liver-lungs-kidneys-muscle-and-brain-by-hplc-esi-ms-ms-method
#12
Michał Romański, Anna Kasprzyk, Artur Teżyk, Agnieszka Widerowska, Czesław Żaba, Franciszek Główka
A prodrug treosulfan (TREO) is currently investigated in clinical trials for conditioning prior to hematopoietic stem cell transplantation. Bioanalysis of TREO and its active derivatives, monoepoxide (S,S-EBDM) and diepoxide, in plasma and urine underlay the pharmacokinetic studies of these compounds but cannot explain an organ pharmacological action or toxicity. Recently, distribution of TREO and S,S-EBDM into brain, cerebrospinal fluid, and aqueous humor of the eye has been investigated in animal models and the obtained results presented clinical relevance...
March 18, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/28346814/nicotinamide-riboside-a-form-of-vitamin-b3-and-nad-precursor-relieves-the-nociceptive-and-aversive-dimensions-of-paclitaxel-induced-peripheral-neuropathy-in-female-rats
#13
Marta V Hamity, Stephanie R White, Roxanne Y Walder, Mark S Schmidt, Charles Brenner, Donna L Hammond
Injury to sensory afferents may contribute to the peripheral neuropathies that develop after administration of chemotherapeutic agents. Manipulations that increase levels of nicotinamide adenine dinucleotide (NAD) can protect against neuronal injury. This study examined whether nicotinamide riboside (NR), a third form of vitamin B3 and precursor of NAD, diminishes tactile hypersensitivity and place escape-avoidance behaviors in a rodent model of paclitaxel-induced peripheral neuropathy. Female Sprague-Dawley rats received 3 intravenous injections of 6...
January 30, 2017: Pain
https://www.readbyqxmd.com/read/28346718/modulation-of-the-rat-micturition-reflex-with-transcutaneous-ultrasound
#14
Daniel P Casella, Anne G Dudley, Douglass B Clayton, John C Pope, Stacy T Tanaka, John Thomas, Mark C Adams, John W Brock, Charles F Caskey
INTRODUCTION: Low intensity focused ultrasound has recently been identified as a novel method of stimulating targeted neurons. We hypothesized that ultrasound stimulation of the posterior tibial nerve would inhibit bladder contractions in an established rat model of rhythmic bladder contractions. METHODS: Cyclical detrusor contractions were initiated by placing a transurethral catheter in female rats and infusing saline into the bladder. Transcutaneous ultrasound pulses were then delivered to the lower extremity of a rat (overlying the posterior tibial nerve) using a single element spherically focused 250 kHz transducer...
March 27, 2017: Neurourology and Urodynamics
https://www.readbyqxmd.com/read/28346707/periurethral-muscle-derived-mononuclear-cell-injection-improves-urethral-sphincter-restoration-in-rats
#15
Marcelo Pitelli Turco, Alex Balduino de Souza, Isida de Campos Sousa, Paula Fratini, Mariana Matera Veras, Marcio Nogueira Rodrigues, José de Bessa, Marina Pandolphi Brolio, Katia Ramos Moreira Leite, Homero Bruschini, Miguel Srougi, Maria Angélica Miglino, Cristiano Mendes Gomes
AIMS: Investigate the effect of a novel cell-based therapy with skeletal muscle-derived mononuclear cells (SMDMCs) in a rat model of stress urinary incontinence. METHODS: Male Wistar-Kyoto rats' hind limb muscles were enzymatically dissociated, and SMDMCs were isolated without needing expansion. The cell population was characterized. Twenty female rats underwent urethrolysis. One week later, 10 rats received periurethral injection of 10(6) cells (SMDMC group), and 10 rats received saline injections (Saline group)...
March 27, 2017: Neurourology and Urodynamics
https://www.readbyqxmd.com/read/28346613/protective-effect-of-met12-a-small-peptide-inhibitor-of-fas-on-the-retinal-pigment-epithelium-and-photoreceptor-after-sodium-iodate-injury
#16
Jianhui Xiao, Jingyu Yao, Lin Jia, Chengmao Lin, David N Zacks
Purpose: A major problem in macular degeneration is the inability to reduce RPE and photoreceptor death. These cells die by necroptosis and apoptosis, respectively, but the upstream activator(s) of these death pathways is unknown. In this study, we use the sodium iodate (NaIO3) model of oxidative stress to test the hypothesis that activation of the Fas receptor contributes to the death of the RPE and photoreceptors. Methods: Sodium iodate was injected in Brown-Norway rats via femoral vein injection...
March 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28346523/a-moderate-diet-restriction-during-pregnancy-alters-the-levels-of-endocannabinoids-and-endocannabinoid-related-lipids-in-the-hypothalamus-hippocampus-and-olfactory-bulb-of-rat-offspring-in-a-sex-specific-manner
#17
María Teresa Ramírez-López, Mariam Vázquez, Ermelinda Lomazzo, Clementine Hofmann, Rosario Noemi Blanco, Francisco Alén, María Antón, Juan Decara, Rocío Arco, Laura Orio, Juan Suárez, Beat Lutz, Raquel Gómez de Heras, Laura Bindila, Fernando Rodríguez de Fonseca
Undernutrition during pregnancy has been associated to increased vulnerability to develop metabolic and behavior alterations later in life. The endocannabinoid system might play an important role in these processes. Therefore, we investigated the effects of a moderate maternal calorie-restricted diet on the levels of the endocannabinoid 2-arachidonoyl glycerol (2-AG), arachidonic acid (AA) and the N-acylethanolamines (NAEs) anandamide (AEA), oleoylethanolamide (OEA) and palmitoylethanolamide (PEA) in the brain of newborn rat offspring...
2017: PloS One
https://www.readbyqxmd.com/read/28346520/downregulation-of-mir-139-5p-contributes-to-the-antiapoptotic-effect-of-liraglutide-on-the-diabetic-rat-pancreas-and-ins-1-cells-by-targeting-irs1
#18
Jin Li, Lei Su, Ying-Ying Gong, Mei-Lin Ding, Shu-Bin Hong, Shuang Yu, Hai-Peng Xiao
Liraglutide is administered as glucagon-like peptide-1 (GLP-1) receptor agonist for diabetic patients and can protect pancreatic β-cells by inhibiting their apoptosis. MicroRNA-139-5p (miRNA-139-5p) participates in the regulation of cancer cell apoptosis. However, it is not clear whether miR-139-5p contributes to the anti-apoptotic effect of liraglutide in β-cells. The objective of the present study was to investigate the role of miR-139-5p on apoptosis of pancreatic β-cells. MicroRNA levels in pancreatic tissue from diabetic rats and INS-1 cells treated with liraglutide were measured by real-time quantitative RT-PCR...
2017: PloS One
https://www.readbyqxmd.com/read/28346482/24s-hydroxycholesterol-and-25-hydroxycholesterol-differentially-impact-hippocampal-neuronal-survival-following-oxygen-glucose-deprivation
#19
Min-Yu Sun, Amanda Taylor, Charles F Zorumski, Steven Mennerick
N-methyl-D-aspartate receptors (NMDARs), a major subtype of glutamate receptor mediating excitatory transmission throughout the CNS, participate in ischemia-induced neuronal death. Unfortunately, undesired side effects have limited the strategy of inhibiting/blocking NMDARs as therapy. Targeting endogenous positive allosteric modulators of NMDAR function may offer a strategy with fewer downsides. Here, we explored whether 24S-hydroxycholesterol (24S-HC), an endogenous positive NMDAR modulator characterized recently by our group, participates in NMDAR-mediated excitotoxicity following oxygen-glucose deprivation (OGD) in primary neuron cultures...
2017: PloS One
https://www.readbyqxmd.com/read/28346435/aav9-mediated-engineering-of-autotransplanted-kidney-of-non-human-primates
#20
S Tomasoni, P Trionfini, N Azzollini, L Zentilin, M Giacca, S Aiello, L Longaretti, E Cozzi, N Baldan, G Remuzzi, A Benigni
Ex vivo gene transfer to the graft before transplantation is an attractive option for circumventing systemic side effects of chronic anti-rejection therapy. Gene delivery of the immunomodulatory protein CTLA4-Ig prevented chronic kidney rejection in a rat model of allotransplantation without the need for systemic immunosuppression. Here, we generated AAV2 and AAV9 vectors encoding for LEA29Y, an optimized version of CTLA4-Ig. Both LEA29Y vectors were equally efficient for reducing T-cell proliferation in vitro...
March 27, 2017: Gene Therapy
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