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https://www.readbyqxmd.com/read/28527325/dyslipidemia-management-update
#1
REVIEW
Yingzi Chang, Jacques Robidoux
Association of hypercholesterolemia and atherosclerotic cardiovascular disease (ASCVD) is well established. Reducing low-density lipoprotein-cholesterol (LDL-C) and raising high-density lipoprotein-cholesterol (HDL-C) have been the therapeutic targets to reduce the risk of ASCVD. Cholesterol-lowering medications have been used to provide both primary and secondary prevention of ASCVD for many years by reducing the absorption and reabsorption, promoting excretion, or decreasing the synthesis of cholesterol. Within the past five years, several new classes of cholesterol-lowering drugs have been tested and approved for patients with hypercholesterolemia that are not well controlled by conventional therapy (ezetimibe, bile-acid sequestrants, and statins)...
May 17, 2017: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/28527154/structure-based-classification-for-bile-salt-export-pump-bsep-inhibitors-using-comparative-structural-modeling-of-human-bsep
#2
Sankalp Jain, Melanie Grandits, Lars Richter, Gerhard F Ecker
The bile salt export pump (BSEP) actively transports conjugated monovalent bile acids from the hepatocytes into the bile. This facilitates the formation of micelles and promotes digestion and absorption of dietary fat. Inhibition of BSEP leads to decreased bile flow and accumulation of cytotoxic bile salts in the liver. A number of compounds have been identified to interact with BSEP, which results in drug-induced cholestasis or liver injury. Therefore, in silico approaches for flagging compounds as potential BSEP inhibitors would be of high value in the early stage of the drug discovery pipeline...
May 19, 2017: Journal of Computer-aided Molecular Design
https://www.readbyqxmd.com/read/28526928/exosomes-in-cardiovascular-medicine
#3
REVIEW
Iain M Dykes
Exosomes are small, extracellular membrane-bound particles that mediate intercellular transport of a cytosolic cargo. Exosomal transfer of micro-RNA can modify gene expression in targeted cells. Exosome-based endocrine/paracrine signaling has been shown to be involved in a wide range of physiological processes including those associated with cardiovascular injury and disease, but remains relatively poorly understood. Exosomes offer great potential to the clinical field, with applications in both diagnostics and therapeutics...
May 19, 2017: Cardiology and Therapy
https://www.readbyqxmd.com/read/28526884/combined-use-of-metformin-and-atorvastatin-attenuates-atherosclerosis-in-rabbits-fed-a-high-cholesterol-diet
#4
Fei Luo, Yuan Guo, Gui-Yun Ruan, Jun-Ke Long, Xi-Long Zheng, Qin Xia, Shui-Ping Zhao, Dao-Quan Peng, Zhen-Fei Fang, Xiang-Ping Li
Statins are widely used to reduce cardiovascular risk. Unfortunately, some patients still experience cardiovascular events though prescribed with high-intensity statins. Metformin, an anti-diabetic drug, was reported to possess anti-atherosclerotic effects. Therefore, the experiments were designed to evaluate whether combined use of metformin and atorvastatin can achieve additional benefits. In rabbits fed a high-cholesterol diet, we evaluated the effects of the combination therapy on atherosclerotic plaques, lipid profiles, blood glucose levels, liver and kidney functions...
May 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28526628/heparin-based-hydrogels-induce-human-renal-tubulogenesis-in-vitro
#5
Heather M Weber, Mikhail V Tsurkan, Valentina Magno, Uwe Freudenberg, Carsten Werner
Dialysis or kidney transplantation is the only therapeutic option for end stage renal disease. Accordingly, there is a large unmet clinical need for new causative therapeutic treatments. Obtaining robust models that mimic the complex nature of the human kidney is a critical step in the development of new therapeutic strategies. Here we establish a synthetic in vitro human renal tubulogenesis model based on a tunable glycosaminoglycan-hydrogel platform. In this system, renal tubulogenesis can be modulated by the adjustment of hydrogel mechanics and degradability, growth factor signaling, and the presence of insoluble adhesion cues, potentially providing new insights for regenerative therapy...
May 16, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28526555/modeling-psychomotor-retardation-using-ipscs-from-mct8-deficient-patients-indicates-a-prominent-role-for-the-blood-brain-barrier
#6
Gad D Vatine, Abraham Al-Ahmad, Bianca K Barriga, Soshana Svendsen, Ariel Salim, Leslie Garcia, Veronica J Garcia, Ritchie Ho, Nur Yucer, Tongcheng Qian, Ryan G Lim, Jie Wu, Leslie M Thompson, Weston R Spivia, Zhaohui Chen, Jennifer Van Eyk, Sean P Palecek, Samuel Refetoff, Eric V Shusta, Clive N Svendsen
Inactivating mutations in the thyroid hormone (TH) transporter Monocarboxylate transporter 8 (MCT8) cause severe psychomotor retardation in children. Animal models do not reflect the biology of the human disease. Using patient-specific induced pluripotent stem cells (iPSCs), we generated MCT8-deficient neural cells that showed normal TH-dependent neuronal properties and maturation. However, the blood-brain barrier (BBB) controls TH entry into the brain, and reduced TH availability to neural cells could instead underlie the diseased phenotype...
May 8, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/28526540/sodium-dependent-glucose-transporters-sglt-in-human-ischemic-heart-a-new-potential-pharmacological-target
#7
Alessandra Di Franco, Giulia Cantini, Alessia Tani, Raffaele Coppini, Sandra Zecchi-Orlandini, Laura Raimondi, Michaela Luconi, Edoardo Mannucci
BACKGROUND: Empagliflozin is reported to reduce cardiovascular mortality and the rate of hospitalization for heart failure in type 2 diabetic patients with prior cardiovascular events. The mechanisms underlying the cardiac effects of this sodium/glucose transporter 2 (SGT2) inhibitor have not yet been clarified, though a direct action of the drug on the cardiomyocytes could be hypothesized. The aim of the present study is to assess the relative expression of SGLT2 and SGLT1, the two most relevant members of the SGLT family being potentially responsive to empagliflozin, in normal, ischemic and hypertrophic human hearts...
May 9, 2017: International Journal of Cardiology
https://www.readbyqxmd.com/read/28526195/alteration-of-human-serum-albumin-binding-properties-induced-by-modifications-a-review
#8
Małgorzata Maciążek-Jurczyk, Agnieszka Szkudlarek, Mariola Chudzik, Jadwiga Pożycka, Anna Sułkowska
Albumin, a major transporting protein in the blood, is the main target of modification that affects the binding of drugs to Sudlow's site I and II. These modification of serum protein moderates its physiological function, and works as a biomarker of some diseases. The main goal of the paper was to explain the possible alteration of human serum albumin binding properties induced by modifications such as glycation, oxidation and ageing, their origin, methods of evaluation and positive and negative meaning described by significant researchers...
May 10, 2017: Spectrochimica Acta. Part A, Molecular and Biomolecular Spectroscopy
https://www.readbyqxmd.com/read/28526150/pharmacogenomics-in-pain-management
#9
REVIEW
Ramsey Saba, Alan D Kaye, Richard D Urman
There is interpatient variability to analgesic administration. Much can be traced to pharmacogenomics variations between individuals. Certain ethnicities are more prone to reduced function of CYP2D6. Weak opioids are subject to interpatient variation based on their CYP2D6 type. Strong opioids have variations based on their transport and individual metabolism. Several cytochrome enzymes have been found to be involved with ketamine but there is no strong evidence of individual polymorphisms manifesting in clinical outcomes...
June 2017: Anesthesiology Clinics
https://www.readbyqxmd.com/read/28525795/the-role-of-secretory-phospholipases-as-therapeutic-targets-for-the-treatment-of-myocardial-ischemia-reperfusion-injury
#10
REVIEW
Sriram Ravindran, Gino A Kurian
Myocardial reperfusion injury is a consequence of restoration of blood flow post ischemia. It is a complex process involving an acute inflammatory response activated by cytokines, chemokines, growth factors, and mediated by free radicals, calcium overload leading to mitochondrial dysfunction. Secretory phospholipases (sPLA2) are a group of pro-inflammatory molecules associated with diseases such as atherosclerosis, which increase the risk of reperfusion injury. This acute response leads to breakdown of phospholipids such as cardiolipin, found in the mitochondrial inner membrane, leading to disruption of energy producing enzymes of the electron transport chain...
May 16, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28524836/effect-of-histone-deacetylase-inhibition-on-the-expression-of-multidrug-resistance-associated-protein-2-in-a-human-placental-trophoblast-cell-line
#11
Hong-Yu Duan, Dan Ma, Kai-Yu Zhou, Tao Wang, Yi Zhang, Yi-Fei Li, Jin-Lin Wu, Yi-Min Hua, Chuan Wang
BACKGROUND: Placental multidrug resistance-associated protein 2 (MRP2), encoded by ABCC2 gene in human, plays a significant role in regulating drugs' transplacental transfer rates. Studies on placental MRP2 regulation could provide more therapeutic targets for individualized and safe pharmacotherapy during pregnancy. Currently, the roles of epigenetic mechanisms in regulating placental drug transporters are still unclear. This study aimed to investigate the effect of histone deacetylases (HDACs) inhibition on MRP2 expression in the placental trophoblast cell line and to explore whether HDAC1/2/3 are preliminarily involved in this process...
June 5, 2017: Chinese Medical Journal
https://www.readbyqxmd.com/read/28524801/association-of-ugt2b7-ugt1a9-abcg2-and-il23r-polymorphisms-with-rejection-risk-in-kidney-transplant-patients
#12
Heloísa Lizotti Cilião, Rossana Batista Oliveira Camargo-Godoy, Marilesia Ferreira de Souza, Mariana Bisarro Dos Reis, Lorena Iastrenski, Vinicius Daher Alvares Delfino, Silvia Regina Rogatto, Ilce Mara de Syllos Cólus
Despite advances in testing compatibility between donor and recipient, graft rejection remains a current concern. Single-nucleotide polymorphisms (SNPs) that codify altered enzymes of metabolism, drug transport, and the immune system may contribute to graft rejection in transplant patients. This study examined the association between SNPs present in genes of these processes and occurrence of graft rejection episodes in 246 kidney transplant patients, 35% of which were diagnosed with rejection. Genotype-gene expression associations were also assessed...
May 19, 2017: Journal of Toxicology and Environmental Health. Part A
https://www.readbyqxmd.com/read/28524363/donor-transmitted-mutation-of-the-abcb11-gene-and-ensuing-intra-hepatic-cholestasis-of-pregnancy-in-a-liver-transplant-recipient
#13
Tiong Yeng Lim, Iona Coltart, Pierre Foskett, Richard Thompson, Sandra Strautnieks, Leonie Penna, Catherine Williamson, Rosa Miquel, Michael A Heneghan
In liver transplant (LT) recipients, the cause of graft dysfunction in pregnancy is often difficult to ascertain. Moreover, a liver biopsy in late pregnancy is often avoided as a consequence of patient and physician factors. Management of graft dysfunction can be difficult in this setting. We report a 30-year-old female LT recipient who developed acutely deranged liver biochemistry during the third trimester of her first pregnancy. At 29 weeks gestation, her liver function test (LFT) became abnormal; AST peaked at 978 IU/L (normal range 10-50), GGT 25 IU/L (normal range 1-55), bilirubin 1...
May 19, 2017: Liver Transplantation
https://www.readbyqxmd.com/read/28524209/understanding-the-biomimetic-properties-of-gallium-in-pseudomonas-aeruginosa-an-xas-and-xps-study
#14
F Porcaro, C Bonchi, A Ugolini, E Frangipani, G Polzonetti, P Visca, C Meneghini, C Battocchio
Pyochelin (PCH) is a siderophore (extracellular chelator) produced by the pathogenic bacterium Pseudomonas aeruginosa (PAO). PCH is implicated in iron (Fe(3+)) transport to PAO, and is crucial for its metabolism and pathogenicity. Due to the chemical similarity with Fe(3+), gallium (Ga(3+)) interferes with vital iron-dependent processes in bacterial cells, thereby opening new perspectives for the design of specific metal-based antibacterial drugs. However, the structural basis for the Fe(3+)-mimetic properties of Ga(3+) complexed with the PCH siderophore is still lacking...
May 19, 2017: Dalton Transactions: An International Journal of Inorganic Chemistry
https://www.readbyqxmd.com/read/28523998/uncovering-drug-mechanism-of-action-by-proteome-wide-identification-of-drug-binding-proteins
#15
Tao Cui, Hai Hou, Yao Sun, Huaixing Cang, Xiangxi Wang
Small molecule drugs obtained from synthetic compounds or natural products show their therapeutic effects by specifically binding to one or a few target proteins and modulating their functions. In contrast, undesirable drug-protein interactions may provoke harmful side effects. Furthermore, drug-protein interactions also play roles in drug activation, transport, metabolism and regulation of drug resistance. Therefore, systematically identifying binding proteins of a drug molecule is critical for understanding the mechanism of action of the drug at molecular level...
May 18, 2017: Medicinal Chemistry
https://www.readbyqxmd.com/read/28522903/oxidative-stress-antioxidants-and-intestinal-calcium-absorption
#16
REVIEW
Gabriela Diaz de Barboza, Solange Guizzardi, Luciana Moine, Nori Tolosa de Talamoni
The disequilibrium between the production of reactive oxygen (ROS) and nitrogen (RNS) species and their elimination by protective mechanisms leads to oxidative stress. Mitochondria are the main source of ROS as by-products of electron transport chain. Most of the time the intestine responds adequately against the oxidative stress, but with aging or under conditions that exacerbate the ROS and/or RNS production, the defenses are not enough and contribute to developing intestinal pathologies. The endogenous antioxidant defense system in gut includes glutathione (GSH) and GSH-dependent enzymes as major components...
April 28, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28522450/lower-risk-of-heart-failure-and-death-in-patients-initiated-on-sglt-2-inhibitors-versus-other-glucose-lowering-drugs-the-cvd-real-study
#17
Mikhail Kosiborod, Matthew A Cavender, Alex Z Fu, John P Wilding, Kamlesh Khunti, Reinhard W Holl, Anna Norhammar, Kåre I Birkeland, Marit Jørgensen, Marcus Thuresson, Niki Arya, Johan Bodegård, Niklas Hammar, Peter Fenici
Background -Reduction in cardiovascular death and hospitalization for heart failure (HHF) was recently reported with the sodium-glucose co-transporter-2 inhibitor (SGLT-2i) empagliflozin in type 2 diabetes patients with atherosclerotic cardiovascular disease. We compared HHF and death in patients newly initiated on any SGLT-2i versus other glucose lowering drugs (oGLDs) in six countries to determine if these benefits are seen in real-world practice, and across SGLT-2i class. Methods -Data were collected via medical claims, primary care/hospital records and national registries from the US, Norway, Denmark, Sweden, Germany and the UK...
May 18, 2017: Circulation
https://www.readbyqxmd.com/read/28521306/visible-light-sensitive-titanium-dioxide-nanoplatform-for-tumor-responsive-fe2-liberating-and-artemisinin-delivery
#18
Huijuan Zhang, Hongling Zhang, Xing Zhu, Xiaoge Zhang, Qianqian Chen, Jianjiao Chen, Lin Hou, Zhenzhong Zhang
Artemisinin is a kind of Fe2+-dependent drugs. Artemisinin and Fe2+ co-transport systems can improve its anti-tumor effect. In this study, a visible light-sensitive nanoplatform (HA-TiO2-IONPs/ART) was developed. Detailed investigation demonstrated that HA-TiO2-IONPs/ART could realize Fe2+ and artemisinin synchronous co-delivery and tumor-responsive release. This feature enhanced the anti-tumor efficiency of artemisinin significantly. In vitro results proved that hyaluronic acid modification could improve the biocompatibility, dispersion stability and cytophagy ability of nanocarriers...
May 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/28518118/harnessing-the-dna-dye-triggered-side-population-phenotype-to-detect-and-purify-cancer-stem-cells-from-biological-samples
#19
Maximilian Boesch, Elisabeth Hoflehner, Dominik Wolf, Guenther Gastl, Sieghart Sopper
Cancer is a stem cell-driven disease and eradication of these cells has become a major therapeutic goal. Deciphering vulnerabilities of Cancer Stem Cells (CSCs) and identifying suitable molecular targets relies on methods that allow their specific discrimination in heterogeneous samples such as cell lines and ex vivo tumor tissue. Flow cytometry/FACS is a powerful technology to multi-parametrically dissect biological samples at the single cell level and is to date the method of choice to recover live cells for downstream analyses...
May 10, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28518007/patient-centric-side-effect-risk-assessment-for-medications-used-during-aeromedical-evacuations
#20
Shana A Huntsberger, William P Butler, Richard R Chapleau
BACKGROUND: The U.S. Air Force performs more than 6000 aeromedical transport flights annually, both internationally and domestically. Many of these flights include patients requiring pain relief medications. The risk of side effects from such medications administered at altitude is unknown, but understanding these risks is vital when selecting the safest pain management strategies to achieve optimal postflight outcomes. METHODS: Using an evidence-based medication side effect risk assessment model, we compared our patient-centric approach to an aircrew-centric approach using medications approved for use in U...
April 1, 2017: Aerospace Medicine and Human Performance
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