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https://www.readbyqxmd.com/read/28929255/carbonic-anhydrase-ix-inhibition-affects-viability-of-cancer-cells-adapted-to-extracellular-acidosis
#1
Elena Andreucci, Silvia Peppicelli, Fabrizio Carta, Giulia Brisotto, Eva Biscontin, Jessica Ruzzolini, Francesca Bianchini, Alessio Biagioni, Claudiu T Supuran, Lido Calorini
Among the players of the adaptive response of cancer cells able to promote a resistant and aggressive phenotype, carbonic anhydrase IX (CAIX) recently has emerged as one of the most relevant drug targets. Indeed, CAIX targeting has received a lot of interest, and selective inhibitors are currently under clinical trials. Hypoxia has been identified as the master inductor of CAIX, but, to date, very few is known about the influence that another important characteristic of tumor microenvironment, i.e., extracellular acidosis, exerts on CAIX expression and activity...
September 19, 2017: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
https://www.readbyqxmd.com/read/28926956/carbonic-anhydrase-inhibition-and-the-management-of-hypoxic-tumors
#2
REVIEW
Claudiu T Supuran
Hypoxia and acidosis are salient features of many tumors, leading to a completely different metabolism compared to normal cells. Two of the simplest metabolic products, protons and bicarbonate, are generated by the catalytic activity of the metalloenzyme carbonic anhydrase (CA, EC 4.2.1.1), with at least two of its isoforms, CA IX and XII, mainly present in hypoxic tumors. Inhibition of tumor-associated CAs leads to an impaired growth of the primary tumors, metastases and reduces the population of cancer stem cells, leading thus to a complex and beneficial anticancer action for this class of enzyme inhibitors...
September 16, 2017: Metabolites
https://www.readbyqxmd.com/read/28920464/absorption-sites-of-orally-administered-drugs-in-the-small-intestine
#3
Teruo Murakami
In pharmacotherapy, drugs are mostly taken orally to be absorbed systemically from the small intestine, and some drugs are known to have preferential absorption sites in the small intestine. It would therefore be valuable to know the absorption sites of orally administered drugs and the influencing factors. Areas covered:In this review, the author summarizes the reported absorption sites of orally administered drugs, as well as, influencing factors and experimental techniques. Information on the main absorption sites and influencing factors can help to develop ideal drug delivery systems and more effective pharmacotherapies...
September 17, 2017: Expert Opinion on Drug Discovery
https://www.readbyqxmd.com/read/28878041/characteristics-of-29-novel-atypical-solute-carriers-of-major-facilitator-superfamily-type-evolutionary-conservation-predicted-structure-and-neuronal-co-expression
#4
Emelie Perland, Sonchita Bagchi, Axel Klaesson, Robert Fredriksson
Solute carriers (SLCs) are vital as they are responsible for a major part of the molecular transport over lipid bilayers. At present, there are 430 identified SLCs, of which 28 are called atypical SLCs of major facilitator superfamily (MFS) type. These are MFSD1, 2A, 2B, 3, 4A, 4B, 5, 6, 6 L, 7, 8, 9, 10, 11, 12, 13A, 14A and 14B; SV2A, SV2B and SV2C; SVOP and SVOPL; SPNS1, SPNS2 and SPNS3; and UNC93A and UNC93B1. We studied their fundamental properties, and we also included CLN3, an atypical SLC not yet belonging to any protein family (Pfam) clan, because its involvement in the same neuronal degenerative disorders as MFSD8...
September 2017: Open Biology
https://www.readbyqxmd.com/read/28840324/patient-specific-mental-rehearsal-with-interactive-visual-aids-a-path-worth-exploring
#5
Marina Yiasemidou, Raffaele Galli, Daniel Glassman, Matthew Tang, Rahoz Aziz, David Jayne, Danilo Miskovic
BACKGROUND: Surgeons of today are faced with unprecedented challenges; necessitating a novel approach to pre-operative preparation which takes into account the specific tests each case poses. In this study, we examine patient-specific mental rehearsal for pre-surgical practice and assess whether this method has an additional effect when compared to generic mental rehearsal. METHODS: Sixteen medical students were trained how to perform a simulated laparoscopic cholecystectomy (SLC)...
August 24, 2017: Surgical Endoscopy
https://www.readbyqxmd.com/read/28827080/stallion-sperm-selection-prior-to-freezing-using-a-modified-colloid-swim-up-procedure-without-centrifugation
#6
M Hidalgo, I Ortiz, J Dorado, J M Morrell, J Gosálvez, C Consuegra, M Diaz-Jimenez, B Pereira, F Crespo
The aims of this study were to: 1) develop a new method for stallion sperm selection using a modified swim-up procedure through a colloid and 2) evaluate its impact in good quality ejaculates from bad freezers in comparison to methods involving centrifugation such as single layer centrifugation and sperm washing. Ejaculates were processed before freezing using three different procedures: sperm washing (SW), colloid single layer centrifugation (SLC) and a modified colloid swim-up (SU). After semen processing, sperm recovery rates were measured and sperm were frozen...
October 2017: Animal Reproduction Science
https://www.readbyqxmd.com/read/28819401/identification-and-validation-of-soluble-carrier-family-expression-signature-for-predicting-poor-outcome-of-renal-cell-carcinoma
#7
Wan Fangning, Ma Chunguang, Zhang Hailiang, Shi Guohai, Zhu Yao, Dai Bo, Shen Yijun, Zhu Yiping, Ye Dingwei
The soluble carrier (SLC) family plays an important role in cell metabolism. The purpose of the current study was to screen SLCs as potential prognostic factors in clear cell renal cell carcinoma (ccRCC). A total of 509 patients with ccRCC from The Cancer Genome Atlas (TCGA) cohort were enrolled in this study. The expression profile of SLCs was obtained from the TCGA RNAseq database. Metadata of the TCGA cohort, including age, sex, TNM stage, tumor grade, American Joint Committee on Cancer stage, laterality, and overall survival, were collected...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28816482/same-location-costs-in-peripheral-cueing-the-role-of-cue-awareness-and-feature-changes
#8
Tobias Schoeberl, Thomas Ditye, Ulrich Ansorge
Prior studies using the peripheral cueing paradigm have shown that singleton cues that do not match to the top-down search settings of the observer can impair performance in visual search when the cue appears at the target location (in valid conditions) compared with when the cue appears at a location away from the target (in invalid conditions). This pattern, the same-location cost (SLC), has recently been suggested to originate from an awareness-dependent updating of object files in working memory. It has also been argued that the processes underlying the SLC could have obscured results of prior studies by masking attentional capture effects by peripheral cues under certain conditions...
August 17, 2017: Journal of Experimental Psychology. Human Perception and Performance
https://www.readbyqxmd.com/read/28801955/single-layer-centrifugation-of-fresh-dromedary-camel-semen-improves-sperm-quality-and-in-vitro-fertilization-capacity-compared-with-simple-sperm-washing
#9
C Malo, E G Crichton, J M Morrell, B S Pukazhenthi, J A Skidmore
Single layer centrifugation (SLC) through a colloid is a tool for selecting viable mammalian spermatozoa but has not been used previously for fresh dromedary camel sperm. Semen from six camels (2 ejaculates/male) was diluted 1:5 (v:v) or 1:10 (v:v) in a Tris-citrate-fructose buffer for mechanical liquefaction by gentle pipetting. Following liquefaction, semen was processed either by SLC or by centrifugation without a colloid (control). Total and progressive motilities, CASA kinematics, vitality and acrosome integrity (eosin-nigrosin) and plasma membrane integrity (Hypo-osmotic swelling test; HOST), and fertilizing ability in a heterologous assay (zona-free goat oocytes) were evaluated...
August 12, 2017: Reproduction in Domestic Animals, Zuchthygiene
https://www.readbyqxmd.com/read/28768834/placentome-nutrient-transporters-and-mammalian-target-of-rapamycin-signaling-proteins-are-altered-by-the-methionine-supply-during-late-gestation-in-dairy-cows-and-are-associated-with-newborn-birth-weight
#10
Fernanda Batistel, Abdulrahman Sm Alharthi, Ling Wang, Claudia Parys, Yuan-Xiang Pan, Felipe C Cardoso, Juan J Loor
Background: To our knowledge, most research demonstrating a link between maternal nutrition and both fetal growth and offspring development after birth has been performed with nonruminants. Whether such relationships exist in large ruminants is largely unknown.Objective: We aimed to investigate whether increasing the methionine supply during late pregnancy would alter uteroplacental tissue nutrient transporters and mammalian target of rapamycin (mTOR) and their relation with newborn body weight.Methods: Multiparous Holstein cows were used in a randomized complete block design experiment...
September 2017: Journal of Nutrition
https://www.readbyqxmd.com/read/28756021/association-of-clinical-severity-of-cystic-fibrosis-with-variants-in-the-slc-gene-family-slc6a14-slc26a9-slc11a1-and-slc9a3
#11
Stéphanie Villa-Nova Pereira, José Dirceu Ribeiro, Carmen Sílvia Bertuzzo, Fernando Augusto Lima Marson
INTRODUCTION: Cystic fibrosis (CF) manifests with clinical and histopathological variability depending on environmental and genetic factors. Moreover, the genes encoding ion channels[rs3788766(SLC6A14), rs7512462(SLC26A9), rs17235416(SLC11A1) and rs17563161(SLC9A3)] have been insufficiently studied as modifier genes. Then, our objective was associate the variants in the genes of SLC family with 43 CF severity markers. METHODS: The variants were identified by real-time-PCR in 188 CF patients considering the CFTR genotype...
September 20, 2017: Gene
https://www.readbyqxmd.com/read/28753996/boron-tolerance-in-aspergillus-nidulans-is-sustained-by-the-slta-pathway-through-the-slc-family-transporters-sbta-and-sbtb
#12
María Villarino, Oier Etxebeste, Gorka Mendizabal, Aitor Garzia, Unai Ugalde, Eduardo A Espeso
Microbial cells interact with the environment by adapting to external changes. Signal transduction pathways participate in both sensing and responding in the form of modification of gene expression patterns, enabling cell survival. The filamentous fungal-specific SltA pathway regulates tolerance to alkalinity, elevated cation concentrations and, as shown in this work, also stress conditions induced by borates. Growth of sltA(-) mutants is inhibited by increasing millimolar concentrations of boric acid or borax (sodium tetraborate)...
July 21, 2017: Genes
https://www.readbyqxmd.com/read/28741664/in-vitro-evaluation-of-an-immediate-response-starling-like-controller-for-dual-rotary-blood-pumps
#13
Andrew F Stephens, Michael C Stevens, Shaun D Gregory, Matthias Kleinheyer, Robert F Salamonsen
Rotary ventricular assist devices (VADs) are used to provide mechanical circulatory support. However, their lack of preload sensitivity in constant speed control mode (CSC) may result in ventricular suction or venous congestion. This is particularly true of biventricular support, where the native flow-balancing Starling response of both ventricles is diminished. It is possible to model the Starling response of the ventricles using cardiac output and venous return curves. With this model, we can create a Starling-like physiological controller (SLC) for VADs which can automatically balance cardiac output in the presence of perturbations to the circulation...
July 25, 2017: Artificial Organs
https://www.readbyqxmd.com/read/28717013/mechanisms-of-carbon-dioxide-acquisition-and-co2-sensing-in-marine-diatoms-a-gateway-to-carbon-metabolism
#14
REVIEW
Yusuke Matsuda, Brian M Hopkinson, Kensuke Nakajima, Christopher L Dupont, Yoshinori Tsuji
Diatoms are one of the most successful marine eukaryotic algal groups, responsible for up to 20% of the annual global CO2 fixation. The evolution of a CO2-concentrating mechanism (CCM) allowed diatoms to overcome a number of serious constraints on photosynthesis in the marine environment, particularly low [CO2]aq in seawater relative to concentrations required by the CO2 fixing enzyme, ribulose-1,5-bisphosphate carboxylase/oxygenase (RubisCO), which is partly due to the slow diffusion rate of CO2 in water and a limited CO2 formation rate from [Formula: see text] in seawater...
September 5, 2017: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
https://www.readbyqxmd.com/read/28698977/pharmacogenetics-and-pharmacogenomics-of-targeted-therapeutics-in-chronic-myeloid-leukemia
#15
REVIEW
Aritro Nath, Jacqueline Wang, R Stephanie Huang
The advent of targeted therapeutics has greatly improved outcomes of chronic myeloid leukemia (CML) patients. Despite increased efficacy and better clinical responses over cytotoxic chemotherapies, many patients receiving targeted drugs exhibit a poor initial response, develop drug resistance, or undergo relapse after initial success. This inter-individual variation in response has heightened the interest in studying pharmacogenetics and pharmacogenomics (PGx) of cancer drugs. In this review, we discuss the influence of various germline and somatic factors on targeted drug response in CML...
July 11, 2017: Molecular Diagnosis & Therapy
https://www.readbyqxmd.com/read/28696229/mdr1-and-bcrp-transporter-mediated-drug-drug-interaction-between-rilpivirine-and-abacavir-and-effect-on-intestinal-absorption
#16
Josef Reznicek, Martina Ceckova, Zuzana Ptackova, Ondrej Martinec, Lenka Tupova, Lukas Cerveny, Frantisek Staud
Rilpivirine (TMC278) is a highly potent nonnucleoside reverse transcriptase inhibitor (NNRTI) representing an effective component of combination antiretroviral therapy (cART) in the treatment of HIV-positive patients. Many antiretroviral drugs commonly used in cART are substrates of ATP-binding cassette (ABC) and/or solute carrier (SLC) drug transporters and, therefore, are prone to pharmacokinetic drug-drug interactions (DDIs). The aim of our study was to evaluate rilpivirine interactions with abacavir and lamivudine on selected ABC and SLC transporters in vitro and assess its importance for pharmacokinetics in vivo Using accumulation assays in MDCK cells overexpressing selected ABC or SLC drug transporters, we revealed rilpivirine as a potent inhibitor of MDR1 and BCRP, but not MRP2, OCT1, OCT2, or MATE1...
September 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28694436/expression-and-regulation-of-drug-transporters-in-vertebrate-neutrophils
#17
Matthew J Foulkes, Katherine M Henry, Julien Rougeot, Edward Hooper-Greenhill, Catherine A Loynes, Phil Jeffrey, Angeleen Fleming, Caroline O Savage, Annemarie H Meijer, Simon Jones, Stephen A Renshaw
There remains a need to identify novel pro-resolution drugs for treatment of inflammatory disease. To date, there are no neutrophil-specific anti-inflammatory treatments in clinical use, perhaps due to our lack of understanding of how drugs access this complex cell type. Here we present the first comprehensive description and expression of both major classes of drug transporters, SLC and ABC, in resting human blood neutrophils. Moreover, we have studied the expression of these carriers in the tractable model system, the zebrafish (Danio rerio), additionally examining the evolutionary relationship between drug transporters in zebrafish and humans...
July 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28693494/variation-of-sentinel-lymphatic-channels-slcs-and-sentinel-lymph-nodes-slns-assessed-by-contrast-enhanced-ultrasound-ceus-in-breast-cancer-patients
#18
Ying Wang, Wenbin Zhou, Cuiying Li, Haiyan Gong, Chunlian Li, Nianzhao Yang, Xiaoming Zha, Lin Chen, Tiansong Xia, Xiaoan Liu, Minghai Wang, Qiang Ding
BACKGROUND: The objective of this study was to assess the feasibility of detecting the variation of sentinel lymphatic channels (SLCs) and sentinel lymph nodes (SLNs) in breast cancer patients using contrast-enhanced ultrasound (CEUS). METHODS: A total of 46 breast cancer patients were prospectively recruited in the study. All the participants received intradermal and peritumoral injection of microbubbles as contrast agent, and SLCs and SLNs were assessed preoperatively...
July 10, 2017: World Journal of Surgical Oncology
https://www.readbyqxmd.com/read/28692097/controlling-the-enthalpy-entropy-competition-in-supramolecular-fullerene-liquid-crystals-by-tuning-the-flexible-chain-length
#19
Tiantian Zhu, Xiaoyan Zhang, Zhikai Li, Chih-Hao Hsu, Wei Chen, Toshikazu Miyoshi, Xiaohong Li, Xiaoming Yang, Yingfeng Tu, Christopher Y Li
We present here that in two-dimensional (2D) fullerene supramolecular liquid crystals (SLCs), the phase diagram and lamella thickness of SLCs and 2D crystals can be tuned by the flexible alkyl tail and spacer length, due to their different effects on enthalpy and entropy changes during SLC formation.
July 10, 2017: Chemical Communications: Chem Comm
https://www.readbyqxmd.com/read/28681281/population-health-outcomes-of-a-student-led-free-health-clinic-for-an-underserved-population-a-naturalistic-study
#20
Cynthia M Stuhlmiller, Barry Tolchard
There are a number of hard to reach and underserved communities who experience inadequate health care. In Australia, the Aboriginal and Torres Strait Islanders peoples experience low life expectancy, higher levels for chronic disease and elevated smoking and drinking. These problems are further exacerbated when living in regional and rural Australia and poverty. There are growing concerns over helping such groups in order to close the health disparity gap. A student-led clinic (SLC) was developed to address clinical placement shortages while providing free health and social services in an underserved community in regional Australia...
July 5, 2017: Journal of Community Health
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