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https://www.readbyqxmd.com/read/28528519/il-6-blockade-in-the-management-of-non-infectious-uveitis
#1
Giuseppe Lopalco, Claudia Fabiani, Jurgen Sota, Orso Maria Lucherini, Gian Marco Tosi, Bruno Frediani, Florenzo Iannone, Mauro Galeazzi, Rossella Franceschini, Donato Rigante, Luca Cantarini
Several pathogenetic studies have paved the way for a newer more rational therapeutic approach to non-infectious uveitis, and treatment of different forms of immune-driven uveitis has drastically evolved in recent years after the advent of biotechnological drugs. Tumor necrosis factor-α targeted therapies, the first-line recommended biologics in uveitis, have certainly led to remarkable results in patients with non-infectious uveitis. Nevertheless, the decision-making process turns out to be extremely difficult in anti-tumor necrosis factor or multidrug-resistant cases...
May 20, 2017: Clinical Rheumatology
https://www.readbyqxmd.com/read/28528286/assessing-the-stable-conformations-of-ibuprofen-in-solution-by-means-of-residual-dipolar-couplings
#2
Maria Enrica Di Pietro, Giorgio Celebre, Christie Aroulanda, Denis Merlet, Giuseppina De Luca
Detailing the conformational equilibria between global and local minimum energy structures of anti-inflammatory α-arylpropionic acids directly in solution is of the utmost importance for a better understanding of the structure-activity relationships, hence providing valuable clues for rational structure-based drug design studies. Here the conformational preferences of the widely used pharmaceutical ibuprofen were investigated in solution by NMR spectroscopy in weakly ordering phases. A thorough theoretical treatment of the anisotropic interactions that are relevant for NMR spectra led to a conformational model characterized by six pairs of symmetry-related conformers, in particular four couples of gauche structures, with a total probability of 93%, and 2 couples of trans structures, counting for the remaining 7%...
May 17, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28527885/maintenance-of-atp-homeostasis-triggers-metabolic-shifts-in-gas-fermenting-acetogens
#3
Kaspar Valgepea, Renato de Souza Pinto Lemgruber, Kieran Meaghan, Robin William Palfreyman, Tanus Abdalla, Björn Daniel Heijstra, James Bruce Behrendorff, Ryan Tappel, Michael Köpke, Séan Dennis Simpson, Lars Keld Nielsen, Esteban Marcellin
Acetogens are promising cell factories for producing fuels and chemicals from waste feedstocks via gas fermentation, but quantitative characterization of carbon, energy, and redox metabolism is required to guide their rational metabolic engineering. Here, we explore acetogen gas fermentation using physiological, metabolomics, and transcriptomics data for Clostridium autoethanogenum steady-state chemostat cultures grown on syngas at various gas-liquid mass transfer rates. We observe that C. autoethanogenum shifts from acetate to ethanol production to maintain ATP homeostasis at higher biomass concentrations but reaches a limit at a molar acetate/ethanol ratio of ∼1...
May 16, 2017: Cell Systems
https://www.readbyqxmd.com/read/28527806/endogenous-synthesis-of-milk-oleic-acid-in-dairy-ewes-in-vivo-measurement-using-13-c-labeled-stearic-acid
#4
P G Toral, P Frutos, D Carreño, G Hervás
The use of stable isotopes is a reliable and risk-free alternative to radioactive tracers for directly examining in vivo fatty acid (FA) metabolism. However, very limited information is available in ruminants, and none is available in sheep. Therefore, we conducted an experiment in dairy ewes to determine, for the first time in this species, the uptake, Δ(9)-desaturation, and secretion of (13)C-labeled stearic acid (SA) into milk with the aim of measuring in vivo endogenous synthesis of milk oleic acid (OA) and stearoyl-CoA desaturase activity...
May 17, 2017: Journal of Dairy Science
https://www.readbyqxmd.com/read/28527805/effects-of-replacement-of-late-harvested-grass-silage-and-barley-with-early-harvested-silage-on-milk-production-and-methane-emissions
#5
E H Cabezas-Garcia, S J Krizsan, K J Shingfield, P Huhtanen
This study evaluated the effects of gradual replacement of a mixture of late-cut grass silage (LS) and barley with early-cut grass silage (ES) on milk production, CH4 emissions, and N utilization in Swedish Red cows. Two grass silages were prepared from the same primary growth of timothy grass sward but harvested 2 wk apart [11.0 and 9.7 MJ of metabolizable energy/kg of dry matter (DM)]. Four diets, fed as a total mixed ration, were formulated to meet the metabolizable energy and protein requirements of 35 kg of energy-corrected milk (ECM) by gradually replacing a mixture of LS and barley with ES (0, 33, 67, and 100% of the forage component of the diet), whereas the proportion of barley decreased from 47...
May 17, 2017: Journal of Dairy Science
https://www.readbyqxmd.com/read/28527803/using-brown-midrib-6-dwarf-forage-sorghum-silage-and-fall-grown-oat-silage-in-lactating-dairy-cow-rations
#6
M T Harper, J Oh, F Giallongo, J C Lopes, G W Roth, A N Hristov
Double cropping and increasing crop diversity could improve dairy farm economic and environmental sustainability. In this experiment, corn silage was partially replaced with 2 alternative forages, brown midrib-6 brachytic dwarf forage sorghum (Sorghum bicolor) or fall-grown oat (Avena sativa) silage, in the diet of lactating dairy cows. We investigated the effect on dry matter (DM) intake, milk yield (MY), milk components and fatty acid profile, apparent total-tract nutrient digestibility, N utilization, enteric methane emissions, and income over feed cost...
May 17, 2017: Journal of Dairy Science
https://www.readbyqxmd.com/read/28527795/the-use-of-mid-infrared-spectrometry-to-estimate-the-ration-composition-of-lactating-dairy-cows
#7
M Klaffenböck, A Steinwidder, C Fasching, G Terler, L Gruber, G Mészáros, J Sölkner
The composition of cow milk is strongly affected by the feeding regimen. Because milk components are routinely determined using mid-infrared (MIR) spectrometry, MIR spectra could also be used to estimate an animal's ration composition. The objective of this study was to determine whether and how well amounts of dry matter intake and the proportions of concentrates, hay, grass silage, maize silage, and pasture in the total ration can be estimated using MIR spectra at an individual animal level. A total of 10,200 milk samples and sets of feed intake data were collected from 90 dairy cows at 2 experimental farms of the Agricultural Research and Education Centre in Raumberg-Gumpenstein, Austria...
May 17, 2017: Journal of Dairy Science
https://www.readbyqxmd.com/read/28527700/failure-of-hightibialvarus-osteotomy-for-lateral-tibio-femoral-osteoarthritis-with-10%C3%A2-of-valgus-outcomes-in-19-patients
#8
G Mirouse, A Dubory, F Roubineau, A Poignard, P Hernigou, J Allain, C H Flouzat Lachaniette
BACKGROUND: Osteotomy is a rational approach to slowing knee osteoarthritis progression by modifying loads, thereby avoiding joint replacement in younger individuals. Varus femoral osteotomy is recommended only in patients with more than 10° of valgus. The objective here was to assess outcomes of tibialvarus osteotomy in patients with lateral compartment tibio-femoral osteoarthritis and less than 10° of valgus. MATERIAL AND METHODS: A single-centre retrospective study was conducted in 19 consecutive patients managed by high tibialvarus osteotomy between January 2005 and May 2012...
May 17, 2017: Orthopaedics & Traumatology, Surgery & Research: OTSR
https://www.readbyqxmd.com/read/28527509/impact-of-qi-invigorating-traditional-chinese-medicines-on-intestinal-flora-a-basis-for-rational-choice-of-prebiotics
#9
REVIEW
Xiao-Meng Wang, Xiao-Bo Li, Ying Peng
According to the theory of traditional Chinese medicine (TCM), Qi (vital energy) is regarded as a driving force of biological activities in human body, including both nutrient substances and organ functions. Qi-invigorating TCMs are widely used to treat various symptoms and disorders, such as fatigue, obesity, immunosuppression, intestinal flora imbalance, and gastrointestinal diseases, in which Qi is considered to be reduced or depleted. Interestingly, abundant clinical evidences suggest that these disorders are associated with the alternation of intestinal flora, which directly affects disease status...
April 2017: Chinese Journal of Natural Medicines
https://www.readbyqxmd.com/read/28527285/-genetic-diversity-of-extraintestinal-escherichia-coli-strains-producers-of-beta-lactamases-tem-shv-and-ctx-m-associated-with-healthcare
#10
Yasmin Varela, Beatriz Millán, María Araque
INTRODUCTION: There are few reports from Venezuela describing the genetic basis that sustains the pathogenic potential and phylogenetics of Escherichia coli extraintestinal strains isolated in health care units. OBJECTIVE: To establish the genetic diversity of extraintestinal E. coli strains producers of betalactamases TEM, SHV and CTX-M associated with healthcare. MATERIALS AND METHODS: We studied a collection of 12 strains of extraintestinal E...
June 1, 2017: Biomédica: Revista del Instituto Nacional de Salud
https://www.readbyqxmd.com/read/28527254/-cross-cultural-adaptation-of-the-community-acquired-pneumonia-score-questionnaire-in-patients-with-mild-to-moderate-pneumonia-in-colombia
#11
Mónica Alejandra Bernal-Vargas, Jorge Alberto Cortés, Ricardo Sánchez
INTRODUCTION: One of the strategies for the rational use of antibiotics is the use of the score for community-acquired pneumonia (CAP Score). This instrument clinically evaluates patients with community-acquired pneumonia, thereby facilitating decision making regarding the early and safe withdrawal of antibiotics. OBJECTIVE: To generate a translation and cross-cultural adaptation of the Community-Acquired Pneumonia (CAP) Score questionnaire in Spanish. MATERIALS AND METHODS: Authorization for cross-cultural adaptation of the Community-Acquired Pneumonia (CAP) Score questionnaire was obtained; the recommendations of the International Society for Pharmacoeconomics and Outcomes Research (ISPOR) and the European Organisation for Research and Treatment of Cancer (EORTC) were carried out through the following stages: forward translation, reconciliation, backward translation, harmonization, obtaining a provisional questionnaire, and applying the questionnaire in a pilot test...
January 24, 2017: Biomédica: Revista del Instituto Nacional de Salud
https://www.readbyqxmd.com/read/28526836/characterisation-of-antibiotic-prescriptions-for-acute-respiratory-tract-infections-in-danish-general-practice-a-retrospective-registry-based-cohort-study
#12
Rune Aabenhus, Malene Plejdrup Hansen, Laura Trolle Saust, Lars Bjerrum
Inappropriate use of antibiotics is contributing to the increasing rates of antimicrobial resistance. Several Danish guidelines on antibiotic prescribing for acute respiratory tract infections in general practice have been issued to promote rational prescribing of antibiotics, however it is unclear if these recommendations are followed. We aimed to characterise the pattern of antibiotic prescriptions for patients diagnosed with acute respiratory tract infections, by means of electronic prescriptions, labeled with clinical indications, from Danish general practice...
May 19, 2017: NPJ Primary Care Respiratory Medicine
https://www.readbyqxmd.com/read/28526832/identification-of-a-novel-chalcone-derivative-that-inhibits-notch-signaling-in-t-cell-acute-lymphoblastic-leukemia
#13
Mattia Mori, Luca Tottone, Deborah Quaglio, Nadezda Zhdanovskaya, Cinzia Ingallina, Marisa Fusto, Francesca Ghirga, Giovanna Peruzzi, Maria Elisa Crestoni, Fabrizio Simeoni, Francesca Giulimondi, Claudio Talora, Bruno Botta, Isabella Screpanti, Rocco Palermo
Notch signaling is considered a rational target in the therapy of several cancers, particularly those harbouring Notch gain of function mutations, including T-cell acute lymphoblastic leukemia (T-ALL). Although currently available Notch-blocking agents are showing anti-tumor activity in preclinical studies, they are not effective in all the patients and often cause severe side-effects, limiting their widespread therapeutic use. Here, by functional and biological analysis of the most representative molecules of an in house library of natural products, we have designed and synthetized the chalcone-derivative 8 possessing Notch inhibitory activity at low micro molar concentration in T-ALL cell lines...
May 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28526743/systematic-identification-of-functional-residues-of-artemisia-annua-amorpha-4-11-diene-synthase
#14
Xin Fang, Jian-Xu Li, Jin-Quan Huang, You-Li Xiao, Peng Zhang, Xiao-Ya Chen
Terpene synthases (TPSs) are responsible for the extremely diversified and complex structure of terpenoids. Amorpha-4,11-diene synthase (ADS) has a high (90%) fidelity in generating the sesquiterpene precursor for biosynthesis of artemisinin, an antimalarial drug, however, little is known about how active site residues of ADS involved in the carbocation rearrangement and cyclization reactions. Here, we identify seven residues that are key to most of the catalytic steps in ADS. By structural modeling and amino acid sequence alignments of ADS with two functionally relevant sesquiterpene synthases from Artemisia annua, we performed site-directed mutagenesis and found that a single substitution, T296V, impaired the ring closure activity almost completely, and tetra-substitutions (L374Y/L404V/L405I/G439S) led to an enzyme generating 80% monocyclic bisabolyl-type sesquiterpenes, whereas a double mutant (T399L/T447G) showed compromised activity in regioselective deprotonation to yield 34...
May 19, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/28526692/understanding-the-interrelationship-between-the-synthesis-of-urea-and-gluconeogenesis-by-formulating-an-overall-balanced-equation
#15
Piero L Ipata, Rossana Pesi
It is well known that a strong metabolic interrelationship exists between ureagenesis and gluconeogenesis. In this paper, we present a detailed, overall equation, describing a possible metabolic link between ureagenesis and gluconeogenesis. We adopted a guided approach in which we strongly suggest that students, when faced with the problem of obtaining the overall equation of a metabolic pathway, carefully account for all atoms and charges of the single reactions, as well as the cellular localizations of the substrates, and the related transport systems...
June 1, 2017: Advances in Physiology Education
https://www.readbyqxmd.com/read/28526681/adoptive-transfer-of-phosphoantigen-specific-%C3%AE-%C3%AE-t-cell-subset-attenuates-mycobacterium-tuberculosis-infection-in-nonhuman-primates
#16
Arwa Qaqish, Dan Huang, Crystal Y Chen, Zhuoran Zhang, Richard Wang, Shengpu Li, Enzhuoa Yang, Yang Lu, Michelle H Larsen, William R Jacobs, Lixia Qian, James Frencher, Ling Shen, Zheng W Chen
The dominant Vγ2Vδ2 T cell subset recognizes phosphoantigen and exists only in humans and nonhuman primates. Despite the discovery of γδ T cells >30 y ago, a proof-of-concept study has not been done to prove the principle that the Vγ2Vδ2 T cell subset is protective against Mycobacterium tuberculosis and other infections. In this study, we used an adoptive cell-transfer strategy to define the protective role of Vγ2Vδ2 T cells in a primate tuberculosis (TB) model. Vγ2Vδ2 T cells for adoptive transfer displayed central/effector memory and mounted effector functions, including the production of anti-M...
May 19, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28525863/optical-nonlinearity-and-charge-transfer-analysis-of-pyrene-adsorbed-on-silver-computational-and-experimental-investigations
#17
U Reeta Felscia, Beulah J M Rajkumar, Pranitha Sankar, Reji Philip, M Briget Mary
The interaction of pyrene on silver has been investigated using both experimental and computational methods. Hyperpolarizabilities computed theoretically together with experimental nonlinear absorption from open aperture Z-scan measurements, point towards a possible use of pyrene adsorbed on silver in the rational design of NLO devices. Presence of a red shift in both simulated and experimental UV-Vis spectra confirms the adsorption on silver, which is due to the electrostatic interaction between silver and pyrene, inducing variations in the structural parameters of pyrene...
May 10, 2017: Spectrochimica Acta. Part A, Molecular and Biomolecular Spectroscopy
https://www.readbyqxmd.com/read/28525855/surface-design-of-magnetic-nanoparticles-for-stimuli-responsive-cancer-imaging-and-therapy
#18
REVIEW
Taegyu Kang, Fangyuan Li, Seungmin Baik, Wei Shao, Daishun Ling, Taeghwan Hyeon
Magnetic nanoparticles (MNPs) have been extensively studied for their potential applications to cancer diagnosis and treatment. However, various obstacles limit the use of nanoparticles for delivery in the tumor microenvironment. As a viable solution to such obstacles, advances in nanoparticle surface engineering augmented by a profound understanding of cancer physiology present new opportunities for MNP-based imaging and therapeutic agents. Stimuli-responsive ligands, rationally designed to interact with various physicochemical aspects, can improve the performance of MNPs in cancer-targeted imaging and therapy...
May 8, 2017: Biomaterials
https://www.readbyqxmd.com/read/28525838/design-synthesis-and-evaluation-of-azaacridine-derivatives-as-dual-target-egfr-and-src-kinase-inhibitors-for-antitumor-treatment
#19
Zhishan Cui, Shaopeng Chen, Yanwei Wang, Chunmei Gao, Yuzong Chen, Chunyan Tan, Yuyang Jiang
Overexpression of EGFR is often associated with advanced stage disease and poor prognosis. In certain cancers, Src works synergistically with EGFR to promote proliferation, survival, invasion and metastasis. Development of dual-target drugs against EGFR and Src is of therapeutic advantage against these cancers. Based on molecular docking and our previous studies, we rationally designed a new series of azaacridine derivatives as potent EGFR and Src dual inhibitors. Most of the synthesized azaacridines displayed good antiproliferative activity against K562 and A549 cells...
May 11, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28525766/rationalizing-the-right-ratios
#20
Johannes Arp, Pierre Stallforth
The three hydroxamate siderophores, avaroferrin, bisucaberin, and putrebactin are synthesized by the same key enzyme AvbD. Rütschlin et al. (2017) show that the ratio of these three compounds is not governed by the enzyme's substrate specificity but rather by the substrate pool. This ensures a large metabolic flexibility and adaptability to new environments.
May 18, 2017: Cell Chemical Biology
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