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https://www.readbyqxmd.com/read/28214753/structural-and-functional-insights-into-corrinoid-iron-sulfur-protein-from-human-pathogen-clostridium-difficile
#1
Yaozhu Wei, Xiaofei Zhu, Sixue Zhang, Xiangshi Tan
The human pathogen Clostridium difficile infection (CDI) is one of the most important healthcare-associated infections. The Wood-Ljungdahl pathway, which is responsible for Acetyl-CoA biosynthesis, is essential for the survival of the pathogen and is absent in humans. The key proteins and enzymes involved in the pathway are attractive targets for the treatment of CDI. Corrinoid iron-sulfur protein (CoFeSP) is a key protein and acts as a methyl transformer in the Wood-Ljungdahl pathway. In this study, CoFeSP from Clostridium difficile (CoFeSPCd) was cloned, expressed in E...
February 13, 2017: Journal of Inorganic Biochemistry
https://www.readbyqxmd.com/read/28214690/safety-and-efficacy-of-a-polyherbal-formulation-for-the-management-of-dyslipidemia-and-hyperglycemia-in-patients-with-advanced-stage-of-type-2-diabetes
#2
Mahdi Zarvandi, Hassan Rakhshandeh, Mohammad Abazari, Reza Shafiee-Nick, Ahmad Ghorbani
The present clinical trial was designed to evaluate the safety and efficacy of a polyherbal formulation (PHF) consisted of Allium sativum, Aloe vera, Nigella sativa, Plantago psyllium, Silybum marianum and Trigonella foenum-graecum for controlling dyslipidemia and hyperglycemia in patients with advanced-stage of type-2 diabetes. An open-label phase I trial was carried out on 30 patients who had hyperlipidemia and hyperglycemia before the beginning of the trial in spite of receiving statins and oral hypoglycemic drugs...
February 16, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28214602/impact-of-fill-level-in-twin-screw-granulation-on-critical-quality-attributes-of-granules-and-tablets
#3
Robin Meier, Klaus-Peter Moll, Markus Krumme, Peter Kleinebudde
In a previous study a change of the fill-level in the barrel exerted a huge influence on the twin-screw granulation (TSG) process of a high drug loaded, simplified formulation. The present work investigated this influence systematically. The specific feed load (SFL) indicating the mass per revolution as surrogate parameter for the fill-level was applied and the correlation to the real volumetric fill level of an extruder could be demonstrated by a newly developed method. A design of experiments was conducted to examine the combined influence of SFL and screw speed on the process and on critical quality attributes of granules and tablets...
February 15, 2017: European Journal of Pharmaceutics and Biopharmaceutics
https://www.readbyqxmd.com/read/28214533/the-effect-and-mechanism-of-inhibiting-glucose-6-phosphate-dehydrogenase-activity-on-the-proliferation-of-plasmodium-falciparum
#4
Zhiqiang Zhang, Xiaodan Chen, Chengrui Jiang, Zishui Fang, Yi Feng, Weiying Jiang
We screened >40,000 patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency and found that the G6PD Kaiping allele was under the most positive selection for fighting against malaria in the Chinese population. However, the mechanism is unknown. The current study was designed to investigate the anti-malarial effect and mechanism of G6PD deficiency. Dehydroepiandrosterone (DHEA) was utilised for inhibiting the G6PD activity of erythrocytes. Giemsa staining of blood smears and quantitative real-time PCR were used for the detection and quantification of Plasmodium falciparum infection...
February 15, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28214449/-they-treated-me-like-crap-and-i-know-it-was-because-i-was-native-the-healthcare-experiences-of-aboriginal-peoples-living-in-vancouver-s-inner-city
#5
Ashley Goodman, Kim Fleming, Nicole Markwick, Tracey Morrison, Louise Lagimodiere, Thomas Kerr
There is growing evidence that Aboriginal peoples often experience healthcare inequalities due to racism. However, research exploring the healthcare experiences of Aboriginal peoples who use illicit substances is limited, and research rarely accounts for how multiple accounts of stigma intersect and contribute to the experiences of marginalized populations. Our research aimed to explore the healthcare experiences of Aboriginal peoples who use illicit drugs and or illicit alcohol (APWUID/A) living in Vancouver's inner city...
January 26, 2017: Social Science & Medicine
https://www.readbyqxmd.com/read/28214150/self-efficacy-for-deprescribing-a-survey-for-health-care-professionals-using-evidence-based-deprescribing-guidelines
#6
Barbara Farrell, Lisa Richardson, Lalitha Raman-Wilms, David de Launay, Mhd Wasem Alsabbagh, James Conklin
BACKGROUND: Although polypharmacy is associated with significant morbidity, deprescribing can be challenging. In particular, clinicians express difficulty with their ability to deprescribe (i.e. reduce or stop medications that are potentially inappropriate). Evidence-based deprescribing guidelines are designed to help clinicians take action on reducing or stopping medications that may be causing more harm than benefit. OBJECTIVES: Determine if implementation of evidence-based guidelines increases self-efficacy for deprescribing proton pump inhibitor (PPI), benzodiazepine receptor agonist (BZRA) and antipsychotic (AP) drug classes...
January 28, 2017: Research in Social & Administrative Pharmacy: RSAP
https://www.readbyqxmd.com/read/28214078/the-optimize-heart-failure-care-program-initial-lessons-from-global-implementation
#7
Martin R Cowie, Yuri M Lopatin, Clara Saldarriaga, Cândida Fonseca, David Sim, Jose Antonio Magaña, Denilson Albuquerque, Marcelo Trivi, Gustavo Moncada, Baldomero A González Castillo, Mario Osvaldo Speranza Sánchez, Edward Chung
Hospitalization for heart failure (HF) places a major burden on healthcare services worldwide, and is a strong predictor of increased mortality especially in the first three months after discharge. Though undesirable, hospitalization is an opportunity to optimize HF therapy and advise clinicians and patients about the importance of continued adherence to HF medication and regular monitoring. The Optimize Heart Failure Care Program (www.optimize-hf.com), which has been implemented in 45 countries, is designed to improve outcomes following HF hospitalization through inexpensive initiatives to improve prescription of appropriate drug therapies, patient education and engagement, and post-discharge planning...
February 12, 2017: International Journal of Cardiology
https://www.readbyqxmd.com/read/28213844/self-nanoemulsified-drug-delivery-system-of-hydrochlorothiazide-for-increasing-dissolution-rate-and-diuretic-activity
#8
Cassiana Mendes, Aline Buttchevitz, Jéssica Henriques Kruger, Thiago Caon, Patricia de Oliveira Benedet, Elenara Lemos-Senna, Marcos Antônio Segatto Silva
Hydrochlorothiazide (HCTZ) is a class IV drug according to the Biopharmaceutical Classification System. This study aimed the development of self-nanoemulsifying drug delivery system (SNEDDS) for HCTZ as an approach to overcome the biopharmaceutical limitations. Pre-formulation screening and ternary phase diagrams were carried out to select the oil phase, the surfactant, and the co-surfactant as the amount of each constituent. The optimized formulations, with reduced amount of surfactant, and composed of medium chain triglycerides, Cremophor EL and Transcutol P did not affect the pH or show drug incompatibilities...
February 17, 2017: AAPS PharmSciTech
https://www.readbyqxmd.com/read/28213330/drug-discovery-strategies-in-the-field-of-tumor-energy-metabolism-limitations-by-metabolic-flexibility-and-metabolic-resistance-to-chemotherapy
#9
REVIEW
N D Amoedo, E Obre, R Rossignol
The search for new drugs capable of blocking the metabolic vulnerabilities of human tumors has now entered the clinical evaluation stage, but several projects already failed in phase I or phase II. In particular, very promising in vitro studies could not be translated in vivo at preclinical stage and beyond. This was the case for most glycolysis inhibitors that demonstrated systemic toxicity. A more recent example is the inhibition of glutamine catabolism in lung adenocarcinoma that failed in vivo despite a strong addiction of several cancer cell lines to glutamine in vitro...
February 14, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28213294/a-low-cost-simplified-and-scaleable-pneumotachograph-and-face-mask-for-neonatal-mouse-respiratory-measurements
#10
Jenny J Sun, Roshan Nanu, Russell S Ray
INTRODUCTION: Neonatal respiratory disorders are a leading cause of perinatal mortality due to complications resulting from premature births and prenatal exposure to drugs of abuse, but optimal treatments for these symptoms are still unclear due to a variety of confounds and risk factors. Mouse models present an opportunity to study the underlying mechanisms and efficacy of potential treatments of these conditions with controlled variables. However, measuring respiration in newborn mice is difficult and commercial components are expensive and often require modification, creating a barrier and limiting our understanding of the short and long-term effects of birth complications on respiratory function...
February 14, 2017: Journal of Pharmacological and Toxicological Methods
https://www.readbyqxmd.com/read/28213276/engineering-approaches-in-sirna-delivery
#11
Anna Angela Barba, Sara Cascone, Diego Caccavo, Gaetano Lamberti, Gianluca Chiarappa, Michela Abrami, Gabriele Grassi, Mario Grassi, Giovanna Tomaiuolo, Stefano Guido, Valerio Brucato, Francesco Carfì Pavia, Giulio Ghersi, Vincenzo La Carrubba, Roberto Andrea Abbiati, Davide Manca
siRNAs are very potent drug molecules, able to silence genes involved in pathologies development. siRNAs have virtually an unlimited therapeutic potential, particularly for the treatment of inflammatory diseases. However, their use in clinical practice is limited because of their unfavorable properties to interact and not to degrade in physiological environments. In particular they are large macromolecules, negatively charged, which undergo rapid degradation by plasmatic enzymes, are subject to fast renal clearance/hepatic sequestration, and can hardly cross cellular membranes...
February 14, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/28213179/the-dispersion-releaser-technology-is-an-effective-method-for-testing-drug-release-from-nanosized-drug-carriers
#12
Christine Janas, Marc-Philip Mast, Li Kirsamer, Carlo Angioni, Fiona Gao, Werner Mäntele, Jennifer Dressman, Matthias G Wacker
The dispersion releaser (DR) is a dialysis-based setup for the analysis of the drug release from nanosized drug carriers. It is mounted into dissolution apparatus2 of the United States Pharmacopoeia. The present study evaluated the DR technique investigating the drug release of the model compound flurbiprofen from drug solution and from nanoformulations composed of the drug and the polymer materials poly (lactic acid), poly (lactic-co-glycolic acid) or Eudragit(®)RSPO. The drug loaded nanocarriers ranged in size between 185...
February 14, 2017: European Journal of Pharmaceutics and Biopharmaceutics
https://www.readbyqxmd.com/read/28213165/hbvcircle-a-novel-tool-to-investigate-hepatitis-b-virus-covalently-closed-circular-dna
#13
Zhipeng Yan, Jing Zeng, Youjun Yu, Kunlun Xiang, Hui Hu, Xue Zhou, Lili Gu, Li Wang, Jie Zhao, John A T Young, Lu Gao
BACKGROUND & AIMS: Hepatitis B virus (HBV) covalently closed circular DNA (cccDNA) persists as a stable episome in infected hepatocytes and serves as a template for the transcription of all viral genes. Due to the narrow host range of HBV, the development of a robust mouse model that supports cccDNA-dependent viral replication is a key hurdle in the development of novel HBV therapeutics. This study aimed to develop a novel tool to investigate HBV cccDNA. METHODS: Through minicircle technology, HBVcircle, a recombinant cccDNA, was easily generated and extracted from a genetically engineered E...
February 14, 2017: Journal of Hepatology
https://www.readbyqxmd.com/read/28213089/monoglyceride-lipase-as-a-drug-target-at-the-crossroads-of-arachidonic-acid-metabolism-and-endocannabinoid-signaling
#14
REVIEW
Gernot F Grabner, Robert Zimmermann, Rudolf Schicho, Ulrike Taschler
Monoglyerides (MGs) are short-lived, intermediary lipids deriving from the degradation of phospho- and neutral lipids, and monoglyceride lipase (MGL), also designated as monoacylglycerol lipase (MAGL), is the major enzyme catalyzing the hydrolysis of MGs into glycerol and fatty acids. This distinct function enables MGL to regulate a number of physiological and pathophysiological processes since both MGs and fatty acids can act as signaling lipids or precursors thereof. The most prominent MG species acting as signaling lipid is 2-arachidonoylglycerol (2-AG) which is the most abundant endogenous agonist of cannabinoid receptors in the body...
February 14, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28212943/effects-of-acute-dopaminergic-and-serotonergic-manipulations-in-the-aci-paradigm-depend-on-the-basal-valence-of-cognitive-judgement-bias-in-rats
#15
Joanna Golebiowska, Rafal Rygula
Recent findings have revealed that pharmacological enhancement of dopaminergic (DA) function by the administration of a DA precursor (dihydroxy-L-phenylalanine; L-DOPA), but not the selective serotonin reuptake inhibitor (SSRI) citalopram, increases an optimism bias in humans. To test whether dopamine might play a similar role in non-human animals, in the present study, we evaluated the effects of acute injections of L-DOPA, the D2 receptor antagonist haloperidol, and the SSRI escitalopram on cognitive judgement bias of rats in the ambiguous-cue interpretation (ACI) paradigm...
February 14, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28212667/assessing-the-interruption-of-the-transmission-of-human-helminths-with-mass-drug-administration-alone-optimizing-the-design-of-cluster-randomized-trials
#16
Roy Anderson, Sam Farrell, Hugo Turner, Judd Walson, Christl A Donnelly, James Truscott
BACKGROUND: A method is outlined for the use of an individual-based stochastic model of parasite transmission dynamics to assess different designs for a cluster randomized trial in which mass drug administration (MDA) is employed in attempts to eliminate the transmission of soil-transmitted helminths (STH) in defined geographic locations. The hypothesis to be tested is: Can MDA alone interrupt the transmission of STH species in defined settings? Clustering is at a village level and the choice of clusters of villages is stratified by transmission intensity (low, medium and high) and parasite species mix (either Ascaris, Trichuris or hookworm dominant)...
February 17, 2017: Parasites & Vectors
https://www.readbyqxmd.com/read/28212339/adamantane-in-drug-delivery-systems-and-surface-recognition
#17
REVIEW
Adela Štimac, Marina Šekutor, Kata Mlinarić-Majerski, Leo Frkanec, Ruža Frkanec
The adamantane moiety is widely applied in design and synthesis of new drug delivery systems and in surface recognition studies. This review focuses on liposomes, cyclodextrins, and dendrimers based on or incorporating adamantane derivatives. Our recent concept of adamantane as an anchor in the lipid bilayer of liposomes has promising applications in the field of targeted drug delivery and surface recognition. The results reported here encourage the development of novel adamantane-based structures and self-assembled supramolecular systems for basic chemical investigations as well as for biomedical application...
February 16, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28212183/cxcl12-cxcr4-signaling-contributes-to-the-pathogenesis-of-opioid-tolerance-a-translational-study
#18
Chih-Peng Lin, Kai-Hsiang Kang, Huang-Ju Tu, Ming-Yueh Wu, Tzu-Hung Lin, Houng-Chi Liou, Wei-Zen Sun, Wen-Mei Fu
BACKGROUND: Long-term opioid therapy for chronic pain may lead to analgesic tolerance, especially when administered intrathecally, thus preventing adequate pain relief. Discovering drug targets to treat opioid tolerance using a mechanism-based approach targeting opioid-induced neuroinflammation provides new therapeutic opportunities. In this study, we provide translational evidence that CXCL12/CXCR4 signaling contributes to the pathogenesis of opioid tolerance. METHODS: The CXCL12 levels in the cerebrospinal fluid of opioid-tolerant patients were compared with those of opioid-naive subjects...
March 2017: Anesthesia and Analgesia
https://www.readbyqxmd.com/read/28212092/modeling-contrast-imaging-assisted-optimal-targeted-drug-delivery-a-touchable-communication-channel-estimation-and-waveform-design-perspective
#19
Yifan Chen, Yu Zhou, Ross Murch, Panagiotis Kosmas
To maximize the effect of treatment and minimize the adverse effect on patients, we propose to optimize nanorobotsassisted targeted drug delivery (TDD) for locoregional treatment of tumor from the perspective of touchable communication channel estimation and waveform design. The drug particles are the information molecules; the loading/injection and unloading of the drug correspond to the transmitting and receiving processes; the concentration-time profile of the drug particles administered corresponds to the signalling pulse...
February 15, 2017: IEEE Transactions on Nanobioscience
https://www.readbyqxmd.com/read/28211784/generic-antiretrovirals-for-the-treatment-of-hiv-a-novel-challenge-for-western-countries-%C3%A2
#20
Dario Cattaneo, Massimo Andreoni, Gianpiero Carosi, Roberto Cauda, Adriano Lazzarin, Giuliano Rizzardini
The introduction of generic antiretroviral medications in developing countries has resulted in significant CD4 cell restoration, HIV viral decline, and a noteworthy reduction in the time to initiation of therapy. Projection models have also predicted significant cost saving associated with the extensive diffusion of generic antiretrovirals in developed countries. However, some uncertainties on generics have recently been raised. These concerns mainly relate to the adequacy of the study design for bioequivalence testing, the potential for uncontrolled switching from one generic to another, and the loss of adherence if patients switched from fixed-dose coformulations to single components in order to incorporate the new generic drugs...
February 17, 2017: International Journal of Clinical Pharmacology and Therapeutics
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