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https://www.readbyqxmd.com/read/28541760/inhibition-of-proteases-activity-in-intestine-needs-a-sustainable-acidic-environment-rather-than-a-transient
#1
Chang Xing, Jin-Feng Xing, Zhi-Qiang Ge
α-Chymotrypsin (α-CT) and trypsin are important components of the enzymatic barrier. They could degrade the therapeutic proteins and peptides, inhibit their activity consequently, and thereby reduce their oral bioavailability. Acidic agents, as one type of indirect protease inhibitors, have shown proof of concept in clinical trials. We report here the inactivated proteases due to acid influence can be reactivated immediately by environmental pH recovery regardless of how long the inactivation last. To keep the inactivation time of proteases for 4 to 5 h, we designed and prepared a sustained-release tablet containing citric acid (CA) which can effectively reduce the pH below 5...
May 25, 2017: Drug Development and Industrial Pharmacy
https://www.readbyqxmd.com/read/28535453/inhibition-of-neddylation-modification-sensitizes-pancreatic-cancer-cells-to-gemcitabine
#2
Hua Li, Weihua Zhou, Lihui Li, Jianfu Wu, Xiaoli Liu, Lili Zhao, Lijun Jia, Yi Sun
Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer death in the USA with a 5-year survival rate less than 3% to 5%. Gemcitabine remains as a standard care for PDAC patients. Although protein neddylation is abnormally activated in many human cancers, whether neddylation dysregulation is involved in PDAC and whether targeting neddylation would sensitize pancreatic cancer cells to gemcitabine remain elusive. Here we report that high expression of neddylation components, NEDD8 and NAE1, are associated with poor survival of PDAC patients...
May 20, 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/28533093/safety-and-immunogenicity-of-a-live-attenuated-influenza-h5-candidate-vaccine-strain-a-17-turkey-turkey-05-133-h5n2-and-its-priming-effects-for-potential-pre-pandemic-use-a-randomised-double-blind-placebo-controlled-trial
#3
Punnee Pitisuttithum, Kobporn Boonnak, Supat Chamnanchanunt, Pilaipan Puthavathana, Viravarn Luvira, Hatairat Lerdsamran, Jaranit Kaewkungwal, Saranath Lawpoolsri, Vipa Thanachartwet, Udomsak Silachamroon, Wanibtisam Masamae, Alexandra Schuetz, Ponthip Wirachwong, Sit Thirapakpoomanunt, Larisa Rudenko, Erin Sparrow, Martin Friede, Marie-Paule Kieny
BACKGROUND: The emergence of highly pathogenic avian influenza H5N1 viruses has raised concerns about their pandemic potential. Vaccination is the most effective way of preventing influenza. In this study, we investigated the safety and immunogenicity of an avian H5N2 live attenuated influenza vaccine (LAIV H5N2) in healthy Thai adults and its priming immune responses with an H5N1 inactivated vaccine boost. METHODS: This study was done at the Vaccine Trial Centre at Mahidol University, Bangkok, Thailand and was divided into two parts...
May 19, 2017: Lancet Infectious Diseases
https://www.readbyqxmd.com/read/28531392/a-randomised-controlled-feasibility-and-proof-of-concept-trial-in-delayed%C3%A2-gastric-emptying-when-metoclopramide-fails-we-should-revisit%C3%A2-nasointestinal-feeding-versus-dual-prokinetic-treatment-achieving-goal-nutrition-in-critical-illness-and-delayed-gastric
#4
Stephen J Taylor, Kaylee Allan, Helen McWilliam, Alex Manara, Jules Brown, Rosemary Greenwood, Deirdre Toher
BACKGROUND & AIMS: Delayed gastric emptying (DGE) commonly limits the use of enteral nutrition (EN) and may increase ventilator-associated pneumonia. Nasointestinal feeding has not been tested against dual prokinetic treatment (Metoclopramide and Erythromycin) in DGE refractory to metoclopramide. This trial tests the feasibility of recruiting this 'treatment-failed' population and the proof of concept that nasointestinal (NI) feeding can increase the amount of feed tolerated (% goal) when compared to nasogastric (NG) feeding plus metoclopramide and erythromycin treatment...
August 2016: Clinical Nutrition ESPEN
https://www.readbyqxmd.com/read/28530684/tackling-hiv-and-aids-contributions-by-non-human-primate-models
#5
Koen K A Van Rompay
During the past three decades, non-human primate (NHP) models have gained an increasing importance in HIV basic and translational research. In contrast to natural host models, infection of macaques with virulent simian or simian-human immunodeficiency viruses (SIV, SHIV) results in a disease that closely resembles HIV infection and AIDS. Although there is no perfect animal model, and each of the available models has its benefits and limitations, carefully designed NHP studies with selection of experimental variables have unraveled important questions of basic pathogenesis and have provided the tools to explore and screen intervention strategies...
May 22, 2017: Lab Animal
https://www.readbyqxmd.com/read/28526488/-targeting-the-gut-liver-axis-in-liver-disease
#6
REVIEW
Reiner Wiest, Agustin Albillos, Michael Trauner, Jashmohan Bajaj, Rajiv Jalan
The gut is open to the outer environment, harbours the microbiome containing several fold more genetic material than the human genome and produces a myriad of metabolites as well as hormones/peptides. The liver is at the nexus between this vast source of nutrients, toxins and hormones and the remaining human body. Not surprisingly, this liver-gut-axis has hence, been demonstrated in experimental models and in-vitro systems to contribute to the pathogenesis of most liver diseases such as alcoholic and non-alcoholic fatty liver disease (NAFLD), -steatohepatitis (NASH), cholestatic liver diseases, hepatocellular carcinoma, acute-on-chronic liver failure, progression to fibrosis/cirrhosis and complications of cirrhosis...
May 16, 2017: Journal of Hepatology
https://www.readbyqxmd.com/read/28515847/pacemaker-recycling-a-notion-whose-time-has-come
#7
REVIEW
Mason W Runge, Timir S Baman, Sheldon Davis, Kevin Weatherwax, Ed Goldman, Kim A Eagle, Thomas C Crawford
The purpose of this paper is to summarize the need, feasibility, safety, legality, and ethical perspectives of pacemaker reutilization in low- and middle-income countries (LMICs). It will also describe, in-depth, Project My Heart Your Heart (PMHYH) as a model for pacemaker reuse in LMICs. The primary source of the discussion points in this paper is a collection of 14 publications produced by the research team at the University of Michigan and its collaborative partners. The need for pacemaker reutilization in LMICs is evident...
April 26, 2017: World Journal of Cardiology
https://www.readbyqxmd.com/read/28499585/multipotent-adult-progenitor-cells-improve-the-hematopoietic-function-in-myelodysplasia
#8
Valerie D Roobrouck, Esther Wolfs, Michel Delforge, Dorien Broekaert, Soumen Chakraborty, Kathleen Sels, Thomas Vanwelden, Bryan Holvoet, Larissa Lhoest, Satish Khurana, Shubham Pandey, Chloé Hoornaert, Peter Ponsaerts, Tom Struys, Nancy Boeckx, Peter Vandenberghe, Christophe M Deroose, Catherine M Verfaillie
BACKGROUND AIMS: Myelodysplastic syndromes (MDS) are a group of clonal stem cell disorders affecting the normal hematopoietic differentiation process and leading to abnormal maturation and differentiation of all blood cell lineages. Treatment options are limited, and there is an unmet medical need for effective therapies for patients with severe cytopenias. METHODS: We demonstrate that multipotent adult progenitor cells (MAPC) improve the function of hematopoietic progenitors derived from human MDS bone marrow (BM) by significantly increasing the frequency of primitive progenitors as well as the number of myeloid colonies...
June 2017: Cytotherapy
https://www.readbyqxmd.com/read/28499418/early-morning-urine-collection-to-improve-urinary-lateral-flow-lam-assay-sensitivity-in-hospitalised-patients-with-hiv-tb-co-infection
#9
Phindile Gina, Philippa J Randall, Tapuwa E Muchinga, Anil Pooran, Richard Meldau, Jonny G Peter, Keertan Dheda
BACKGROUND: Urine LAM testing has been approved by the WHO for use in hospitalised patients with advanced immunosuppression. However, sensitivity remains suboptimal. We therefore examined the incremental diagnostic sensitivity of early morning urine (EMU) versus random urine sampling using the Determine® lateral flow lipoarabinomannan assay (LF-LAM) in HIV-TB co-infected patients. METHODS: Consenting HIV-infected inpatients, screened as part of a larger prospective randomized controlled trial, that were treated for TB, and could donate matched random and EMU samples were included...
May 12, 2017: BMC Infectious Diseases
https://www.readbyqxmd.com/read/28498501/ppar-gamma-agonist-pioglitazone-modifies-craving-intensity-and-brain-white-matter-integrity-in-patients-with-primary-cocaine-use-disorder-a-double-blind-randomized-controlled-pilot-trial
#10
Joy M Schmitz, Charles E Green, Khader M Hasan, Jessica Vincent, Robert Suchting, Michael F Weaver, F Gerard Moeller, Ponnada A Narayana, Kathryn A Cunningham, Kelly T Dineley, Scott D Lane
BACKGROUND AND AIMS: Pioglitazone (PIO), a potent agonist of PPAR-gamma, is a promising candidate treatment for cocaine use disorder (CUD). We tested the effects of PIO on targeted mechanisms relevant to CUD: cocaine craving and brain white matter (WM) integrity. Feasibility, medication compliance, and tolerability were evaluated. DESIGN: Two-arm double-blind randomized controlled proof-of-concept pilot trial of PIO or placebo (PLC). SETTING: Single-site outpatient treatment research clinic in Houston, Texas, USA...
May 12, 2017: Addiction
https://www.readbyqxmd.com/read/28490518/chk1-inhibition-in-small-cell-lung-cancer-produces-single-agent-activity-in-biomarker-defined-disease-subsets-and-combination-activity-with-cisplatin-or-olaparib
#11
Triparna Sen, Pan Tong, C Allison Stewart, Sandra Cristea, Aly Valliani, David S Shames, Abena Redwood, Youhong Fan, Lerong Li, Bonnie S Glisson, John Minna, Julien Sage, Don L Gibbons, Helen Piwnica-Worms, John Heymach, Jing Wang, Lauren Averett Byers
Effective targeted therapies for small cell lung cancer (SCLC), the most aggressive form of lung cancer, remain urgently needed. Here we report evidence of preclinical efficacy evoked by targeting the overexpressed cell cycle checkpoint kinase CHK1 in SCLC. Our studies employed RNAi-mediated attenuation or pharmacological blockade with the novel second-generation CHK1 inhibitor prexasertib (LY2606368), currently in clinical trials. In SCLC models in vitro and in vivo, LY2606368 exhibited strong single-agent efficacy, augmented the effects of cisplatin or the PARP inhibitor olaparib, and improved the response of platinum-resistant models...
May 10, 2017: Cancer Research
https://www.readbyqxmd.com/read/28489642/pupillary-reflex-for-evaluation-of-thoracic-paravertebral-block-a-prospective-observational-feasibility-study
#12
Baptiste Duceau, Mélanie Baubillier, Gaëlle Bouroche, Aline Albi-Feldzer, Christian Jayr
BACKGROUND: Although thoracic paravertebral block (TPVB) is recommended in major breast surgery, there is no gold standard to assess the success of TPVB. Pupillary dilation reflex (PDR) is the variation of the pupillary diameter after a noxious stimulus. The objective was to evaluate the feasibility of recording the PDR to assess analgesia in an anesthetized thoracic dermatome after TPVB. METHODS: This prospective, observational, single-center study included 32 patients requiring breast surgery under general anesthesia and TPVB...
May 4, 2017: Anesthesia and Analgesia
https://www.readbyqxmd.com/read/28480302/efficacy-of-gene-therapy-is-dependent-on-disease-progression-in-dystrophic-mice-with-mutations-in-the-fkrp-gene
#13
Charles Harvey Vannoy, Will Xiao, Peijuan Lu, Xiao Xiao, Qi Long Lu
Loss-of-function mutations in the Fukutin-related protein (FKRP) gene cause limb-girdle muscular dystrophy type 2I (LGMD2I) and other forms of congenital muscular dystrophy-dystroglycanopathy that are associated with glycosylation defects in the α-dystroglycan (α-DG) protein. Systemic administration of a single dose of recombinant adeno-associated virus serotype 9 (AAV9) vector expressing human FKRP to a mouse model of LGMD2I at various stages of disease progression was evaluated. The results demonstrate rescue of functional glycosylation of α-DG and muscle function, along with improvements in muscle structure at all disease stages versus age-matched untreated cohorts...
June 16, 2017: Molecular Therapy. Methods & Clinical Development
https://www.readbyqxmd.com/read/28474383/intraperitoneal-insulin-delivery-provides-superior-glycemic-regulation-to-subcutaneous-insulin-delivery-in-model-predictive-control-based-fully-automated-artificial-pancreas-in-patients-with-type-1-diabetes-a-pilot-study
#14
Eyal Dassau, Eric Renard, Jérôme Place, Anne Farret, Marie-José Pelletier, Justin Lee, Lauren M Huyett, Ankush Chakrabarty, Francis J Doyle, Howard C Zisser
AIMS: To compare intraperitoneal (IP) to subcutaneous (SC) insulin delivery in an artificial pancreas (AP). MATERIALS AND METHODS: Ten adults with type 1 diabetes participated in a non-randomized, non-blinded sequential AP study using the same SC glucose sensing and Zone Model Predictive Control (ZMPC) algorithm adjusted for insulin clearance. On first admission, subjects underwent closed-loop control with SC delivery of a fast-acting insulin analogue for 24 hr...
May 5, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28469496/use-and-misuse-of-aspirin-in-primary-cardiovascular-prevention
#15
REVIEW
Sergio Coccheri
The use of low-dose aspirin in primary prevention of cardiovascular (CV) events in healthy or apparently healthy people is a widely debated topic. Many arguments indicate that "primary prevention" is only a conventional definition and that the transition from primary to secondary prevention represents a continuum of increasing levels of CV risk. Although there are no direct proofs of a different efficacy of aspirin at different CV risk levels, in low-risk populations aspirin will appear to be less efficient...
2017: Clinical Medicine Insights. Cardiology
https://www.readbyqxmd.com/read/28467301/introduction-of-a-male-harming-mitochondrial-haplotype-via-trojan-females-achieves-population-suppression-in-fruit-flies
#16
Jonci Nikolai Wolff, Neil J Gemmell, Daniel M Tompkins, Damian K Dowling
Pests are a global threat to biodiversity, ecosystem function, and human health. Pest control approaches are thus numerous, but their implementation costly, damaging to non-target species, and ineffective at low population densities. The Trojan Female Technique (TFT) is a prospective self-perpetuating control technique that is species-specific and predicted to be effective at low densities. The goal of the TFT is to harness naturally occurring mutations in the mitochondrial genome that impair male fertility while having no effect on females...
May 3, 2017: ELife
https://www.readbyqxmd.com/read/28459045/re-engineering-alzheimer-clinical-trials-global-alzheimer-s-platform-network
#17
J Cummings, P Aisen, R Barton, J Bork, R Doody, J Dwyer, J C Egan, H Feldman, D Lappin, L Truyen, S Salloway, R Sperling, G Vradenburg
Alzheimer's disease (AD) drug development is costly, time-consuming, and inefficient. Trial site functions, trial design, and patient recruitment for trials all require improvement. The Global Alzheimer Platform (GAP) was initiated in response to these challenges. Four GAP work streams evolved in the US to address different trial challenges: 1) registry-to-cohort web-based recruitment; 2) clinical trial site activation and site network construction (GAP-NET); 3) adaptive proof-of-concept clinical trial design; and 4) finance and fund raising...
June 2016: Journal of Prevention of Alzheimer's Disease
https://www.readbyqxmd.com/read/28450365/critical-issues-for-the-translation-of-cardioprotection
#18
REVIEW
Gerd Heusch
The translation from numerous successful animal experiments on cardioprotection beyond that by reperfusion to clinical practice has to date been disappointing. Animal experiments often use reductionist approaches and are mostly performed in young and healthy animals which lack the risk factors, comorbidities, and comedications which are characteristics of patients suffering an acute myocardial infarction or undergoing cardiovascular surgery. Conceptually, it is still unclear by how much the time window for successful reperfusion is extended by preconditioning, and how long the duration of ischemia can be so that adjunct cardioprotection by postconditioning at reperfusion still protects...
April 28, 2017: Circulation Research
https://www.readbyqxmd.com/read/28449038/real-time-imaging-of-single-neuronal-cell-apoptosis-in-patients-with-glaucoma
#19
Maria F Cordeiro, Eduardo M Normando, M Jorge Cardoso, Serge Miodragovic, Seham Jeylani, Benjamin M Davis, Li Guo, Sebastien Ourselin, Roger A'Hern, Philip A Bloom
HASH(0x48c4078)
June 1, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/28448426/orexin-receptor-antagonism-in-painful-diabetic-neuropathy-a-phase-2-trial-with-filorexant
#20
W Joseph Herring, Joy Y Ge, Saheeda Jackson, Christopher Assaid, Kathryn M Connor, David Michelson
OBJECTIVES: To evaluate whether orexin receptor antagonism with filorexant provides pain relief in patients with painful diabetic neuropathy (PDN). METHODS: In this double-blind, placebo-controlled, enriched-enrollment, randomized-withdrawal proof-of-concept study, patients with PDN (aged 18-75 y) entered a 2-week, single-blind active run-in period with filorexant 10 mg nightly, before randomization 1:1 to placebo or filorexant in a 2-week, double-blind treatment period...
April 26, 2017: Clinical Journal of Pain
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