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https://www.readbyqxmd.com/read/29688015/a-peripherally-restricted-purine-antagonist-of-type-1-cannabinoid-cb1-receptor-blocks-alcoholic-steatosis-in-mice
#1
George Amato, Amruta Manke, Danni L Harris, Robert W Wiethe, Vineetha Vasukuttan, Rodney W Snyder, Timothy W Lefever, Ricardo Cortes, Yanan Zhang, Shaobin Wang, Scott P Runyon, Rangan Maitra
Type 1 cannabinoid receptor (CB1) antagonists have demonstrated promise for the treatment of obesity, liver disease, metabolic syndrome and dyslipidemias. However, inhibition of CB1 receptors in the central nervous system can produce adverse effects including depression, anxiety and suicidal ideation. Efforts are now underway to produce peripherally restricted CB1 antagonists to circumvent CNS-associated undesirable effects. In this study, a series of analogs were explored in which the 4-aminopiperidine group of 2 was replaced with aryl and heteroaryl substituted piperazine groups both with and without a spacer...
April 24, 2018: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29686657/naphthoquinone-derivatives-as-scaffold-to-develop-new-drugs-for-tuberculosis-treatment
#2
Priscila C B Halicki, Laís A Ferreira, Kelly C G De Moura, Paula F Carneiro, Karina P Del Rio, Tatiane Dos S C Carvalho, Maria do C F R Pinto, Pedro E A da Silva, Daniela F Ramos
Despite being a curable disease, tuberculosis (TB) remains a public health problem worldwide mainly due to lengthy treatment, as well as its toxic effects, TB/HIV co-infection and the emergence of resistant Mycobacterium tuberculosis strains. These barriers reinforcing the need for development of new antimicrobial agents, that ideally should reduce the time of treatment and be active against susceptible and resistant strains. Quinones are compounds found in natural sources and among them, the naphthoquinones show antifungal, antiparasitic, and antimycobacterial activity...
2018: Frontiers in Microbiology
https://www.readbyqxmd.com/read/29684988/influence-of-electrocautery-induced-electromagnetic-interference-on-quantitative-electroencephalographic-monitoring-of-hypnosis-during-general-anesthesia-comparison-between-the-adms%C3%A2-and-the-bis-vistatm
#3
Dae-Hee Kim, Ji-Young Yoo, Jong-Yeop Kim, Soo-Hwan Ahn, Seongsu Kim, Sang-Kee Min
Background: Hypnosis monitors analyze small-amplitude electrical signals transmitted from the brain that could be exposed to the electromagnetic field that occurs around the body during electrocautery (ECT). We investigated the influence of ECT on hypnosis monitoring during anesthesia. Methods: We simultaneously monitored BIS and uCON during 50 gynecologic oncology surgeries. During the episodes of ECT, we compared the absolute difference (a-Diff) between the baseline index and the most deviated index after ECT over either 30-60 s (ECT30-60) or more than 60 s (ECT > 60) between the monitors...
April 24, 2018: Korean Journal of Anesthesiology
https://www.readbyqxmd.com/read/29684687/arsenic-trioxide-inhibits-proliferation-and-induced-apoptosis-of-leukemia-stem-cells-with-drug-resistance
#4
Chunxia Liu, Hulai Wei, Xiaojian Yao, Bei Liu, Yaming Xi, Li Zhao
Acute myeloid leukemia (AML) patients show high relapse rates and some develop conventional chemotherapy resistance. Leukemia Stem Cells (LSCs) are the main player for AML relapses and drug resistance. K562/ADM cell, a leukemia resistant cell subtype, was used as leukemia multidrug resistant model to explore drug resistance of leukemia cells. We found that CD34+ CD38- , CD34+ CD38- CD123+ , cell surface markers of LSCs were significantly high expressed in K562/ADM cell, not in K562 cell with less drug resistance; compared with LSCs from K562, multidrug resistance protein P-gp and BCRP expression were significantly higher in K562/ADM cell...
March 2, 2018: Leukemia Research
https://www.readbyqxmd.com/read/29682897/an-aseptically-processed-acellular-reticular-allogenic-human-dermis-improves-healing-in-diabetic-foot-ulcers-a-prospective-randomised-controlled-multicentre-follow-up-trial
#5
Charles M Zelen, Dennis P Orgill, Thomas E Serena, Robert E Galiano, Marissa J Carter, Lawrence A DiDomenico, Jennifer Keller, Jarrod P Kaufman, William W Li
Aseptically processed human reticular acellular dermal matrix (HR-ADM) has been previously shown to improve wound closure in 40 diabetic patients with non-healing foot ulcers. The study was extended to 40 additional patients (80 in total) to validate and extend the original findings. The entire cohort of 80 patients underwent appropriate offloading and standard of care (SOC) during a 2-week screening period and, after meeting eligibility criteria, were randomised to receive weekly applications of HR-ADM plus SOC or SOC alone for up to 12 weeks...
April 22, 2018: International Wound Journal
https://www.readbyqxmd.com/read/29682695/two-decades-long-journey-from-riluzole-to-edaravone-revisiting-the-clinical-pharmacokinetics-of-the-only-two-amyotrophic-lateral-sclerosis-therapeutics
#6
REVIEW
Ranjeet Prasad Dash, R Jayachandra Babu, Nuggehally R Srinivas
The recent approval of edaravone has provided an intravenous option to treat amyotrophic lateral sclerosis (ALS) in addition to the existing oral agent, riluzole. The present work was primarily undertaken to provide a comprehensive clinical pharmacokinetic summary of the two approved ALS therapeutics. The key objectives of the review were to (i) tabulate the clinical pharmacokinetics of riluzole and edaravone with emphasis on absorption, distribution, metabolism and excretion (ADME) properties; (ii) provide a comparative scenario of the pharmacokinetics of the two drugs wherever possible; and (iii) provide perspectives and introspection on the gathered clinical pharmacokinetic data of the two drugs with appropriate conjectures to quench scientific curiosity...
April 23, 2018: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/29676776/gene-expression-analysis-of-neuropeptides-in-oral-mucosa-during-periodontal-disease-in-nonhuman-primates
#7
John Ferrin, Jeffrey L Ebersole, Sreenatha Kirakodu, David Jensen, Ahmad Al-Attar, Rebecca Peyyala, M John Novak, Dolph Dawson, Mohanad Al-Sabbagh, Arnold J Stromberg, Luis Orraca, Janis Gonzalez-Martinez, Armando Burgos, Octavio A Gonzalez
BACKGROUND: Neuropeptides (NPs) are innate pivotal regulators of the immunoinflammatory response. Nevertheless, their role in the pathogenesis of the periodontal disease remains unknown. We determined changes in gene expression of 10 NPs and 16 NP receptors (NPRs) coincident with the initiation, progression and resolution of periodontitis. METHODS: The ligature-induced periodontitis model was used in rhesus monkeys (n = 18). Gingival tissue samples were taken at baseline pre-ligature, 2 weeks and 1 month (Initiation), and 3 months (Progression) post-ligation...
April 20, 2018: Journal of Periodontology
https://www.readbyqxmd.com/read/29674661/donor-dependent-variation-of-human-umbilical-cord-blood-mesenchymal-stem-cells-in-response-to-hypoxic-preconditioning-and-amelioration-of-limb-ischemia
#8
Insung Kang, Byung-Chul Lee, Soon Won Choi, Jin Young Lee, Jae-Jun Kim, Bo-Eun Kim, Da-Hyun Kim, Seung Eun Lee, Nari Shin, Yoojin Seo, Hyung-Sik Kim, Dong-Ik Kim, Kyung-Sun Kang
With the rapidly growing demand for mesenchymal stem cell (MSC) therapy, numerous strategies using MSCs for different diseases have been studied and reported. Because of their immunosuppressive properties, MSCs are commonly used as an allogeneic treatment. However, for the many donors who could potentially be used, it is important to understand the capacity for therapeutic usage with donor-to-donor heterogeneity. In this study, we aimed to investigate MSCs as a promising therapeutic strategy for critical limb ischemia...
April 20, 2018: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/29673791/the-effects-of-polysaccharides-from-auricularia-auricula-huaier-in-adjuvant-anti-gastrointestinal-cancer-therapy-a-systematic-review-and-network-meta-analysis
#9
REVIEW
Yan Ma, Chen Wang, Qi Zhang, Xia Peng, Ying Feng, Xianjun Meng
The aim of this study was to assess the comparative efficacy and safety of polysaccharides from Auricularia auricula (Huaier) for patients with gastrointestinal cancers (GICs) through a systematic review and network meta-analysis. We performed a network meta-analysis to identify evidence from clinical trials. We searched databases for publications up to February 2018. The prespecified primary efficacy outcomes were clinical therapeutic effects, which included the treatment response rate, 0.5-year overall survival rate, 1-year overall survival rate, 2-year overall survival rate, KPS improved rate and AFP decreased rate...
April 16, 2018: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/29672633/design-synthesis-dft-docking-studies-and-adme-prediction-of-some-new-coumarinyl-linked-pyrazolylthiazoles-potential-standalone-or-adjuvant-antimicrobial-agents
#10
Sunil Kumar, Vikram Saini, Indresh K Maurya, Jayant Sindhu, Mukesh Kumari, Ramesh Kataria, Vinod Kumar
The control of antimicrobial resistance (AMR) seems to have come to a dead end. The major consequences of the use and abuse of antibacterial drugs are the development of resistant strains due to genetic mutability of both pathogenic and nonpathogenic microorganisms. We, herein, report the synthesis, characterization and biological activities of coumarin-thiazole-pyrazole (CTP) molecular hybrids with an effort to explore and overcome the increasing antimicrobial resistance. The compounds were characterized by analyzing their IR, Mass, 1H and13C NMR spectral data and elemental analysis...
2018: PloS One
https://www.readbyqxmd.com/read/29671277/reduced-adrenomedullin-parallels-microtubule-dismantlement-in-frontotemporal-lobar-degeneration
#11
Hilda Ferrero, Ignacio M Larrayoz, Maite Solas, Alfredo Martínez, María J Ramírez, Francisco J Gil-Bea
Tau is a microtubule-associated protein highly expressed in neurons with a chief role in microtubule dynamics and axonal maintenance. Adrenomedullin gene (ADM) codifies for various peptides that exert broad range of actions in the body. Previous works in our groups have shown that increased ADM products are positively correlated to microtubule disruption and tau pathology in Alzheimer's disease brains. In the present study, we explore the involvement of ADM in the neuropathology of frontotemporal lobar degeneration that presents with primary tauopathy (FTLD-tau)...
April 18, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/29670707/modulating-adme-properties-by-fluorination-mk2-inhibitors-with-improved-oral-exposure
#12
Juraj Velcicky, Achim Schlapbach, Richard Heng, Laszlo Revesz, Daniel Pflieger, Ernst Blum, Stuart Hawtin, Christine Huppertz, Roland Feifel, Rene Hersperger
MAP-activated protein kinase 2 (MK2) plays an important role in the regulation of innate immune response as well as in cell survival upon DNA damage. Despite its potential for the treatment of inflammation and cancer, to date no MK2 low molecular weight inhibitors have reached the clinic, mainly due to inadequate absorption, distribution, metabolism, and excretion (ADME) properties. We describe here an approach based on specifically placed fluorine within a recently described pyrrole-based MK2 inhibitor scaffold for manipulation of its physicochemical and ADME properties...
April 12, 2018: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/29668947/incidence-and-predictors-of-success-of-adalimumab-dose-escalation-and-de-escalation-in-ulcerative-colitis-a-real-world-belgian-cohort-study
#13
Saartje Van de Vondel, Filip Baert, Christine Reenaers, Stijn Vanden Branden, Leila Amininejad, Pieter Dewint, Wouter Van Moerkercke, Jean-François Rahier, Pieter Hindryckx, Peter Bossuyt, Marc Ferrante
Background: Adalimumab (ADM) has been shown efficacious in ulcerative colitis (UC). In randomized controlled trials, dose escalation from 40 mg ADM every other week to 40 mg every week was required in 20%-25% of patients within 1 year. Real-life data suggest higher escalation rates. Attempts for dose de-escalation have not been studied yet. We assessed the need for, outcome of, and predictors of dose escalation and de-escalation in a large retrospective cohort of UC patients treated with ADM...
April 13, 2018: Inflammatory Bowel Diseases
https://www.readbyqxmd.com/read/29667556/ultrasound-promoted-green-synthesis-docking-study-of-indole-spliced-thiadiazole-%C3%AE-amino-phosphonates-as-anticancer-agents-and-anti-tyrosinase-agents
#14
Anna Pratima G Nikalje, Pramod Gawhane, Shailee Tiwari, Jaiprakash Sangshetti, Manoj Damale
In this work, a new series of diethyl ((1H-indole-3-yl)((5-phenyl-1,3,4-thiadiazole-2- yl)amino)methyl)phosphonate derivatives 6(a-j) were designed and synthesized in Ultrasound by green protocol using Kabachnik-Fields reaction. The structures of the synthesized compounds were confirmed by spectral analysis such as elemental analyses, IR, 1H NMR, 13C NMR, 31P NMR and mass spectra. The synthesized compounds 6(a-j) were appraised for their in vitro anticancer activity against human cancer cell lines such as SK-MEL-2 (melanoma), IMR-32 (Neuroblastoma), HT-29(Colon) and also on normal murine embryonic fibroblast NIH/3T3 by Sulforhodamine B (SRB) assay, using Adriamycin as a standard drug...
April 17, 2018: Anti-cancer Agents in Medicinal Chemistry
https://www.readbyqxmd.com/read/29666911/dual-coverage-of-the-inferior-pole-with-conjoined-fascial-flap-and-acellular-dermal-matrix-for-immediate-one-stage-breast-reconstruction-with-a-prosthetic-implant
#15
Seo H Lee, Yong S Chun, Heung K Park, Yang W Kim, Young W Cheon
BACKGROUND: Elevation of a conjoined fascial flap composed of the pectoralis major, serratus anterior, and external oblique fascia is a type of surgical technique using autologous tissue to cover the lower pole after immediate one-stage direct-to-implant (DTI) breast reconstruction. However, volumetric breast implants hinder use of this technique alone. For better structural stability and more aesthetically favorable breast contour in large breasts, we have devised a technique involving dual coverage of the lower pole by a conjoined fascial flap and acellular dermal matrix (ADM)...
April 17, 2018: Aesthetic Plastic Surgery
https://www.readbyqxmd.com/read/29665687/identification-of-fast-acting-2-6-disubstituted-imidazopyridines-that-are-efficacious-in-the-in-vivo-humanized-plasmodium-falciparum-nodscidil2r%C3%AE-null-mouse-model-of-malaria
#16
Aloysius T Nchinda, Claire Le Manach, Tanya Paquet, Diego Gonzalez Cabrera, Kathryn J Wicht, Christel Brunschwig, Mathew Njoroge, Efrem Abay, Dale Taylor, Nina Lawrence, Sergio Wittlin, Maria-Belen Jimenez-Diaz, Maria Santos Martínez-Martínez, Santiago Ferrer, Iñigo Angulo-Barturen, Maria Jose Lafuente-Monasterio, James Duffy, Jeremy N Burrows, Leslie J Street, Kelly Chibale
Optimization of a chemical series originating from whole-cell phenotypic screening against the human malaria parasite, Plasmodium falciparum, led to the identification of two promising 2,6-disubstituted imidazopyridine compounds, 43 and 74. These compounds exhibited potent activity against asexual blood stage parasites that, together with their in vitro Absorption, Distribution, Metabolism, and Excretion (ADME) properties, translated to in vivo efficacy with clearance of parasites in the PfSCID mouse model for malaria within 48 h of treatment...
April 17, 2018: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29663841/novel-heart-failure-biomarkers-why-do-we-fail-to-exploit-their-potential
#17
Arnold Piek, Weijie Du, Rudolf A de Boer, Herman H W Silljé
Plasma biomarkers are useful tools in the diagnosis and prognosis of heart failure (HF). In the last decade, numerous studies have aimed to identify novel HF biomarkers that would provide superior and/or additional diagnostic, prognostic, or stratification utility. Although numerous biomarkers have been identified, their implementation in clinical practice has so far remained largely unsuccessful. Whereas cardiac-specific biomarkers, including natriuretic peptides (ANP and BNP) and high sensitivity troponins (hsTn), are widely used in clinical practice, other biomarkers have not yet proven their utility...
April 17, 2018: Critical Reviews in Clinical Laboratory Sciences
https://www.readbyqxmd.com/read/29663320/predictors-of-complications-after-direct-to-implant-breast-reconstruction-with-an-acellular-dermal-matrix-from-a-multicentre-randomized-clinical-trial
#18
V L Negenborn, R E G Dikmans, M B Bouman, H A H Winters, J W R Twisk, P Q Ruhé, M A M Mureau, J M Smit, S Tuinder, J Hommes, Y Eltahir, N A S Posch, J M van Steveninck-Barends, M A Meesters-Caberg, R R W J van der Hulst, M J P F Ritt, M G Mullender
BACKGROUND: In the multicentre randomized trial BRIOS (Breast Reconstruction In One Stage), direct-to-implant (DTI) breast reconstruction with an acellular dermal matrix (ADM) was associated with a markedly higher postoperative complication rate compared with two-stage tissue expander/implant breast reconstruction. This study aimed to identify factors that contribute to the occurrence of complications after DTI ADM-assisted breast reconstruction. METHODS: Data were obtained from the BRIOS study, including all patients treated with DTI ADM-assisted breast reconstruction...
April 16, 2018: British Journal of Surgery
https://www.readbyqxmd.com/read/29660671/computational-study-of-molecular-electrostatic-potential-docking-and-dynamics-simulations-of-gallic-acid-derivatives-as-abl-inhibitors
#19
K R Raghi, D R Sherin, M J Saumya, P S Arun, V N Sobha, T K Manojkumar
Chronic myeloid leukemia (CML), a hematological malignancy arises due to the spontaneous fusion of the BCR and ABL gene, resulting in a constitutively active tyrosine kinase (BCR-ABL). Pharmacological activity of Gallic acid and 1,3,4-Oxadiazole as potential inhibitors of ABL kinase has already been reported. Objective of this study is to evaluate the ABL kinase inhibitory activity of derivatives of Gallic acid fused with 1,3,4-Oxadiazole moieties. Attempts have been made to identify the key structural features responsible for drug likeness of the Gallic acid and the 1,3,4-Oxadiazole ring using molecular electrostatic potential maps (MESP)...
April 5, 2018: Computational Biology and Chemistry
https://www.readbyqxmd.com/read/29659450/aseptic-freeze-dried-vs-sterile-wet-packaged-human-cadaveric-acellular-dermal-matrix-adm-in-immediate-tissue-expander-breast-reconstruction-a-propensity-score-analysis-study
#20
Summer E Hanson, Jesse D Meaike, Jesse C Selber, Jun Liu, Liang Li, Victor J Hassid, Donald P Baumann, Charles E Butler, Patrick B Garvey
BACKGROUND: Although multiple acellular dermal matrix (ADM) sources exist, it is unclear how ADM processing impacts complication rates. We compared complications between two preparations of human cadaveric ADM (freeze dried [hADM-FD] and ready to use [hADM-RTU]) in immediate tissue expander (TE) breast reconstruction to analyze the effect of processing on complications. HADM-FD is aseptic while hADM-RTU is sterilized and wet-packaged. METHODS: We retrospectively reviewed all TE breast reconstructions with hADM-FD or hADM-RTU at a single center between 2006 and 2016...
January 20, 2018: Plastic and Reconstructive Surgery
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