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https://www.readbyqxmd.com/read/30221554/discovery-of-novel-fragments-inhibiting-o-acetylserine-sulphhydrylase-by-combining-scaffold-hopping-and-ligand-based-drug-design
#1
Joana Magalhães, Nina Franko, Giannamaria Annunziato, Martin Welch, Stephen K Dolan, Agostino Bruno, Andrea Mozzarelli, Stefano Armao, Aigars Jirgensons, Marco Pieroni, Gabriele Costantino, Barbara Campanini
Several bacteria rely on the reductive sulphur assimilation pathway, absent in mammals, to synthesise cysteine. Reduction of virulence and decrease in antibiotic resistance have already been associated with mutations on the genes that codify cysteine biosynthetic enzymes. Therefore, inhibition of cysteine biosynthesis has emerged as a promising strategy to find new potential agents for the treatment of bacterial infection. Following our previous efforts to explore OASS inhibition and to expand and diversify our library, a scaffold hopping approach was carried out, with the aim of identifying a novel fragment for further development...
December 2018: Journal of Enzyme Inhibition and Medicinal Chemistry
https://www.readbyqxmd.com/read/30221456/-1-aryloxy-2-hydroxypropyl-phenylpiperazine-derivatives-suppress-candida-albicans-virulence-by-interfering-with-morphological-transition
#2
Shuo Zhao, Jun-Jun Huang, Xiuyun Sun, Xiaorong Huang, Shuna Fu, Liang Yang, Xue-Wei Liu, Fei He, Yinyue Deng
Clinical treatment of Candida albicans infections has become more difficult due to the limited development of antifungal agents and the rapid emergence of drug resistance. In this study, we demonstrate the synthesis of a series of piperazine derivatives and the evaluation of their inhibitory activity against C. albicans virulence. Thirty-four (1-aryloxy-2-hydroxypropyl)-phenylpiperazine derivatives, including 25 new compounds, were synthesized and assessed for their efficacy against the physiology and pathogenesis of C...
September 17, 2018: Microbial Biotechnology
https://www.readbyqxmd.com/read/30221440/phenolic-building-blocks-for-the-assembly-of-functional-materials
#3
Md Arifur Rahim, Samantha L Kristufek, Shuaijun Pan, Joseph J Richardson, Frank Caruso
Phenolic materials have long been known for their use in inks, wood coatings, and leather tanning. However, recently there has been a renewed interest in engineering advanced materials from phenolic building blocks. The intrinsic properties of phenolic compounds, such as metal chelation, hydrogen bonding, pH responsiveness, redox potentials, radical scavenging, polymerization, and light absorbance, have made them a distinct class of structural motifs for the synthesis of functional materials. Materials prepared from phenolic compounds often retain many of these useful properties with synergistic effects in applications ranging from catalysis to biomedicine...
September 16, 2018: Angewandte Chemie
https://www.readbyqxmd.com/read/30220703/central-nervous-system-bleeding-after-a-lumbar-puncture-still-an-ongoing-complication
#4
Christer Sawaya, Raja Sawaya
BACKGROUND A lumbar puncture is a procedure performed to uncover the state of the central nervous system by analysis of the cerebrospinal fluid. It is done also to infuse medications in the subdural space. A lumbar puncture should not cause central nervous system bleeding, but this complication is still occurring in certain cases. CASE REPORT We present 2 cases where a lumbar puncture was performed in the emergency department. The first patient had severe inflammatory lower back pain and received epidural steroids through a lumbar puncture and the second case presented with the clinical picture of meningitis and a lumbar puncture was performed for diagnostic purposes...
September 17, 2018: American Journal of Case Reports
https://www.readbyqxmd.com/read/30220578/the-open-insulin-project-a-case-study-for-biohacked-medicines
#5
REVIEW
Jenna E Gallegos, Christopher Boyer, Eleanore Pauwels, Warren A Kaplan, Jean Peccoud
New innovation ecosystems are emerging that challenge the complex intellectual property and regulatory landscape surrounding drug development in the United States (US). A prime example is an initiative known as the Open Insulin Project. The goal of the project is to sidestep patents and enable generic manufacturers to produce cheaper insulin. However, the US regulatory environment, not patent exclusivity, is the main barrier to insulin affordability. If the Open Insulin Project succeeds in releasing an open protocol for insulin manufacturing, follow-on work could enable a number of new insulin production ecosystems, including 'home-brewed' insulin...
August 9, 2018: Trends in Biotechnology
https://www.readbyqxmd.com/read/30220531/dynamics-of-the-hiv-outbreak-and-response-in-scott-county-in-usa-2011-15-a-modelling-study
#6
Gregg S Gonsalves, Forrest W Crawford
BACKGROUND: In November, 2014, a cluster of HIV infections was detected among people who inject drugs in Scott County, IN, USA, with 215 HIV infections eventually attributed to the outbreak. This study examines whether earlier implementation of a public health response could have reduced the scale of the outbreak. METHODS: In this modelling study, we derived weekly case data from the HIV outbreak in Scott County, IN, and on the uptake of HIV testing, treatment, and prevention services from publicly available reports from the US Centers for Disease Control and Prevention (CDC) and researchers from Indiana...
September 13, 2018: Lancet HIV
https://www.readbyqxmd.com/read/30220453/angioedema-and-emergency-medicine-from-pathophysiology-to-diagnosis-and-treatment
#7
REVIEW
Federica Depetri, Alberto Tedeschi, Massimo Cugno
Angioedema is a self-limiting edema of the subcutaneous or submucosal tissues due to localised increase of microvascular permeability whose mediator may be histamine or bradykinin. Patients present to emergency department when angioedema involves oral cavity and larynx (life-threatening conditions) or gut (mimicking an acute abdomen). After initial evaluation of consciousness and vital signs to manage breathing and to support circulation if necessary, a simple approach can be applied for a correct diagnosis and treatment...
September 13, 2018: European Journal of Internal Medicine
https://www.readbyqxmd.com/read/30220280/-effects-of-insulin-caliper-for-blood-glucose-control-on-glucose-control-in-emergent-and-critical-patients
#8
Huijie Yu, Lingfang Zhang, Songao Xu, Jun Xu, Hui Sun, Xiangyun Zhu, Xiaoqin Xu, Weizhong Cao
OBJECTIVE: To observe the effects of insulin caliper for blood glucose control on glycemic central tendency, fluctuation and incidence of hypoglycemia, etc., in emergent and critical patients to evaluate its application value. METHODS: A prospective single-blinded randomized parallel controlled intervention study was conducted. One hundred patients with severe hyperglycemia requiring treatment with insulin infusion admitted to emergency department and intensive care unit (ICU) of the First Hospital of Jiaxing from November 2015 to November 2017 were enrolled, and they were divided into the caliper group (used patented product insulin calipers for blood glucose control to adjust insulin dose for blood glucose control) and the conventional group (used paper-based insulin dose modification scheme to adjust insulin dose for blood glucose control) on average by random number table, 50 in each group...
August 2018: Zhonghua Wei Zhong Bing Ji Jiu Yi Xue
https://www.readbyqxmd.com/read/30220082/new-fda-approved-and-emerging-novel-treatment-options-for-acute-myeloid-leukemia
#9
Zach R Click, Amanda N Seddon, Young R Bae, Justin D Fisher, Adebayo Ogunniyi
Advancements in the treatment of acute myeloid leukemia (AML) have been sparse over the last several decades, and the disease continues to have a poor prognosis. However, in 2017 alone, four new medications approved by the United States Food and Drug Administration (FDA) for the treatment of AML reached the market. Midostaurin, liposomal cytarabine and daunorubicin, enasidenib, and gemtuzumab ogozamicin all showed benefit in respective clinical trials to gain approval for the treatment of AML in various patient populations...
September 16, 2018: Pharmacotherapy
https://www.readbyqxmd.com/read/30219952/nanomedicines-for-developing-cancer-nanotherapeutics-from-benchtop-to-bedside-and-beyond
#10
REVIEW
Javed Iqbal, Banzeer Ahsan Abbasi, Riaz Ahmad, Tariq Mahmood, Barkat Ali, Ali Talha Khalil, Sobia Kanwal, Sayed Afzal Shah, Muhammad Maqsood Alam, Hussain Badshah, Akhtar Munir
Cancer is a devastating disease and remains a significant cause of mortality and morbidity in both developed and developing countries. Although there are large number of drugs that can be used for the treatment of cancer, the problem is selective and specific killing of cancerous cells without harming the normal cells. There are some biological barriers to potential drug delivery in cancer cells like hepatic, renal, abnormal vasculature, dense extracellular matrix, and high interstitial fluid pressure. The physicochemical characteristics of nanoparticles (NPs) such as size, shape, and surface charge may also have significant effects on tumor penetration...
September 15, 2018: Applied Microbiology and Biotechnology
https://www.readbyqxmd.com/read/30219946/stimulation-history-affects-vasomotor-responses-in-rat-mesenteric-arterioles
#11
Bjørn Olav Hald, Rasmus B Sørensen, Preben G Sørensen, Charlotte M Sørensen, Jens Chr Brings Jacobsen
Resistance vessels regulate blood flow by continuously adjusting activity of the wall smooth muscle cells. These cells integrate a variety of stimuli from blood, endothelium, autonomic nerves, and surrounding tissues. Each stimulus elicits an intracellular signaling cascade that eventually influences activation of the contractile machinery. The characteristic time scale of each cascade and the sharing of specific reactions between cascades provide for complex behavior when a vessel receives multiple stimuli...
September 15, 2018: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/30219797/uninformed-refusals-objections-to-enrolment-in-clinical-trials-conducted-under-an-exception-from-informed-consent-for-emergency-research
#12
Victoria Vorholt, Neal W Dickert
Clinical trials in emergency situations present unique challenges, because they involve enrolling individuals who lack capacity to consent in the context of acute illness or injury. The US Department of Health and Human Services and Food and Drug Administration regulations allowing an Exception from Informed Consent (EFIC) in these circumstances contain requirements for community consultation, public disclosure and restrictions on study risks and benefits. In this paper, we analyse an issue raised in the regulations that has received little attention or analysis but is ethically complex...
September 15, 2018: Journal of Medical Ethics
https://www.readbyqxmd.com/read/30219695/oral-administration-of-the-casein-kinase-2-inhibitor-tbb-leads-to-persistent-k-ca-2-2-channel-up-regulation-in-the-epileptic-ca1-area-and-cortex-but-lacks-anti-seizure-efficacy-in-the-pilocarpine-epilepsy-model
#13
Rika Bajorat, Katrin Porath, Johannes Kuhn, Elke Goßla, Doreen Goerss, Tina Sellmann, Rüdiger Köhling, Timo Kirschstein
Temporal lobe epilepsy (TLE) is the most common epileptic syndrome in adults and often presents with seizures that prove intractable with currently available anticonvulsants. Thus, there is still a need for new anti-seizure drugs in this condition. Recently, we found that the casein kinase 2 inhibitor 4,5,6,7-tetrabromotriazole (TBB) prevented the emergence of spontaneous epileptic discharges in an acute in vitro epilepsy model. This prompted us to study the anti-seizure effects of TBB in the pilocarpine model of chronic epilepsy in vivo...
September 8, 2018: Epilepsy Research
https://www.readbyqxmd.com/read/30218951/opportunities-for-plant-natural-products-in-infection-control
#14
REVIEW
Akram M Salam, Cassandra L Quave
The continued spread of antimicrobial resistance represents one of the most serious infectious disease threats to global health. There is consensus that a key component of addressing this threat is to replenish the waning pipeline of antimicrobials, with attention being paid to novel mechanisms of action. This includes the development of new classes of classic bacteriostatic and bactericidal antibiotics as well as antivirulence drugs, and it is especially in these areas where plant natural products demonstrate great potential...
September 12, 2018: Current Opinion in Microbiology
https://www.readbyqxmd.com/read/30218682/superior-efficacy-of-hi-6-dimethanesulfonate-over-pralidoxime-methylsulfate-against-russian-vx-poisoning-in-cynomolgus-monkeys-macaca-fascicularis
#15
Chloé Reymond, Nina Jaffré, Nicolas Taudon, Mathilde Menneteau, Hervé Chaussard, Josiane Denis, Cédric Castellarin, Franck Dhote, Frédéric Dorandeu
Organophosphorus nerve agents still represent a serious risk to human health. In the French armed forces, the current emergency treatment against OP intoxications is a fully licensed wet-dry dual-chambered autoinjector (Ineurope ®), that contains pralidoxime methylsulfate (2-PAM) to reactivate inhibited acetylcholinesterase (AChE), atropine sulfate (AS) and avizafone chlorhydrate (AVZ). While this treatment is effective against several of the known nerve agents, it shows little efficacy against the Russian VX (VR), one of the most toxic compounds...
September 12, 2018: Toxicology
https://www.readbyqxmd.com/read/30218618/chronic-nicotine-administration-restores-brain-region-specific-up-regulation-of-oxytocin-receptor-binding-levels-in-a-g72-mouse-model-of-schizophrenia
#16
Panos Zanos, Helen Keyworth, Polymnia Georgiou, Ian Kitchen, Andreas Zimmer, Alexis Bailey
Nicotine dependence and schizophrenia are two mental health disorders with remarkably high comorbidity. Cigarette smoking is particularly prevalent among schizophrenic patients and it is hypothesized to comprise a form of self-medication for relieving cognitive deficits in these patients. Emerging evidence suggests a role of the neurohypophysial peptide oxytocin in the modulation of drug addiction, as well as schizophrenia symptomology; however, the underlying mechanism remains unclear. Therefore, we sought to investigate the effects of chronic nicotine administration on oxytocin receptor (OTR) binding in the brain of a transgenic mouse model of schizophrenia that carries a bacterial artificial chromosome of the human G72/G30 locus (G72Tg)...
September 15, 2018: European Journal of Neuroscience
https://www.readbyqxmd.com/read/30218438/the-walking-wounded-emerging-treatments-for-ptsd
#17
REVIEW
Durga Bestha, Layla Soliman, Kelly Blankenship, James Rachal
PURPOSE OF REVIEW: We review the published literature over the last 24 months in the treatment of PTSD for our military men and women. We examined the updated clinical practice guidelines published in June 2017 by the Veteran's administration and Department of Defense and contrasted the guidelines with the most recent literature. We also discuss new directions in PTSD research. RECENT FINDINGS: Psychotherapy remains one of the most effective treatments for PTSD; unfortunately, few participants remain in treatment to completion...
September 14, 2018: Current Psychiatry Reports
https://www.readbyqxmd.com/read/30218345/an-update-of-efficacy-and-safety-of-cetuximab-in-metastatic-colorectal-cancer-a-narrative-review
#18
REVIEW
Giulia Fornasier, Sara Francescon, Paolo Baldo
Colorectal cancer is the second most common cancer, representing 13% of all diagnosed cancers. Cetuximab is a recombinant chimeric monoclonal IgG1 antibody and epidermal growth factor receptor (EGFR) inhibitor. Cetuximab is approved for the first-line treatment in combination with chemotherapy or as a single agent in patients who have failed or are intolerant to chemotherapy in patients with EGFR-expressing, RAS wild-type metastatic colorectal cancer. Cetuximab efficacy emerged from studies that were conducted to approve the drug...
September 14, 2018: Advances in Therapy
https://www.readbyqxmd.com/read/30218296/the-emerging-role-of-lncrnas-in-the-regulation-of-cancer-stem-cells
#19
REVIEW
Rosario Castro-Oropeza, Jorge Melendez-Zajgla, Vilma Maldonado, Karla Vazquez-Santillan
BACKGROUND: Tumors contain a functional subpopulation of cells that exhibit stem cell properties. These cells, named cancer stem cells (CSCs), play significant roles in the initiation and progression of cancer. Long non-coding RNAs (lncRNAs) can act at the transcriptional, posttranscriptional and translational level. As such, they may be involved in various biological processes such as DNA damage repair, inflammation, metabolism, cell survival, cell signaling, cell growth and differentiation...
September 14, 2018: Cellular Oncology (Dordrecht)
https://www.readbyqxmd.com/read/30217854/precise-and-efficient-genome-editing-in-klebsiella-pneumoniae-using-crispr-cas9-and-crispr-assisted-cytidine-deaminase
#20
Yu Wang, Shanshan Wang, Weizhong Chen, Liqiang Song, Yifei Zhang, Zhen Shen, Fangyou Yu, Min Li, Quanjiang Ji
Klebsiella pneumoniae is a promising industrial microorganism as well as a major human pathogen. The recent emergence of carbapenem-resistant K. pneumoniae has posed a serious threat to public health worldwide, emphasizing a dire need for novel therapeutic means against drug-resistant K. pneumoniae Despite the critical importance of genetics in bioengineering, physiology study, and therapeutic-means development, genome editing, in particular, the highly desirable scarless genetic manipulation in K. pneumoniae is often time-consuming and laborious...
September 14, 2018: Applied and Environmental Microbiology
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