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https://www.readbyqxmd.com/read/29678564/prescription-medication-use-among-community-based-us-adults-with-chronic-low-back-pain-a-cross-sectional-population-based-study
#1
Anna Shmagel, Linh Ngo, Kristine Ensrud, Robert Foley
Many classes of medications have been evaluated in chronic low back pain (cLBP), however their utilization in the community remains unclear. We examine patterns of prescription medication use among Americans with cLBP in a nationally representative, community-based sample. The Back Pain Survey was administered to a representative sample of US adults aged 20-69 (N = 5103) during the 2009-2010 cycle of the National Health and Nutrition Examination Survey (NHANES). cLBP was defined as self-reported pain in the area between the lower posterior margin of the ribcage and the horizontal gluteal fold on most days for at least 3 months (N = 700)...
April 17, 2018: Journal of Pain: Official Journal of the American Pain Society
https://www.readbyqxmd.com/read/29678476/cabazitaxel-plus-lapatinib-as-therapy-for-her2-metastatic-breast-cancer-with-intracranial-metastases-results-of-a-dose-finding-study
#2
Denise A Yardley, Lowell L Hart, Patrick J Ward, Gail L Wright, Mythili Shastry, Lindsey Finney, Laura M DeBusk, John D Hainsworth
BACKGROUND: Lapatinib is an oral small molecule tyrosine kinase epidermal growth factor receptor-1/HER2 inhibitor that crosses the blood-brain barrier and is active against central nervous system (CNS) metastases. Cabazitaxel is a taxoid that is effective against taxane-resistant metastatic breast cancer (MBC) and has distinguished itself by its ability to cross the blood-brain barrier. The present phase II study (ClinicalTrials.gov identifier, NCT01934894) evaluated the combination of these agents to treat HER2+ MBC patients with CNS metastases...
March 8, 2018: Clinical Breast Cancer
https://www.readbyqxmd.com/read/29678111/discovery-and-optimization-of-potent-and-cns-penetrant-m5-preferring-pams-derived-from-a-novel-chiral-n-indanyl-piperidine-amide-scaffold
#3
Aaron M Bender, Hyekyung P Cho, Kellie D Nance, Kaelyn S Lingenfelter, Vincent B Luscombe, Patrick R Gentry, Karl Voigtritter, Alice E Berizzi, Patrick M Sexton, Christopher Langmead, Arthur Christopoulos, Charles W Locuson, Thomas M Bridges, Sichen Chang, Jordan C O'Neil, Xiaoyan Zhan, Colleen M Niswender, Carrie K Jones, P Jeffrey Conn, Craig W Lindsley
The pharmacology of the M5 muscarinic acetylcholine receptor (mAChR) is the least understood of the five mAChR subtypes due to a historic lack of selective small molecule tools. To address this shortcoming, we have continued the optimization effort around the prototypical M5 PAM, ML380, and have discovered and optimized a new series of M5 PAMs based on a chiral N-(indanyl)piperidine amide core with robust SAR, human and rat M5 PAM EC50s < 100 nM and rat brain:plasma Kps of ~0.40. Interestingly, unlike M1 and M4 PAMs with unprecedented mAChR subtype selectivity, this series of M5 PAMs displayed varying degrees of PAM activity at the other two natively Gq-coupled mAChRs, M1 and M3, yet were inactive at M2 and M4...
April 20, 2018: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/29676170/discovery-of-novel-dual-acetylcholinesterase-inhibitors-with-antifibrillogenic-activity-related-to-alzheimer-s-disease
#4
Jonathan R de Almeida, Micheli Figueiro, Wanda Pereira Almeida, Carlos Henrique Tomich de Paula da Silva
AIM: Alzheimer's disease is a progressive and neurodegenerative disorder of the CNS, affecting elderly people. The current pharmacological approach is based on the improvement of cholinergic neurotransmission by inhibiting acetylcholinesterase (AChE) with AChE inhibitors. The disease is also characterized by the accelerated accumulation of β-amyloid plaques around neurons. Furthermore, in vitro studies revealed that AChE can induce β-amyloid peptide (Aβ) aggregation. METHODOLOGY: Computer-aided molecular design by virtual screening was here employed to discover novel potential AChE inhibitors, with antifibrillogenic properties, in other words, inhibiting Aβ aggregation...
April 20, 2018: Future Medicinal Chemistry
https://www.readbyqxmd.com/read/29676112/-effect-of-animal-medicines-for-extinguishing-wind-to-arrest-convulsions-on-central-nervous-system-diseases
#5
REVIEW
Zhi-Jie Yu, Jin-Song Li, Wei Peng, Ping Wang, Liang Xiong, Yu-Jie Liu, Ying Xu, Tao Sun
The human health is seriously affected by central nervous system(CNS) diseases, but the pathogenesis of CNS diseases is still not completely clear. Currently, the drugs used to treat CNS diseases are mainly receptor modulators and neurotransmitter inhibitors, which have serious side effects; and there are short of drugs for treating CNS diseases clinically. Studies suggest that animal medicines mainly include protein, polypeptide and small-molecule compounds, and have such pharmacological effects in calming, resisting convulsions and improving brain tissues...
March 2018: Zhongguo Zhong Yao za Zhi, Zhongguo Zhongyao Zazhi, China Journal of Chinese Materia Medica
https://www.readbyqxmd.com/read/29675012/histidine-metabolism-and-igpd-play-a-key-role-in-cefquinome-inhibiting-biofilm-formation-of-staphylococcus-xylosus
#6
Yong-Hui Zhou, Chang-Geng Xu, Yan-Bei Yang, Xiao-Xu Xing, Xin Liu, Qian-Wei Qu, Wen-Ya Ding, God'spower Bello-Onaghise, Yan-Hua Li
Staphylococcus xylosus ( S. xylosus ) is an AT-rich and coagulase-negative Staphylococcus (CNS). It is normally regarded as non-pathogenic, however, recent studies have demonstrated that it is related to human opportunistic infections and bovine mastitis. In addition, S. xylosus strains have the ability to form biofilm. Biofilms are also involved in chronic infections and antibiotic resistance, there are only a few reports about cefquinome inhibiting S. xylosus biofilm formation and the protein targets of cefquinome...
2018: Frontiers in Microbiology
https://www.readbyqxmd.com/read/29673365/human-central-nervous-system-astrocytes-support-survival-and-activation-of-b-cells-implications-for-ms-pathogenesis
#7
Hanane Touil, Antonia Kobert, Nathalie Lebeurrier, Aja Rieger, Philippe Saikali, Caroline Lambert, Lama Fawaz, Craig S Moore, Alexandre Prat, Jennifer Gommerman, Jack P Antel, Yasuto Itoyama, Ichiro Nakashima, Amit Bar-Or
BACKGROUND: The success of clinical trials of selective B cell depletion in patients with relapsing multiple sclerosis (MS) indicates B cells are important contributors to peripheral immune responses involved in the development of new relapses. Such B cell contribution to peripheral inflammation likely involves antibody-independent mechanisms. Of growing interest is the potential that B cells, within the MS central nervous system (CNS), may also contribute to the propagation of CNS-compartmentalized inflammation in progressive (non-relapsing) disease...
April 19, 2018: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/29671795/4-hydroxypiperidines-and-their-flexible-3-amino-propyloxy-analogues-as-non-imidazole-histamine-h%C3%A2-receptor-antagonist-further-structure%C3%A2-activity-relationship-exploration-and-in-vitro-and-in-vivo-pharmacological-evaluation
#8
Beata Olszewska, Anna Stasiak, Daniel McNaught Flores, Wiesława Agnieszka Fogel, Rob Leurs, Krzysztof Walczyński
Presynaptic histamine H₃ receptors (H₃R) act as auto- or heteroreceptors controlling, respectively, the release of histamine and of other neurotransmitters in the central nervous system (CNS). The extracellular levels of several neurotransmitters are enhanced by H₃R antagonists, and there is a great interest for potent, brain-penetrating H₃ receptor antagonists/inverse agonists to compensate for the neurotransmitter deficits present in various neurological disorders. We have shown that 1-[(benzylfuran-2-yl)methyl]piperidinyl-4-oxyl- and benzyl- derivatives of N -propylpentan-1-amines exhibit high in vitro potencies toward the guinea pig H₃ receptor (jejunum), with pA₂ = 8...
April 19, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29671419/trpm2-a-candidate-therapeutic-target-for-treating-neurological-diseases
#9
REVIEW
Jillian Corinne Belrose, Michael Frederick Jackson
Transient receptor potential melastatin 2 (TRPM2) is a calcium (Ca2+ )-permeable non-selective cation channel belonging to the TRP ion channel family. Oxidative stress-induced TRPM2 activation provokes aberrant intracellular Ca2+ accumulation and cell death in a variety of cell types, including neurons. Aberrant TRPM2 function has been implicated in several neurological disorders including ischemia/stroke, Alzheimer's disease, neuropathic pain, Parkinson's disease and bipolar disorder. In addition to research identifying a role for TRPM2 in disease, progress has been made in the identification of physiological functions of TRPM2 in the brain, including recent evidence that TRPM2 is necessary for the induction of N-methyl-D-aspartate (NMDA) receptor-dependent long-term depression, an important form of synaptic plasticity at glutamate synapses...
April 19, 2018: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/29670465/emerging-roles-of-immune-cells-in-postoperative-cognitive-dysfunction
#10
REVIEW
Yue Liu, Yiqing Yin
Postoperative cognitive dysfunction (POCD), a long-lasting cognitive decline after surgery, is currently a major clinical problem with no clear pathophysiological mechanism or effective therapy. Accumulating evidence suggests that neuroinflammation plays a critical role in POCD. After surgery, alarmins are leaked from the injury sites and proinflammatory cytokines are increased in the peripheral circulation. Neurons in the hippocampus, which is responsible for learning and memory, can be damaged by cytokines transmitted to the brain parenchyma...
2018: Mediators of Inflammation
https://www.readbyqxmd.com/read/29670213/quercetin-attenuates-azt-induced-neuroinflammation-in-the-cns
#11
Yi Yang, Xiaokang Liu, Ting Wu, Wenping Zhang, Jianhong Shu, Yulong He, Shao-Jun Tang
Highly active anti-retroviral therapy (HAART) is very effective in suppressing HIV-1 replication in patients. However, continuous HAART is required to prevent viral rebound, which may have detrimental effects in various tissues, including persistent neuroinflammation in the central nervous system (CNS). Here, we show that quercetin (3,5,7,3',4'-pentahydroxy flavones), a natural antioxidant used in Chinese traditional medicines, suppresses the neuroinflammation that is induced by chronic exposure to Zidovudine (azidothymidine, AZT), a nucleoside reverse transcriptase inhibitor (NRTI) that is commonly part of HAART regimens...
April 18, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29670176/activity-dependent-modulation-of-hippocampal-synaptic-plasticity-via-pirb-and-endocannabinoids
#12
Maja Djurisic, Barbara K Brott, Nay L Saw, Mehrdad Shamloo, Carla J Shatz
The threshold for Hebbian synaptic plasticity in the CNS is modulated by prior synaptic activity. At adult CA3-CA1 synapses, endocannabinoids play a role in this process, but how activity engages and maintains this retrograde signaling system is not well understood. Here we show that conditional deletion of Paired Immunoglobulin-like receptor B (PirB) from pyramidal neurons in adult mouse hippocampus results in deficient LTD at CA3-CA1 synapses over a range of stimulation frequencies, accompanied by an increase in LTP...
April 18, 2018: Molecular Psychiatry
https://www.readbyqxmd.com/read/29668471/evaluation-of-the-role-of-abcb1gene-polymorphic-variants-on-psychiatric-disorders-predisposition-in-macedonian-population
#13
Zorica Naumovska, Aleksandra K Nestorovska, Zoran Sterjev, Ana Filipce, Aleksandra Grozdanova, Aleksandar Dimovski, Ljubica Suturkova, Vladimir Serafimoski
The psychiatric and other CNS disorders are characterized with unregulated neuro-inflammatory processes and chronic microglia cell activation resulting with detrimental effect. ABCB1gene polymorphismsC1236T, G2677T/Aand C3435T are associated with P-glycoprotein expression and function andare linked with predisposition to psychiatric disorders such as schizophrenia and bipolar disorders. The relationship between mood disorders and glucocorticoids has been confirmed and ABCB1 SNPs influence the glucocorticoids access to the brain...
December 1, 2017: Prilozi (Makedonska Akademija Na Naukite i Umetnostite. Oddelenie za Medicinski Nauki)
https://www.readbyqxmd.com/read/29667756/pharmacokinetic-profiling-of-anticancer-phytocompounds-using-computational-approach
#14
Ashish Sharma, Shilpa Sharma, Mansi Gupta, Shehnaz Fatima, Ravi Saini, Subhash Mohan Agarwal
INTRODUCTION: Natural products exhibit diverse scaffolds and are considered as suitable candidates for development of leads. However, poor pharmacokinetics often acts as a hindrance during the drug discovery process. OBJECTIVE: With a view of exploring the absorption, distribution, metabolism, excretion and toxicity (ADMET) profile of plant-based anticancer compounds, open-access databases (NPACT, CancerHSP and TaxKB) were analysed to identify molecules having properties favourable for drug ability...
April 18, 2018: Phytochemical Analysis: PCA
https://www.readbyqxmd.com/read/29666949/precision-medicine-against-alk-positive-non-small-cell-lung-cancer-beyond-crizotinib
#15
REVIEW
Biagio Ricciuti, Andrea De Giglio, Carmen Mecca, Cataldo Arcuri, Sabrina Marini, Giulio Metro, Sara Baglivo, Angelo Sidoni, Guido Bellezza, Lucio Crinò, Rita Chiari
Anaplastic lymphoma kinase (ALK) rearrangements represent the molecular driver of a subset of non-small cell lung cancers (NSCLCs). Despite the initial response, virtually all ALK-positive patients develop an acquired resistance to the ALK inhibitor crizotinib, usually within 12 months. Several next-generation ALK inhibitors have been developed in order to overcome crizotinib limitation, providing an unprecedented survival for this subset of patients. The aim of this review to summarize the current knowledge on ALK tyrosine kinase inhibitors (TKIs) in the treatment of advanced ALK-positive NSCLC, focusing on the role of novel ALK inhibitors in this setting...
April 17, 2018: Medical Oncology
https://www.readbyqxmd.com/read/29666622/chemotactic-cues-for-notch1-dependent-leukemia
#16
REVIEW
Erich Piovan, Valeria Tosello, Alberto Amadori, Paola Zanovello
The NOTCH signaling pathway is a conserved signaling cascade that regulates many aspects of development and homeostasis in multiple organ systems. Aberrant activity of this signaling pathway is linked to the initiation and progression of several hematological malignancies, exemplified by T-cell acute lymphoblastic leukemia (T-ALL). Interestingly, frequent non-mutational activation of NOTCH1 signaling has recently been demonstrated in B-cell chronic lymphocytic leukemia (B-CLL), significantly extending the pathogenic significance of this pathway in B-CLL...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29665503/zebrafish-extracellular-matrix-improves-neuronal-viability-and-network-formation-in-a-3-dimensional-culture
#17
Sung-Min Kim, Daniel Ward Long, Michael Wai Kok Tsang, Yadong Wang
Mammalian central nervous system (CNS) has limited capacity for regeneration. CNS injuries cause life-long debilitation and lead to $50 billion in healthcare costs in U.S. alone each year. Despite numerous efforts in the last few decades, CNS-related injuries remain as detrimental as they were 50 years ago. Some functional recovery can occur, but most regeneration are limited by an extracellular matrix (ECM) that actively inhibits axonal repair and promotes glial scarring. In most tissues, the ECM is an architectural foundation that plays an active role in supporting cellular development and regenerative response after injury...
April 6, 2018: Biomaterials
https://www.readbyqxmd.com/read/29662940/large-scale-in-vivo-recording-of-sensory-neuron-activity-with-gcamp6
#18
Kim I Chisholm, Nikita Khovanov, Douglas M Lopes, Federica La Russa, Stephen B McMahon
Greater emphasis on the study of intact cellular networks in their physiological environment has led to rapid advances in intravital imaging of the central nervous system (CNS), while the peripheral system remains largely unexplored. To assess large networks of sensory neurons, we selectively label primary afferents with GCaMP6s in male and female C57bl/6 mice and visualize their functional responses to peripheral stimulation in vivo . We show that we are able to monitor the activity of hundreds of sensory neurons simultaneously, with sufficient sensitivity to detect, in most cases, single action potentials with a typical rise time of around 200 ms, and an exponential decay with a time constant of approximately 700 ms...
January 2018: ENeuro
https://www.readbyqxmd.com/read/29662627/analysis-of-the-pi3k-akt-mtor-pathway-in-penile-cancer-evaluation-of-a-therapeutically-targetable-pathway
#19
Anthony Adimonye, Elzbieta Stankiewicz, Sakunthala Kudahetti, Giorgia Trevisan, Brendan Tinwell, Cathy Corbishley, Yong-Jie Lu, Nick Watkin, Daniel Berney
Objectives: To determine whether phosphatidylinositol-4,5-bisphosphate 3- kinase, catalytic subunit alpha (PIK3CA) copy number gain is common and could prove a useful marker for the activation status of the PI3K-AKT-mTOR pathway in penile squamous cell carcinoma (PSCC). Methods: Fresh frozen tissue and archival blocks were collected from 24 PSCC patients with 15 matched normal penile epithelium (NPE) tissue from St George's Hospital. PIK3CA mutational and copy number status (CNS) was assessed via Sanger sequencing and fluorescence in-situ hybridisation, respectively...
March 23, 2018: Oncotarget
https://www.readbyqxmd.com/read/29662531/cystic-brain-metastases-in-alk-rearranged-non-small-cell-lung-cancer
#20
REVIEW
Guilherme Nader Marta, Renata Rodrigues da Cunha Colombo Bonadio, Renata Eiras Martins, Henrique Bortot Zuppani, Gilberto de Castro
The central nervous system (CNS) is a common site of disease progression in patients with non-small-cell lung cancer (NSCLC) with anaplastic lymphoma kinase (ALK)-rearrangement treated with crizotinib. Cystic brain metastases (CBM) have been recently identified as one possible variant of this disease. An illustrative case report is presented along with a literature review performed in order to track relevant papers about CBM in ALK-rearranged NSCLC, including possible pathophysiology, differential diagnosis and treatment options for this condition...
2018: Ecancermedicalscience
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