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https://www.readbyqxmd.com/read/28931097/-approaching-new-pharmacotherapy-options-in-pain-treatment
#1
András Telekes
The evolution of medicine is noticeable in most therapeutic areas, the worse the current therapeutic result, the more quick the improvement. This is especially true in such areas that require substantial social resources, namely oncology, diabetology and CNS diseases. Pain is not a disease, it is a symptom. Pain is one of the most important components of human suffering thus it deserves special attention. In recent years new formulations of old medicines were introduced rather than new medicines. Maybe ziconitide is the last pain killer with new mechanism of action which was approved by FDA in 2004...
September 20, 2017: Magyar Onkologia
https://www.readbyqxmd.com/read/28930747/quantification-of-bisoprolol-and-metoprolol-in-simultaneous-human-serum-and-cerebrospinal-fluid-samples
#2
Ali Sigaroudi, Martina Kinzig, Oliver Wahl, Christoph Stelzer, Michael Schroeter, Uwe Fuhr, Ulrike Holzgrabe, Fritz Sörgel
BACKGROUND: Bisoprolol and metoprolol are moderately lipophilic, beta(1)-selective betablockers reported to cause adverse effects in the central nervous system (CNS), such as sleep disturbance, suggesting that both drugs may reach relevant concentrations in the brain. CNS beta(2)-receptor blockade has been suspected to be related to such effects. The higher molecular size of bisoprolol (325 Dalton) and the higher beta(1)-selectivity compared to metoprolol (267 Dalton) would suggest a lower rate of CNS effects...
September 21, 2017: Pharmacology
https://www.readbyqxmd.com/read/28930690/the-self-inactivating-kamicas9-system-for-the-editing-of-cns-disease-genes
#3
Nicolas Merienne, Gabriel Vachey, Lucie de Longprez, Cécile Meunier, Virginie Zimmer, Guillaume Perriard, Mathieu Canales, Amandine Mathias, Lucas Herrgott, Tim Beltraminelli, Axelle Maulet, Thomas Dequesne, Catherine Pythoud, Maria Rey, Luc Pellerin, Emmanuel Brouillet, Anselme L Perrier, Renaud du Pasquier, Nicole Déglon
Neurodegenerative disorders are a major public health problem because of the high frequency of these diseases. Genome editing with the CRISPR/Cas9 system is making it possible to modify the sequence of genes linked to these disorders. We designed the KamiCas9 self-inactivating editing system to achieve transient expression of the Cas9 protein and high editing efficiency. In the first application, the gene responsible for Huntington's disease (HD) was targeted in adult mouse neuronal and glial cells. Mutant huntingtin (HTT) was efficiently inactivated in mouse models of HD, leading to an improvement in key markers of the disease...
September 19, 2017: Cell Reports
https://www.readbyqxmd.com/read/28930471/possible-way-to-study-cononsolvency-in-confinement-lattice-density-functional-theory-approach
#4
Xueqian Chen, Wei Feng, Xia Han, Honglai Liu
The polymer lattice density functional theory (PLDFT) is used to investigate the cononsolvency (CNS) phenomena related to polymer adsorption in a slit pore. Specifically, two simplest types of CNS are examined: CNS1 with solvent-cosolvent binding as the dominate factor and CNS2 with polymer-cosolvent binding as the dominate factor. The simplified models for CNS1/CNS2 well capture the symmetrical/asymmetrical reentrant swelling transition of polymers positively/negatively adsorbed on the solid surface as confirmed by the calculation of PLDFT...
September 20, 2017: Langmuir: the ACS Journal of Surfaces and Colloids
https://www.readbyqxmd.com/read/28930275/anti-aging-and-antioxidant-potential-of-paullinia-cupana-var-sorbilis-findings-in-caenorhabditis-elegans-indicate-a-new-utilization-for-roasted-seeds-of-guarana
#5
Herbenya Peixoto, Mariana Roxo, Teresa Röhrig, Elke Richling, Xiaojuan Wang, Michael Wink
Background: Roasted seeds of Amazonian guarana (Paullinia cupana var. sorbilis; Sapindaceae) are popular in South America due to their stimulant activity on the central nervous system (CNS). Rich in purine alkaloids, markedly caffeine, the seeds are extensively used in the Brazilian beverage industry for the preparation of soft drinks and as additives in energy drinks. Methods: To investigate the putative anti-aging and antioxidant activity of guarana, we used the model organism Caenorhabditis elegans. Chemical analyses were performed using high-performance liquid chromatography (HPLC) and electrospray ionization-mass spectrometry (ESI-MS/MS)...
August 15, 2017: Medicines (Basel, Switzerland)
https://www.readbyqxmd.com/read/28930228/interaction-of-plant-extracts-with-central-nervous-system-receptors
#6
REVIEW
Kenneth Lundstrom, Huyen Thanh Pham, Long Doan Dinh
Background: Plant extracts have been used in traditional medicine for the treatment of various maladies including neurological diseases. Several central nervous system receptors have been demonstrated to interact with plant extracts and components affecting the pharmacology and thereby potentially playing a role in human disease and treatment. For instance, extracts from Hypericum perforatum (St. John's wort) targeted several CNS receptors. Similarly, extracts from Piper nigrum, Stephania cambodica, and Styphnolobium japonicum exerted inhibition of agonist-induced activity of the human neurokinin-1 receptor...
February 23, 2017: Medicines (Basel, Switzerland)
https://www.readbyqxmd.com/read/28929959/-in-vitro-effect-of-vancomycin-and-daptomycin-on-biofilm-formation-of-coagulase-negative-staphylococci-strains
#7
Duygu Nilüfer Öcal, İştar Dolapçı, Zeynep Gençtürk, Alper Tekeli
Coagulase-negative staphylococci (CNS) are one of the primer agents of blood stream infections (BSI) and catheter-related bloodstream infections (CR-BSI) which are associated mostly with the usage of central venous catheters and, important causes of morbidity and mortality despite the usage of antibacterial and supportive treatment. It is important to determine the properties of these causative microorganisms in order to make appropriate treatment of such infections. The aims of our study were to evaluate the biofilm formation of coagulase negative staphylococci (CNS) which were causative agents of bloodstream (BSI) and catheter related bloodstream infections (CR-BSI), to determine the minimum inhibitory concentration (MIC) of planktonic forms and minimal biofilm eradication concentration (MBEC) of sessile forms for vancomycin and daptomycin and to evaluate the efficacy of these antibiotics in infections with biofilm-forming isolates in vitro...
July 2017: Mikrobiyoloji Bülteni
https://www.readbyqxmd.com/read/28929759/selective-inhibitors-of-dual-leucine-zipper-kinase-dlk-map3k12-with-activity-in-a-model-of-alzheimer-s-disease
#8
Snahel Patel, William J Meilandt, Rebecca I Erickson, Jinhua Chen, Gauri Deshmukh, Anthony A Estrada, Reina N Fuji, Paul Gibbons, Amy Gustafson, Seth F Harris, Jose Imperio, Wendy Liu, Xingrong Liu, Yichin Liu, Joseph P Lyssikatos, Changyou Ma, Jianping Yin, Joseph W Lewcock, Michael Siu
Significant data exists to suggest that dual leucine zipper kinase (DLK, MAP3K12) is a conserved regulator of neuronal degeneration following neuronal injury and in chronic neurodegenerative disease. Consequently, there is considerable interest in the identification of DLK inhibitors with a profile compatible with development for these indications. Herein, we use structure-based drug design combined with a focus on CNS drug-like properties to generate compounds with superior kinase selectivity and metabolic stability as compared to previously disclosed DLK inhibitors...
September 20, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28929564/prefronto-temporal-white-matter-microstructural-alterations-20%C3%A2-years-after-the-diagnosis-of-type-1-diabetes-mellitus
#9
Sujung Yoon, Jungyoon Kim, Gail Musen, Perry F Renshaw, Jaeuk Hwang, Nicolas R Bolo, Jieun E Kim, Donald C Simonson, Katie Weinger, Christopher M Ryan, In Kyoon Lyoo, Alan M Jacobson
OBJECTIVE: Microvascular pathophysiology that uniquely manifests as white matter (WM) abnormalities is often implicated in type 1 diabetes mellitus (T1DM)-related central nervous system (CNS) complications. This study sought to identify regional WM abnormalities in young adults diagnosed with T1DM and further examine their association with cognitive and emotional dysfunction. RESEARCH DESIGN AND METHODS: Diffusion tensor images (DTI) obtained from 34 young adults with T1DM for ≥15 years (mean duration, 20...
September 20, 2017: Pediatric Diabetes
https://www.readbyqxmd.com/read/28929408/yokukansan-reduces-cuprizone-induced-demyelination-in-the-corpus-callosum-through-anti-inflammatory-effects-on-microglia
#10
Taichi Nomura, Yoshio Bando, Hua You, Tatsuhide Tanaka, Shigetaka Yoshida
Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS). The release of inflammatory cytokines and pro-oxidant molecules from microglia has been shown to play a key role in the pathology of MS. Thus, suppression of microglial cell activation is an attractive therapeutic option. Yokukansan, a traditional Japanese herbal medicine, has been shown to suppress microglial activity in the CNS. However, whether or not yokukansan reduces demyelination observed in the CNS during MS remains unknown...
September 19, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28928747/modulation-of-multiple-sclerosis-and-its-animal-model-experimental-autoimmune-encephalomyelitis-by-food-and-gut-microbiota
#11
REVIEW
Ward J van den Hoogen, Jon D Laman, Bert A 't Hart
Multiple sclerosis (MS) is an autoimmune neurological disease characterized by chronic inflammation of the central nervous system (CNS), leading to demyelination, axonal damage, and symptoms such as fatigue and disability. Although the cause of MS is not known, the infiltration of peripherally activated immune cells into the CNS has a key pathogenic role. Accumulating evidence supports an important role of diet and gut microbiota in immune-mediated diseases. Preclinical as well as clinical studies suggest a role for gut microbiota and dietary components in MS...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28928746/ccl5-glutamate-cross-talk-in-astrocyte-neuron-communication-in-multiple-sclerosis
#12
REVIEW
Anna Pittaluga
The immune system (IS) and the central nervous system (CNS) are functionally coupled, and a large number of endogenous molecules (i.e., the chemokines for the IS and the classic neurotransmitters for the CNS) are shared in common between the two systems. These interactions are key elements for the elucidation of the pathogenesis of central inflammatory diseases. In recent years, evidence has been provided supporting the role of chemokines as modulators of central neurotransmission. It is the case of the chemokines CCL2 and CXCL12 that control pre- and/or post-synaptically the chemical transmission...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28928740/microbiome-derived-lipopolysaccharide-enriched-in-the-perinuclear-region-of-alzheimer-s-disease-brain
#13
Yuhai Zhao, Lin Cong, Vivian Jaber, Walter J Lukiw
Abundant clinical, epidemiological, imaging, genetic, molecular, and pathophysiological data together indicate that there occur an unusual inflammatory reaction and a disruption of the innate-immune signaling system in Alzheimer's disease (AD) brain. Despite many years of intense study, the origin and molecular mechanics of these AD-relevant pathogenic signals are still not well understood. Here, we provide evidence that an intensely pro-inflammatory bacterial lipopolysaccharide (LPS), part of a complex mixture of pro-inflammatory neurotoxins arising from abundant Gram-negative bacilli of the human gastrointestinal (GI) tract, are abundant in AD-affected brain neocortex and hippocampus...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28928705/the-role-of-t1-weighted-derived-measures-of-neurodegeneration-for-assessing-disability-progression-in-multiple-sclerosis
#14
REVIEW
Maria A Rocca, Giancarlo Comi, Massimo Filippi
INTRODUCTION: Multiple sclerosis (MS) is characterised by the accumulation of permanent neurological disability secondary to irreversible tissue loss (neurodegeneration) in the brain and spinal cord. MRI measures derived from T1-weighted image analysis (i.e., black holes and atrophy) are correlated with pathological measures of irreversible tissue loss. Quantifying the degree of neurodegeneration in vivo using MRI may offer a surrogate marker with which to predict disability progression and the effect of treatment...
2017: Frontiers in Neurology
https://www.readbyqxmd.com/read/28928632/neurophysiology-of-the-celiac-brain-disentangling-gut-brain-connections
#15
REVIEW
Manuela Pennisi, Alessia Bramanti, Mariagiovanna Cantone, Giovanni Pennisi, Rita Bella, Giuseppe Lanza
Celiac disease (CD) can be considered a complex multi-organ disorder with highly variable extra-intestinal, including neurological, involvement. Cerebellar ataxia, peripheral neuropathy, seizures, headache, cognitive impairment, and neuropsychiatric diseases are complications frequently reported. These manifestations may be present at the onset of the typical disease or become clinically evident during its course. However, CD subjects with subclinical neurological involvement have also been described, as well as patients with clear central and/or peripheral nervous system and intestinal histopathological disease features in the absence of typical CD manifestations...
2017: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/28928193/the-course-and-prognostic-factors-of-cognitive-status-after-central-nervous-system-trauma-a-systematic-review-protocol
#16
Tatyana Mollayeva, Nicole Pacheco, Andrea D'Souza, Angela Colantonio
INTRODUCTION: Traumatic brain injury (TBI) is among the most disabling injuries, resulting in a range of cognitive impairments. Traumatic spinal cord injury (SCI) often occurs in conjunction with TBI; the two are best considered together in the context of trauma to the central nervous system (CNS). Despite strong indications of cognitive dysfunction in CNS trauma, little is known about its natural history or relationship with other factors. The current protocol outlines a strategy for a systematic review of the current evidence examining CNS trauma as a prognostic factor of cognitive decline in the adult population...
September 18, 2017: BMJ Open
https://www.readbyqxmd.com/read/28927234/metabolic-profiling-of-central-nervous-system-disease-in-trypanosoma-brucei-rhodesiense-infection
#17
Sabrina D Lamour, Vincent P Alibu, Elaine Holmes, Jeremy M Sternberg
Background: The progression of Human African Trypanosomiasis from the early hemolymphatic stage to the late meningoencephalitic stage is of critical diagnostic importance as it determines the choice of potentially toxic drug regimens. Current diagnostic criteria involving analysis of cerebrospinal fluid (CSF) for parasites and/or pleiocytosis are sensitive, but recent evidence suggests that specificity may be poor. Methods: We used an untargeted global metabolic profiling approach for the discovery of novel candidate stage diagnostic markers in CSF from Trypanosoma brucei rhodesiense patients using 1H nuclear magnetic resonance (NMR) spectroscopy...
September 12, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28927153/clinicoradiological-characteristics-management-and-prognosis-of-primary-myeloid-sarcoma-of-the-central-nervous-system-a-report-of-four-cases
#18
Bao Yang, Chenlong Yang, Jingyi Fang, Jun Yang, Yulun Xu
Myeloid sarcoma (MS) is a localized tumor composed of premature precursors of granulocytic cells, which may occur in any organ and most commonly involves the soft tissue and musculoskeletal system. This malignancy may occur in the presence or absence of hematological disorders. Primary MS involving the central nervous system (CNS-MS) is rare, and has only been described in a small number of isolated case reports. The diagnosis of CNS-MS is challenging and strategies for its management are undefined. The present study describes 4 cases of CNS-MS...
September 2017: Oncology Letters
https://www.readbyqxmd.com/read/28926622/a-high-mitochondrial-transport-rate-characterizes-cns-neurons-with-high-axonal-regeneration-capacity
#19
Romain Cartoni, Gulcin Pekkurnaz, Chen Wang, Thomas L Schwarz, Zhigang He
Improving axonal transport in the injured and diseased central nervous system has been proposed as a promising strategy to improve neuronal repair. However, the contribution of each cargo to the repair mechanism is unknown. DRG neurons globally increase axonal transport during regeneration. Because the transport of specific cargos after axonal insult has not been examined systematically in a model of enhanced regenerative capacity, it is unknown whether the transport of all cargos would be modulated equally in injured central nervous system neurons...
2017: PloS One
https://www.readbyqxmd.com/read/28926546/-t-betting-on-innate-lymphoid-cells-in-cns-inflammatory-disease
#20
Melissa A Brown, Abigail E Russi
No abstract text is available yet for this article.
September 19, 2017: Nature Immunology
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