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https://www.readbyqxmd.com/read/28214290/evaluate-the-efficacy-and-safety-of-anti-epileptic-medications-for-partial-seizures-of-epilepsy-a-network-meta-analysis
#1
Teng Zhao, Xuemin Feng, Jingyao Liu, Jiguo Gao, Chunkui Zhou
Epilepsy is a brain and neurological disorder with high prevalence. It was reported that more than 70% of epileptic seizures were controlled by anti-epileptic medications, whereas the lack of evidence with respect to head-to-head comparisons motivated researchers to seek alternative approaches that are able to provide deep insights into the profile of anti-epileptic medications. In this study, we performed a network meta-analysis (NMA) to evaluate the efficacy and safety of anti-epileptic medications for partial seizures of epilepsy...
February 18, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28213892/opportunities-for-repurposing-of-poly-adp-ribose-polymerase-parp-inhibitors-for-the-therapy-of-non-oncological-diseases
#2
REVIEW
Nathan A Berger, Valerie C Besson, A Hamid Boulares, Alexander Bürkle, Alberto Chiarugi, Robert S Clark, Nicola J Curtin, Salvatore Cuzzocrea, Ted M Dawson, Valina L Dawson, György Haskó, Lucas Liaudet, Flavio Moroni, Pál Pacher, Peter Radermacher, Andrew L Salzman, Solomon H Snyder, Francisco Garcia Soriano, Robert P Strosznajder, Balázs Sümegi, Raymond A Swanson, Csaba Szabo
The recent clinical availability of the PARP inhibitor Lynparza (olaparib) opens the door for potential therapeutic repurposing for non-oncological indications. Considering (a) the preclinical efficacy data with PARP inhibitors in non-oncological diseases and (b) the risk-benefit ratio of treating patients with a compound that inhibits an enzyme that has physiological roles in the regulation of DNA repair, indications where (a) the severity of the disease is high, (b) the available therapeutic options are limited, and (c) the duration of PARP inhibitor administration could be short, provide first-line options for therapeutic repurposing...
February 18, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28213761/psychomotor-effect-differences-between-l-methamphetamine-and-d-methamphetamine-are-independent-of-murine-plasma-and-brain-pharmacokinetics-profiles
#3
Tetsuya Nishimura, Kazue Takahata, Yuri Kosugi, Takaaki Tanabe, Shizuko Muraoka
l-Methamphetamine has been occasionally referred to as a stimulant similar to d-methamphetamine, probably owing to insufficient comparative studies. Here, we directly compared psychomotor efficacies and pharmacokinetics of methamphetamine enantiomers in mice. Only d-methamphetamine, but not l-methamphetamine, induced stereotypy and sensitization at 1-10 mg/kg. However, plasma pharmacokinetic parameters of 10 mg/kg l-methamphetamine were ≥tenfold those of 1 mg/kg d-methamphetamine. These results clearly indicate that differential psychomotor efficacies of methamphetamine enantiomers are independent of their pharmacokinetic profiles...
February 17, 2017: Journal of Neural Transmission
https://www.readbyqxmd.com/read/28212985/nonsteroidal-anti-inflammatory-drugs-in-clinical-and-experimental-epilepsy
#4
REVIEW
Beatrice Mihaela Radu, Florin Bogdan Epureanu, Mihai Radu, Paolo Francesco Fabene, Giuseppe Bertini
Current antiepileptic drugs have limited efficacy and provide little or no benefits in 30% of the patients. Given that a role for brain inflammation in epilepsy has been repeatedly reported in recent years, the potential of anti-inflammatory drugs should be explored in depth, as they may provide new therapeutical approaches in preventing or reducing epileptogenesis. Here, we review preclinical (both in vivo and in vitro) and clinical epilepsy studies in which nonsteroidal antiinflammatory drugs (NSAIDs), i...
February 9, 2017: Epilepsy Research
https://www.readbyqxmd.com/read/28212323/low-intensity-extracorporeal-shock-wave-therapy-enhances-brain-derived-neurotrophic-factor-expression-through-perk-atf4-signaling-pathway
#5
Bohan Wang, Hongxiu Ning, Amanda B Reed-Maldonado, Jun Zhou, Yajun Ruan, Tie Zhou, Hsun Shuan Wang, Byung Seok Oh, Lia Banie, Guiting Lin, Tom F Lue
Low-intensity extracorporeal shock wave therapy (Li-ESWT) is used in the treatment of erectile dysfunction, but its mechanisms are not well understood. Previously, we found that Li-ESWT increased the expression of brain-derived neurotrophic factor (BDNF). Here we assessed the underlying signaling pathways in Schwann cells in vitro and in penis tissue in vivo after nerve injury. The result indicated that BDNF were significantly increased by the Li-ESWT after nerve injury, as well as the expression of BDNF in Schwann cells (SCs, RT4-D6P2T) in vitro...
February 16, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28212021/discovery-and-development-of-1-2-bromophenyl-sulfonyl-5-methoxy-3-4-methyl-1-piperazinyl-methyl-1h-indole-dimesylate-monohydrate-suvn-502-a-novel-potent-selective-and-orally-active-serotonin-6-5-ht6-receptor-antagonist-for-potential-treatment-of-alzheimer-s
#6
Ramakrishna Nirogi, Anil Shinde, Rama Sastry Kambhampati, Abdul Rasheed Mohammed, Sangram Keshari Saraf, Rajesh Kumar Badange, Thrinath Reddy Bandyala, Venugopalarao Bhatta, Kumar Bojja, Veena Reballi, Ramkumar Subramanian, Vijay Benade, Raghava Choudary Palacharla, Gopinadh Bhyrapuneni, Pradeep Jayarajan, Vinod Goyal, Venkat Jasti
Optimization of a novel series of 3-(piperazinylmethyl) indole derivatives as 5-hydroxytryptamine-6 receptor (5-HT6R) antagonists resulted in identification of 1-[(2-bromophenyl)sulfonyl]-5-methoxy-3-[(4-methyl-1-piperazinyl)methyl]-1H-indole dimesylate monohydrate (5al, SUVN-502) as a clinical candidate for potential treatment of cognitive disorders. It has high affinity at human 5-HT6R (Ki = 2.04 nM) and selectivity over 100 target sites which include receptors, enzymes, peptides, growth factors, ion channels, steroids, immunological factors, second messengers, and prostaglandins...
February 17, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28211828/self-efficacy-and-quality-of-life-after-low-intensity-neuropsychological-rehabilitation-a-pre-post-intervention-study
#7
Ingrid Brands, Maud Custers, Caroline van Heugten
BACKGROUND: Being highly self-efficacious is a key factor in successful chronic disease self-management. It is unknown whether neuropsychological rehabilitation improves self-efficacy in managing the consequences of brain injury. OBJECTIVE: To investigate whether levels of general and brain injury specific self-efficacy and quality of life (QoL) increased after neuropsychological rehabilitation and whether cognitive performance was associated with self-efficacy...
February 15, 2017: NeuroRehabilitation
https://www.readbyqxmd.com/read/28211823/symptom-severity-and-life-satisfaction-in-brain-injury-the-mediating-role-of-disability-acceptance-and-social-self-efficacy
#8
Nicole Ditchman, Connie Sung, Amanda B Easton, Kristina S Johnson, Elisabeth Batchos
BACKGROUND: Although the negative impact of symptom severity on subjective well-being outcomes has been established among individuals with brain injury, the mediating and protective role that positive human traits might have on this relationship has not been adequately explored. OBJECTIVE: The purpose of this study was to examine the impact of social self-efficacy and disability acceptance on the relationship between symptom severity and life satisfaction among individuals with brain injury...
February 15, 2017: NeuroRehabilitation
https://www.readbyqxmd.com/read/28210908/updates-in-outcomes-of-stereotactic-radiation-therapy-in-acromegaly
#9
REVIEW
Monica Livia Gheorghiu
Purpose Treatment of acromegaly has undergone important progress in the last 20 years mainly due to the development of new medical options and advances in surgical techniques. Pituitary surgery is usually first-line therapy, and medical treatment is indicated for persistent disease, while radiation (RT) is often used as third-line therapy. The benefits of RT (tumor volume control and decreased hormonal secretion) are hampered by the long latency of the effect and the high risk of adverse effects. Stereotactic RT methods have been developed with the aim to provide more precise targeting of the tumor with better control of the radiation dose received by the adjacent brain structures...
February 16, 2017: Pituitary
https://www.readbyqxmd.com/read/28210506/combined-supplementation-of-choline-and-docosahexaenoic-acid-during-pregnancy-enhances-neurodevelopment-of-fetal-hippocampus
#10
Huban Thomas Rajarethnem, Kumar Megur Ramakrishna Bhat, Malsawmzuali Jc, Siva Kumar Gopalkrishnan, Ramesh Babu Mugundhu Gopalram, Kiranmai Sesappa Rai
Choline is an essential nutrient for humans which plays an important role in structural integrity and signaling functions. Docosahexaenoic acid (DHA) is a polyunsaturated fatty acid, highly enriched in cell membranes of the brain. Dietary intake of choline or DHA alone by pregnant mothers directly affects fetal brain development and function. But no studies show the efficacy of combined supplementation of choline and DHA on fetal neurodevelopment. The aim of the present study was to analyze fetal neurodevelopment on combined supplementation of pregnant dams with choline and DHA...
2017: Neurology Research International
https://www.readbyqxmd.com/read/28209738/optogenetic-low-frequency-stimulation-of-specific-neuronal-populations-abates-ictogenesis
#11
Zahra Shiri, Maxime Lévesque, Guillaume Etter, Frédéric Manseau, Sylvain Williams, Massimo Avoli
Despite many advances made in understanding the pathophysiology of epileptic disorders, seizures remain poorly controlled in approximately one third of mesial temporal lobe epilepsy patients. Here, we established the efficacy of cell type-specific low-frequency stimulation (LFS) in controlling ictogenesis in the mouse entorhinal cortex (EC) in an in vitro brain slice preparation. Specifically, we used 1 Hz optogenetic stimulation of Ca(2+)/calmodulin-dependent protein kinase II-positive principal cells as well as of parvalbumin- or somatostatin-positive interneurons to study the effects of such repetitive activation on epileptiform discharges induced by 4-aminopyridine...
February 16, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28208742/aav-vector-mediated-gene-delivery-to-substantia-nigra-dopamine-neurons-implications-for-gene-therapy-and-disease-models
#12
REVIEW
Katrina Albert, Merja H Voutilainen, Andrii Domanskyi, Mikko Airavaara
Gene delivery using adeno-associated virus (AAV) vectors is a widely used method to transduce neurons in the brain, especially due to its safety, efficacy, and long-lasting expression. In addition, by varying AAV serotype, promotor, and titer, it is possible to affect the cell specificity of expression or the expression levels of the protein of interest. Dopamine neurons in the substantia nigra projecting to the striatum, comprising the nigrostriatal pathway, are involved in movement control and degenerate in Parkinson's disease...
February 8, 2017: Genes
https://www.readbyqxmd.com/read/28208698/advances-in-molecular-imaging-of-locally-delivered-targeted-therapeutics-for-central-nervous-system-tumors
#13
REVIEW
Umberto Tosi, Christopher S Marnell, Raymond Chang, William C Cho, Richard Ting, Uday B Maachani, Mark M Souweidane
Thanks to the recent advances in the development of chemotherapeutics, the morbidity and mortality of many cancers has decreased significantly. However, compared to oncology in general, the field of neuro-oncology has lagged behind. While new molecularly targeted chemotherapeutics have emerged, the impermeability of the blood-brain barrier (BBB) renders systemic delivery of these clinical agents suboptimal. To circumvent the BBB, novel routes of administration are being applied in the clinic, ranging from intra-arterial infusion and direct infusion into the target tissue (convection enhanced delivery (CED)) to the use of focused ultrasound to temporarily disrupt the BBB...
February 8, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28207759/investigations-on-therapeutic-glucocerebrosidases-through-paired-detection-with-fluorescent-activity-based-probes
#14
Wouter W Kallemeijn, Saskia Scheij, Sascha Hoogendoorn, Martin D Witte, Daniela Herrera Moro Chao, Cindy P A A van Roomen, Roelof Ottenhoff, Herman S Overkleeft, Rolf G Boot, Johannes M F G Aerts
Deficiency of glucocerebrosidase (GBA) causes Gaucher disease (GD). In the common non-neuronopathic GD type I variant, glucosylceramide accumulates primarily in the lysosomes of visceral macrophages. Supplementing storage cells with lacking enzyme is accomplished via chronic intravenous administration of recombinant GBA containing mannose-terminated N-linked glycans, mediating the selective uptake by macrophages expressing mannose-binding lectin(s). Two recombinant GBA preparations with distinct N-linked glycans are registered in Europe for treatment of type I GD: imiglucerase (Genzyme), contains predominantly Man(3) glycans, and velaglucerase (Shire PLC) Man(9) glycans...
2017: PloS One
https://www.readbyqxmd.com/read/28207604/memory-rehabilitation-strategies-in-nonsurgical-temporal-lobe-epilepsy-a-review
#15
Alessandra Del Felice, Marzia Alderighi, Matteo Martinato, Davide Grisafi, Anna Bosco, Pamela J Thompson, Josemir W Sander, Stefano Masiero
People with temporal lobe epilepsy (TLE) who have not undergone epilepsy surgery often complain of memory deficits. Cognitive rehabilitation is employed as a remedial intervention in clinical settings, but research is limited and findings concerning efficacy and the criteria for choosing different approaches have been inconsistent. We aimed to appraise existing evidence on memory rehabilitation in nonsurgical individuals with temporal lobe epilepsy and to ascertain the effectiveness of specific strategies. A scoping review was preferred given the heterogeneous nature of the interventions...
February 15, 2017: American Journal of Physical Medicine & Rehabilitation
https://www.readbyqxmd.com/read/28204960/sites-and-functional-consequence-of-alkylphenol-anesthetic-binding-to-kv1-2-channels
#16
Weiming Bu, Qiansheng Liang, Lianteng Zhi, Lina Maciunas, Patrick J Loll, Roderic G Eckenhoff, Manuel Covarrubias
Inhalational general anesthetics, such as sevoflurane and isoflurane, modulate a subset of brain Kv1 potassium channels. However, the Kv1.2 channel is resistant to propofol, a commonly used intravenous alkylphenol anesthetic. We hypothesize that propofol binds to a presumed pocket involving the channel's S4-S5 linker, but functional transduction is poor and, therefore, propofol efficacy is low. To test this hypothesis, we used a photoactive propofol analog (meta-aziPropofol = AziPm) to directly probe binding and electrophysiological and mutational analyses in Xenopus oocytes to probe function...
February 15, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28199828/hucns-sc-human-nscs-fail-to-differentiate-form-ectopic-clusters-and-provide-no-cognitive-benefits-in-a-transgenic-model-of-alzheimer-s-disease
#17
Samuel E Marsh, Stephen T Yeung, Maria Torres, Lydia Lau, Joy L Davis, Edwin S Monuki, Wayne W Poon, Mathew Blurton-Jones
Transplantation of neural stem cells (NSCs) can improve cognition in animal models of Alzheimer's disease (AD). However, AD is a protracted disorder, and prior studies have examined only short-term effects. We therefore used an immune-deficient model of AD (Rag-5xfAD mice) to examine long-term transplantation of human NSCs (StemCells Inc.; HuCNS-SCs). Five months after transplantation, HuCNS-SCs had engrafted and migrated throughout the hippocampus and exhibited no differences in survival or migration in response to β-amyloid pathology...
February 14, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28199114/curcumin-loaded-blood-stable-polymeric-micelles-for-enhancing-therapeutic-effect-on-erythroleukemia
#18
Feirong Gong, Dan Chen, Xin Teng, Junhua Ge, Xianfeng Ning, Ya-Ling Shen, Jian Li, Shanfeng Wang
Curcumin has high potential in suppressing many types of cancer and overcoming multi-drug resistance in a multi-faceted manner by targeting diverse molecular targets. However, the rather low systemic bioavailability resulted from its extremely low aqueous solubility and rapid metabolism and excretion in vivo has hampered its application in cancer therapy. With the primary aim to increase the aqueous solubility of curcumin while retaining its stability in the blood circulation before it accesses the tumor site, here we report preparation of curcumin-loaded N-(tert-butoxycarbonyl)-L-phenylalanine end-capped methoxy-poly(ethylene glycol)-block-poly(ε-caprolactone) (mPEG-PCL-Phe(Boc)) micelles with high stability both in vitro and in vivo and anti-tumor efficacy...
February 15, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28197174/extremely-low-frequency-electromagnetic-fields-stimulation-modulates-autoimmunity-and-immune-responses-a-possible-immuno-modulatory-therapeutic-effect-in-neurodegenerative-diseases
#19
REVIEW
Fabio Guerriero, Giovanni Ricevuti
Increasing evidence shows that extremely low frequency electromagnetic fields (ELF-EMFs) stimulation is able to exert a certain action on autoimmunity and immune cells. In the past, the efficacy of pulsed ELF-EMFs in alleviating the symptoms and the progression of multiple sclerosis has been supported through their action on neurotransmission and on the autoimmune mechanisms responsible for demyelination. Regarding the immune system, ELF-EMF exposure contributes to a general activation of macrophages, resulting in changes of autoimmunity and several immunological reactions, such as increased reactive oxygen species-formation, enhanced phagocytic activity and increased production of chemokines...
December 2016: Neural Regeneration Research
https://www.readbyqxmd.com/read/28195034/treatment-of-spinocerebellar-ataxia-with-mesenchymal-stem-cells-a-phase-i-iia-clinical-study
#20
Yun-An Tsai, Ren-Shyan Liu, Jiing-Feng Lirng, Bang-Hung Yang, Chin-Hao Chang, YiChen Wang, Yu-Shan Wu, Jennifer Hui-Chun Ho, Oscar K Lee, Bing-Wen Soong
Ataxia is one of the most devastating symptoms of many neurodegenerative disorders. As of today, there isn’tany effective treatment to retard its progression. Mesenchymal stem cells (MSCs) have shown promise in treating neurodegenerative diseases. We hereby report the results of a phase I/IIa clinical study conducted in Taiwan to primarily evaluate the safety, tolerability and, secondarily, the possible efficacy of intravenous administration of allogeneic adipose tissuederived MSCs from healthy donors...
February 14, 2017: Cell Transplantation
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