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https://www.readbyqxmd.com/read/28637008/cytotoxic-profiling-of-artesunic-and-betulinic-acids-and-their-synthetic-hybrid-compound-on-neurons-and-gliomas
#1
Annemarie Ackermann, Aysun Çapcı Karagöz, Ali Ghoochani, Michael Buchfelder, Ilker Eyüpoglu, Svetlana B Tsogoeva, Nicolai Savaskan
Gliomas are brain-born tumors with devastating impact on their brain microenvironment. Novel approaches employ multiple combinations of chemical compounds in synthetic hybrid molecules to target malignant tumors. Here, we report on the chemical hybridization approach exemplified by artesunic acid (ARTA) and naturally occurring triterpene betulinic acid (BETA). Artemisinin derived semisynthetic compound artesunic acid (ARTA) and naturally occurring triterpene BETA were used to synthetically couple to the hybrid compound termed 212A...
June 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28634084/drug-delivery-to-melanoma-brain-metastases-can-current-challenges-lead-to-new-opportunities
#2
Gautham Gampa, Shruthi Vaidhyanathan, Jann N Sarkaria, William F Elmquist
Melanoma has a high propensity to metastasize to the brain, and patients with melanoma brain metastases (MBM) have an extremely poor prognosis. The recent approval of several molecularly-targeted agents (e.g., BRAF, MEK inhibitors) and biologics (anti-CTLA-4, anti-PD-1 and anti-PD-L1 antibodies) has brought new hope to patients suffering from this formerly untreatable and lethal disease. Importantly, there have been recent reports of success in some clinical studies examining the efficacy of both targeted agents and immunotherapies that show similar response rates in both brain metastases and extracranial disease...
June 17, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28634000/dose-dependent-effects-of-abobotulinumtoxina-dysport%C3%A2-on-spasticity-and-active-movements-in-adults-with-upper-limb-spasticity-secondary-analysis-of-a-phase-3-study
#3
Michael W O'Dell, Allison Brashear, Robert Jech, Thierry Lejeune, Philippe Marque, Djamel Bensmail, Ziyad Ayyoub, David M Simpson, Magali Volteau, Claire Vilain, Philippe Picaut, Jean Michel Gracies
BACKGROUND: AbobotulinumtoxinA has beneficial effects on spasticity and active movements in hemiparetic adults with upper limb spasticity (ULS). However, evidence-based information on optimal dosing for clinical use is limited. OBJECTIVE: To describe joint-specific dose effects of abobotulinumtoxinA in adults with ULS. DESIGN: Secondary analysis of a phase 3 study (NCT01313299). SETTING: Multi-center, international, double-blind, placebo-controlled clinical trial...
June 17, 2017: PM & R: the Journal of Injury, Function, and Rehabilitation
https://www.readbyqxmd.com/read/28633970/unified-neural-field-theory-of-brain-dynamics-underlying-oscillations-in-parkinson-s-disease-and-generalized-epilepsies
#4
E J Müller, S J van Albada, J W Kim, P A Robinson
The mechanisms underlying pathologically synchronized neural oscillations in Parkinson's disease (PD) and generalized epilepsies are explored in parallel via a physiologically-based neural field model of the corticothalamic-basal ganglia (CTBG) system. The basal ganglia (BG) are approximated as a single effective population and their roles in the modulation of oscillatory dynamics of the corticothalamic (CT) system and vice versa are analyzed. In addition to normal EEG rhythms, enhanced activity around 4 Hz and 20 Hz exists in the model, consistent with the characteristic frequencies observed in PD...
June 17, 2017: Journal of Theoretical Biology
https://www.readbyqxmd.com/read/28633490/isolated-fourth-ventricle-to-shunt-or-stent
#5
Aaron Mohanty, Kim Manwaring
BACKGROUND: Of the various management options for isolated fourth ventricle (IFV), fourth ventriculoperitoneal shunts (FVPS) and aqueductal stents (AST) have been the most favored. Though effective, FVPS are often difficult to place and have higher complication rates than conventional ventricular shunts. OBJECTIVE: To assess the efficacy of AST in IFV and compare the outcome with FVPS. METHODS: Twenty-five patients surgically treated for IFV were analyzed...
June 17, 2017: Operative Neurosurgery (Hagerstown, Md.)
https://www.readbyqxmd.com/read/28632395/design-synthesis-and-multitarget-biological-profiling-of-second-generation-anti-alzheimer-rhein-huprine-hybrids
#6
Francisco Javier Pérez-Areales, Nibal Betari, Antonio Viayna, Caterina Pont, Alba Espargaró, Manuela Bartolini, Angela De Simone, José Fernando Rinaldi Alvarenga, Belén Pérez, Raimon Sabate, Rosa Maria Lamuela-Raventós, Vincenza Andrisano, Francisco Javier Luque, Diego Muñoz-Torrero
AIM: Simultaneous modulation of several key targets of the pathological network of Alzheimer's disease (AD) is being increasingly pursued as a promising option to fill the critical gap of efficacious drugs against this condition. MATERIALS & METHODS: A short series of compounds purported to hit multiple targets of relevance in AD has been designed, on the basis of their distinct basicities estimated from high-level quantum mechanical computations, synthesized, and subjected to assays of inhibition of cholinesterases, BACE-1, and Aβ42 and tau aggregation, of antioxidant activity, and of brain permeation...
June 20, 2017: Future Medicinal Chemistry
https://www.readbyqxmd.com/read/28632204/successful-pharmacotherapy-for-the-treatment-of-severe-feeding-aversion-with-mechanistic-insights-from-cross-species-neuronal-remodeling
#7
W G Sharp, A G Allen, K H Stubbs, K K Criado, R Sanders, C E McCracken, R G Parsons, L Scahill, S L Gourley
Pediatric feeding disorders affect up to 5% of children, causing severe food intake problems that can result in serious medical and developmental outcomes. Behavioral intervention (BI) is effective in extinguishing feeding aversions, and also expert-dependent, time/labor-intensive and not well understood at a neurobiological level. Here we first conducted a double-blind, placebo-controlled trial comparing BI with BI plus d-cycloserine (DCS). DCS is a partial N-methyl-d-aspartate (NMDA) receptor agonist shown to augment extinction therapies in multiple anxiety disorders...
June 20, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28631870/thalamic-deep-brain-stimulation-for-neuropathic-pain-efficacy-at-three-years-follow-up
#8
Vasco Abreu, Rui Vaz, Virgínia Rebelo, Maria José Rosas, Clara Chamadoira, Martin J Gillies, Tipu Z Aziz, Erlick A C Pereira
OBJECT: Chronic neuropathic pain is estimated to affect 3-4.5% of the worldwide population, posing a serious burden to society. Deep Brain Stimulation (DBS) is already established for movement disorders and also used to treat some "off-label" conditions. However, DBS for the treatment of chronic, drug refractory, neuropathic pain, has shown variable outcomes with few studies performed in the last decade. Thus, this procedure has consensus approval in parts of Europe but not the USA. This study prospectively evaluated the efficacy at three years of DBS for neuropathic pain...
June 20, 2017: Neuromodulation: Journal of the International Neuromodulation Society
https://www.readbyqxmd.com/read/28631509/comparison-of-quince-with-vitamin-b6-for-treatment-of-nausea-and-vomiting-in-pregnancy-a-randomised-clinical-trial
#9
Effat Jafari-Dehkordi, Fataneh Hashem-Dabaghian, Fatemeh Aliasl, Jaleh Aliasl, Maryam Taghavi-Shirazi, Omid Sadeghpour, Farnaz Sohrabvand, Bagher Minaei, Roshanak Ghods
This trial was performed to compare quince (Cydonia oblonga) fruit with vitamin B6 on 76 pregnant women with a gestational age of 6-14 weeks and mild-to-moderate nausea and vomiting (NVP) (40 in the quince and 36 in the B6 group). The 'Pregnancy-Unique Quantification of Emesis' (PUQE-24) scale was used to examine the severity of NVP. The quince syrup (1 tablespoon/TDS) or vitamin B6 tablets (20 mg/TDS) were used as intervention for 1 week. The mean (±SD) age was 27.5 (±5.2) years. The score of the PUQE was decreased from 9...
June 20, 2017: Journal of Obstetrics and Gynaecology: the Journal of the Institute of Obstetrics and Gynaecology
https://www.readbyqxmd.com/read/28630251/valnoctamide-inhibits-cytomegalovirus-infection-in-developing-brain-and-attenuates-neurobehavioral-dysfunctions-and-brain-abnormalities
#10
Sara Ornaghi, Lawrence S Hsieh, Angélique Bordey, Patrizia Vergani, Michael J Paidas, Anthony N van den Pol
Cytomegalovirus (CMV) is the most common infectious cause of brain defects and neurological dysfunction in developing human babies. Due to the teratogenicity and toxicity of available CMV antivirals, treatment options during early development are markedly limited. Valnoctamide (VCD), a neuroactive mood stabilizer with no known teratogenic activity, was recently demonstrated to have anti-CMV potential. However, it is not known whether this can be translated into an efficacious therapeutic effect to improve CMV-induced adverse neurological outcomes...
June 19, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28629741/establishment-of-an-ideal-time-window-model-in-hypothermic-targeted-temperature-management-after-traumatic-brain-injury-in-rats
#11
Wan-Yong Zhao, Shao-Bo Chen, Jing-Jing Wang, Chao Xu, Ming-Liang Zhao, Hua-Jiang Dong, Hai-Qian Liang, Xiao-Hong Li, Yue Tu, Sai Zhang, Chong Chen, Hong-Tao Sun
Although hypothermic-targeted temperature management (HTTM) holds great potential for the treatment of traumatic brain injury (TBI), translation of the efficacy of hypothermia from animal models to TBI patientshas no entire consistency. This study aimed to find an ideal time window model in experimental rats which was more in accordance with clinical practice through the delayed HTTM intervention. Sprague-Dawley rats were subjected to unilateral cortical contusion injury and received therapeutic hypothermia at 15 mins, 2 hours, 4 hours respectively after TBI...
June 16, 2017: Brain Research
https://www.readbyqxmd.com/read/28629387/an-updated-assessment-of-microglia-depletion-current-concepts-and-future-directions
#12
REVIEW
Jinming Han, Robert A Harris, Xing-Mei Zhang
Microglia are the principal resident immune cells in the central nervous system and are believed to be versatile players in both inflammatory and physiological contexts. On the one hand, in order to safeguard the microenvironment microglia can be rapidly activated by contact with microbial products or cell debris, thereby exerting the functions of innate immunity via phagocytosis and secretion of cytokines and chemokines. Conversely, microglia can also assist in brain development, synaptic plasticity and neural repair through the production of neurotrophic factors and clearance of myelin debris...
June 19, 2017: Molecular Brain
https://www.readbyqxmd.com/read/28629376/radiation-therapy-for-older-patients-with-brain-tumors
#13
REVIEW
Giuseppe Minniti, Andrea Riccardo Filippi, Mattia Falchetto Osti, Umberto Ricardi
The incidence of brain tumors in the elderly population has increased over the last few decades. Current treatment includes surgery, radiotherapy and chemotherapy, but the optimal management of older patients with brain tumors remains a matter of debate, since aggressive radiation treatments in this population may be associated with high risks of neurological toxicity and deterioration of quality of life. For such patients, a careful clinical status assessment is mandatory both for clinical decision making and for designing randomized trials to adequately evaluate the optimal combination of radiotherapy and chemotherapy...
June 19, 2017: Radiation Oncology
https://www.readbyqxmd.com/read/28628913/age-dependent-effects-of-alk5-inhibition-and-mechanism-of-neuroprotection-in-neonatal-hypoxic-ischemic-brain-injury
#14
Brian H Kim, Mariano Guardia Clausi, Michelle Frondelli, Israel C Nnah, Chaitali Saqcena, Radek Dobrowolski, Steven W Levison
Neonatal encephalopathy due to hypoxic-ischemic (HI) brain injury triggers a wave of neuroinflammatory events attributed to causing the progressive degeneration and functional deficits seen weeks after the initial insult. In a recent set of studies, we evaluated the therapeutic efficacy of a small molecule antagonist for ALK5 (activin-like kinase 5 ), TGF-β receptor in a rat model of moderate perinatal HI and found significant improvements in neurologic outcomes. Here, we have extended those studies to evaluate the efficacy of delayed TGF-β receptor antagonism on postnatal day (P) 6 and P9 HI rat pups with and without hypothermia...
June 20, 2017: Developmental Neuroscience
https://www.readbyqxmd.com/read/28628860/in-silico-modeling-on-adme-properties-of-natural-products-classification-models-for-blood-brain-barrier-permeability-its-application-to-traditional-chinese-medicine-and-in-vitro-experimental-validation
#15
Xiuqing Zhang, Ting Liu, Xiaohui Fan, Ni Ai
In silico modeling of blood-brain barrier (BBB) permeability plays an important role in early discovery of central nervous system (CNS) drugs due to its high-throughput and cost-effectiveness. Natural products (NP) have demonstrated considerable therapeutic efficacy against several CNS diseases. However, BBB permeation property of NP is scarcely evaluated both experimentally and computationally. It is well accepted that significant difference in chemical spaces exists between NP and synthetic drugs, which calls into doubt on suitability of available synthetic chemical based BBB permeability models for the evaluation of NP...
June 7, 2017: Journal of Molecular Graphics & Modelling
https://www.readbyqxmd.com/read/28628538/memory-rehabilitation-strategies-in-nonsurgical-temporal-lobe-epilepsy-a-review
#16
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...
July 2017: American Journal of Physical Medicine & Rehabilitation
https://www.readbyqxmd.com/read/28627968/severe-myelinopathy-in-49-xxxxy-syndrome
#17
Mark A Buller, Cory M Pfeifer
49,XXXXY is a rare aneuploidy with neuroanatomic findings scarcely reported in the literature. Given the fact that many of its phenotypic characteristics are similar to Klinefelter patients, 49,XXXXY has been treated as a variant of Klinefelter syndrome in the past. Newer studies have shown that intellectual disabilities and cardiac sequelae are more common in 49,XXXXY making the need for more precise characterization of the disorder essential. Prior case studies have demonstrated focal (and to a lesser extent confluent) white abnormalities as well as enlarged perivascular cysts (often in clustered arrangements) in the brains of these patients, but high resolution magnetic resonance images of severe myelinopathy are infrequently documented...
January 1, 2017: Neuroradiology Journal
https://www.readbyqxmd.com/read/28627419/arx-polyalanine-expansion-mutations-lead-to-migration-impediment-in-the-rostral-cortex-coupled-with-a-developmental-deficit-of-calbindin-positive-cortical-gabaergic-interneurons
#18
K Lee, K Ireland, M Bleeze, C Shoubridge
The Aristaless-related homeobox gene (ARX) is indispensable for interneuron development. Patients with ARX polyalanine expansion mutations of the first two tracts (namely PA1 and PA2) suffer from intellectual disability of varying severity, with seizures a frequent comorbidity. The impact of PA1 and PA2 mutations on the brain development is unknown, hindering the search for therapeutic interventions. Here, we characterised the disturbances to cortical interneuron development in mice modelling the two most common ARX polyalanine expansion mutations in human...
June 13, 2017: Neuroscience
https://www.readbyqxmd.com/read/28626112/experience-with-long-term-administration-of-tolvaptan-to-patients-with-acute-decompensated-heart-failure
#19
Shunsuke Kiuchi, Takahiro Fujii, Shinji Hisatake, Takayuki Kabuki, Oka Takashi, Shintaro Dobashi, Takanori Ikeda
Tolvaptan (TLV) is an oral selective vasopressin type 2 receptor antagonist. Long-term use of TLV is not recommended in patients with heart failure (HF) if fluid retention disappears and/or body weight is within the target range. However, some patients require long-term use of TLV. The current study investigated the efficacy and safety of long-term use of TLV. Subjects were 258 consecutive patients with HF who received TLV during hospitalization from January 2011 to March 2015. The rate of continuing administration of TLV was evaluated...
June 19, 2017: Drug Discoveries & Therapeutics
https://www.readbyqxmd.com/read/28625831/engineering-challenges-for-brain-tumor-immunotherapy
#20
Johnathan G Lyon, Nassir Mokarram, Tarun Saxena, Sheridan L Carroll, Ravi V Bellamkonda
Malignant brain tumors represent one of the most devastating forms of cancer with abject survival rates that have not changed in the past 60years. This is partly because the brain is a critical organ, and poses unique anatomical, physiological, and immunological barriers. The unique interplay of these barriers also provides an opportunity for creative engineering solutions. Cancer immunotherapy, a means of harnessing the host immune system for anti-tumor efficacy, is becoming a standard approach for treating many cancers...
June 15, 2017: Advanced Drug Delivery Reviews
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