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CNS disease

Vivienne H Tam, Chris Sosa, Rui Liu, Nan Yao, Rodney D Priestley
The blood brain barrier (BBB) is a major obstacle to drug delivery for diseases of the central nervous system (CNS). This brief review highlights the current invasive and non-invasive technologies available to address this problem. In particular, nanomedicine has shown much promise as a non-invasive strategy due to its drug loading capabilities, ease of targeting to the BBB, and small size. The versatility of this technology in terms of type of drug and imaging agent, carrier material, and targeting mechanism is highlighted in this review...
October 18, 2016: International Journal of Pharmaceutics
Da-Shi Qi, Jin-Hao Tao, Lian-Qin Zhang, Mei Wang, Rui Qu, Lian-Qin Zhang, Pei Liu, Jian-Cheng Miu, Jing-Yi Ma, Xin-Yu Mei
Cilostazol(CTL) is a phosphodiesterase inhibitor, which has been widely used as anti-platelet agent. It also has preventive effects on various central nervous system (CNS) diseases, including ischemic stroke, Parkinson's disease and Alzheimer disease. However, the molecular mechanism underlying the protective effects of CTL is still unclear, and whether CTL can prevent I/R induced cognitive deficit has not been reported. Transient global brain ischemia was induced by 4-vessel occlusion in adult male Sprague-Dawley rats...
October 18, 2016: Brain Research
Julien Muffat, Yun Li, Rudolf Jaenisch
In vitro differentiation of human pluripotent stem cells provides a systematic platform to investigate the physiological development and function of the human nervous system, as well as the etiology and consequence when these processes go awry. Recent development in three-dimensional (3D) organotypic culture systems allows modeling of the complex structure formation of the human CNS, and the intricate interactions between various resident neuronal and glial cell types. Combined with an ever-expanding genome editing and regulation toolkit such as CRISPR/Cas9, it is now a possibility to study human neurological disease in the relevant molecular, cellular and anatomical context...
October 18, 2016: Current Opinion in Cell Biology
Siddharth Jain, Animesh Ray, Manish Soneja, S Leve Joseph Devarajan, Shyam Madabhushi, Anitha Swamy, T Naveen, S K Sharma
A known case of primary Sjogren's syndrome with chronic kidney disease presented with respiratory symptoms and subsequent altered sensorium. Chest imaging suggested cavitating lung lesions in both the lungs. Serum c-ANCA was positive without any upper respiratory tract involvement or active urinary sediments. Treatment with appropriate anti-microbials produced no improvement in the respiratory or neurological parameters. MRI brain revealed tell-tale signs of CNS vascultis. A diagnosis of GPA was made as per European Medical Agency algorithm and the patient was started on immune-suppressants to which there was dramatic response...
October 2016: Journal of the Association of Physicians of India
J M Koshy, S Mohan, D Deodhar, M John, A Oberoi, A Pannu
BACKGROUND: Though cryptococcal meningitis (CM) is recognized as a disease of the immunocompromised, studies have implicated that it also affect immunocompetent patients. METHODOLOGY: This was a cross sectional study conducted in the Department of Medicine of a tertiary teaching institution in North India. All the patients diagnosed with CM on the basis of detection of cryptococcal antigen or the presence of capsulated budding yeast cells on India ink preparation, from April 2009 to March2015 were included in the study...
October 2016: Journal of the Association of Physicians of India
Liron Frishman-Levy, Shai Izraeli
Central nervous system acute lymphoblastic leukaemia (CNS-ALL) is a major clinical problem. CNS-directed 'prophylactic' chemo- or radio - therapy is associated with significant early and long-term toxicity. Moreover, greater than a third of the relapses occur in the CNS. To design specific, more effective and less toxic therapy and for personalized precise adjustment of prophylactic therapy there is a need for better understanding of the biology of this disease. Specifically, the precise neurotropic mechanisms of ALL are currently unclear, as is the pathogenesis of CNS relapse...
October 21, 2016: British Journal of Haematology
Britta Wandschneider, Matthias J Koepp
Functional MRI studies have helped to elucidate underlying mechanisms in complex neurological and neuropsychiatric disorders. Disease processes often involve complex large-scale network interactions, extending beyond the presumed main disease focus. Given both the complexity of the clinical phenotype and the underlying dysfunctional brain circuits, so called pharmaco-fMRI (ph-MRI) studies probe pharmacological effects on functional neuro-anatomy, and can help to determine early treatment response, mechanisms of drug efficacy and side effects, and potentially advance CNS drug development...
2016: NeuroImage: Clinical
Catherine S Hubbard, Lino Becerra, Jonathan H Smith, Justin M DeLange, Ryan M Smith, David F Black, Kirk M Welker, Rami Burstein, Fred M Cutrer, David Borsook
The aim of this study was to identify structural and functional brain changes that accompanied the transition from chronic (CM; ≥15 headache days/month) to episodic (EM; <15 headache days/month) migraine following prophylactic treatment with onabotulinumtoxinA (BoNT-A). Specifically, we examined whether CM patients responsive to prophylaxis (responders; n = 11), as evidenced by a reversal in disease status (defined by at least a 50% reduction in migraine frequency and <15 headache days/month), compared to CM patients whose migraine frequency remained unchanged (non-responders; n = 12), showed differences in cortical thickness using surface-based morphometry...
2016: Frontiers in Human Neuroscience
A Hosseini, H R Sadeghnia, A Rajabian
Oxidative stress and apoptosis contribute to neuronal degeneration in many neurodegenerative diseases such as Alzheimer's disease. Glutamate is a major excitatory neurotransmitter in the central nervous system (CNS) and is considered responsible for the pathogenesis of many neurological disorders. Reactive oxygen species (ROS) production is thought to be involved in glutamate-induced apoptosis process. In this study, the neuroprotective effects of Citrus aurantium in the glutamate-induced rat's adrenal pheochromocytoma cell line (PC12 cells) were investigated...
2016: Folia Neuropathologica
Mythily Srinivasan, Baindu Bayon, Nipun Chopra, Debomoy K Lahiri
In the central nervous system (CNS), activation of the transcription factor nuclear factor-kappa B (NF-κβ) is associated with both neuronal survival and increased vulnerability to apoptosis. The mechanisms underlying these dichotomous effects are attributed to the composition of NF-κΒ dimers. In Alzheimer's disease (AD), β-amyloid (Aβ) and other aggregates upregulate activation of p65:p50 dimers in CNS cells and enhance transactivation of pathological mediators that cause neuroinflammation and neurodegeneration...
2016: PloS One
W Oliver Tobin, Chiara Costanzi, Yong Guo, Joseph E Parisi, Stephen D Weigand, Claudia F Lucchinetti
BACKGROUND: The spectrum of central nervous system-idiopathic inflammatory demyelinating disease (CNS-IIDD) in the elderly is uncertain. OBJECTIVE: To describe the clinical, radiological, and pathological features of a cohort of 30 pathologically proven CNS-IIDD patients ⩾65 years. METHODS: Elderly multiple sclerosis (MS)/clinically isolated syndrome (CIS) patients were compared to a cohort of 125 patients with pathologically proven MS/CIS and symptom onset <65 years...
October 19, 2016: Multiple Sclerosis: Clinical and Laboratory Research
Ke-Wei Tian, Fan Zhang, Hong Jiang, Beibei Wang, Shu Han
Multiple sclerosis (MS) is a chronic neurological disorder that affects the central nervous system (CNS), and results in CNS inflammation and damage to myelin. In this study, we examined the possible synergistic effects of C16, angiopoietin-1 (Ang-1) and regeneration gene protein 2 (Reg-2) in alleviating inflammation in an acute experimental autoimmune encephalomyelitis (EAE) model. We employed multiple histological, morphological and iconographic assays to examine the effect of those drugs on disease onset, clinical scores and behavioral deficits...
October 19, 2016: Journal of Anatomy
Kiyohiro Sakai, Masayuki Takeda, Hidetoshi Hayashi, Kaoru Tanaka, Takeshi Okuda, Amami Kato, Yasumasa Nishimura, Tetsuya Mitsudomi, Atsuko Koyama, Kazuhiko Nakagawa
INTRODUCTION: The concept of "oligometastasis" has emerged as a basis on which to identify patients with stage IV non-small cell lung cancer (NSCLC) who might be most amenable to curative treatment. Limited data have been available regarding the survival of patients with node-negative oligometastatic NSCLC. PATIENTS AND METHODS: Consecutive patients with advanced NSCLC who attended Kindai University Hospital between January 2007 and January 2016 were recruited to this retrospective study...
September 12, 2016: Thoracic Cancer
Samina Salim
Biochemical integrity of the brain is vital for normal functioning of the central nervous system (CNS). One of the contributing factors of cerebral biochemical impairment is a chemical process called oxidative stress. Oxidative stress occurs upon excessive free radical production due to insufficiency of counteracting antioxidant response system. The brain with its high oxygen consumption and lipid-rich content is highly susceptible to oxidative stress. Therefore, oxidative stress-induced damage to the brain has a strong potential to negatively impact normal CNS functions...
October 17, 2016: Journal of Pharmacology and Experimental Therapeutics
George Bakris
Resistant hypertension is defined as a blood pressure above 140/90 mmHg despite adherence to a combination of at least three optimally dosed antihypertensive medications, one of which is a diuretic. Chronic kidney disease (CKD) is one of the more common patient comorbidities associated with resistant hypertension. Recommended low-salt diet and triple antihypertensive drug regimens that include a diuretic, should be complemented by the sequential addition of other antihypertensive drugs. CKD is associated with premature vascular ageing, characterized by accelerated arteriosclerosis or atherosclerosis and endothelial dysfunction...
September 2016: Journal of Hypertension
João Casaca-Carreira, Yasin Temel, Iñaki Larrakoetxea, Ali Jahanshahi
Antisense oligonucleotide (AON) therapy is emerging as a potential treatment strategy for neurodegenerative diseases, such as spinal muscular atrophy, Huntington's disease, and amyotrophic lateral sclerosis. AONs function at the cellular level by, for example, direct interference with the expression of gene products or the molecular activation of neuroprotective pathways. However, AON therapy faces a major obstacle limiting its clinical application for central nervous system (CNS) disorders: the blood-brain barrier...
October 18, 2016: Nucleic Acid Therapeutics
Kitsada Wudhikarn, Udomsak Bunworasate, Jakrawadee Julamanee, Arnuparp Lekhakula, Suporn Chuncharunee, Pimjai Niparuck, Supachai Ekwattanakit, Archrob Khuhapinant, Lalita Norasetthada, Weerasak Nawarawong, Nisa Makruasi, Nonglak Kanitsap, Chittima Sirijerachai, Kanchana Chansung, Peerapon Wong, Tontanai Numbenjapon, Kannadit Prayongratana, Tawatchai Suwanban, Somchai Wongkhantee, Pannee Praditsuktavorn, Tanin Intragumtornchai
Secondary central nervous system (CNS) relapse is a serious and fatal complication of diffuse large B cell lymphoma (DLBCL). Data on secondary CNS (SCNS) relapse were mostly obtained from western countries with limited data from developing countries. We analyzed the data of 2034 newly diagnosed DLBCL patients enrolled into the multi-center registry under Thai Lymphoma Study Group from setting. The incidence, September 2006 to December 2013 to represent outcome from a resource limited pattern, management, and outcome of SCNS relapse were described...
October 18, 2016: Annals of Hematology
Glenwood Goss, Chun-Ming Tsai, Frances A Shepherd, Lyudmila Bazhenova, Jong Seok Lee, Gee-Chen Chang, Lucio Crino, Miyako Satouchi, Quincy Chu, Toyoaki Hida, Ji-Youn Han, Oscar Juan, Frank Dunphy, Makoto Nishio, Jin-Hyoung Kang, Margarita Majem, Helen Mann, Mireille Cantarini, Serban Ghiorghiu, Tetsuya Mitsudomi
BACKGROUND: Osimertinib (AZD9291) is an oral, potent, irreversible EGFR tyrosine-kinase inhibitor selective for EGFR tyrosine-kinase inhibitor sensitising mutations, and the EGFR Thr790Met resistance mutation. We assessed the efficacy and safety of osimertinib in patients with EGFR Thr790Met-positive non-small-cell lung cancer (NSCLC), who had progressed after previous therapy with an approved EGFR tyrosine-kinase inhibitor. METHODS: In this phase 2, open-label, single-arm study (AURA2), patients aged at least 18 years with centrally confirmed EGFR Thr790Met-positive mutations, locally advanced or metastatic (stage IIIB/IV) NSCLC who progressed on previous EGFR tyrosine-kinase inhibitor therapy received osimertinib 80 mg orally once daily; treatment could continue beyond progression if the investigator observed a clinical benefit...
October 14, 2016: Lancet Oncology
Rodrigo Fabrizzio Inácio, Renata Gacielle Zanon, Mateus Vidigal de Castro, Henrique Marques de Souza, Marcio Chaim Bajgelman, Liana Verinaud, Alexandre Leite Rodrigues de Oliveira
Astrocytes are multifunctional glial cells that actively participate in synaptic plasticity in health and disease. Little is known about molecular interactions between neurons and glial cells that result in synaptic stability or elimination. In this sense, the main histocompatibility complex of class I (MHC I) has been shown to play a role in the synaptic plasticity process during development and after lesion of the CNS. MHC I levels in neurons appear to be influenced by astrocyte secreted molecules, which may generate endoplasmic reticulum stress...
October 14, 2016: Neuroscience Letters
Bassem Yousef Sheikh, S M Neamul Kabir Zihad, Nazifa Sifat, Shaikh J Uddin, Jamil A Shilpi, Omer A A Hamdi, Hemayet Hossain, Razina Rouf, Ismet Ara Jahan
In addition to the rich nutritional value, date palm is also used in various ethnobotanical practices for the treatment of various disease conditions. Present investigation was undertaken to examine the neuropharmacological and antinociceptive effect of the ethanol extract of three date cultivars growing in Saudi Arabia, namely Ajwah, Safawy and Sukkari. Neuropharmacological effect was observed by pentobarbitone induced sleeping time, open field, and hole board test. Antinociceptive activity was tested by acetic acid induced writhing and hot plate test...
2016: Oriental Pharmacy and Experimental Medicine
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