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https://www.readbyqxmd.com/read/29036600/brain-cancer-cluster-investigation-around-a-factory-emitting-dichloromethane
#1
Konstantinos C Makris, Michael Voniatis
Background: The health risks associated with dichloromethane (DCM) for the general population living near industrial activities have not yet been quantified, primarily due to lack of epidemiological datasets. In the absence of such human data, we undertook a cancer cluster investigation in Cyprus around a historically using DCM plant producing shoe soles that were globally exported. We designed the methodology to investigate the possible existence of a cancer cluster in the area around the factory (point zero) and within a radius of 500 meters...
October 4, 2017: European Journal of Public Health
https://www.readbyqxmd.com/read/29035279/cannabis-in-fat-high-hopes-to-treat-obesity
#2
Melody N Hawkins, Tamas L Horvath
Cannabinoid receptor type-1 (CB1s) is known to have a substantial impact on the regulation of energy metabolism via central and peripheral mechanisms. In this issue of the JCI, Ruiz de Azua and colleagues provide important insights into the regulation of adipocyte physiology by CB1. Mice with adipocyte-specific deletion of the CB1-encoding gene had an overall improved metabolic profile in addition to reduced body weight and total adiposity. These changes were associated with an increase in sympathetic tone of the adipose tissue and expansion of activated macrophages, both of which occurred prior to changes in body weight, lending support to a causal relationship between loss of CB1 in adipocytes and systemic metabolic changes...
October 16, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29033788/zinc-as-a-neuromodulator-in-the-central-nervous-system-with-a-focus-on-the-olfactory-bulb
#3
REVIEW
Laura J Blakemore, Paul Q Trombley
The olfactory bulb (OB) is central to the sense of smell, as it is the site of the first synaptic relay involved in the processing of odor information. Odor sensations are first transduced by olfactory sensory neurons (OSNs) before being transmitted, by way of the OB, to higher olfactory centers that mediate olfactory discrimination and perception. Zinc is a common trace element, and it is highly concentrated in the synaptic vesicles of subsets of glutamatergic neurons in some brain regions including the hippocampus and OB...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/29033481/adverse-drug-reaction-monitoring-in-patients-on-antiretroviral-therapy-in-a-tertiary-care-hospital-in-eastern-india
#4
Shatavisa Mukherjee, Nikhil Era, Bibhuti Saha, Santanu Kumar Tripathi
BACKGROUND: Besides unparalleled benefits, highly active antiretroviral therapy is also associated with wide range of potential adverse drug reactions (ADRs), which hinders treatment adherence. The present study was thus designed to monitor and explore the pattern of occurrence of ADRs to various antiretroviral therapy (ART) regimens in a tertiary care ART setup. MATERIALS AND METHODS: A prospective, observational clinical study was carried out in the outpatient setting of nodal ART center of Eastern India...
May 2017: Indian Journal of Pharmacology
https://www.readbyqxmd.com/read/29032144/peroxisome-proliferator-activated-receptor-%C3%AE-ppar%C3%AE-a-master-gatekeeper-in-cns-injury-and-repair
#5
REVIEW
Wei Cai, Tuo Yang, Huan Liu, Lijuan Han, Kai Zhang, Xiaoming Hu, Xuejing Zhang, Ke-Jie Yin, Yanqin Gao, Michael V L Bennett, Rehana K Leak, Jun Chen
Peroxisome proliferator-activated receptor γ (PPARγ) is a widely expressed ligand-modulated transcription factor that governs the expression of genes involved in inflammation, redox equilibrium, trophic factor production, insulin sensitivity, and the metabolism of lipids and glucose. Synthetic PPARγ agonists (e.g. thiazolidinediones) are used to treat Type II diabetes and have the potential to limit the risk of developing brain injury by mitigating the influence of comorbidities. If brain injury develops, PPARγ serves as a master gatekeeper of cytoprotective stress responses, improving the chances of survival and recovery of homeostatic equilibrium...
October 11, 2017: Progress in Neurobiology
https://www.readbyqxmd.com/read/29032033/effect-of-mofezolac-galactose-distance-in-conjugates-targeting-cyclooxygenase-cox-1-and-cns-glut-1-carrier
#6
Maria Grazia Perrone, Paola Vitale, Savina Ferorelli, Angelina Boccarelli, Mauro Coluccia, Alessandra Pannunzio, Federica Campanella, Giuseppe Di Mauro, Carmela Bonaccorso, Cosimo G Fortuna, Antonio Scilimati
Neuroinflammation is the earliest stage of several neurological and neurodegenerative diseases. In the case of neurodegenerative disorders, it takes place about 15-20 years before the appearance of specific neurodegenerative clinical symptoms. Constitutive microglial COX-1 is one of the pro-inflammatory players of the neuroinflammation. Novel compounds 3, 14 and 15 (Galmof0, Galmof5 and Galmof11, respectively) were projected, and their synthetic methodologies developed, by linking by an ester bond, directly or through a C5 or C11 unit linker the highly selective COX-1 inhibitor mofezolac (COXs selectivity index > 6000) to galactose in order to obtain substances capable to cross blood-brain barrier (BBB) and control the CNS inflammatory response...
September 30, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29031957/exercise-training-attenuates-experimental-autoimmune-encephalomyelitis-by-peripheral-immunomodulation-rather-than-direct-neuroprotection
#7
Ofira Einstein, Nina Fainstein, Olga Touloumi, Roza Lagoudaki, Ester Hanya, Nikolaos Grigoriadis, Abram Katz, Tamir Ben-Hur
BACKGROUND: Conflicting results exist on the effects of exercise training (ET) on Experimental Autoimmune Encephalomyelitis (EAE), nor is it known how exercise impacts on disease progression. OBJECTIVE: We examined whether ET ameliorates the development of EAE by modulating the systemic immune system or exerting direct neuroprotective effects on the CNS. METHODS: Healthy mice were subjected to 6weeks of motorized treadmill running. The Proteolipid protein (PLP)-induced transfer EAE model in mice was utilized...
October 11, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/29031145/small-molecule-mediated-upregulation-of-ccr7-ameliorates-murine-experimental-autoimmune-encephalomyelitis-by-accelerating-t-cell-homing
#8
Xin Li, Tingting Lu, Wenwen Xue, Yixuan Wang, Qiong Luo, Huiming Ge, Renxiang Tan, Yan Shen, Qiang Xu
Impairing the infiltration of immune cells into the CNS is a promising target for suppressing the development of multiple sclerosis (MS) and its animal model experimental autoimmune encephalomyelitis (EAE). Here, we found that oral administration of a synthetic small molecular compound Fc24 showed potential preventive effects on the development of EAE, including the reduction in EAE severity and a delay in the onset of the disease. Fc24 facilitated the accumulation of both CD4(+) and CD8(+) T cells within spleen and lymph nodes, while having no effect on MOG-specific T cell responses...
October 11, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/29030454/infliximab-for-the-treatment-of-cns-sarcoidosis-a-multi-institutional-series
#9
Jeffrey M Gelfand, Michael J Bradshaw, Barney J Stern, David B Clifford, Yunxia Wang, Tracey A Cho, Laura L Koth, Stephen L Hauser, Jason Dierkhising, NgocHanh Vu, Subramaniam Sriram, Harold Moses, Francesca Bagnato, Jeffrey A Kaufmann, Deidre J Ammah, Tsion H Yohannes, Mark J Hamblin, Nagagopal Venna, Ari J Green, Siddharama Pawate
OBJECTIVE: To describe clinical and imaging responses in neurosarcoidosis to infliximab, a monoclonal antibody against tumor necrosis factor-α. METHODS: Investigators at 6 US centers retrospectively identified patients with CNS sarcoidosis treated with infliximab, including only patients with definite or probable neurosarcoidosis following rigorous exclusion of other causes. RESULTS: Of 66 patients with CNS sarcoidosis (27 definite, 39 probable) treated with infliximab for a median of 1...
October 13, 2017: Neurology
https://www.readbyqxmd.com/read/29030054/inhibiting-the-cd38-cadpr-pathway-protected-rats-against-sepsis-associated-brain-injury
#10
Qian-Yi Peng, Yi-Min Wang, Cai-Xia Chen, Yu Zou, Li-Na Zhang, Song-Yun Deng, Yu-Hang Ai
BACKGROUND: The CD38/cADPR pathway has been found to play roles in various inflammatory conditions. However, whether CD38 plays a protective or detrimental effect in the central nervous system (CNS) is controversial. The aim of this study was to determine the effect of CD38/cADPR pathway in sepsis associated brain injury. MATERIALS AND METHODS: Male Sprague-Dawley rats were undergone cecal ligation and puncture (CLP) or sham laparotomies. NAD(+), cADPR and CD38 were measured in the hippocampus of septic rats at 0, 6, 12, 24, and 48 h after CLP surgery...
October 10, 2017: Brain Research
https://www.readbyqxmd.com/read/29028353/activated-microglia-targeting-dendrimer-minocycline-conjugate-as-therapeutics-for-neuroinflammation
#11
Rishi Sharma, Soo-Young Kim, Anjali Sharma, Zhi Zhang, Siva Pramodh Kambhampati, Sujatha Kannan, Rangaramanujam M Kannan
Brain related disorders have outmatched cancer and cardiovascular diseases worldwide as the leading cause of morbidity and mortality. The lack of effective therapies and the relatively dry central nervous system (CNS) drug pipeline pose formidable challenge. Superior, targeted delivery of current clinically approved drugs may offer significant potential. Minocycline has shown promise for the treatment of neurological diseases owing to its ability to penetrate the blood brain barrier (BBB), and potency. Despite its potential in the clinic, and in preclinical models, the high doses needed to affect a positive therapeutic response has led to side effects...
October 13, 2017: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/29027376/adenosine-a2a-receptor-agonist-ameliorates-eae-and-correlates-with-th1-cytokine-induced-blood-brain-barrier-dysfunction-via-suppression-of-mlck-signaling-pathway
#12
Ying Liu, Marwan Alahiri, Bianca Ulloa, Boxun Xie, Saud A Sadiq
INTRODUCTION: Multiple sclerosis (MS) disease activity is associated with blood-brain barrier (BBB) disruption, which is mediated by inflammatory cytokines released by CD4+ lymphocytes. To assess the effects of adenosine A2A receptors on BBB permeability in vitro and in vivo. METHODS: A2A receptor expression was detected by immunostaining in experimental autoimmune encephalomyelitis (EAE) C57BL/6 mice immunized with myelin oligodendrocyte glycoprotein (MOG)35-55 , and human MS brain...
October 12, 2017: Immunity, Inflammation and Disease
https://www.readbyqxmd.com/read/29025878/elevated-postoperative-endogenous-glp-1-levels-mediate-effects-of-roux-en-y-gastric-bypass-on-neural-responsivity-to-food-cues
#13
Jennifer S Ten Kulve, Dick J Veltman, Victor E A Gerdes, Liselotte van Bloemendaal, Frederik Barkhof, Carolyn F Deacon, Jens J Holst, Madeleine L Drent, Michaela Diamant, Richard G IJzerman
OBJECTIVE: It has been suggested that weight reduction and improvements in satiety after Roux-en-Y gastric bypass (RYGB) are partly mediated via postoperative neuroendocrine changes. Glucagon-like peptide-1 (GLP-1) is a gut hormone secreted after food ingestion and is associated with appetite and weight reduction, mediated via effects on the central nervous system (CNS). Secretion of GLP-1 is greatly enhanced after RYGB. We hypothesized that postoperative elevated GLP-1 levels contribute to the improved satiety regulation after RYGB via effects on the CNS...
October 12, 2017: Diabetes Care
https://www.readbyqxmd.com/read/29025286/-thalidomide-therapy-in-relapsed-diffuse-large-b-cell-lymphoma-in-elderly-patients-three-cases
#14
Nikolett Wohner, Gergely Varga, Péter Szloboda, Péter Farkas, András Masszi, Laura Horváth, Gergely Szombath, Judit Várkonyi, Szabolcs Benedek, Tamás Masszi
Diffuse large B-cell lymphoma (DLBCL), a high-grade lymphoproliferative disease, is the most common lymphoma in adults, representing 31% of non-Hodgkin lymphomas (NHL). In elderly patients treatment is problematic because of the high toxicity of standard chemotherapy protocols, especially in relapsed cases, where high-dose chemotherapy and haematopoietic stem cell transplantation would be the best choice. More and more data is becoming available on alternative treatment of refractory/relapsed NHL, including studies on the positive effect of thalidomide and second generation IMiDs in DLBCL, which are already part of the standard treatment protocol in myeloma multiplex and myelodysplasia...
October 2017: Orvosi Hetilap
https://www.readbyqxmd.com/read/29024742/cyp-mediated-drug-metabolism-in-the-brain-impacts-drug-response
#15
REVIEW
Douglas M McMillan, Rachel F Tyndale
The functional role of cytochrome P450 (CYP) enzymes in the brain is an exciting and evolving field of research. CYPs are present and active in the brain, with heterogeneous patterns of expression, activity, and sensitivity to modulation across cell types, regions, and species. Despite total brain CYP expression being a fraction of hepatic CYP expression, the expanding literature of in vitro and in vivo experiments have provided evidence that brain CYPs can impact acute and chronic drug response, susceptibility to damage by neurotoxins, and are associated with altered personality, behaviour, and risk of neurological disease...
October 9, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/29024008/immunization-with-%C3%AE-synuclein-grp94-reshapes-peripheral-immunity-and-suppresses-microgliosis-in-a-chronic-parkinsonism-model
#16
Javier Villadiego, Adahir Labrador-Garrido, Jaime M Franco, Magdalena Leal-Lasarte, Erwin J De Genst, Christopher M Dobson, David Pozo, Juan J Toledo-Aral, Cintia Roodveldt
Neuroinflammation mediated by chronically activated microglia, largely caused by abnormal accumulation of misfolded α-synuclein (αSyn) protein, is known to contribute to the pathophysiology of Parkinson's disease (PD). In this work, based on the immunomodulatory activities displayed by particular heat-shock proteins (HSPs), we tested a novel vaccination strategy that used a combination of αSyn and Grp94 (HSPC4 or Gp96) chaperone and a murine PD model. We used two different procedures, first, the adoptive transfer of splenocytes from αSyn/Grp94-immunized mice to recipient animals, and second, direct immunization with αSyn/Grp94, to study the effects in a chronic mouse MPTP-model of parkinsonism...
October 11, 2017: Glia
https://www.readbyqxmd.com/read/29023630/the-hmgb1-is-increased-in-csf-of-patients-with-an-anti-nmdar-encephalitis
#17
P Ai, X Zhang, Z Xie, G Liu, X Liu, S Pan, H Wang
BACKGROUND: Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is an autoimmune disorder of the central nervous system (CNS). Interleukin (IL)-6 and IL-17A may play important roles in the pathogenesis of this disease. High-mobility group box protein 1 (HMGB1), a small but highly conserved ubiquitous protein, is recognized to be a potent innate inflammatory mediator that can activate the nuclear factor light chain enhancer of activated B cells and release cytokines such as IL-6 and IL-17A when released extracellularly...
October 12, 2017: Acta Neurologica Scandinavica
https://www.readbyqxmd.com/read/29023471/combinatorial-action-of-grainyhead-extradenticle-and-notch-in-regulating-hox-mediated-apoptosis-in-drosophila-larval-cns
#18
Risha Khandelwal, Rashmi Sipani, Sriivatsan Govinda Rajan, Raviranjan Kumar, Rohit Joshi
Hox mediated neuroblast apoptosis is a prevalent way to pattern larval central nervous system (CNS) by different Hox genes, but the mechanism of this apoptosis is not understood. Our studies with Abdominal-A (Abd-A) mediated larval neuroblast (pNB) apoptosis suggests that AbdA, its cofactor Extradenticle (Exd), a helix-loop-helix transcription factor Grainyhead (Grh), and Notch signaling transcriptionally contribute to expression of RHG family of apoptotic genes. We find that Grh, AbdA, and Exd function together at multiple motifs on the apoptotic enhancer...
October 12, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/29023416/neuro-coagulopathy-blood-coagulation-factors-in-central-nervous-system-diseases
#19
REVIEW
Ciro De Luca, Assunta Virtuoso, Nicola Maggio, Michele Papa
Blood coagulation factors and other proteins, with modulatory effects or modulated by the coagulation cascade have been reported to affect the pathophysiology of the central nervous system (CNS). The protease-activated receptors (PARs) pathway can be considered the central hub of this regulatory network, mainly through thrombin or activated protein C (aPC). These proteins, in fact, showed peculiar properties, being able to interfere with synaptic homeostasis other than coagulation itself. These specific functions modulate neuronal networks, acting both on resident (neurons, astrocytes, and microglia) as well as circulating immune system cells and the extracellular matrix...
October 12, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29021960/relapsing-ebv-encephalitis-in-a-renal-transplant-recipient
#20
Joshua A Stone, Bettina M Knoll, Dimitrios Farmakiotis
In solid organ transplant recipients, Epstein-Barr virus (EBV) can cause active central nervous system (CNS) infection or malignant transformation of latently infected cells in the CNS, known as post-transplant lymphoproliferative disease (PTLD). Reduction of T-cell immunosuppression is the cornerstone of management. The role of antivirals with in-vitro activity against herpesviruses in EBV-related CNS syndromes is controversial, as they have no effect on latent virus. We report an unusual case of relapsing EBV encephalitis in a donor-positive, EBV-negative renal transplant recipient, with response to valganciclovir...
2017: IDCases
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