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https://www.readbyqxmd.com/read/29444478/detection-of-drug-safety-signals-from-clinical-trials-data-role-of-susars
#1
Christelle Perez, Pascale Olivier, Barbara Lortal, Sophie Duranton, Jean-Louis Montastruc, Anne-Laurène Colin, Emilie Toulza, Madlyne Becker, Laura Hamy, Sabrina Crepin, Caroline Roussillon, Anne Gimbert, Nadine Petitpain, Francesco Salvo
One of the main goals of safety management in clinical trials is to detect suspected unexpected serious adverse reactions (SUSARs). The unexpectedness concerns the nature, frequency or severity of an adverse reaction. Drug safety signals could thus be retrieved, and a study was performed to investigate whether SUSARs allow signal detection in pharmacovigilance. Data from six academic safety units were collected from 2005 to 2016. Characteristics of SUSARs were analysed and signals were identified i) by evaluating the presence of other causes, ii) by assessing the summary of product characteristics (SPC), iii) by searching for specific safety information in Pubmed and health agencies, and iv) by investigating the narrative of each case...
February 11, 2018: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/29443098/a-novel-in-vitro-live-imaging-assay-of-astrocyte-mediated-phagocytosis-using-ph-indicator-conjugated-synaptosomes
#2
Youkyeong Gloria Byun, Won-Suk Chung
Astrocytes are the major cell type in the brain and directly contact synapses and blood vessels. Although microglial cells have been considered the major immune cells and only phagocytes in the brain, recent studies have shown that astrocytes also participate in various phagocytic processes, such as developmental synapse elimination and clearance of amyloid beta plaques in Alzheimer's disease (AD). Despite these findings, the efficiency of astrocyte engulfment and degradation of their targets is unclear compared with that of microglia...
February 5, 2018: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29436577/rp105-protects-pc12-cells-from-oxygen%C3%A2-glucose-deprivation-reoxygenation-injury-via-activation-of-the-pi3k-akt-signaling-pathway
#3
Yanpeng Sun, Lu Liu, Jiang Yuan, Qiang Sun, Na Wang, Yunfu Wang
Radioprotective 105 kDa protein (RP105) has been reported to produce favorable outcomes in various cardiovascular disorders via a toll‑like receptor 4‑dependent or ‑independent manner. However, whether RP105 exerts neuroprotective effects against oxygen‑glucose deprivation (OGD)/reoxygenation (OGD/R) injury remains to be elucidated. In the present study, the PC12 neuronal cell line was exposed to 4 h of OGD followed by 24 h of reoxygenation. Adenoviral vectors encoding RP105 were utilized to upregulate the level of RP105 in PC12 cells prior to OGD/R induction...
February 12, 2018: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29436097/amyloids-of-multiple-species-are-they-helpful-in-survival
#4
Arun Upadhyay, Amit Mishra
Amyloids are primarily known for their roles in neurodegenerative disorders, as well as in systemic diseases like diabetes. Evolutionary forces tend to maintain a healthy set of heritable characteristics, while eliminating toxic or unfavourable elements; but amyloids seem to represent an exception to this fundamental concept. In addition to their presence in mammals, amyloids also persist in the proteome of many lower organisms that may be linked with possible roles in survival, which are still unexplored. Herein, we address some unanswered questions regarding amyloids: are these well-structured proteinaceous aggregates a by-product of inefficient folding events, or have they been retained in our protein repertoire for as yet unknown functional roles; and how do protein misfolding and associated disorders originate, despite the presence of protein quality-control systems inside the cells? This review aims to extend our current understanding about the multifaceted useful properties of amyloids and their functional interactions with other molecular pathways in various species; this may provide new insights to identify novel therapeutic strategies for ageing and neurodegenerative diseases...
February 13, 2018: Biological Reviews of the Cambridge Philosophical Society
https://www.readbyqxmd.com/read/29435980/the-diabetes-drug-liraglutide-reverses-cognitive-impairment-in-mice-and-attenuates-insulin-receptor-and-synaptic-pathology-in-a-non-human-primate-model-of-alzheimer-s-disease
#5
Andre F Batista, Leticia Forny-Germano, Julia R Clarke, Natalia M Lyra E Silva, Jordano Brito-Moreira, Susan E Boehnke, Andrew Winterborn, Brian C Coe, Ann Lablans, Juliana F Vital, Suelen A Marques, Ana M B Martinez, Matthias Gralle, Christian Holscher, William L Klein, Jean-Christophe Houzel, Sergio T Ferreira, Douglas P Munoz, Fernanda G De Felice
Alzheimer's disease (AD) is a devastating neurological disorder that still lacks an effective treatment, and this has stimulated an intense pursuit of disease-modifying therapeutics. Given the increasingly recognized link between AD and defective brain insulin signaling, we investigated the actions of liraglutide, a glucagon-like peptide-1 (GLP-1) analog marketed for treatment of type 2 diabetes, in experimental models of AD. Insulin receptor pathology is an important feature of AD brains that impairs the neuroprotective actions of central insulin signaling...
February 12, 2018: Journal of Pathology
https://www.readbyqxmd.com/read/29434814/metformin-and-pioglitazone-combination-therapy-ameliorate-polycystic-ovary-syndrome-through-ampk-pi3k-jnk-pathway
#6
Yuanyuan Wu, Pengfen Li, Dan Zhang, Yingpu Sun
Polycystic ovary syndrome (PCOS) is a common gynecological endocrine disorder, which results in health problems such as menstrual disorders, hyperandrogenism and persistent anovulation. Hyperandrogenism and insulin resistance are the basic characteristics of PCOS. To investigate the combined effect of metformin and pioglitazone on POCS and the potential mechanisms, a rat model of PCOS was established by intramuscular injection of estradiol valerate (EV). The effect of metformin and pioglitazone monotherapy or combination therapy in control rats and PCOS rats was evaluated, involving the testosterone level, follicular development and insulin resistance...
February 2018: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29434586/bioactive-lipids-and-chronic-inflammation-managing-the-fire-within
#7
REVIEW
Valerio Chiurchiù, Alessandro Leuti, Mauro Maccarrone
Inflammation is an immune response that works as a contained fire that is pre-emptively sparked as a defensive process during infections or upon any kind of tissue insult, and that is spontaneously extinguished after elimination or termination of the damage. However, persistent and uncontrolled immune reactions act as a wildfire that promote chronic inflammation, unresolved tissue damage and, eventually, chronic diseases. A wide network of soluble mediators, among which endogenous bioactive lipids, governs all immune processes...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29434172/new-improved-version-of-the-mcop-pcr-screening-system-for-detection-of-spinal-muscular-atrophy-gene-smn1-deletion
#8
Masakazu Shinohara, Mawaddah Ar Rochmah, Kenta Nakanishi, Nur Imma Fatimah Harahap, Emma Tabe Eko Niba, Toshio Saito, Kayoko Saito, Atsuko Takeuchi, Yoshihiro Bouike, Hisahide Nishio
BACKGROUND: Spinal muscular atrophy (SMA) is a frequent autosomal recessive disorder, characterized by lower motor neuron loss in the spinal cord. More than 95% of SMA patients show homozygous survival motor neuron 1 (SMN1) deletion. We previously developed a screening system for SMN1 deletion based on a modified competitive oligonucleotide priming-PCR (mCOP-PCR) technique. However, non-specific amplification products were observed with mCOP-PCR, which might lead to erroneous interpretation of the screening results...
September 7, 2017: Kobe Journal of Medical Sciences
https://www.readbyqxmd.com/read/29433808/vmat2-inhibitors-for-the-treatment-of-tardive-dyskinesia
#9
REVIEW
Laura M Scorr, Stewart A Factor
Tardive dyskinesia (TD) is an often disabling hyperkinetic movement disorder caused by exposure to dopamine receptor blocking agents. Although initially thought to most commonly occur with typical antipsychotics, the incidence is likely similar with atypical antipsychotics and antiemetics such as metoclopramide. Increased prescribing of these agents as well as low rates of remission have contributed to a rising prevalence of TD. Although this condition was described nearly 60 years ago, it is only within the past year that two novel therapeutic agents were FDA approved...
February 5, 2018: Journal of the Neurological Sciences
https://www.readbyqxmd.com/read/29432441/fas-promoter-polymorphisms-and-serum-sfas-level-are-associated-with-increased-risk-of-nerve-damage-in-bangladeshi-patients-with-guillain-barr%C3%A3-syndrome
#10
Zhahirul Islam, Israt Jahan, Rijwan U Ahammad, Mohammad Shahnaij, Shamsun Nahar, Quazi D Mohammad
Guillain-Barré syndrome (GBS) is an autoimmune disorder of the peripheral nervous system triggered by molecular mimicry between pathogen lipopolysaccharides and host nerve gangliosides. Polymorphisms in the Fas receptor (FAS) and Fas ligand (FASL) genes may potentially alter the elimination of autoreactive immune cells and affect disease susceptibility or disease severity in GBS. We detected single nucleotide polymorphisms (SNPs) in FAS (-1377G/A and -670A/G) and FASL (-843C/T) in a prospective cohort of 300 patients with GBS and 300 healthy controls from the Bangladeshi population...
2018: PloS One
https://www.readbyqxmd.com/read/29428834/uncensored-eeg-the-role-of-dc-potentials-in-neurobiology-of-the-brain
#11
REVIEW
Stjepana Kovac, Erwin-Josef Speckmann, Ali Gorji
Brain direct current (DC) potentials denote sustained shifts and slow deflections of cerebral potentials superimposed with conventional EEG waves and reflect alterations in the excitation level of the cerebral cortex and subcortical structures. Using galvanometers, such sustained displacement of the EEG baseline was recorded in the early days of electroencephalography. To stabilize the EEG baseline and eliminate artefacts, EEG was performed later by voltage amplifiers with high-pass filters that dismiss slow DC potentials...
February 8, 2018: Progress in Neurobiology
https://www.readbyqxmd.com/read/29428123/innovations-reviews-and-proposals-on-the-dsm-5-the-case-of-sexual-dysfunctions-gender-dysphoria-and-paraphilic-disorders
#12
Adalberto Campo-Arias, Edwin Herazo
Human behaviours have different meanings according to the historical moment and context. In this article sexual behaviours are taken as a category in order to analyse how psychiatric nosology is structured, as manifested in texts such as the DSM-5. The development of these diagnostic manuals are tools that are far from being free of subjectivities and interference of elements of power, expressed in the way health, illness, mental health, and mental disorders, are assumed; in short, the normal and pathological...
January 2018: Revista Colombiana de Psiquiatría
https://www.readbyqxmd.com/read/29426890/guanosine-monophosphate-reductase-1-is-a-potential-therapeutic-target-for-alzheimer-s-disease
#13
Hongde Liu, Kun Luo, Donghui Luo
Alzheimer's disease (AD) is a severe neurodegenerative disorder for which identification of differentially expressed genes is one way to find new therapeutic targets. Here, we conducted analysis to identify age-independent, AD-specific genes. We found that the MET, WIF1, and NPTX2 genes are downregulated in AD. WIF1 and MET are implicated in Wnt and MET signaling and regulate GSK3β activity and are thus linked with AD. Importantly, we found that the GMPR gene exhibited a gradual increase in AD progression...
February 9, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29426407/seroprevalence-and-risk-factors-for-selected-respiratory-and-reproductive-tract-pathogen-exposure-in-european-bison-bison-bonasus-in-poland
#14
Michał K Krzysiak, Artur Jabłoński, Wojciech Iwaniak, Monika Krajewska, Julia Kęsik-Maliszewska, Magdalena Larska
After the complete extinction from the wild of European bison (Bison bonasus) at the beginning of the twentieth century, the worldwide species population was restored to approximately 5500 individuals, with the species however remaining endangered. Despite numerous studies on the ecology and genetics of European bison, the threats of infectious diseases have been largely unexamined. The aim of this study was to screen the exposure of the world's largest population of European bison to the pathogens, which may influence the condition and development of the endangered species...
February 2018: Veterinary Microbiology
https://www.readbyqxmd.com/read/29425337/self-assembly-of-fus-through-its-low-complexity-domain-contributes-to-neurodegeneration
#15
Taisei Matsumoto, Koji Matsukawa, Naruaki Watanabe, Yuya Kishino, Hayato Kunugi, Ryoko Ihara, Tomoko Wakabayashi, Tadafumi Hashimoto, Takeshi Iwatsubo
Aggregation of fused in sarcoma (FUS) protein, and mutations in FUS gene, are causative to a range of neurodegenerative disorders including amyotrophic lateral sclerosis (ALS) and frontotemporal dementia. To gain insights into the molecular mechanism whereby FUS causes neurodegeneration, we generated transgenic Drosophila melanogaster overexpressing human FUS in the photoreceptor neurons, which exhibited mild retinal degeneration. Expression of familial ALS-mutant FUS aggravated the degeneration, which was associated with an increase in cytoplasmic localization of FUS...
February 7, 2018: Human Molecular Genetics
https://www.readbyqxmd.com/read/29423558/automated-sleep-staging-of-osas-based-on-ica-preprocessing-and-consolidation-of-temporal-correlations
#16
Somayeh Raiesdana
An automated sleep staging based on analyzing long-range time correlations in EEG is proposed. These correlations, indicating time-scale invariant property or self-similarity at different time scales, are known to be salient dynamical characteristics of stage succession for a sleeping brain even when the subject suffers a destructive disorder such as Obstructive Sleep Apnea (OSA). The goal is to extract a set of complementary features from cerebral sources mapped onto the scalp electrodes or from a number of denoised EEG channels...
February 8, 2018: Australasian Physical & Engineering Sciences in Medicine
https://www.readbyqxmd.com/read/29422899/sensing-bacterial-induced-dna-damaging-effects-via-natural-killer-group-2-member-d-immune-receptor-from-dysbiosis-to-autoimmunity-and-carcinogenesis
#17
REVIEW
J Luis Espinoza, Mika Minami
The human genome is constantly exposed to exogenous and endogenous DNA damaging factors that frequently cause DNA damages. Unless repaired, damaged DNA can result in deleterious mutations capable of causing malignant transformation. Accordingly, cells have developed an advanced and effective surveillance system, the DNA damage response (DDR) pathway, which maintains genetic integrity. In addition to well-defined outcomes, such as cell cycle arrest, apoptosis, and senescence, another consequence of DDR activation is the induction of natural killer group 2 member D ligands (NKG2D-Ls) on the surface of stressed cells...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29421990/measurement-of-soluble-cd59-in-csf-in-demyelinating-disease-evidence-for-an-intrathecal-source-of-soluble-cd59
#18
Wioleta M Zelek, Lewis M Watkins, Owain W Howell, Rhian Evans, Sam Loveless, Neil P Robertson, Marijke Beenes, Loek Willems, Ricardo Brandwijk, B Paul Morgan
BACKGROUND: CD59, a broadly expressed glycosylphosphatidylinositol-anchored protein, is the principal cell inhibitor of complement membrane attack on cells. In the demyelinating disorders, multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD), elevated complement protein levels, including soluble CD59 (sCD59), were reported in cerebrospinal fluid (CSF). OBJECTIVES: We compared sCD59 levels in CSF and matched plasma in controls and patients with MS, NMOSD and clinically isolated syndrome (CIS) and investigated the source of CSF sCD59 and whether it was microparticle associated...
February 1, 2018: Multiple Sclerosis: Clinical and Laboratory Research
https://www.readbyqxmd.com/read/29417375/dependence-of-nanoparticle-toxicity-on-their-physical-and-chemical-properties
#19
REVIEW
Alyona Sukhanova, Svetlana Bozrova, Pavel Sokolov, Mikhail Berestovoy, Alexander Karaulov, Igor Nabiev
Studies on the methods of nanoparticle (NP) synthesis, analysis of their characteristics, and exploration of new fields of their applications are at the forefront of modern nanotechnology. The possibility of engineering water-soluble NPs has paved the way to their use in various basic and applied biomedical researches. At present, NPs are used in diagnosis for imaging of numerous molecular markers of genetic and autoimmune diseases, malignant tumors, and many other disorders. NPs are also used for targeted delivery of drugs to tissues and organs, with controllable parameters of drug release and accumulation...
February 7, 2018: Nanoscale Research Letters
https://www.readbyqxmd.com/read/29417179/the-dna-double-strand-breakome-of-mouse-spermatids
#20
Marie-Chantal Grégoire, Frédéric Leduc, Martin H Morin, Tiphanie Cavé, Mélina Arguin, Martin Richter, Pierre-Étienne Jacques, Guylain Boissonneault
De novo germline mutations arise preferentially in male owing to fundamental differences between spermatogenesis and oogenesis. Post-meiotic chromatin remodeling in spermatids results in the elimination of most of the nucleosomal supercoiling and is characterized by transient DNA fragmentation. Using three alternative methods, DNA from sorted populations of mouse spermatids was used to confirm that double-strand breaks (DSB) are created in elongating spermatids and repaired at later steps. Specific capture of DSB was used for whole-genome mapping of DSB hotspots (breakome) for each population of differentiating spermatids...
February 7, 2018: Cellular and Molecular Life Sciences: CMLS
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