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https://www.readbyqxmd.com/read/28107167/activity-of-the-liver-enzyme-ornithine-carbamoyltransferase-otc-in-blood-lc-ms-ms-assay-for-non-invasive-diagnosis-of-ornithine-carbamoyltransferase-deficiency
#1
Jakub Krijt, Jitka Sokolová, Pavel Ješina, Lenka Dvořáková, Martin Řeboun, Katarína Brennerová, Martin Mistrík, Jiří Zeman, Tomáš Honzík, Viktor Kožich
BACKGROUND: Liver enzymes are released from hepatocytes into circulation and their activity can be measured in the blood. We examined whether the plasma activity of the liver enzyme ornithine carbamoyltransferase, determined by a novel liquid chromatography-mass spectrometry (LC-MS/MS) assay, could be utilized for the detection of OTC deficiency (OTCD), an X-linked inborn error of the urea cycle. METHODS: The plasma ornithine carbamoyltransferase (OTC) activity was assayed in the reverse reaction using isotopically labeled citrulline-d4 as a substrate and by determination of the product, ornithine-d4, by LC-MS/MS analysis...
January 20, 2017: Clinical Chemistry and Laboratory Medicine: CCLM
https://www.readbyqxmd.com/read/28106928/diagnostic-considerations-for-cholestatic-liver-disease
#2
REVIEW
Galia Pollock, Gerald Y Minuk
Cholestatic liver disease results from insufficient bile synthesis, secretion and/or flow through the biliary tract. Common presenting features include fatigue, pruritus and cholestatic liver enzyme abnormalities wherein elevations of serum alkaline phosphatase and gamma-glutamyltransferases levels exceed those of alanine and aspartate aminotransferases. With prolonged cholestasis, fat soluble vitamin deficiencies, fibrosis, cirrhosis and on occasion, carcinoma of the biliary tract or liver can occur. Once mechanical obstruction to bile flow has been ruled out, the majority of causes can be classified as immune-mediated, infectious or miscellaneous...
January 20, 2017: Journal of Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/28106835/highly-expression-of-cd11b-and-cd32-on-peripheral-blood-mononuclear-cells-from-patients-with-adult-onset-still-s-disease
#3
Hyoun-Ah Kim, Bunsoon Choi, Chang-Hee Suh, Mi Hwa Han, Ju-Yang Jung, Hasan M Sayeed, Ye Won Kim, Seonghyang Sohn
BACKGROUND: We investigated the potential role of several pattern-recognition receptors (PRRs; CD11b, CD11c, CD32, CD206, CD209, and dectin-1) in adult-onset Still's disease (AOSD). METHODS: The study included 13 untreated AOSD patients, 19 rheumatoid arthritis (RA) patients (as a disease control), and 19 healthy controls (HCs). The PRRs were quantified in peripheral blood using flow cytometry. The serum levels of interleukin-17 (IL-17), IL-18, and IL-23 were measured by enzyme-linked immunosorbent assay...
January 19, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28106787/anti-nmda-receptor-encephalitis-and-vaccination
#4
Hsiuying Wang
Anti-N-methyl-d-aspartate (Anti-NMDA) receptor encephalitis is an acute autoimmune neurological disorder. The cause of this disease is often unknown, and previous studies revealed that it might be caused by a virus, vaccine or tumor. It occurs more often in females than in males. Several cases were reported to be related to vaccination such as the H1N1 vaccine and tetanus/diphtheria/pertussis and polio vaccines. In this study, we reported an anti-NMDA receptor encephalitis case that may be caused by Japanese encephalitis vaccination...
January 18, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28106547/phenotype-dependent-interactions-between-n-acetyl-l-aspartate-and-acetyl-coa-in-septal-sn56-cholinergic-cells-exposed-to-an-excess-of-zinc
#5
Marlena Zyśk, Hanna Bielarczyk, Sylwia Gul-Hinc, Aleksandra Dyś, Beata Gapys, Anna Ronowska, Monika Sakowicz-Burkiewicz, Andrzej Szutowicz
Pyruvate dehydrogenase reaction utilizing glucose-derived pyruvate is an almost exclusive source of acetyl-CoA in different cell mitochondrial compartments of the brain. In neuronal mitochondria, the largest fraction of acetyl-CoA is utilized for energy production and the much smaller one for N-acetyl-L-aspartate (NAA) synthesis. Cholinergic neurons, unlike others, require additional amounts of acetyl-CoA for acetylcholine synthesis. Therefore, several neurotoxic signals, which inhibit pyruvate dehydrogenase, generate deeper shortages of acetyl-CoA and greater mortality of cholinergic neurons than noncholinergic ones...
January 20, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28106035/esterase-mutation-is-a-mechanism-of-resistance-to-antimalarial-compounds
#6
Eva S Istvan, Jeremy P Mallari, Victoria C Corey, Neekesh V Dharia, Garland R Marshall, Elizabeth A Winzeler, Daniel E Goldberg
Pepstatin is a potent peptidyl inhibitor of various malarial aspartic proteases, and also has parasiticidal activity. Activity of pepstatin against cultured Plasmodium falciparum is highly variable depending on the commercial source. Here we identify a minor contaminant (pepstatin butyl ester) as the active anti-parasitic principle. We synthesize a series of derivatives and characterize an analogue (pepstatin hexyl ester) with low nanomolar activity. By selecting resistant parasite mutants, we find that a parasite esterase, PfPARE (P...
January 20, 2017: Nature Communications
https://www.readbyqxmd.com/read/28105280/glun2a-selective-pyridopyrimidinone-series-of-nmdar-positive-allosteric-modulators-with-an-improved-in-vivo-profile
#7
Elisia Villemure, Matthew Volgraf, Yu Jiang, Guosheng Wu, Cuong Q Ly, Po-Wai Yuen, Aijun Lu, Xifeng Luo, Mingcui Liu, Shun Zhang, Patrick J Lupardus, Heidi J A Wallweber, Bianca M Liederer, Gauri Deshmukh, Emile Plise, Suzanne Tay, Tzu-Ming Wang, Jesse E Hanson, David H Hackos, Kimberly Scearce-Levie, Jacob B Schwarz, Benjamin D Sellers
The N-methyl-d-aspartate receptor (NMDAR) is an ionotropic glutamate receptor, gated by the endogenous coagonists glutamate and glycine, permeable to Ca(2+) and Na(+). NMDAR dysfunction is associated with numerous neurological and psychiatric disorders, including schizophrenia, depression, and Alzheimer's disease. Recently, we have disclosed GNE-0723 (1), a GluN2A subunit-selective and brain-penetrant positive allosteric modulator (PAM) of NMDARs. This work highlights the discovery of a related pyridopyrimidinone core with distinct structure-activity relationships, despite the structural similarity to GNE-0723...
January 12, 2017: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28104713/multimerization-properties-of-piggymac-a-domesticated-piggybac-transposase-involved-in-programmed-genome-rearrangements
#8
Emeline Dubois, Nathalie Mathy, Vinciane Régnier, Julien Bischerour, Céline Baudry, Raphaëlle Trouslard, Mireille Bétermier
During sexual processes, the ciliate Paramecium eliminates 25-30% of germline DNA from its somatic genome. DNA elimination includes excision of ∼45 000 short, single-copy internal eliminated sequences (IESs) and depends upon PiggyMac (Pgm), a domesticated piggyBac transposase that is essential for DNA cleavage at IES ends. Pgm carries a core transposase region with a putative catalytic domain containing three conserved aspartic acids, and a downstream cysteine-rich (CR) domain. A C-terminal extension of unknown function is predicted to adopt a coiled-coil (CC) structure...
January 18, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28104395/methionine-sulfoxide-reductase-a-deficiency-exacerbates-acute-liver-injury-induced-by-acetaminophen
#9
Mahendra Pratap Singh, Ki Young Kim, Hwa-Young Kim
Acetaminophen (APAP) overdose induces acute liver injury via enhanced oxidative stress and glutathione (GSH) depletion. Methionine sulfoxide reductase A (MsrA) acts as a reactive oxygen species scavenger by catalyzing the cyclic reduction of methionine-S-sulfoxide. Herein, we investigated the protective role of MsrA against APAP-induced liver damage using MsrA gene-deleted mice (MsrA(-/-)). We found that MsrA(-/-) mice were more susceptible to APAP-induced acute liver injury than wild-type mice (MsrA(+/+))...
January 16, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28103993/-effects-of-hypertonic-sodium-saline-resuscitation-on-the-liver-damage-of-rats-at-early-stage-of-severe-scald
#10
J P Zhou, Z Gao, Y X Sun, X L Chen, X S Wu, F Wang
Objective: To explore the effects of hypertonic sodium saline (HSS) resuscitation on the liver damage of rats at early stage of severe scald. Methods: Fifty-six SD rats were divided into sham injury group (SI, n=8), lactated Ringer's solution group (LRS, n=24), and group HSS (n=24) according to the random number table. Rats in group SI were sham injured without resuscitation, while rats in the other two groups were reproduced deep partial-thickness to full-thickness scald model with 30% total body surface area on the back...
January 20, 2017: Zhonghua Shao Shang za Zhi, Zhonghua Shaoshang Zazhi, Chinese Journal of Burns
https://www.readbyqxmd.com/read/28103636/limited-excessive-voluntary-alcohol-drinking-leads-to-liver-dysfunction-in-mice
#11
Scott A Wegner, Katherine A Pollard, Viktor Kharazia, David Darevsky, Luz Perez, Sanjoy Roychowdhury, Allison Xu, Dorit Ron, Laura E Nagy, Frederic Woodward Hopf
BACKGROUND: Liver damage is a serious and sometimes fatal consequence of long-term alcohol intake, which progresses from early-stage fatty liver (steatosis) to later-stage steatohepatitis with inflammation and fibrosis/necrosis. However, very little is known about earlier stages of liver disruption that may occur in problem drinkers, those who drink excessively but are not dependent on alcohol. METHODS: We examined how repeated binge-like alcohol drinking in C57BL/6 mice altered liver function, as compared with a single binge-intake session and with repeated moderate alcohol consumption...
January 19, 2017: Alcoholism, Clinical and Experimental Research
https://www.readbyqxmd.com/read/28102519/nmdar-encephalitis-following-herpes-simplex-virus-encephalitis
#12
REVIEW
Jonathan Galli, Stacey L Clardy, Amanda L Piquet
PURPOSE OF REVIEW: Herpes simplex virus encephalitis (HSVE) is often associated with significant morbidity and mortality, and despite appropriate treatment with antivirals, worsening of neurological symptoms or relapse occurs in a subset of patients. Recent data suggests that many relapses are likely caused by a secondary immune response, with the N-methyl-D-aspartate receptor (NMDAR) antibody being the most commonly associated autoantibody. We provide a review of the relevant literature, examining the relationship between HSVE and development of autoimmunity...
January 2017: Current Infectious Disease Reports
https://www.readbyqxmd.com/read/28102465/risks-and-benefits-of-phase-i-liver-dysfunction-studies-should-patients-with-severe-liver-dysfunction-be-included-in-these-trials
#13
Christos Fountzilas, Selena Stuart, Brian Hernandez, Elizabeth Bowhay-Carnes, Joel Michalek, John Sarantopoulos, Anand Karnad, Sukeshi Patel, Steven Weitman, Devalingam Mahalingam
Introduction The goal of organ dysfunction Phase I trials is to characterize the safety and pharmacokinetics of novel agents in cancer patients with liver or kidney dysfunction, but the clinical benefit is not well established. Methods We reviewed 170 patients across 15 liver dysfunction studies at our institution, grouped based on the NCI-Organ Dysfunction Working Group criteria or Child-Pugh Score. Results The median survival for the entire cohort was two months and just one month amongst patients with severe liver dysfunction...
January 19, 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/28101991/clinically-distinct-phenotypes-of-canavan-disease-correlate-with-residual-aspartoacylase-enzyme-activity
#14
Marisa I Mendes, Desirée Ec Smith, Ana Pop, Pascal Lennertz, Matilde R Fernandez Ojeda, Warsha A Kanhai, Silvy J M van Dooren, Yair Anikster, Ivo Barić, Carolien Boelen, Jaime Campistol, Lonneke de Boer, Ariana Kariminejad, Hulya Kayserili, Agathe Roubertie, Krijn T Verbruggen, Christine Vianey-Saban, Monique Williams, Gajja S Salomons
We describe 14 patients with 12 novel missense mutations in ASPA, the gene causing Canavan disease (CD). We developed a method to study the effect of these 12 variants on the function of aspartoacylase - the hydrolysis of N-acetyl-L-aspartic acid (NAA) to aspartate and acetate. The wild-type ASPA open reading frame (ORF) and the ORFs containing each of the variants were transfected into HEK293 cells. Enzyme activity was determined by incubating cell lysates with NAA and measuring the released aspartic acid by LC-MS/MS...
January 19, 2017: Human Mutation
https://www.readbyqxmd.com/read/28101932/amino-acid-profiling-of-zinc-resistant-prostate-cancer-cell-lines-associations-with-cancer-progression
#15
Monika Kratochvilova, Martina Raudenska, Zbynek Heger, Lukas Richtera, Natalia Cernei, Vojtech Adam, Petr Babula, Marie Novakova, Michal Masarik, Jaromir Gumulec
BACKGROUND: Failure in intracellular zinc accumulation is a key process in prostate carcinogenesis. Nevertheless, epidemiological studies of zinc administration have provided contradicting results. In order to examine the impact of the artificial intracellular increase of zinc(II) ions on prostate cancer metabolism, PNT1A, 22Rv1, and PC-3 prostatic cell lines-depicting different stages of cancer progression-and their zinc-resistant counterparts were used. To determine "benign" and "malignant" metabolic profiles, amino acid patterns, gene expression, and antioxidant capacity of these cell lines were assessed...
January 19, 2017: Prostate
https://www.readbyqxmd.com/read/28101773/what-is-the-appropriate-strategy-for-diagnosing-nafld-using-ultrasonography-in-obese-children
#16
Jee Hyun Lee, Su Jin Jeong
BACKGROUND: The aim of this study is to identify obese children who are candidates for a potential diagnosis of non-alcoholic fatty liver disease (NAFLD). METHODS: We enrolled 242 obese children (122 boys and 120 girls) aged 7-16 years who were examined with abdominal ultrasonography in our pediatric obesity clinic. We compared patients in the normal group with those in the NAFLD group (mild disease, moderate to severe disease) and identified the optimal anthropometric parameters among height, weight, body mass index (BMI), waist circumference, hip circumference, waist to height ratio (WHtR), and waist to hip ratio to predict NAFLD using a receiver operating characteristic curve analysis...
January 19, 2017: World Journal of Pediatrics: WJP
https://www.readbyqxmd.com/read/28101360/successful-treatment-of-anti-nmda-receptor-encephalitis-with-a-prompt-ovarian-tumour-removal-and-prolonged-course-of-plasmapheresis-a-case-report
#17
Elzbieta Rypulak, Michal Borys, Pawel Piwowarczyk, Magdalena Fijalkowska, Beata Potrec, Justyna Sysiak, Janusz Spustek, Alicja Bartkowska-Sniatkowska, Jan Kotarski, Waldemar A Turski, Konrad Rejdak, Miroslaw Czuczwar
Anti-N-methyl-d-aspartate-receptor (NMDAR) encephalitis is an uncommon autoimmune disorder with a wide spectrum of neuropsychiatric symptoms. There is a great requirement to emphasize the importance of a multidisciplinary team approach in the process of diagnosis and treatment of the potentially fatal condition, including psychiatrists, neurologists, gynaecologists and intensivists. Physicians must be aware that psychiatric and neurological disorders, which are typical features for NMDAR encephalitis in young women with ovarian tumours, may progress into status epilepticus and respiratory insufficiency...
December 2016: Molecular and Clinical Oncology
https://www.readbyqxmd.com/read/28101036/anti-n-methyl-d-aspartate-receptor-encephalitis-in-hiv-infection
#18
Eunice Patarata, Vera Bernardino, Ana Martins, Rui Pereira, Conceição Loureiro, Maria Francisca Moraes-Fontes
Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis is a rare condition characterized by emotional and behavioral disturbances, dyskinesias, and extrapyramidal signs. It occurs in young women of reproductive age and is classically described as a paraneoplastic phenomenon. We present a 36-year-old, HIV-positive female who was admitted to the hospital in an acute confusional state, with a stiff posture, periods of motor agitation, and myoclonic jerks of the hands. Her mental state progressively deteriorated...
September 2016: Case Reports in Neurology
https://www.readbyqxmd.com/read/28100738/mir-142-3p-is-a-key-regulator-of-il-1%C3%AE-dependent-synaptopathy-in-neuroinflammation
#19
Georgia Mandolesi, Francesca De Vito, Alessandra Musella, Antonietta Gentile, Silvia Bullitta, Diego Fresegna, Helena Sepman, Claudio Di Sanza, Nabila Haji, Francesco Mori, Fabio Buttari, Emerald Perlas, Maria Teresa Ciotti, Eran Hornstein, Irene Bozzoni, Carlo Presutti, Diego Centonze
: MicroRNAs (miRNA) play an important role in post-transcriptional gene regulation of several physiological and pathological processes. In multiple sclerosis (MS), a chronic inflammatory and degenerative disease of the CNS, and in its mouse model, the experimental autoimmune encephalomyelitis (EAE), miRNA dysregulation has been mainly related to immune system dysfunction and white matter (WM) pathology. However, little is known about their role in gray matter pathology. Here, we explored miRNA involvement in the inflammation-driven alterations of synaptic structure and function, collectively known as synaptopathy, a neuropathological process contributing to excitotoxic neurodegeneration in MS/EAE...
January 18, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28100693/viral-genome-packaging-terminase-cleaves-dna-using-the-canonical-ruvc-like-two-metal-catalysis-mechanism
#20
Rui-Gang Xu, Huw T Jenkins, Maria Chechik, Elena V Blagova, Anna Lopatina, Evgeny Klimuk, Leonid Minakhin, Konstantin Severinov, Sandra J Greive, Alfred A Antson
Bacteriophages and large dsDNA viruses encode sophisticated machinery to translocate their DNA into a preformed empty capsid. An essential part of this machine, the large terminase protein, processes viral DNA into constituent units utilizing its nuclease activity. Crystal structures of the large terminase nuclease from the thermophilic bacteriophage G20c show that it is most similar to the RuvC family of the RNase H-like endonucleases. Like RuvC proteins, the nuclease requires either Mn(2+), Mg(2+) or Co(2+) ions for activity, but is inactive with Zn(2+) and Ca(2+) High resolution crystal structures of complexes with different metals reveal that in the absence of DNA, only one catalytic metal ion is accommodated in the active site...
January 18, 2017: Nucleic Acids Research
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