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Amino Acid Therapy

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https://www.readbyqxmd.com/read/29786184/-protein-carbamylation-what-it-is-and-why-it-concerns-nephrologists
#1
Emanuele De Simone, Lucia Di Micco, Gaetano La Manna, Biagio Di Iorio
Spontaneous urea dissociation in water solution is a prominent source of protein carbamylation in our body. Protein carbamylation is a well-known phenomenon since early seventies. Some years ago, much interest in the diagnostic power of carbamylated protein arouse. Recently the target of the researches focused on its potential cardiovascular pathogenicity. Some authors claimed that this could be a reason for higher cardiovascular mortality in uremic patients. Nutritional therapy, amino acids supplementation and intensive dialysis regimen are some of the therapeutic tools tested to lower the carbamylation burst in this population...
May 2018: Giornale Italiano di Nefrologia: Organo Ufficiale Della Società Italiana di Nefrologia
https://www.readbyqxmd.com/read/29785508/lacosamide-a-review-in-focal-onset-seizures-in-patients-with-epilepsy
#2
Sheridan M Hoy
Lacosamide (Vimpat® ) is a functionalized amino acid (available orally and intravenously) approved in the EU and the USA for use as monotherapy and adjunctive therapy for the treatment of focal-onset seizures in adults, adolescents and children aged ≥ 4 years with epilepsy. In adults and adolescents (aged ≥ 16 years), oral lacosamide as adjunctive therapy to other antiepileptic drugs was generally effective in reducing seizure frequency during short-term (up to 18 weeks) treatment, with efficacy sustained over the longer-term (up to 8 years)...
May 21, 2018: CNS Drugs
https://www.readbyqxmd.com/read/29785078/detection-of-hyper-conserved-regions-in-hepatitis-b-virus-x-gene-potentially-useful-for-gene-therapy
#3
Carolina González, David Tabernero, Maria Francesca Cortese, Josep Gregori, Rosario Casillas, Mar Riveiro-Barciela, Cristina Godoy, Sara Sopena, Ariadna Rando, Marçal Yll, Rosa Lopez-Martinez, Josep Quer, Rafael Esteban, Maria Buti, Francisco Rodríguez-Frías
AIM: To detect hyper-conserved regions in the hepatitis B virus (HBV) X gene ( HBX ) 5' region that could be candidates for gene therapy. METHODS: The study included 27 chronic hepatitis B treatment-naive patients in various clinical stages (from chronic infection to cirrhosis and hepatocellular carcinoma, both HBeAg-negative and HBeAg-positive), and infected with HBV genotypes A-F and H. In a serum sample from each patient with viremia > 3.5 log IU/mL, the HBX 5' end region [nucleotide (nt) 1255-1611] was PCR-amplified and submitted to next-generation sequencing (NGS)...
May 21, 2018: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/29785047/rationally-designed-aav2-and-aavrh8r-capsids-provide-improved-transduction-in-the-retina-and-brain
#4
Jennifer A Sullivan, Lisa M Stanek, Michael J Lukason, Jie Bu, Shayla R Osmond, Elizabeth A Barry, Catherine R O'Riordan, Lamya S Shihabuddin, Seng H Cheng, Abraham Scaria
The successful application of adeno-associated virus (AAV) gene delivery vectors as a therapeutic paradigm will require efficient gene delivery to the appropriate cells in affected organs. In this study, we utilized a rational design approach to introduce modifications to the AAV2 and AAVrh8R capsids and the resulting variants were evaluated for transduction activity in the retina and brain. The modifications disrupted either capsid/receptor binding or altered capsid surface charge. Specifically, we mutated AAV2 amino acids R585A and R588A, which are required for binding to its receptor, heparan sulfate proteoglycans, to generate a variant referred to as AAV2-HBKO...
May 22, 2018: Gene Therapy
https://www.readbyqxmd.com/read/29782494/ubiquitin-dependent-proteolysis-of-cxcl7-leads-to-posterior-longitudinal-ligament-ossification
#5
Michiyo Tsuru, Atsushi Ono, Hideaki Umeyama, Masahiro Takeuchi, Kensei Nagata
Ossification of the posterior longitudinal ligament (OPLL), a spinal ligament, reduces the range of motion in limbs. No treatment is currently available for OPLL, which is why therapies are urgently needed. OPLL occurs in obesity, is more common in men, and has an onset after 40 years of age. The mechanisms underlying OPLL remain unclear. In this study, we performed a serum proteomic analysis in both OPLL patients and healthy subjects to identify factors potentially involved in the development of OPLL, and found reduced levels of a protein that might underlie the pathology of OPLL...
2018: PloS One
https://www.readbyqxmd.com/read/29781749/oncogenic-pkc-%C3%AE-activates-vimentin-during-epithelial-mesenchymal-transition-in-melanoma-a-study-based-on-pkc-%C3%AE-and-pkc-%C3%AE-specific-inhibitors
#6
Wishrawana S Ratnayake, Christopher A Apostolatos, André H Apostolatos, Ryan J Schutte, Monica A Huynh, David A Ostrov, Mildred Acevedo-Duncan
Melanoma is one of the fastest growing cancers in the United States and is accompanied with a poor prognosis owing to tumors being resistant to most therapies. Atypical protein kinase Cs (aPKC) are involved in malignancy in many cancers. We previously reported that aPKCs play a key role in melanoma's cell motility by regulating cell signaling pathways which induce epithelial-mesenchymal Transition (EMT). We tested three novel inhibitors; [4-(5-amino-4-carbamoylimidazol-1-yl)-2,3-dihydroxycyclopentyl] methyl dihydrogen phosphate (ICA-1T) along with its nucleoside analog 5-amino-1-((1R,2S,3S,4R)-2,3-dihydroxy-4-methylcyclopentyl)-1H-imidazole-4-carboxamide (ICA-1S) which are specific to protein kinase C-iota (PKC-ι) and 8-hydroxy-1,3,6-naphthalenetrisulfonic acid (ζ-Stat) which is specific to PKC-zeta (PKC-ζ) on cell proliferation, apoptosis, migration and invasion of two malignant melanoma cell lines compared to normal melanocytes...
May 21, 2018: Cell Adhesion & Migration
https://www.readbyqxmd.com/read/29779385/nutritional-available-seleno-amino-acid-derivative-antagonizes-cisplatin-induced-nephrotoxicity-through-inhibition-of-ros-mediated-signaling-pathways
#7
Xiaoling Li, Haobin Zhang, Leung Chan, Chang Liu, Tianfeng Chen
Discovery of nutritionally available agents that could antagonize cisplatin-induced nephrotoxicity is of great significance and clinical application potential. 3,3'-Diselenodipropionic acid (DSePA) is a seleno-amino acid derivative that exhibits strong antioxidant activity. Therefore, this study aimed to examine the protective effects of DSePA on cisplatin-induced nephrotoxicity as well as the molecular mechanisms. The results revealed that DSePA effectively inhibited cell apoptosis induced by cisplatin, through suppressing the caspases activation and PARP cleavage...
May 20, 2018: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/29774776/memory-deficit-in-an-object-location-task-after-mild-tbi-is-associated-with-impaired-early-object-exploration-and-both-are-restored-by-branched-chain-amino-acid-dietary-therapy
#8
Rosalia Paterno, Hannah Metheny, Akiva S Cohen
The relation between traumatic brain injury (TBI) and memory dysfunction is well established, yet imprecise. Here, we investigate whether mild TBI causes a specific deficit in spatial episodic memory. Fifty-eight (29 TBI, 29 Sham) mice were run in a spatial recognition task. To determine which phase of memory might be affected in our task, we assessed rodent performance at three different delay times (3 min, 1 hour, and 24 hours). We found that sham and TBI mice performed equally well at 3 minutes, but TBI mice had significantly impaired spatial recognition memory after a delay time of one hour...
May 18, 2018: Journal of Neurotrauma
https://www.readbyqxmd.com/read/29774053/postherpes-simplex-encephalitis-a-case-series-of-viral-triggered-autoimmunity-synaptic-autoantibodies-and-response-to-therapy
#9
Harry Alexopoulos, Sofia Akrivou, Sotiria Mastroyanni, Maria Antonopoulou, Argirios Dinopoulos, Melpo Giorgi, Kostas Konstantinou, Evangelos Kouremenos, Maria Lariou, Dimitrios Naoumis, Efterpi Pavlidou, Evaggelos Pavlou, Konstantinos Voudris, Panayotis Vlachoyiannopoulos, Marinos C Dalakas
Background: Recent evidence suggests that patients with herpes simplex virus (HSV) encephalitis may relapse because of autoimmunity against the N-methyl-D-aspartate receptor (NMDAR). We present a case series of post-HSV relapsing encephalopathy associated with antibodies to central nervous system (CNS) synaptic antigens. Patient/Methods: Sera and cerebrospinal fluid (CSF) from five patients with HSV encephalitis who relapsed after antiviral therapy were tested for anti-NMDAR, gamma-aminobutyric acid b receptor (GABAbR), α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR), Leucine-rich, glioma inactivated 1 (LGI1), anti -contactin-associated protein-like 2 (CASPR2) and dipeptidyl-peptidase-like protein-6 (DDPX) antibodies using cell-based assays...
2018: Therapeutic Advances in Neurological Disorders
https://www.readbyqxmd.com/read/29768695/evolution-and-persistence-of-the-resistance-associated-substitutions-of-hepatitis-c-virus-after-direct-acting-antiviral-treatment-failures
#10
Yechan Jeong, Bora Jin, Hye Won Lee, Hye Jung Park, Jun Yong Park, Do Young Kim, Kwang-Hyub Han, Sang Hoon Ahn, Seungtaek Kim
Daclatasvir plus asunaprevir (DCV+ASV) treatment is an all-oral direct-acting antiviral (DAA) therapy for the genotype 1b HCV-infected patients. In this study, we investigated how resistance-associated substitutions (RASs) evolved after treatment failures and assessed the effect of those substitutions on viral fitness. Sequencing of NS5A and NS3 revealed typical RASs after treatment failures. Interestingly, the RASs of NS3 reverted to the wild-type amino acid within one year after treatment failures. However, the RASs of NS5A were stable and did not change...
May 16, 2018: Journal of Viral Hepatitis
https://www.readbyqxmd.com/read/29765472/development-of-novel-cyclic-ngr-peptide-daunomycin-conjugates-with-dual-targeting-property
#11
Andrea Angelo Pierluigi Tripodi, Szilárd Tóth, Kata Nóra Enyedi, Gitta Schlosser, Gergely Szakács, Gábor Mező
Cyclic NGR peptides as homing devices are good candidates for the development of drug conjugates for targeted tumor therapy. In our previous study we reported that the Dau=Aoa-GFLGK(c[KNGRE]-GG-)-NH2 conjugate has a significant antitumor activity against both CD13+ HT-1080 human fibrosarcoma and CD13- but integrin positive HT-29 human colon adenocarcinoma cells. However, it seems that the free ε-amino group of Lys in the cycle is not necessary for the biological activity. Therefore, we developed novel cyclic NGR peptide-daunomycin conjugates in which Lys was replaced by different amino acids (Ala, Leu, Nle, Pro, Ser)...
2018: Beilstein Journal of Organic Chemistry
https://www.readbyqxmd.com/read/29761789/ph-and-redox-responsive-nanoparticles-composed-of-charge-reversible-pullulan-based-shells-and-disulfide-containing-poly-%C3%AE-amino-ester-cores-for-co-delivery-of-gene-and-chemotherapeutic-agent
#12
Sipei Zhang, Dan Wang, Yating Li, Ling Li, Hongli Chen, Qingqing Xiong, Yuan-Yuan Liu, Yingsong Wang
A novel pH- and redox-responsive nanoparticle system was designed based on charge-reversible pullulan derivative (CAPL) and disulfide-containing poly(β-amino ester) (ssPBAE) for the co-delivery of gene and chemotherapeutic agent targeting hepatoma. The end-alkene groups of ssPBAE were reacted with diethylenetriamine to form amino-modified ssPBAE (NH-ssPBAE). Methotrexate (MTX), a chemotherapy agent, was then conjugated to NH-ssPBAE via amide bond to obtain a polymeric prodrug ssPBAE-MTX. ssPBAE-MTX exhibited a good capability for condensing genes including plasmid DNA (pDNA) and tetramethyl rhodamine-labeled DNA (TAMRA-DNA), and almost completely condensed pDNA at the weight ratio of 5/1 to form spherical nanocomplexes with an uniform size...
May 15, 2018: Nanotechnology
https://www.readbyqxmd.com/read/29761169/prolonged-cenicriviroc-therapy-reduces-hepatic-fibrosis-despite-steatohepatitis-in-a-diet-induced-mouse-model-of-nonalcoholic-steatohepatitis
#13
Annie J Kruger, Bryan C Fuchs, Ricard Masia, Jacinta A Holmes, Shadi Salloum, Mozhdeh Sojoodi, Diego S Ferreira, Stephanie M Rutledge, Peter Caravan, Nadia Alatrakchi, Pam Vig, Eric Lefebvre, Raymond T Chung
Nonalcoholic steatohepatitis (NASH) is a progressive liver disease projected to become the leading cause of cirrhosis and liver transplantation in the next decade. Cenicriviroc (CVC), a dual chemokine receptor 2 and 5 antagonist, prevents macrophage trafficking and is under clinical investigation for the treatment of human NASH fibrosis. We assessed the efficacy and durability of short and prolonged CVC therapy in a diet-induced mouse model of NASH, the choline deficient, L-amino acid-defined, high-fat diet (CDAHFD) model...
May 2018: Hepatology Communications
https://www.readbyqxmd.com/read/29757724/neuroimaging-findings-of-organic-acidemias-and-aminoacidopathies
#14
Nihaal Reddy, Sonia F Calloni, Hilary J Vernon, Eugen Boltshauser, Thierry A G M Huisman, Bruno P Soares
Although individual cases of inherited metabolic disorders are rare, overall they account for a substantial number of disorders affecting the central nervous system. Organic acidemias and aminoacidopathies include a variety of inborn errors of metabolism that are caused by defects in the intermediary metabolic pathways of carbohydrates, amino acids, and fatty acid oxidation. These defects can lead to the abnormal accumulation of organic acids and amino acids in multiple organs, including the brain. Early diagnosis is mandatory to initiate therapy and prevent permanent long-term neurologic impairments or death...
May 2018: Radiographics: a Review Publication of the Radiological Society of North America, Inc
https://www.readbyqxmd.com/read/29755574/branched-chain-amino-acids-in-health-and-disease-metabolism-alterations-in-blood-plasma-and-as-supplements
#15
REVIEW
Milan Holeček
Branched-chain amino acids (BCAAs; valine, leucine, and isoleucine) are essential amino acids with protein anabolic properties, which have been studied in a number of muscle wasting disorders for more than 50 years. However, until today, there is no consensus regarding their therapeutic effectiveness. In the article is demonstrated that the crucial roles in BCAA metabolism play: (i) skeletal muscle as the initial site of BCAA catabolism accompanied with the release of alanine and glutamine to the blood; (ii) activity of branched-chain keto acid dehydrogenase (BCKD); and (iii) amination of branched-chain keto acids (BCKAs) to BCAAs...
2018: Nutrition & Metabolism
https://www.readbyqxmd.com/read/29753318/successful-pregnancy-in-maple-syrup-urine-disease-a-case-report-and-review-of-the-literature
#16
Sarah Catharina Grünert, Stefanie Rosenbaum-Fabian, Anke Schumann, Karl Otfried Schwab, Nadja Mingirulli, Ute Spiekerkoetter
BACKGROUND: Maple syrup urine disease (MSUD) is an autosomal recessive disorder of branched-chain amino acid metabolism. Patients with MSUD are at risk of life-threatening metabolic decompensations with ketoacidosis and encephalopathy. These episodes are often triggered by physiological stress. Only few cases of pregnancies in MSUD mothers have been reported so far. CASE PRESENTATION: We present the favorable outcome of a pregnancy in a woman with classical MSUD...
May 12, 2018: Nutrition Journal
https://www.readbyqxmd.com/read/29752915/increase-in-insulin-secretion-and-decrease-in-muscle-degradation-by-fat-free-milk-intake-are-attenuated-by-physical-exercise
#17
Tetsuo Yamada, Masami Matsuzaki, Akira Tanaka
BACKGROUND: Protein intake, particularly branched chain amino acids (BCAAs), and exercise have opposing actions on insulin secretion, but the same action on protein anabolism. We examined the effects of BCAA-rich fat-free milk intake and/or exercise on levels of insulin secretion and indices related to muscle protein metabolism in order to assess the potency of dietary and exercise therapies against metabolic and locomotive disorders. METHODS: Eight adult female volunteers participated in all four 24 h experiments; control diet intake with or without exercise, and fat-free milk-containing diet intake with or without exercise...
May 9, 2018: Clinica Chimica Acta; International Journal of Clinical Chemistry
https://www.readbyqxmd.com/read/29751795/inhibition-of-glutamate-oxaloacetate-transaminase-1-in-cancer-cell-lines-results-in-altered-metabolism-with-increased-dependency-of-glucose
#18
Xiaoshan Zhou, Sophie Curbo, Fuqiang Li, Shuba Krishnan, Anna Karlsson
BACKGROUND: Glutamate oxaloacetate transaminase 1 (GOT1) regulates cellular metabolism through coordinating the utilization of carbohydrates and amino acids to meet nutrient requirements. KRAS mutated cancer cells were recently shown to rely on GOT1 to support long-term cell proliferation. The aim of the present study was to address the role of GOT1 in the metabolic adaption of cancer cells. METHODS: GOT1-null and knockdown cell lines were established through CRISPR/Cas9 and shRNA techniques...
May 11, 2018: BMC Cancer
https://www.readbyqxmd.com/read/29751531/computational-analysis-of-the-interaction-energies-between-amino-acid-residues-of-the-measles-virus-hemagglutinin-and-its-receptors
#19
Fengqi Xu, Shigenori Tanaka, Hirofumi Watanabe, Yasuhiro Shimane, Misako Iwasawa, Kazue Ohishi, Tadashi Maruyama
Measles virus (MV) causes an acute and highly devastating contagious disease in humans. Employing the crystal structures of three human receptors, signaling lymphocyte-activation molecule (SLAM), CD46, and Nectin-4, in complex with the measles virus hemagglutinin (MVH), we elucidated computationally the details of binding energies between the amino acid residues of MVH and those of the receptors with an ab initio fragment molecular orbital (FMO) method. The calculated inter-fragment interaction energies (IFIEs) revealed a number of significantly interacting amino acid residues of MVH that played essential roles in binding to the receptors...
May 3, 2018: Viruses
https://www.readbyqxmd.com/read/29748334/genetic-variant-in-human-par-protease-activated-receptor-4-enhances-thrombus-formation-resulting-in-resistance-to-antiplatelet-therapeutics
#20
Benjamin E Tourdot, Hannah Stoveken, Derek Trumbo, Jennifer Yeung, Yogendra Kanthi, Leonard C Edelstein, Paul F Bray, Gregory G Tall, Michael Holinstat
OBJECTIVE: Platelet activation after stimulation of PAR (protease-activated receptor) 4 is heightened in platelets from blacks compared with those from whites. The difference in PAR4 signaling by race is partially explained by a single-nucleotide variant in PAR4 encoding for either an alanine or threonine at amino acid 120 in the second transmembrane domain. The current study sought to determine whether the difference in PAR4 signaling by this PAR4 variant is because of biased Gq signaling and whether the difference in PAR4 activity results in resistance to traditional antiplatelet intervention...
May 10, 2018: Arteriosclerosis, Thrombosis, and Vascular Biology
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