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https://www.readbyqxmd.com/read/28431470/engineering-and-characterization-of-an-enzyme-replacement-therapy-for-classical-homocystinuria
#1
Tomas Majtan, Insun Park, Jan P Kraus
Homocystinuria due to loss of cystathionine beta-synthase (CBS) causes accumulation of homocysteine and depletion of cysteine. Current treatments are suboptimal and thus the development of an enzyme replacement therapy based on PEGylated human truncated CBS (PEG-CBS) has been initiated. Attenuation of potency was observed, necessitating a screen of several PEG-CBS conjugates for their efficacy to correct and maintain the plasma metabolite profile of murine homocystinuria after repeated administrations interrupted with washouts...
April 21, 2017: Biomacromolecules
https://www.readbyqxmd.com/read/28430117/fluvastatin-therapy-could-not-decrease-progression-of-paroxysmal-atrial-fibrillation-in-non-valvular-disease-patients
#2
Qiang Tan, Shuangyue Zhang, Xiaoyi Zou, Jun Zhao, Jia Hao, Qian Sun
OBJECTIVE: This study aimed to evaluate whether fluvastatin therapy could decrease the probability of atrial fibrillation (AF) progression from paroxysmal AF to permanent AF and decrease the recurrence frequency of AF. METHODS: Analyses were performed using two-tailed Student's t test or Mann-Whitney U tests. Categorical variables were compared with the χ2 statistics or Fisher's exact test. Patients with paroxysmal AF were randomized case-control, prospective into either the fluvastatin group (n=61) or control group (n=57)...
April 10, 2017: Anatolian Journal of Cardiology
https://www.readbyqxmd.com/read/28429027/a-metabolomic-study-on-high-risk-stroke-patients-determines-low-levels-of-serum-lysine-metabolites-a-retrospective-cohort-study
#3
Yeseung Lee, Adnan Khan, Seri Hong, Sun Ha Jee, Youngja H Park
Identifying changes in serum metabolites during cerebral ischemia is an important approach for early diagnosis of thrombotic stroke. Herein, we highlight novel biomarkers for early diagnosis of patients at high risk of thrombotic stroke using high resolution metabolomics (HRM). In this retrospective cohort study, serum samples obtained from patients at risk of thrombotic stroke (n  =  62) and non-risk individuals (n  =  348) were tested using HRM, coupled with LC-MS/MS, to discriminate between metabolic profiles of control and stroke risk patients...
April 21, 2017: Molecular BioSystems
https://www.readbyqxmd.com/read/28424785/the-impact-of-homocysteine-vitamin-b12-and-vitamin-d-levels-on-functional-outcome-after-first-ever-ischaemic-stroke
#4
Merdin Markišić, Aleksandra M Pavlović, Dragan M Pavlović
We explored the relationship between acute ischaemic stroke (IS) early functional outcome and serum levels of homocysteine, vitamin B12, and D in a noninterventional prospective clinical study. We enrolled 50 patients with first-ever IS and performed laboratory tests and functional assessment at three time points: on admission and three and six months after stroke. Modified Rankin Scale (mRS), NIHSS scale, and Barthel index (BI) scores were assessed in all participants by trained examiner blinded to laboratory data...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28423345/homocysteine-induced-peripheral-microcirculation-dysfunction-in-zebrafish-and-its-attenuation-by-l-arginine
#5
Sang Joon Lee, Sung Ho Park, Jinhyuk Fred Chung, Woorak Choi, Hyung Kyu Huh
Elevated blood homocysteine (Hcy) level is frequently observed in aged individuals and those with age-related vascular diseases. However, its effect on peripheral microcirculation is still not fully understood. Using in vivo zebrafish model, the degree of Hcy-induced peripheral microcirculation dysfunction is assessed in this study with a proposed dimensionless velocity parameter V¯CV/V¯PCV, where V¯CV and V¯PCV represent the peripheral microcirculation perfusion and the systemic perfusion levels, respectively...
April 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28422052/folic-acid-reduces-tau-phosphorylation-by-regulating-pp2a-methylation-in-streptozotocin-induced-diabetic-mice
#6
Miaoyan Zheng, Chen Zou, Mengyue Li, Guowei Huang, Yuxia Gao, Huan Liu
High incidence rate of Alzheimer's disease (AD) is observed in patients with type 2 diabetes. Aggregated β-amyloid (Aβ) and hyperphosphorylated tau are the hallmarks of AD. Hyperphosphorylated tau has been detected in diabetic animals as well as in diabetic patients. Folates mediate the transfer of one carbon unit, required in various biochemical reactions. The effect of folate on tau phosphorylation in diabetic models still remains unknown. In this study, we investigated the effect and mechanism of folic acid on hyperphosphorylation of tau in streptozotocin (STZ)-induced diabetic mice...
April 19, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28421567/early-biomarker-response-and-patient-preferences-to-oral-and-intramuscular-vitamin-b12-substitution-in-primary-care-a-randomised-parallel-group-trial
#7
Corina Metaxas, Deborah Mathis, Cyrill Jeger, Kurt Eduard Hersberger, Isabelle Arnet, Philipp Walter
BACKGROUND: Vitamin B12 (VB12) deficiency can be treated with oral high-dose substitution or intramuscular (i.m.) injection of VB12. Whenever alternative routes of administration exist, patient preferences should be considered when choosing the treatment. We aimed to assess outpatient preferences towards oral or IM VB12 substitution and confirm noninferiority of early biomarker response with oral treatment, in a typical primary care population. METHODS: Prospective randomised nonblinded parallel-group trial...
April 19, 2017: Swiss Medical Weekly
https://www.readbyqxmd.com/read/28421540/maternal-folic-acid-supplementation-during-pregnancy-improves-neurobehavioral-development-in-rat-offspring
#8
Xinyan Wang, Wen Li, Shou Li, Jing Yan, John X Wilson, Guowei Huang
Maternal folate status during pregnancy may influence central nervous system (CNS) development in offspring. However, the recommended intakes of folic acid for women of childbearing age differ among countries and there is still no consensus about whether folic acid should be supplemented continuously throughout pregnancy. We hypothesized that folic acid supplementation may be more beneficial for offspring's neurobehavioral development if prolonged throughout pregnancy instead of being limited to the periconceptional period...
April 18, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28421282/associations-between-a-mediterranean-diet-pattern-and-inflammatory-biomarkers-in-european-adolescents
#9
Aline Arouca, Nathalie Michels, Luis A Moreno, Esther M González-Gil, Ascensión Marcos, Sonia Gómez, Ligia Esperanza Díaz, Kurt Widhalm, Dénes Molnár, Yannis Manios, Frederic Gottrand, Antonio Kafatos, Mathilde Kersting, Michael Sjöström, Alejandro de la O, Marika Ferrari, Inge Huybrechts, Marcela Gonzalez-Gross, Stefaan De Henauw
AIM: To test whether the Mediterranean diet score and each food-subgroup is associated with inflammatory biomarkers in European adolescents. METHODS: In 464 adolescents (13-17 years) of the European HELENA study, data were available on body composition, inflammation markers, and food intake determined by two computerized 24-h recalls. The Mediterranean diet score and its food-subgroups (Vegetables, Fruits and Nuts, Pulses, Cereal and Roots, Monounsaturated/Saturated fat ratio, Dairy, Fish, Meat and Alcohol) were evaluated...
April 18, 2017: European Journal of Nutrition
https://www.readbyqxmd.com/read/28421128/a-clinically-relevant-variant-of-the-human-hydrogen-sulfide-synthesizing-enzyme-cystathionine-%C3%AE-synthase-increased-co-reactivity-as-a-novel-molecular-mechanism-of-pathogenicity
#10
João B Vicente, Henrique G Colaço, Francesca Malagrinò, Paulo E Santo, André Gutierres, Tiago M Bandeiras, Paula Leandro, José A Brito, Alessandro Giuffrè
The human disease classical homocystinuria results from mutations in the gene encoding the pyridoxal 5'-phosphate- (PLP-) dependent cystathionine β-synthase (CBS), a key enzyme in the transsulfuration pathway that controls homocysteine levels, and is a major source of the signaling molecule hydrogen sulfide (H2S). CBS activity, contributing to cellular redox homeostasis, is positively regulated by S-adenosyl-L-methionine (AdoMet) but fully inhibited upon CO or NO• binding to a noncatalytic heme moiety. Despite extensive studies, the molecular basis of several pathogenic CBS mutations is not yet fully understood...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28419824/effect-of-risperidone-on-serum-homocysteine-levels-in-first-episode-drug-na%C3%A3-ve-patients-with-schizophrenia
#11
Ning Fan, Yunlong Tan, Fude Yang, Li Tian, Song Chen, Jia Li, Zhiren Wang, Xiangyang Zhang
Some studies have shown that homocysteine (Hcy) levels are increased in patients with schizophrenia, and may be involved in its pathophysiology. The purpose of this study was to investigate the effect of the atypical antipsychotic drug risperidone on serum Hcy levels and to explore the relationship between the changes in Hcy levels and the therapeutic outcome, which, to our best knowledge have not been investigated. Fifty-six first-episode and drug-naïve inpatients with schizophrenia were assigned to a 12-week treatment regime with risperidone...
April 15, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28414812/deficiency-of-superoxide-dismutase-promotes-cerebral-vascular-hypertrophy-and-vascular-dysfunction-in-hyperhomocysteinemia
#12
Sanjana Dayal, Gary L Baumbach, Erland Arning, Teodoro Bottiglieri, Frank M Faraci, Steven R Lentz
There is an emerging consensus that hyperhomocysteinemia is an independent risk factor for cerebral vascular disease and that homocysteine-lowering therapy protects from ischemic stroke. However, the mechanisms by which hyperhomocysteinemia produces abnormalities of cerebral vascular structure and function remain largely undefined. Our objective in this study was to define the mechanistic role of superoxide in hyperhomocysteinemia-induced cerebral vascular dysfunction and hypertrophy. Unlike previous studies, our experimental design included a genetic approach to alter superoxide levels by using superoxide dismutase 1 (SOD1)-deficient mice fed a high methionine/low folate diet to produce hyperhomocysteinemia...
2017: PloS One
https://www.readbyqxmd.com/read/28406766/homocysteine-as-a-biomarker-for-thrombosis-what-is-the-learning-curve
#13
EDITORIAL
Bushra Moiz
No abstract text is available yet for this article.
March 2017: Journal of the College of Physicians and Surgeons—Pakistan: JCPSP
https://www.readbyqxmd.com/read/28402961/combination-of-susceptibility-gene-and-traditional-risk-factors-might-enhance-the-performance-of-coronary-heart-disease-screening-strategy
#14
Shiyan Nian, Lei Feng, Yang Zhao, Feng Luo, Shu Zhang, Dan Li, Wenbo Xu, Xingfeng Zhang, Dan Ye, Xuejing Bai
Coronary heart disease (CHD) associated risk factors and susceptibility genes were studied in parallel for decades, however, the combination of the classic CHD risk factors and genetic risk factors has been rarely studied. Previously; we reported that a single nucleotide polymorphism (SNP) in the stromal cell-derived factor 1 (SDF-1) gene was associated with CHD risk; in addition, we also established a CHD screening strategy using traditional CHD risk factors as independent variables. To explore how to combine genetic factors and traditional risk factors in CHD screening strategy, the CHD probabilities were tested in 218 males and 121 females according to their stromal cell-derived factor 1 (SDF-1) genotypes using CHD screening equations we reported previously...
March 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28401801/thrombophilia-in-153-patients-with-premature-cardiovascular-disease-%C3%A2-age-45
#15
Alexander Milgrom, Kevin Lee, Matan Rothschild, Frini Makadia, Greg Duhon, Sarah Min, Ping Wang, Charles J Glueck
We assessed contributions of thrombophilia to premature cardiovascular disease (CVD) events (≤ age 45) in 153 patients. Test results of thrombophilia-hypofibrinolysis were obtained in 153 patients with CVD ≤ age 45, 110 healthy normal controls, and 110 patients who had venous thromboembolism (VTE) without CVD. Of the 153 patients with CVD, 121 (79%) had sustained myocardial infarction, 70 (46%) had coronary artery stenting, and 53 (35%) had coronary artery bypass grafts. The first CVD events occurred at ages >20 to 35 in 47 patients and at ages >35 to 45 in 106 patients...
January 1, 2017: Clinical and Applied Thrombosis/hemostasis
https://www.readbyqxmd.com/read/28400561/a-hybrid-stochastic-model-of-folate-mediated-one-carbon-metabolism-effect-of-the-common-c677t-mthfr-variant-on-de-novo-thymidylate-biosynthesis
#16
Karla Misselbeck, Luca Marchetti, Martha S Field, Marco Scotti, Corrado Priami, Patrick J Stover
Folate-mediated one-carbon metabolism (FOCM) is an interconnected network of metabolic pathways, including those required for the de novo synthesis of dTMP and purine nucleotides and for remethylation of homocysteine to methionine. Mouse models of folate-responsive neural tube defects (NTDs) indicate that impaired de novo thymidylate (dTMP) synthesis through changes in SHMT expression is causative in folate-responsive NTDs. We have created a hybrid computational model comprised of ordinary differential equations and stochastic simulation...
April 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28398657/study-exploring-the-effects-of-daily-supplementation-with-400-%C3%AE-g-of-folic-acid-on-the-nutritional-status-of-folate-in-women-of-reproductive-age
#17
Laidy D Arias, Beatriz E Parra, Angélica M Muñoz, Diana L Cárdenas, Tiffany G Duque, Luz M Manjarrés
BACKGROUND: This investigation determines the nutritional state of serum and red blood cell (RBC) folate concentration and their relation with intake of folate, B6 ,and B12 , with serum vitamin B12 , and with genetic variants after provision of 400 μg/day of folic acid for 3 months to a group of 34 Colombian women of reproductive age. METHODS: We evaluated nutrient intake using 24-hr recall, assessing the levels of serum folate, RBC folate, serum B12 , and homocysteine, as well as determining genetic variants of the enzyme MTHFR (C677T and A1298C) and CβS (844ins68pb)...
March 15, 2017: Birth Defects Res
https://www.readbyqxmd.com/read/28398583/clsi-based-validation-of-manufacturer-derived-reference-intervals-on-the-cobas-8000-platform
#18
Veronika Leitner-Ferenc, Johanna Atamaniuk, Sonja Jansen-Skoupy, Brigitta Stöckelmeier, Katharina Grohs, Manuela Födinger
Background: Reference intervals provided by diagnostic test manufacturers should be transferred to clinical laboratories after validation. Although protocols exist, laboratories rarely perform and report on results of validation studies. Methods: We validated reference intervals (RIs) of 87 analytes on a Cobas 8000 platform according to standards published by the Clinical and Laboratory Standards Institute (CLSI). Results: For 8 analytes, decision limits were provided in the package inserts...
April 8, 2017: Laboratory Medicine
https://www.readbyqxmd.com/read/28397471/interactions-of-methylenetetrahydrofolate-reductase-gene-polymorphisms-folate-and-homocysteine-on-blood-pressure-in-a-chinese-hypertensive-population
#19
Wen-Xing Li, Peng Liao, Chao-Yue Hu, Fei Cheng, Tao Zhang, Yuan-Yuan Sun, Ling Tang, Man-Man Wang, Kui-Sheng Liu, Dahai Liu, Fang Liu
BACKGROUND: High blood pressure is related to cardiovascular diseases. We aimed to explore the interactions of methylenetetrahydrofolate reductase (MTHTR) gene C677T and A1298C mutations and folate/homocysteine (Hcy) status on blood pressure in a Chinese hypertensive population. METHODS: The clinical data in the present study derived from a previous trial (NCT00520247). Genotypes in Hcy pathway enzymes were detected by PCR-RFLP methods. Supine blood pressure was measured with a mercury sphygmomanometer...
April 1, 2017: Clinical Laboratory
https://www.readbyqxmd.com/read/28397458/mapping-of-dna-hypermethylation-and-hypomethylation-induced-by-folate-deficiency-in-sporadic-colorectal-cancer-and-clinical-implication-analysis-of-hypermethylation-pattern-in-cbs-promoter
#20
Zaizhong Zhang, Yang He, Xiaohuang Tu, Sheng Huang, Zhuo Chen, Lie Wang, Jingxiang Song
BACKGROUND: Aberrant DNA methylation patterns play a major role in tumorigenesis and the effects of nutrients, especially folate in the diet, on methylation changes is of great importance in colorectal cancer (CRC). Folate deficiency would disrupt methylation patterns; however, its exact effects on DNA methylation patterns in CRC are unclear. This study was performed to gain insight into the methylation changes induced by folate deficiency and the putative role of methylation pattern diversities of related genes in the clinical outcome of CRC...
April 1, 2017: Clinical Laboratory
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