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albumin human [keywords]
- Enamel maturation: a brief background with implications for some enamel dysplasias. [Journal Article, Review]
- Front Physiol 2014.:388.
The maturation stage of enamel development begins once the final tissue thickness has been laid down. Maturation includes an initial transitional pre-stage during which morphology and function of the enamel organ cells change. When this is complete, maturation proper begins. Fully functional maturation stage cells are concerned with final proteolytic degradation and removal of secretory matrix components which are replaced by tissue fluid. Crystals, initiated during the secretory stage, then grow replacing the tissue fluid. Crystals grow in both width and thickness until crystals abut each other occupying most of the tissue volume i.e. full maturation. If this is not complete at eruption, a further post eruptive maturation can occur via mineral ions from the saliva. During maturation calcium and phosphate enter the tissue to facilitate crystal growth. Whether transport is entirely active or not is unclear. Ion transport is also not unidirectional and phosphate, for example, can diffuse out again especially during transition and early maturation. Fluoride and magnesium, selectively taken up at this stage can also diffuse both in an out of the tissue. Crystal growth can be compromised by excessive fluoride and by ingress of other exogenous molecules such as albumin and tetracycline. This may be exacerbated by the relatively long duration of this stage, 10 days or so in a rat incisor and up to several years in human teeth rendering this stage particularly vulnerable to ingress of foreign materials, incompletely mature enamel being the result.
- Pathophysiological, cardiovascular and neuroendocrine changes in hypertensive patients during the hemodialysis session. [JOURNAL ARTICLE]
- J Hum Hypertens 2014 Oct 23.
The pathophysiological mechanisms of arterial hypertension during hemodialysis (HD) in patients with end-stage renal disease (ESRD) are still poorly understood. The aim of this study is to investigate physiological, cardiovascular and neuroendocrine changes in patients with ESRD and its correlation with changes in blood pressure (BP) during the HD session. The present study included 21 patients with ESRD undergoing chronic HD treatment. Group A (study) consisted of patients who had BP increase and group B (control) consisted of those who had BP reduction during HD session. Echocardiograms were performed during the HD session to evaluate cardiac output (CO) and systemic vascular resistance (SVR). Before and after the HD session, blood samples were collected to measure brain natriuretic peptide (BNP), catecholamines, endothelin-1 (ET-1), nitric oxide (NO), electrolytes, hematocrit, albumin and nitrogen substances. The mean age of the studied patients was 43±4.9 years, and 54.6% were males. SVR significantly increased in group A (P<0.001). There were no differences in the values of BNP, NO, adrenalin, dopamin and noradrenalin, before and after dialysis, between the two groups. The mean value of ET-1, post HD, was 25.9 pg ml(-1) in group A and 13.3 pg ml(-1) in group B (P=<0.001). Patients with ESRD showed different hemodynamic patterns during the HD session, with significant BP increase in group A, caused by an increase in SVR possibly due to endothelial dysfunction, evidenced by an increase in serum ET-1 levels.Journal of Human Hypertension advance online publication, 23 October 2014; doi:10.1038/jhh.2014.93.
- Industry Update. [JOURNAL ARTICLE]
- Ther Deliv 2014 Aug; 5(8):879-883.
The month of May 2014 brought the news that AstraZeneca had rejected Pfizer's last and final offer to take over the company, while Valeant's attempts to acquire Allergan continued (both topics are covered in detail in last month's edition of Therapeutic Delivery). Companies that did agree to work together in May, at least in the form of licensing and collaboration agreements, included Avalanche and Regeneron (gene therapy via an adeno-associated virus-based delivery system), AADi and Celgene (in-licensing of sirolimus or rapamycin, formulated as albumin-bound nanoparticles), AntiOp and Reckitt Benckiser (nasal naloxone), Bristol-Myers Squibb and CytomX (Probody™ antibodies against immuno-oncology targets) and PolyTherics and Alpha Cancer Technologies (novel drug conjugates of alpha-fetoprotein). May also brought good news for Veloxis in the form of a positive opinion from the Committee for Medicinal Products for Human Use for its MeltDose(®) formulation of tacrolimus, and for RXi Pharmaceuticals which received a Notice of Allowance from the United States Patent and Trademark Office on a key patent for its self-delivering RNAi technology.
- MicroRNA-147b Regulates Vascular Endothelial Barrier Function by Targeting ADAM15 Expression. [JOURNAL ARTICLE]
- PLoS One 2014; 9(10):e110286.
A disintegrin and metalloproteinase15 (ADAM15) has been shown to be upregulated and mediate endothelial hyperpermeability during inflammation and sepsis. This molecule contains multiple functional domains with the ability to modulate diverse cellular processes including cell adhesion, extracellular matrix degradation, and ectodomain shedding of transmembrane proteins. These characteristics make ADAM15 an attractive therapeutic target in various diseases. The lack of pharmacological inhibitors specific to ADAM15 prompted our efforts to identify biological or molecular tools to alter its expression for further studying its function and therapeutic implications. The goal of this study was to determine if ADAM15-targeting microRNAs altered ADAM15-induced endothelial barrier dysfunction during septic challenge by bacterial lipopolysaccharide (LPS). An in silico analysis followed by luciferase reporter assay in human vascular endothelial cells identified miR-147b with the ability to target the 3' UTR of ADAM15. Transfection with a miR-147b mimic led to decreased total, as well as cell surface expression of ADAM15 in endothelial cells, while miR-147b antagomir produced an opposite effect. Functionally, LPS-induced endothelial barrier dysfunction, evidenced by a reduction in transendothelial electric resistance and increase in albumin flux across endothelial monolayers, was attenuated in cells treated with miR-147b mimics. In contrast, miR-147b antagomir exerted a permeability-increasing effect in vascular endothelial cells similar to that caused by LPS. Taken together, these data suggest the potential role of miR147b in regulating endothelial barrier function by targeting ADAM15 expression.
- Serum albumin promotes ATP-binding Cassette Transporter- dependent sterol uptake in yeast. [JOURNAL ARTICLE]
- FEMS Yeast Res 2014 Oct 21.
Sterol uptake in fungi is a multistep process that involves interaction between external sterols and the cell wall, incorporation of sterol molecules into the plasma membrane and subsequent integration into intracellular membranes for turnover. ATP-binding cassette (ABC) transporters have been implicated in sterol uptake, but key features of their activity remain to be elucidated. Here we apply fluorescent cholesterol (NBD-cholesterol) to monitor sterol uptake under anaerobic and aerobic conditions in two fungal species, Candida glabrata and Saccharomyces cerevisiae. We found that in both fungal species ABC transporter-dependent uptake of cholesterol under anaerobic conditions and in mutants lacking HEM1 gene is promoted in the presence of the serum protein albumin that is able to bind the sterol molecule. Furthermore, the C. glabrata ABC transporter CgAus1p expressed in S. cerevisiae requires the presence of serum or albumin for efficient cholesterol uptake. These results suggest that albumin can serve as sterol donor in ABC-transporter-dependent sterol uptake, a process potentially important for growth of C. glabrata inside infected humans. This article is protected by copyright. All rights reserved.
- [Effect of advanced glycosylation end products on oxidative stress and MCP-1 in human renal mesangial cells]. [English Abstract, Journal Article]
- Zhongguo Ying Yong Sheng Li Xue Za Zhi 2014 Jul; 30(4):306-10, 313.
To investigate the effects of advanced glycosylation end products(AGEs)modified bovine serum albumin (AGE-BSA) on the expression of reactive oxygen species (ROS) and monocyte chemoattractant protein-1 (MCP-1) in human renal mesangial cells (HRMCs).HRMCs were cultured in vitro with medium containing different doses of AGE-BSA or BSA (50,100, 200, 400 mg/L) for 48 hours,or with AGE-BSA (200 mg/L) for different times (12,24,48,72 h). Immunocytochemistry assay was used to estimate the protein level of RAGE. The ROS in cells were measured by flow cytometry and the mRNA expression of MCP-1 were analyzed by semi-quantiative reverse transcription-polymerase chain reaction (RT-PCR)after treatment with AGE-BSA or BSA.The protein level of RAGE was upregulated in the HRMCs with AGE-BSA. The expression of ROS and MCP-1 significantly enhanced by incubation of AGE-BSA in a time- and dose-dependent manner. The effects of AGE-BSA-induced up-regulation of ROS and MCP-1 level was significantly blocked by neutralizing antibodies to RAGE,while the expression of ROS and MCP-1 stood nearly unchanged after cultured with huamn IgG.The expression of ROS and MCP-1 in HRMCs is induced by AGE-BSA through RAGE, which may have potential effects in the pathgenic mechanism of diabetic nephropathy.
- Perinatal outcomes for transfer of blastocysts vitrified and warmed in defined solutions with recombinant human albumin: 374 babies born after 898 embryo transfers. [JOURNAL ARTICLE]
- J Assist Reprod Genet 2014 Oct 19.
To assess the efficacy of a novel, defined vitrification procedure using recombinant human albumin (rHA) for cryopreservation of human blastocysts. Design: Retrospective study. Setting: Private IVF clinic. Patients: 1,496 patients received vitrified/warmed embryo transfer (ET).Surplus blastocysts, and blastocysts from patients undergoing elective embryo cryopreservation, were vitrified/warmed using Cryotop carriers in homemade solutions containing either human serum albumin (HSA) or rHA. Main Outcome Measures: Clinical and neonatal outcomes regarding the vitrified/warmed ET procedures.The HSA and rHA groups had a total of 1,163 and 898 vitrified/warmed cycles, respectively. Embryo survival rates (98.7 % vs. 98.9 %, respectively) and the number of embryos transferred (1.08 ± 0.01 vs. 1.06 ± 0.01, respectively) were similar in the HSA and rHA groups. Clinical pregnancy rates/ET were higher (P < 0.05) in the rHA group (56.0 %) than in the HSA group (51.5 %). The HSA and rHA groups had similar live delivery rates/pregnancy (72.2 % vs. 72.3 %, respectively) and perinatal outcomes, including birth weight (2,988 ± 28 vs. 3,046 ± 26 g, respectively). Birth defects occurred in 0.9 % and 1.6 % of neonates in the HSA and rHA groups, respectively.rHA effectively replaced HSA for human embryo vitrification procedures, and yielded high rates of pregnancy and live births after vitrified/warmed ET. This new approach will support the development of defined ART systems, which will eliminate the variation and risks associated with the use of blood-derived products.
- Formation of a Protein Corona on Silver Nanoparticles Mediates Cellular Toxicity via Scavenger Receptors. [JOURNAL ARTICLE]
- Toxicol Sci 2014 Oct 17.
Addition of a protein corona (PC) or protein adsorption layer on the surface of nanomaterials following their introduction into physiological environments may modify their activity, bio-distribution, cellular uptake, clearance and toxicity. We hypothesize that silver nanoparticles (AgNPs) will associate with proteins common to human serum and cell culture media forming a PC that will impact cell activation and cytotoxicity. Furthermore, the role of scavenger receptor BI (SR-BI) in mediating this toxicity was evaluated. Citrate-suspended 20 nm AgNPs were incubated with human serum albumin (HSA), bovine serum albumin (BSA), high-density lipoprotein (HDL), or water (control) to form a PC. AgNPs associated with each protein (HSA, BSA, HDL) forming PCs as assessed by electron microscopy, hyperspectral analysis, ζ-potential, and hydrodynamic size. Addition of the PC decreased uptake of AgNPs by rat lung epithelial (RLE) and rat aortic endothelial (RAEC) cells. Hyperspectral analysis demonstrated a loss of the AgNP PC following internalization. Cells demonstrated concentration-dependent cytotoxicity following exposure to AgNPs with or without PCs (0, 6.25, 12.5, 25 or 50 μg/ml). All PC-coated AgNPs were found to activate cells by inducing IL-6 mRNA expression. A small molecule SR-BI inhibitor was utilized to determine the role of SR-BI in the observed effects. Pretreatment with the SR-BI inhibitor decreased internalization of AgNPs with or without PCs, and reduced both cytotoxicity and IL-6 mRNA expression. This study characterizes the formation of a PC on AgNPs and demonstrates its influence on cytotoxicity and cell activation through a cell surface receptor.
- Human blood glycosaminoglycans: isolation and analysis. [Journal Article]
- Methods Mol Biol 2015.:95-103.
Glycosaminoglycans (GAGs) are linear polysaccharides having disaccharide building blocks consisting of an amino sugar (N-acetylglucosamine, or N-acetylgalactosamine) and a uronic acid (glucuronic acid or iduronic acid) or galactose. Glycosaminoglycans have sulfated residues at various positions except for hyaluronan, and those sulfated residues regulate the biological functions of a wide variety of proteins, primarily through high-affinity interactions mediated by specific patterns/densities of sulfation and sugar sequences. Alteration of GAG structure is associated with a number of disease conditions and therefore the analyses of GAG structures and their sulfation patterns are important for the development of disease biomarkers and for treatment options. Extensive structural and quantitative analyses of GAGs from human blood are largely unexplored which may be due to the exhaustive isolation process because of the presence of too much interfering proteins and lipids such as serum albumin. Therefore we established a new GAG isolation method using the least amount (~200 μl) of human blood, consisting of a combination of proteolytic digestion and selective ethanol precipitation of GAGs, digestion of GAGs recovered on the filter cup by direct addition of GAG lyase reaction solution, and subsequent high-pressure liquid chromatography of unsaturated disaccharide products that enable to analyze GAG structures and contents. This isolation method offers an 80 % recovery of GAGs and can be applied to analyze a minute GAG content (≥1 nmol) from the least amount of biological fluids. Hence the method could be useful for the development of disease biomarkers.
- Enzymatic fingerprinting of structurally similar homologous proteins using polyion complex library constructed by tuning PEGylated polyamine functionalities. [JOURNAL ARTICLE]
- Analyst 2014 Oct 17.
Human plasma proteins and even structurally similar homologous albumins were fingerprinted and discriminated by a sensor array consisting of a polyion complex library with artificial differentiation constructed by facile tuning of PEGylated polyamine functionalities.