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albumin human [keywords]
- Effects of pulse-delivered inhaled nitric oxide administration on pulmonary perfusion and arterial oxygenation in dorsally recumbent isoflurane-anesthetized horses. [Journal Article]
- Am J Vet Res 2014 Nov; 75(11):949-55.
Objective-To image the spatial distribution of pulmonary blood flow by means of scintigraphy, evaluate ventilation-perfusion (VA/Q) matching and pulmonary blood shunting (Qs/Qt) by means of the multiple inert gas elimination technique (MIGET), and measure arterial oxygenation and plasma endothelin-1 concentrations before, during, and after pulse-delivered inhaled nitric oxide (PiNO) administration to isoflurane-anesthetized horses in dorsal recumbency. Animals-3 healthy adult Standardbreds. Procedures-Nitric oxide was pulsed into the inspired gases in dorsally recumbent isoflurane-anesthetized horses. Assessment of VA/Q matching, Qs/Qt, and Pao2 content was performed by use of the MIGET, and spatial distribution of pulmonary blood flow was measured by perfusion scintigraphy following IV injection of technetium Tc 99m-labeled macroaggregated human albumin before, during, and 30 minutes after cessation of PiNO administration. Results-During PiNO administration, significant redistribution of blood flow from the dependent regions to the nondependent regions of the lungs was found and was reflected by improvements in VA/Q matching, decreases in Qs/Qt, and increases in Pao2 content, all of which reverted to baseline values at 30 minutes after PiNO administration. Conclusions and Clinical Relevance-Administration of PiNO in anesthetized dorsally recumbent horses resulted in redistribution of pulmonary blood flow from dependent atelectatic lung regions to nondependent aerated lung regions. Because hypoxemia is commonly the result of atelectasis in anesthetized dorsally recumbent horses, the addition of nitric oxide to inhaled gases could be used clinically to alleviate hypoxemia in horses during anesthesia.
- Nanometric Resolution in the Hydrodynamic Size Analysis of Ligand-Stabilized Gold Nanorods. [JOURNAL ARTICLE]
- Langmuir 2014 Oct 28.
The stability and hydrodynamic size of ligand-coated gold nanorods (GNRs; aspect ratio 3.6) have been characterized by nanoparticle tracking analysis (NTA), a single-particle counting method that can measure size distributions with low nanometer resolution. Stable aqueous suspensions of citrate-stabilized GNRs (cit-GNRs) are amenable to surface functionalization without loss of dispersion control. Cit-GNRs can be treated with chemisorptive ligands (thiols and dithiocarbamates), nonionic surfactants (Tween 20), and proteins (human serum albumin), all of which produce stable suspensions at low surfactant concentrations. The precision of NTA (relative standard deviation 10-12%, standard error <2%) is sufficient to allow differences in the hydrodynamic size of coated GNRs to be interpreted in terms of surfactant structure and conformation.
- Albuminoid genes: evolving at the interface of dispensability and selection. [JOURNAL ARTICLE]
- Genome Biol Evol 2014 Oct 27.
The albuminoid gene family comprises vitamin D-binding protein (GC), alpha-fetoprotein (AFP), afamin (AFM), and albumin (ALB). Albumin is the most abundant human serum protein, and, as the other family members, acts as a transporter of endogenous and exogenous substances including thyroxine, fatty acids, and drugs. Instead, the major cargo of GC is 25-hydroxyvitamin D. We performed an evolutionary study of albuminoid genes and we show that ALB evolved adaptively in mammals. Most positively selected sites are located within albumin binding sites for fatty acids and thyroxine, as well as at the contact surface with neonatal Fc receptor. Positive selection was also detected for residues forming the prostaglandin-binding pocket. Adaptation to hibernation/torpor might explain the signatures of episodic positive selection we detected for few mammalian lineages. Application of a population genetics-phylogenetics approach showed that purifying selection represented a major force acting on albuminoid genes in both humans and chimpanzees, with the strongest constraint observed for human GC. Population genetic analysis revealed that GC was also the target of locally-exerted selective pressure, which drove the frequency increase of different haplotypes in distinct human populations. A search for known variants that modulate GC and 25-hydroxyvitamin D concentrations revealed linkage disequilibrium with positively selected variants, although European and Asian major GC haplotypes carry alleles with reported opposite effect on GC concentration. Data herein indicate that albumin, an extremely abundant housekeeping protein, was the target of pervasive and episodic selection in mammals, whereas GC represented a selection target during the recent evolution of human populations.
- Bioactive Albumin-Based Carriers for Tumour Chemotherapy. [JOURNAL ARTICLE]
- Curr Cancer Drug Targets 2014 Oct 27.
Proteins are posed as the natural counterpart of the synthetic polymers for the development of drug delivery systems and few of them have been regarded safe for drug delivery purposes by the United States Food and Drug Administration. Serum albumin is the most abundant protein in human blood. Interest in the exploration of pharmaceutical applications of albumin-based drug delivery carriers, for the delivery of chemotherapeutic agents, has increased in recent years. Albumin has several advantages to synthetic polymers, as it is biocompatible, biodegradable, has low cytotoxicity and has an excellent binding capacity with various drugs. Micro- and nano-carriers not only protect active pharmaceutical ingredients against degradation, but also offer a prolonged release of drugs in a controlled fashion. Since existing tumour chemotherapeutic agents neither target tumour cells, nor are they specific to tumour cells, a slow release of drugs from carriers would be beneficial in targeting carcinogenic cells intracellularly. This article aims at providing an overview of pharmaceutical applications of albumin as a drug delivery carrier in tumour chemotherapy.
- Protective Effect of Different Anti-Rabies Virus VHH Constructs against Rabies Disease in Mice. [JOURNAL ARTICLE]
- PLoS One 2014; 9(10):e109367.
Rabies virus causes lethal brain infection in about 61000 people per year. Each year, tens of thousands of people receive anti-rabies prophylaxis with plasma-derived immunoglobulins and vaccine soon after exposure. Anti-rabies immunoglobulins are however expensive and have limited availability. VHH are the smallest antigen-binding functional fragments of camelid heavy chain antibodies, also called Nanobodies. The therapeutic potential of anti-rabies VHH was examined in a mouse model using intranasal challenge with a lethal dose of rabies virus. Anti-rabies VHH were administered directly into the brain or systemically, by intraperitoneal injection, 24 hours after virus challenge. Anti-rabies VHH were able to significantly prolong survival or even completely rescue mice from disease. The therapeutic effect depended on the dose, affinity and brain and plasma half-life of the VHH construct. Increasing the affinity by combining two VHH with a glycine-serine linker into bivalent or biparatopic constructs, increased the neutralizing potency to the picomolar range. Upon direct intracerebral administration, a dose as low as 33 µg of the biparatopic Rab-E8/H7 was still able to establish an anti-rabies effect. The effect of systemic treatment was significantly improved by increasing the half-life of Rab-E8/H7 through linkage with a third VHH targeted against albumin. Intraperitoneal treatment with 1.5 mg (2505 IU, 1 ml) of anti-albumin Rab-E8/H7 prolonged the median survival time from 9 to 15 days and completely rescued 43% of mice. For comparison, intraperitoneal treatment with the highest available dose of human anti-rabies immunoglobulins (65 mg, 111 IU, 1 ml) only prolonged survival by 2 days, without rescue. Overall, the therapeutic benefit seemed well correlated with the time of brain exposure and the plasma half-life of the used VHH construct. These results, together with the ease-of-production and superior thermal stability, render anti-rabies VHH into valuable candidates for development of alternative post exposure treatment drugs against rabies.
- Compared Binding Properties between Resveratrol and Other Polyphenols to Plasmatic Albumin: Consequences for the Health Protecting Effect of Dietary Plant Microcomponents. [REVIEW]
- Molecules 2014; 19(11):17066-17077.
Phytophenols are considered to have beneficial effects towards human physiology. They are food microcomponents with potent chemopreventive properties towards the most three frequent contemporary human diseases, e.g., cardiovascular alterations, cancer and neurodegenerative pathologies. Related to this, the plasmatic form and plasmatic level of plant polyphenols in the body circulation are crucial for their efficiency. Thus, determinations of the binding process of resveratrol and of common flavonoids produced by major edible plants, berries and fruits to plasma proteins are essential. The interactions between resveratrol and albumin, a major plasma protein, were compared with those already published, involving curcumin, genistein, quercetin and other well-known food-containing polyphenols. The approaches used are usually intrinsic fluorescence intensity changes, quenching of protein intrinsic fluorescence and infrared spectroscopy. It appears that: (1) all of the studied polyphenols interact with albumin; (2) while most of the studied polyphenols interact at one albumin binding site, there are two different types of resveratrol binding sites for bovine serum albumin, one with the highest affinity (apparent KD of 4 µM) with a stoichiometry of one per monomer and a second with a lower affinity (apparent KD of 20 µM) with also a stoichiometry of one per monomer; (3) at least one binding site is in the vicinity of one tryptophanyl residue of bovine serum albumin; and (4) resveratrol binding to bovine serum albumin produces a very small structural conformation change of the polypeptide chain. These results support a role played by polyphenols-albumin interactions in the plasma for the bio-activities of these food microcomponents in the body.
- Different Interaction Modes of Biomolecules with Citrate-Capped Gold Nanoparticles. [JOURNAL ARTICLE]
- ACS Appl Mater Interfaces 2014 Oct 27.
In this study, we investigated the interaction between five bio-relevant molecules and citrate-capped gold nanoparticles using dynamic light scattering, zeta potential analysis, UV-Vis absorption spectroscopy and transmission electron microscopy. The five biomolecules are: bovine serum albumin (BSA), two immunoglobulin G (IgG) proteins, immunoglobulin M (IgM), and a polysaccharide molecule, hyaluronan. BSA, IgG and IgM are high abundance proteins in blood. Hyaluronan is a major component of the extracellular matrix. Abnormal level of hyaluronan in blood is associated with a number of medical conditions including rheumatoid arthritis and malignancy. Five different interaction modes were observed from these molecules. While BSA and IgM interact with the gold nanoparticles by forming electrostatic interactions with the citrate ligands, IgG and hyaluronan adsorb to the nanoparticle metal core by displacing the citrate ligands. BSA, rabbit IgG, and hyaluronan formed a stable monolayer on the nanoparticle surface. Human IgG and IgM caused nanoparticle cluster formation upon interacting with the gold nanoparticles. For the first time, we discovered that hyaluronan, a highly negatively charged polyglycosaminoglycan, exhibits an exceptionally strong affinity towards the citrate-gold nanoparticles. It can effectively compete with IgG to adsorb to the gold nanoparticles. This finding has exciting implications for future research: the molecular composition of a protein corona formed on a nanoparticle surface upon mixing the nanoparticle with blood or other biological fluids may vary according to the pathological conditions of individuals, and the analysis of these compositions could potentially lead to new biomarker discovery with diagnostic applications.
- Interaction with both domain I and III of albumin is required for optimal pH dependent binding to the neonatal Fc Receptor (FcRn). [JOURNAL ARTICLE]
- J Biol Chem 2014 Oct 24.
Albumin is an abundant blood protein that acts as a transporter of a plethora of small molecules like fatty acids, hormones, toxins and drugs. In addition, it has an unusual long serum half-life in humans of nearly 3 weeks, which is attributed to its interaction with the neonatal Fc receptor (FcRn). FcRn protects albumin from intracellular degradation via a pH dependent cellular recycling mechanism. To understand how FcRn impacts the role of albumin as a distributor, it is of importance to unravel the structural mechanism that determines pH dependent binding. Here, we show that while the C-terminal domain III (DIII) of human serum albumin (HSA) contains the principal binding site, the N-terminal domain I (DI) is important for optimal FcRn binding. Specifically, structural inspection of human FcRn (hFcRn) in complex with HSA revealed that two exposed loops of DI were in proximity with the receptor. To investigate to what extent these contacts affected hFcRn binding, we targeted selected amino acid residues of the loops by mutagenesis. Screening by in vitro interaction assays revealed that several of the engineered HSA variants showed decreased binding to hFcRn, which was also the case for two missense variants with mutations within these loops. In addition, four of the variants showed improved binding. Our findings demonstrate that both DI and DIII are required for optimal binding to FcRn, which has implications for our understanding of the FcRn-albumin relationship and how albumin acts as a distributor. Such knowledge may inspire development of novel HSA based diagnostics and therapeutics.
- 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.