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albumin human [keywords]
- Adduct levels from benzo[a]pyrene diol epoxide: Relative formation to histidine in serum albumin and to deoxyguanosine in DNA in vitro and in vivo in mice measured by LC/MS-MS methods. [JOURNAL ARTICLE]
- Toxicol Lett 2014 Sep 24.
Stable and specific biomacromolecular adducts can be used to measure in vivo doses of reactive compounds. An LC/MS-MS method to measure adducts from the benzo[a]pyrene (BP) metabolite (±)-anti-BP-7,8-diol-9,10-epoxide ((±)-anti-BPDE) to His(146) in serum albumin (SA), earlier evaluated on in vitro alkylated human SA, was tested for its applicability to mouse. It was shown that (+)-anti-BPDE form BPDE-His adducts to mouse SA. The method was applied to samples from BP-exposed mice (100mg/kg of body weight for 1, 3, 7 and 28 days). BPDE-His in SA was close to the limit of quantification and showed the highest level (13fmol/mg) 3 days after exposure. The level was 400 times lower (calculated per g macromolecule) than earlier measured level of BPDE-adduct to deoxyguanosine (dG) in DNA in the livers. The relative rate of formation of adducts from BPDE with His in SA and with dG in DNA was investigated. Quantification by LC/MS-MS of the adducts in human blood alkylated in vitro with (±)-anti-BPDE showed a 1850 times higher level of BPDE-dG compared to BPDE-His. The specific and stable BPDE-adducts to His in SA are potential biomarkers of in vivo dose of BPDE, though this requires a considerable improved analytical sensitivity of the LC/MS-MS method.
- Albumin reverses the echinocytic shape transformation of stored erythrocytes. [JOURNAL ARTICLE]
- Clin Hemorheol Microcirc 2014 Sep 26.
The storage of red blood cells (RBCs) leads to storage lesions, which have a negative impact on the clinical outcome after transfusion. A hallmark of storage lesions is echinocytosis. Albumin may reverse this shape transformation, which was the topic of this study. Echinocytosis was generated by incubation of blood for 48 h at room temperature or in RBC units stored 48 days at 5°C. Human serum albumin was diluted in phosphate-buffered saline. RBCs were fixed in 1% glutaraldehyde and examined by light and scanning electron microscopy. The degree of echinocytosis was quantified by calculating the morphological index. Incubation and storage of RBCs led to an echinocytic shape transformation, which was reversible upon incubation in albumin solutions. This process was time-, concentration- and hematocrit-dependent. Treating RBC units at the end of their shelf-life by adding 20% albumin or washing them in 0.2% albumin reversed all degrees of echinocytosis towards discocytosis. In conclusion, albumin has the capacity to reverse echinocytosis generated by RBC storage. This observation may improve the quality of RBC units stored for longer periods of time.
- Composition of protein supplements used for human embryo culture. [JOURNAL ARTICLE]
- J Assist Reprod Genet 2014 Sep 27.
To determine the composition of commercially available protein supplements for embryo culture media and test if differences in protein supplement composition are biologically relevant in a murine model.Amino acid, organic acid, ion and metal content were determined for 6 protein supplements: recombinant human albumin (AlbIX), human serum albumin (HSA and Buminate), and three complex protein supplements (SSS, SPS, LGPS). To determine if differences in the composition of these supplements are biologically relevant, mouse one-cell embryos were collected and cultured for 120 hours in each protein supplement in Global media at 5 and 20 % oxygen in an EmbryoScope time-lapse incubator. The compositions of six protein supplements were analyzed for concentrations of 39 individual amino acids, organic acids, ions and elements. Blastocyst development and cell cycle timings were calculated at 96-hours of culture and the experiments were repeated in triplicate. Blastocyst gene expression was analyzed.Recombinant albumin had the fewest undefined components , the lowest concentration of elements detected, and resulted in high blastocyst development in both 5 and 20 % oxygen. Buminate, LGPS and SPS had high levels of transition metals whereas SSS had high concentrations of amino acids. Pre-compaction mouse embryo development was delayed relative to embryos in AlbIX for all supplements and blastocyst formation was reduced in Buminate, SPS and SSS.The composition of protein supplements are variable, consisting of previously undescribed components. High concentrations of pro-oxidant transition metals were most notable. Blastocyst development was protein dependent and showed an interaction with oxygen concentration and pro-oxidant supplements.
- In Vivo and In Vitro Toxicity and Anti-Inflammatory Properties of Gold Nanoparticle Bioconjugates to the Vascular System. [JOURNAL ARTICLE]
- Toxicol Sci 2014 Sep 25.
Gold nanoparticle (AuNP) bioconjugates have been applied as therapeutic and diagnostic tools, however in vivo biocompatibility and cytotoxicity continue to be two fundamental issues. The effect of AuNPs conjugated (20 nm) with antibody (IgG), albumin, protein A, PEG4000 and citrate (cit) were evaluated in vitro using primary human cells of the vascular system. AuNP bioconjugates did not cause lysis of human erythrocytes, apoptosis or necrosis of human leukocytes and endothelial cells in vitro, although AuNPs had been internalized and detected in the cytoplasm. Moreover, the influence of AuNPs on rheological parameters, blood and vessel wall characteristics was investigated in vivo by intravital microscopy assay using male Wistar rats mesentery microcirculation as model. Intravenous injection of AuNP-IgG or cit-AuNP did not cause hemorrhage, hemolysis or thrombus formation; instead suppressed the leukocyte adhesion to postcapillary vessel walls, an early stage of a inflammatory process. Furthermore, AuNP-IgG abrogated the expression of platelet-endothelial cell adhesion molecule-1, chemotaxis and oxidative burst activation on neutrophils after leukotriene B4 (LTB4) stimulation, a membrane receptor dependent stimulus, thus confirming their anti-inflammatory effects in vitro. The expression of oxidative burst activation was also suppressed after stimulating AuNP-IgG-treated neutrophils with lipid soluble phorbol-mysristate acetate (PMA), confirming the direct intracellular action of AuNP-IgG on the inflammatory process in vitro. Our in vitro and in vivo experimental approach highlighted the great potentiality of AuNP bioconjugates for therapeutic and diagnostic applications by parenteral routes.
- Collective hydration dynamics of guanidinium chloride solutions and its possible role in protein denaturation: a terahertz spectroscopic study. [JOURNAL ARTICLE]
- Phys Chem Chem Phys 2014 Sep 26.
The remarkable ability of guanidinium chloride (GdmCl) to denature proteins is a well studied yet controversial phenomenon; the exact molecular mechanism is still debatable, especially the role of hydration dynamics, which has been paid less attention. In the present contribution, we have addressed the issue of whether the collective hydrogen bond dynamics of water gets perturbed in the presence of GdmCl and its possible impact on the denaturation of a globular protein human serum albumin (HSA), using terahertz (THz) time domain spectroscopy (TTDS) in the frequency range of 0.3-2.0 THz. The collective hydrogen bond dynamics is determined by fitting the obtained complex dielectric response in a multiple Debye relaxation model. To compare the results, the studies were extended to two more salts: tetramethylguanidinium chloride (TMGdmCl) and sodium chloride (NaCl). It was concluded that the change in hydration dynamics plays a definite role in the protein denaturation process.
- Preclinical Evaluation of the Thrombogenicity and Endothelialization of Bare Metal and Surface-Coated Neurovascular Stents. [JOURNAL ARTICLE]
- AJNR Am J Neuroradiol 2014 Sep 25.
Stent-assisted coiling is routinely used for the endovascular treatment of complex or wide-neck intracranial aneurysms. However, in-stent thrombosis, thromboembolic events, and ischemic complications remain a major concern associated with stent implants. Therefore, a novel low-profile neurovascular stent with a bare metal surface was investigated with regard to thrombogenicity and endothelialization and compared with the same stent coated with albumin or heparin.The bare metal and heparin- or albumin-coated stents were loaded in heparin-coated tubing, which was then filled with heparinized human blood (n = 5) and circulated at 150 mL/min and 37°C for 60 minutes. Before and after circulation, measurement of various inflammation and coagulation markers and scanning electron microscopy were performed. Endothelialization of the stents was investigated in an in vitro model including human umbilical vascular endothelial cells.Our results showed that platelet loss and platelet activation and activation of the coagulation cascade, which are induced by the bare metal stents, were significantly reduced by heparin or albumin coating. Adverse effects on erythrocytes, leukocytes, and the complement cascade were not induced by the bare metal or coated stents. Moreover, the bare metal and albumin-coated stents showed good endothelialization properties.Albumin and heparin coatings clearly improve the thrombogenicity of the stents and thus may represent fundamental progress in the treatment of intracranial aneurysms. Moreover, preclinical evaluation of neurovascular stents under physiologic conditions supports and accelerates the development of more biocompatible neurovascular stents.
- Biophysical study on the interaction of an anesthetic, vecuronium bromide with human serum albumin using spectroscopic and calorimetric methods. [JOURNAL ARTICLE]
- J Photochem Photobiol B 2014 Sep 10.:381-389.
The interactions between an anesthetic, vecuronium bromide (VB) and human serum albumin (HSA) have been investigated systematically by steady-state/time-resolved fluorescence, circular dichroism (CD), UV-vis absorption, Fourier transform infrared spectroscopy (FTIR), mass spectroscopy and differential scanning calorimetry (DSC) methods under physiological conditions. The fluorescence quenching observed is attributed to the formation of a complex between HSA and VB, and the reverse temperature effect of the fluorescence quenching has been found and discussed. Fluorescence analysis has proved that there is one classical binding site on HSA for VB with a relative weak binding constant of 1.07×10(4)M(-1) at 298K. The primary binding pattern is determined by hydrogen bonding or van der Waals forces occurring in site I of HSA with ΔG°=-2.30×10(4)Jmol(-1), ΔS°=-233Jmol(-1)K(-1) and ΔH°=-9.23×10(4)Jmol(-1) at 298K. VB could slightly change the secondary structure and induce unfolding of the polypeptides of protein. The DSC results provide quantitative information on the effect of VB on the stability of serum albumin. It is shown that VB can efficiently bind with HSA and be transported to the focuses needed.
- Fortification of blood plasma from cancer patients with human serum albumin decreases the concentration of cisplatin-derived toxic hydrolysis products in vitro. [JOURNAL ARTICLE]
- Metallomics 2014 Sep 25.
While cisplatin (CP) is still one of the world's bestselling anticancer drugs, its intravenous administration is inherently associated with severe, dose limiting toxic side-effects. Although the molecular basis of the latter are not well understood, biochemical transformations of CP in blood and the interaction of the generated platinum species with plasma proteins likely play a critical role since these processes will ultimately determine which platinum-species reach the intended tumor cells as well as non-target cells. Compared to healthy subjects, cancer patients often have decreased plasma human serum albumin (HSA) concentrations. Little, however, is known about how the plasma HSA concentration will affect the metabolism of CP. To gain insight, we obtained blood plasma from healthy adults (n = 20, 42 ± 4 g HSA per L) and pediatric cancer patients (n = 11, 26 ± 7 g HSA per L). After the incubation of plasma at 37 °C, a pharmacologically relevant dose of CP was added and the Pt-distribution therein was determined by size-exclusion chromatography coupled on-line to an inductively coupled plasma atomic emission spectrometer. At the 2 h time point, a 5.9% increase of toxic CP-derived hydrolysis products was detected in pediatric cancer patient plasma, while 9.8% less platinum was protein bound compared to plasma from healthy controls. These in vitro results suggest that the elevated concentration of highly reactive free CP-derived hydrolysis products in plasma may cause the toxic side-effects in cancer patients. More importantly, the deliberate increase of the plasma HSA concentration in cancer patients prior to CP treatment would represent a simple strategy to possibly alleviate the fraction of patients that suffer from drug induced toxic side-effects.
- Systematic Review of Clinical Studies Examining Biomarkers of Brain Injury in Athletes Following Sports-Related Concussion. [JOURNAL ARTICLE]
- J Neurotrauma 2014 Sep 25.
The objective of this study was to systematically review clinical studies examining biofluid biomarkers of brain injury for concussion in athletes. Data Sources included PubMed®, MEDLINE® and the Cochrane Database from 1966 to October 2013. Studies were included if they recruited athletes participating in organized sports who experienced concussion or head injury during a sports-related activity and had brain injury biomarkers measured. Acceptable research designs included experimental, observational, and case control studies. Review articles, opinion papers and editorials were excluded. After title and abstract screening of potential articles, full texts were independently reviewed to identify articles that met inclusion criteria. A composite evidentiary table was then constructed and documented the study title, design, population, methods, sample size, outcome measures, and results. The search identified fifty two publications, of which thirteen were selected and critically reviewed. All of the included studies were prospective and were published either in or after the year 2000. Sports included boxing (6 studies), soccer (5 studies), running/jogging (2 studies), hockey (1 study), basketball (1 study), cycling (1 study), and swimming (1 study). The majority of studies (92%) had fewer than 100 patients. Three studies (23%) evaluated biomarkers in cerebrospinal fluid (CSF), one in both serum and CSF, and 10 (77%) in serum exclusively. There were eleven different biomarkers assessed including S100β, GFAP, NSE, tau, NFL, amyloid beta, BDNF, CK and h-FABP, prolactin, cortisol, and albumin. A handful of biomarkers showed correlation with number of hits to the head (soccer), acceleration/deceleration forces (jumps, collisions, and falls), post-concussive symptoms, trauma to the body versus the head, and dynamics of different sports. Although there are no validated biomarkers for concussion yet, there is potential for biomarkers to provide diagnostic, prognostic, and monitoring information post-injury. They could also be combined with neuroimaging to assess injury evolution and recovery.
- A Novel, Stable, Aqueous Glucagon Formulation Using Ferulic Acid as an Excipient. [JOURNAL ARTICLE]
- J Diabetes Sci Technol 2014 Sep 24.
Commercial glucagon is unstable due to aggregation and degradation. In closed-loop studies, it must be reconstituted frequently. For use in a portable pump for 3 days, a more stable preparation is required. At alkaline pH, curcumin inhibited glucagon aggregation. However, curcumin is not sufficiently stable for long-term use. Here, we evaluated ferulic acid, a stable breakdown product of curcumin, for its ability to stabilize glucagon. Ferulic acid-formulated glucagon (FAFG), composed of ferulic acid, glucagon, L-methionine, polysorbate-80, and human serum albumin in glycine buffer at pH 9, was aged for 7 days at 37°C. Glucagon aggregation was assessed by transmission electron microscopy (TEM) and degradation by high-performance liquid chromatography (HPLC). A cell-based protein kinase A (PKA) assay was used to assess in vitro bioactivity. Pharmacodynamics (PD) of unaged FAFG, 7-day aged FAFG, and unaged synthetic glucagon was determined in octreotide-treated swine. No fibrils were observed in TEM images of fresh or aged FAFG. Aged FAFG was 94% intact based on HPLC analysis and there was no loss of bioactivity. In the PD swine analysis, the rise over baseline of glucose with unaged FAFG, aged FAFG, and synthetic native glucagon (unmodified human sequence) was similar. After 7 days of aging at 37°C, an alkaline ferulic acid formulation of glucagon exhibited significantly less aggregation and degradation than that seen with native glucagon and was bioactive in vitro and in vivo. Thus, this formulation may be stable for 3-7 days in a portable pump for bihormonal closed-loop treatment of T1D.