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albumin human [keywords]
- Pharmacological and Molecular Effects of Platinum(II) Complexes Involving 7-Azaindole Derivatives. [Journal Article]
- PLoS One 2014; 9(3):e90341.
The in vitro antitumour activity studies on a panel of human cancer cell lines (A549, HeLa, G-361, A2780, and A2780R) and the combined in vivo and ex vivo antitumour testing on the L1210 lymphocytic leukaemia model were performed on the cis-[PtCl2(naza)2] complexes (1-3) involving the 7-azaindole derivatives (naza). The platinum(II) complexes showed significantly higher in vitro cytotoxic effects on cell-based models, as compared with cisplatin, and showed the ability to avoid the acquired resistance of the A2780R cell line to cisplatin. The in vivo testing of the complexes (applied at the same dose as cisplatin) revealed their positive effect on the reduction of cancerous tissues volume, even if it is lower than that of cisplatin, however, they also showed less serious adverse effects on the healthy tissues and the health status of the treated mice. The results of ex vivo assays revealed that the complexes 1-3 were able to modulate the levels of active forms of caspases 3 and 8, and the transcription factor p53, and thus activate the intrinsic (mitochondrial) pathway of apoptosis. The pharmacological observations were supported by both the histological and immunohistochemical evaluation of isolated cancerous tissues. The applicability of the prepared complexes and their fate in biological systems, characterized by the hydrolytic stability and the thermodynamic aspects of the interactions with cysteine, reduced glutathione, and human serum albumin were studied by the mass spectrometry and isothermal titration calorimetric experiments.
- Cell Behavior on Surface Modified Polydimethylsiloxane (PDMS). [JOURNAL ARTICLE]
- Macromol Biosci 2014 Mar 6.
Designing complex tissue culture systems requires cell alignment and directed extracellular matrix (ECM) and gene expression. Here, a micro-rough, polydimethylsiloxane (PDMS) surface, that also integrates a micro-pattern of 50 µm wide lines of fibronectin (FN) separated by 60 µm wide lines of bovine serum albumin (BSA), is developed. Human fibroblasts cultured on the rough, patterned substrate have aligned growth and a significant change in morphology when compared to cells on a flat, patterned surface. The rough PDMS topography significantly decreases cell area and induces the upregulation of several ECM related genes by two-fold when compared to cells cultured on flat PDMS. This study describes a simple surface engineering procedure for creating surface architecture for scaffolds to design and control the cell-surface interface.
- Diagnostic ability of (99m)Tc-HSA-DTPA scintigraphy in combination with SPECT/CT for gastrointestinal bleeding. [JOURNAL ARTICLE]
- Abdom Imaging 2014 Mar 6.
Gastrointestinal (GI) bleeding scintigraphy in combination with single-photon emission computed tomography/computed tomography (SPECT/CT) remains to be studied in detail. This study aimed to examine the diagnostic ability of this tool.GI bleeding scintigraphy using (99m)Tc-human serum albumin-diethylenetriaminepentaacetic acid was performed for 38 patients with suspected GI bleeding. Twenty-four patients were diagnosed using planar images alone (planar group) and 14 patients were diagnosed using planar images and additional SPECT/CT images (planar + SPECT/CT group). The diagnostic ability of each method was analyzed.GI bleeding was observed in 20 of the 38 patients. For the existence of GI bleeding, planar images alone showed a sensitivity of 70%, specificity of 93%, positive predictive value (PPV) of 88%, negative predictive value (NPV) of 81%, and an overall accuracy of 83%, whereas planar images + SPECT/CT showed a sensitivity of 100%, specificity of 75%, PPV of 91%, NPV of 100%, and an overall accuracy of 93%. The source of bleeding was accurately diagnosed in 50% in the planar group and 78% in the planar + SPECT/CT group. In the planar + SPECT/CT group, 44% of the evaluable patients showed correct localization of the source of GI bleeding by additional SPECT/CT images, although planar images only showed incorrect localization.GI bleeding scintigraphy in combination with SPECT/CT is a noninvasive and useful tool for the examination of GI bleeding.
- A 3D in vitro model of differentiated HepG2 cell spheroids with improved liver-like properties for repeated dose high-throughput toxicity studies. [JOURNAL ARTICLE]
- Arch Toxicol 2014 Mar 6.
Immortalized hepatocyte cell lines show only a weak resemblance to primary hepatocytes in terms of gene expression and function, limiting their value in predicting drug-induced liver injury (DILI). Furthermore, primary hepatocytes cultured on two-dimensional tissue culture plastic surfaces rapidly dedifferentiate losing their hepatocyte functions and metabolic competence. We have developed a three-dimensional in vitro model using extracellular matrix-based hydrogel for long-term culture of the human hepatoma cell line HepG2. HepG2 cells cultured in this model stop proliferating, self-organize and differentiate to form multiple polarized spheroids. These spheroids re-acquire lost hepatocyte functions such as storage of glycogen, transport of bile salts and the formation of structures resembling bile canaliculi. HepG2 spheroids also show increased expression of albumin, urea, xenobiotic transcription factors, phase I and II drug metabolism enzymes and transporters. Consistent with this, cytochrome P450-mediated metabolism is significantly higher in HepG2 spheroids compared to monolayer cultures. This highly differentiated phenotype can be maintained in 384-well microtiter plates for at least 28 days. Toxicity assessment studies with this model showed an increased sensitivity in identifying hepatotoxic compounds with repeated dosing regimens. This simple and robust high-throughput-compatible methodology may have potential for use in toxicity screening assays and mechanistic studies and may represent an alternative to animal models for studying DILI.
- Significant association of poor glycemic control with increased resistance in efferent arterioles - Study of inulin and para-aminohippuric acid clearance in humans. [JOURNAL ARTICLE]
- Diabetes Res Clin Pract 2014 Feb 11.
To examine whether glomerular hemodynamic parameters in humans are associated with glycemic control indices, by simultaneously measuring clearance of inulin (Cin) and para-aminohippuric acid (CPHA).Thirty-one subjects (age 55.4±14.7 years; 15 men and 16 women; 21 diabetics and 10 non-diabetics) were enrolled. Cin and CPAH were measured simultaneously. Afferent arteriolar resistance (Ra), efferent arteriolar resistance (Re), glomerular hydrostatic pressure (Pglo) and glomerular filtration fraction (FF) were calculated according to Gomez' formula.FF correlated significantly and positively with fasting plasma glucose (FPG), hemoglobin A1c (HbA1c) and glycated albumin (GA) (r=0.396, p=0.0303; r=0.587, p=0.0007; r=0.525, p=0.0070, respectively). Pglo correlated significantly and positively with FPG, HbA1c and GA (r=0.572, p=0.0008; r=0.535, p=0.0019; r=0.540, p=0.0053, respectively). Although there was no significant correlation between Ra and glycemic control indices, Re correlated significantly and positively with HbA1c and GA (r=0.499, p=0.0043; r=0.592, p=0.0018, respectively). FF, Pglo and Re were associated significantly with HbA1c and GA after adjustment for age.These results demonstrate, in humans, that poor glycemic control is associated with increased Re, but not Ra. It is suggested that increased Re causes increased Pglo, leading to increased FF. Thus, hemodynamic abnormalities with poor glycemic control may be related to glomerular hypertension in humans.
- Low copy target detection by Droplet Digital PCR through application of a novel open access bioinformatic pipeline, 'definetherain' [JOURNAL ARTICLE]
- J Virol Methods 2014 Mar 2.
- Compression garments to prevent delayed onset muscle soreness in soccer players. [Journal Article]
- Muscles Ligaments Tendons J 2013 Oct; 3(4):295-302.
The purpose of this study was to evaluate the use of a compression garment as DOMS prevention. This was accomplished by provoking a DOMS in 15 athletes, running on a treadmill at 73% of their maximal aerobic velocity, during 40 minutes with a 10% negative slope; wearing the compression garments on one thigh, protected thigh (PT), and not in the contralateral thigh, control thigh (CT). A clinical and MRI diagnosis of DOMS was performed. Biopsies in both vastus lateralis were done, and the amount and severity of the DOMS was estimated by measuring intracellular albumin, and lymphocytes CD3+ and neutrophils intra/interfibrilar infiltrates, 48h after the induced damaging exercise. There was less total injury in the PT than in the CT, a 26.7% average. These data indicate that this compression garment is an effective method to reduce the histological injury in DOMS.
- Regioselective Hydrolysis of Human Serum Albumin by Zr(IV) -Substituted Polyoxotungstates at the Interface of Positively Charged Protein Surface Patches and Negatively Charged Amino Acid Residues. [JOURNAL ARTICLE]
- Chemistry 2014 Mar 5.
Complexes comprising the Lewis acidic Zr(IV) metal and protein binding polyoxotungstate ligands of Lindqvist-, Keggin- and Wells-Dawson-type were found to region selectively hydrolyze human serum albumin at four distinct positions. Higher reactivities were found for structures with higher polyoxometalate charges and the cleavage positions were found in protein regions of mixed charge. Both findings suggest an electrostatic nature of the observed reactivity.
- Epitope mapping and targeted quantitation of the cardiac biomarker troponin by SID-MRM mass spectrometry. [JOURNAL ARTICLE]
- Proteomics 2014 Mar 4.
The absolute quantitation of the targeted protein using mass spectrometry provides a promising method to evaluate/verify biomarkers used in clinical diagnostics. In this study, a cardiac biomarker, troponin I (TnI), was used as a model protein for method development. The epitope peptide of TnI was characterized by epitope excision followed with LC/MS/MS method and acted as the surrogate peptide for the targeted protein quantitation. The MRM based mass spectrometry assay using a stable internal standard that improved the selectivity, specificity, and sensitivity of the protein quantitation. Also, plasma albumin depletion and affinity enrichment of TnI by anti-TnI mAb coated microparticles reduced the sample complexity, enhanced the dynamic range, and further improved the detecting sensitivity of the targeted protein in the biological matrix. Therefore, quantitation of troponin I, a low abundant protein in human plasma, has demonstrated the applicability of the targeted protein quantitation strategy through its epitope peptide determined by epitope mapping method. This article is protected by copyright. All rights reserved.
- Human serum albumin binding to silica nanoparticles - effect of protein fatty acid ligand. [JOURNAL ARTICLE]
- Phys Chem Chem Phys 2014 Mar 5.
Neutron reflectivity shows that fatted (F-HSA) and defatted (DF-HSA) versions of human serum albumin behave differently in their interaction with silica nanoparticles premixed in buffer solutions although these proteins have close to the same surface excess when the silica is absent. In both cases a silica containing film is quickly established at the air-water interface. This film is stable for F-HSA at all relative protein-silica concentrations measured. This behaviour has been verified for two small silica nanoparticle radii (42 Å and 48 Å). Contrast variation and co-refinement have been used to find the film composition for the F-HSA-silica system. The film structure changes with protein concentration only for the DF-HSA-silica system. The different behaviour of the two proteins is interpreted as a combination of three factors: increased structural stability of F-HSA induced by the fatty acid ligand, differences in the electrostatic interactions, and the higher propensity of defatted albumin to self-aggregate. The interfacial structures of the proteins alone in buffer are also reported and discussed.