Showing papers on "Serum albumin published in 2017"
TL;DR: Higher transfer efficiencies of PFASs were associated with advancing maternal age, higher education, and lower glomerular filtration rate (GFR), and Physiological factors were observed for the first time to play critical roles in PFAS placental transfer.
Abstract: Per- and polyfluoroalkyl substances (PFASs) may cross the placental barrier and lead to fetal exposure. However, little is known about the factors that influence maternal-fetal transfer of these chemicals. PFAS concentrations were analyzed in 100 paired samples of human maternal sera collected in each trimester and cord sera at delivery; these samples were collected in Wuhan, China, 2014. Linear regression was used to estimate associations of transfer efficiencies with factors. Chlorinated polyfluorinated ether sulfonates (Cl-PFAESs, 6:2 and 8:2) were frequently detected (>99%) in maternal and cord sera. A significant decline in PFAS levels during the three trimesters was observed. A U-shape trend for transfer efficiency with increasing chain length was observed for both carboxylates and sulfonates. Higher transfer efficiencies of PFASs were associated with advancing maternal age, higher education, and lower glomerular filtration rate (GFR). Cord serum albumin was a positive factors for higher transfer efficiency (increased 1.1-4.1% per 1g/L albumin), whereas maternal serum albumin tended to reduce transfer efficiency (decreased 2.4-4.3% per 1g/L albumin). Our results suggest that exposure to Cl-PFAESs may be widespread in China. The transfer efficiencies among different PFASs were structure-dependent. Physiological factors (e.g., GFR and serum albumin) were observed for the first time to play critical roles in PFAS placental transfer.
168 citations
TL;DR: An easily synthesized albumin-binding ligand based on a peptide-fatty acid chimera that has a high affinity for human albumin is developed that prolongs the elimination half-life of cyclic peptides in rats 25-fold and substantially broadens the application range of peptides as therapeutics.
Abstract: A major challenge for the application of peptide therapeutics is their short half-life in vivo . Here, the authors design peptide-fatty acid chimeras bearing an engineered linker that promotes albumin binding and allows longer circulation times of therapeutic peptid…
100 citations
TL;DR: An oxaliplatin-based platinum(iv) drug which specifically binds to albumin after i.v. application led to several complete responses in tumor-bearing mice.
Abstract: The design of targeted platinum(iv) prodrugs is a very promising approach to enhance the low selectivity of platinum(ii) drugs towards cancerous tissue in order to reduce the impact on healthy tissue and, consequently, the often severe side-effects. Herein, we report a set of mono-functionalized cis- and oxaliplatin-based platinum(iv) complexes bearing a maleimide moiety, which allows selective binding to serum albumin in the bloodstream. This leads not only to a prolonged plasma half-life by avoidance of fast renal clearance, but also to preferential accumulation of the drug in the tumor tissue due to the EPR-effect. Additionally, analogous succinimide-functionalized derivatives were prepared to verify the influence of the maleimide moiety. First experiments showed that all the maleimide compounds are stable and also possess good albumin-binding properties in whole serum. Further analytical studies on in vivo samples proved the highly increased plasma half-life, as well as tumor accumulation of the maleimide-functionalized substances. In vivo antitumor experiments with CT-26-bearing mice showed that, in contrast to the cisplatin derivatives, the oxaliplatin-based complexes had exceptionally better activity than the free drug resulting in the cure of the majority of treated mice. Subsequent analysis suggested that a distinctly faster reduction as well as reduced tumor accumulation of the cisplatin derivative might explain the worse performance compared to the oxaliplatin(iv) complexes. Taken together, a novel lead platinum(iv) complex with outstanding antitumor activity is presented, which will now be further developed towards clinical phase I trials.
94 citations
TL;DR: The strong, unexplained correlation between minor decreases in CP and subsequent mortality in seemingly healthy individuals raises the question of whether subclinical PLE could account for the decreased CP and, if so, could the mechanism responsible for PLE play a role in the increased mortality.
Abstract: Protein losing enteropathy (PLE) has been associated with more than 60 different conditions, including nearly all gastrointestinal diseases (Crohn's disease, celiac, Whipple's, intestinal infections, and so on) and a large number of non-gut conditions (cardiac and liver disease, lupus, sarcoidosis, and so on). This review presents the first attempt to quantitatively understand the magnitude of the PLE in relation to the associated pathology for three different disease categories: 1) increased lymphatic pressure (e.g., lymphangiectasis); 2) diseases with mucosal erosions (e.g., Crohn's disease); and 3) diseases without mucosal erosions (e.g., celiac disease). The PLE with lymphangiectasis results from rupture of the mucosal lymphatics, with retrograde drainage of systemic lymph into the intestinal lumen with the resultant loss of CD4 T cells, which is diagnostic. Mucosal erosion PLE results from macroscopic breakdown of the mucosal barrier, with the epithelial capillaries becoming the rate-limiting factor in albumin loss. The equation derived to describe the relationship between the reduction in serum albumin (CP) and PLE indicates that gastrointestinal albumin clearance must increase by at least 17 times normal to reduce the CP by half. The strengths and limitations of the two quantitative measures of PLE (51Cr-albumin or α1-antitrypsin [αAT] clearance) are reviewed. αAT provides a simple quantitative diagnostic test that is probably underused clinically. The strong, unexplained correlation between minor decreases in CP and subsequent mortality in seemingly healthy individuals raises the question of whether subclinical PLE could account for the decreased CP and, if so, could the mechanism responsible for PLE play a role in the increased mortality? A large-scale study correlating αAT clearance with serum albumin concentrations will be required in order to determine the role of PLE in the regulation of the serum albumin concentration of seemingly healthy subjects.
92 citations
TL;DR: MCO-Ci Dialyzers modulate inflammation in chronic HD patients to a greater extent compared to High-flux dialyzers and Transcription of pro-inflammatory cytokines in peripheral leukocytes is markedly reduced and removal of soluble mediators is enhanced with MCO dialysis.
Abstract: Background To increase the removal of middle-sized uremic toxins a new membrane with enhanced permeability and selectivity, called Medium Cut-Off membrane (MCO-Ci) has been developed that at the same time ensures the retention of albumin. Because many middle-sized substances may contribute to micro-inflammation we hypothesized that the use of MCO-Ci influences the inflammatory state in hemodialysis patients. Methods The randomized crossover trial in 48 patients compared MCO-Ci dialysis to High-flux dialysis of 4 weeks duration each plus 8 weeks extension phase. Primary endpoint was the gene expression of TNF-α and IL-6 in peripheral blood mononuclear cells (PBMCs), secondary endpoints were plasma levels of specified inflammatory mediators and cytokines. Results After four weeks of MCO-Ci the expression of TNF-α mRNA (Relative quantification (RQ) from 0.92 ± 0.34 to 0.75 ± 0.31, -18.5%, p<0.001)-α and IL-6 mRNA (RQ from 0.78 ± 0.80 to 0.60 ± 0.43, -23.1%, p<0.01) was reduced to a significantly greater extent than with High-flux dialyzers (TNF mRNA-RQ: -14.3%; IL-6 mRNA-RQ: -3.5%). After retransformation of logarithmically transformed data, measurements after MCO were reduced to 82% of those after HF (95% CI 74%–91%). 4 weeks use of MCO-Ci resulted in long-lasting change in plasma levels of several cytokines and other substances with a significant decrease for sTNFR1, kappa and lambda free light chains, urea and an increase for Lp-PLA2 (PLA2G7) compared to High-flux. Albumin levels dropped significantly after 4 weeks of MCO dialysis but increased after additional 8 weeks of MCO dialysis. Twelve weeks treatment with MCO-Ci was well tolerated regarding the number of (S)AEs. In the extension period levels of CRP, TNF-α-mRNA and IL-6 mRNA remained stable in High-flux as well as in MCO-Ci. Conclusions MCO-Ci dialyzers modulate inflammation in chronic HD patients to a greater extent compared to High-flux dialyzers. Transcription of pro-inflammatory cytokines in peripheral leukocytes is markedly reduced and removal of soluble mediators is enhanced with MCO dialysis. Serum albumin concentrations stabilize after an initial drop. These results encourage further trials with longer treatment periods and clinical endpoints.
88 citations
TL;DR: Systemic inflammation impairs blood-brain barrier (BBB) in preclinical models and the diseased BBB has an increased susceptibility to systemic inflammation.
Abstract: The blood-brain barrier (BBB) plays an important role in the clinical expression of neuropsychiatric symptoms during systemic illness in health and neurological disease. Evidence from in vitro and preclinical in vivo studies indicate that systemic inflammation impairs blood-brain barrier function. In order to investigate this hypothesis, we evaluated the association between systemic inflammatory markers (leucocytes, erythrocyte sedimentation rate and C-reactive protein) and BBB function (cerebrospinal fluid/serum albumin ratio) in 1273 consecutive lumbar punctures. In the absence of cerebrospinal fluid (CSF) abnormality, systemic inflammation did not affect the CSF/serum albumin ratio. When CSF abnormality was present, systemic inflammation significantly predicted the CSF/serum albumin ratio. Amongst the systemic inflammatory markers, C-reactive protein was the predominant driver of this effect. Temporal analysis in this association study suggested causality. In conclusion, the diseased BBB has an increased susceptibility to systemic inflammation.
87 citations
TL;DR: The history of Alb as a target protein for adduction to environmental and dietary genotoxicants, pesticides, and herbicides, common classes of medicinal drugs, and endogenous electrophiles, and the emerging analytical mass spectrometry technologies to identify Alb-toxicant adducts in humans are highlighted.
Abstract: Serum albumin (Alb) is the most abundant protein in blood plasma. Alb reacts with many carcinogens and/or their electrophilic metabolites. Studies conducted over 20 years ago showed that Alb forms adducts with the human carcinogens aflatoxin B1 and benzene, which were successfully used as biomarkers in molecular epidemiology studies designed to address the role of these chemicals in cancer risk. Alb forms adducts with many therapeutic drugs or their reactive metabolites such as β-lactam antibiotics, acetylsalicylic acid, acetaminophen, nonsteroidal anti-inflammatory drugs, chemotherapeutic agents, and antiretroviral therapy drugs. The identification and characterization of the adduct structures formed with Alb have served to understand the generation of reactive metabolites and to predict idiosyncratic drug reactions and toxicities. The reaction of candidate drugs with Alb is now exploited as part of the battery of screening tools to assess the potential toxicities of drugs. The use of gas chromatography-...
86 citations
TL;DR: It can be concluded that, SP supplementation attenuated the toxic effect of DZN toxicity in Nile tilapia through improving liver and kidney functions with a significant enhancement of tissue antioxidant status.
84 citations
TL;DR: A meta-analysis demonstrated that an albumin level <3.5 g/dL had an almost 2.5 fold increased risk of SSI in orthopaedics, although this conclusion requires well-designed prospective cohort studies to be confirmed further.
Abstract: Surigical site infection has been a challenge for surgeons for many years, the prevalence of serum albumin 3.5 was 2.39 (95 % CI 1.57 3.64), which was statistically significant (z = 4.06, P < 0.0001). Heterogeneity were found in the pooled MD of albumin and in the pooled RR for infection (P = 0.05, I2 = 61 % and P = 0.003, I2 = 68 %). No publication bias occurred based on two basically symmetrical funnel plots. Our meta-analysis demonstrated that an albumin level <3.5 g/dL had an almost 2.5 fold increased risk of SSI in orthopaedics, although this conclusion requires well-designed prospective cohort studies to be confirmed further.
84 citations
TL;DR: Track the concentration-dependent influence of albumin on blood coagulation in vitro found albumin exerted significant anticoagulant action, which might contribute to the frequently occurring venous thromboembolism.
Abstract: Albumin is the most abundant plasma protein. Critical illness is often associated with altered, predominately decreased, serum albumin levels. This hypoalbuminaemia is usually corrected by administration of exogenous albumin. This study aimed to track the concentration-dependent influence of albumin on blood coagulation in vitro. Whole blood (WB) samples from 25 volunteers were prepared to contain low (19.3 ± 7.7 g/L), physiological (45.2 ± 7.8 g/L), and high (67.5 ± 18.1 g/L) levels of albumin. Haemostatic profiling was performed using a platelet function analyzer (PFA) 200, impedance aggregometry, a Cone and Platelet analyzer (CPA), calibrated automated thrombogram, and thrombelastometry (TEM). Platelet aggregation-associated ATP release was assessed via HPLC analysis. In the low albumin group, when compared to the physiological albumin group, we found: i) shortened PFA 200-derived closure times indicating increased primary haemostasis; ii) increased impedance aggregometry-derived amplitudes, slopes, ATP release, as well as CPA-derived average size indicating improved platelet aggregation; iii) increased TEM-derived maximum clot firmness and alpha angles indicating enhanced clot formation. TEM measurements indicated impaired clot formation in the high albumin group compared with the physiological albumin group. Thus, albumin exerted significant anticoagulant action. Therefore, low albumin levels, often present in cancer or critically ill patients, might contribute to the frequently occurring venous thromboembolism.
83 citations
TL;DR: CSF/serum albumin ratio correlated with CSF neurofilament light in LAD, MIX, VaD, and other groups but not with AD biomarkers, which suggests that BBB leakage is common in dementias.
TL;DR: Serum albumin level ≤3.50 g/dl is an independent predictor of new-onset heart failure and in-hospital mortality in patients with ACS and the inflammatory state may be a mechanism underlying hypoalbuminemia in this clinical setting.
Abstract: Hypoalbuminemia is a long-term risk factor for incident of both myocardial infarction and heart failure. We assessed whether serum albumin levels at admission are associated with new-onset heart failure and in-hospital mortality in patients with acute coronary syndrome (ACS). The study included 7,192 patients with ACS with no previous history of heart failure. Patients were divided into quartiles according to serum albumin levels (Q1: ≤3.50 g/dl; Q2: 3.51 to 3.80 g/dl; Q3: 3.81 to 4.08 g/dl; and Q4: >4.08 g/dl). Logistic regressions were used to explore the relations among serum albumin quartiles, new-onset heart failure, and in-hospital mortality. Serum albumin levels were negatively correlated with both high-sensitivity C-reactive protein and white blood cell count at admission. The unadjusted rate for both new-onset heart failure (37.7%, 20.2%, 14.7%, and 11.4% for Q1, Q2, Q3, and Q4, respectively; p
TL;DR: It is demonstrated that mice with global or liver-specific FcRn deletion exhibit hypoalbuminemia, albumin loss into the bile, and increased albumin levels in the hepatocyte, and that the main function of hepatic F cRn is to direct albumin into the circulation, thereby also increasing hepatocyte sensitivity to toxicity.
Abstract: The neonatal crystallizable fragment receptor (FcRn) is responsible for maintaining the long half-life and high levels of the two most abundant circulating proteins, albumin and IgG. In the latter case, the protective mechanism derives from FcRn binding to IgG in the weakly acidic environment contained within endosomes of hematopoietic and parenchymal cells, whereupon IgG is diverted from degradation in lysosomes and is recycled. The cellular location and mechanism by which FcRn protects albumin are partially understood. Here we demonstrate that mice with global or liver-specific FcRn deletion exhibit hypoalbuminemia, albumin loss into the bile, and increased albumin levels in the hepatocyte. In vitro models with polarized cells illustrate that FcRn mediates basal recycling and bidirectional transcytosis of albumin and uniquely determines the physiologic release of newly synthesized albumin into the basal milieu. These properties allow hepatic FcRn to mediate albumin delivery and maintenance in the circulation, but they also enhance sensitivity to the albumin-bound hepatotoxin, acetaminophen (APAP). As such, global or liver-specific deletion of FcRn results in resistance to APAP-induced liver injury through increased albumin loss into the bile and increased intracellular albumin scavenging of reactive oxygen species. Further, protection from injury is achieved by pharmacologic blockade of FcRn–albumin interactions with monoclonal antibodies or peptide mimetics, which cause hypoalbuminemia, biliary loss of albumin, and increased intracellular accumulation of albumin in the hepatocyte. Together, these studies demonstrate that the main function of hepatic FcRn is to direct albumin into the circulation, thereby also increasing hepatocyte sensitivity to toxicity.
TL;DR: Glycosylated platinum(IV) complexes were synthesized as substrates for GLUTs and OCTs for the first time, and the cytotoxicity and detailed mechanism were determined in vitro and in vivo.
Abstract: Glycosylated platinum(IV) complexes were synthesized as substrates for GLUTs and OCTs for the first time, and the cytotoxicity and detailed mechanism were determined in vitro and in vivo. Galactoside Pt(IV), glucoside Pt(IV), and mannoside Pt(IV) were highly cytotoxic and showed specific cancer-targeting properties in vitro and in vivo. Glycosylated platinum(IV) complexes 5, 6, 7, and 8 (IC50 0.24–3.97 μM) had better antitumor activity of nearly 166-fold higher than the positive controls cisplatin (1a), oxaliplatin (3a), and satraplatin (5a). The presence of a hexadecanoic chain allowed binding with human serum albumin (HSA) for drug delivery, which not only enhanced the stability of the inert platinum(IV) prodrugs but also decreased their reduction by reductants present in human whole blood. Their preferential accumulation in cancer cells compared to noncancerous cells (293T and 3T3 cells) suggested that they were potentially safe for clinical therapeutic use.
TL;DR: Levels of serum albumin have recently emerged, together with C-reactive protein, as an important prognostic indicator for hepatocellular carcinoma, and results indicate that in addition to its role as a monitor of systemic inflammation, albumin may have a direct role in HCC growth inhibition, either through modulation of α-fetoprotein or through its actions on growth-controlling kinases.
Abstract: Objective: Levels of serum albumin have recently emerged, together with C-reactive protein, as an important prognostic indicator for hepatocellular carcinoma (HCC
TL;DR: It is demonstrated that microcapsules released Lf in small intestine allowing 6.5 times higher concentration than in control group dosed with the same amount of free Lf.
Abstract: Lactoferrin (Lf) has considerable potential as a functional ingredient in food, cosmetic and pharmaceutical applications. However, the bioavailability of Lf is limited as it is susceptible to digestive enzymes in gastrointestinal tract. The shells comprising alternate layers of bovine serum albumin (BSA) and tannic acid (TA) were tested as Lf encapsulation system for oral administration. Lf absorption by freshly prepared porous 3 μm CaCO3 particles followed by Layer-by-Layer assembly of the BSA-TA shells and dissolution of the CaCO3 cores was suggested as the most efficient and harmless Lf loading method. The microcapsules showed high stability in gastric conditions and effectively protected encapsulated proteins from digestion. Protective efficiency was found to be 76 ± 6% and 85 ± 2%, for (BSA-TA)4 and (BSA-TA)8 shells, respectively. The transit of Lf along the gastrointestinal tract (GIT) of mice was followed in vivo and ex vivo using NIR luminescence. We have demonstrated that microcapsules released Lf in small intestine allowing 6.5 times higher concentration than in control group dosed with the same amount of free Lf. Significant amounts of Lf released from microcapsules were then absorbed into bloodstream and accumulated in liver. Suggested encapsulation system has a great potential for functional foods providing lactoferrin.
TL;DR: In this paper, the van der Waals force and hydrogen bonding were the main intermolecular forces stabilizing the complex in a spontaneous association reaction, and the number of binding sites for juglone on serum albumins was determined to be equal to one.
Abstract: The interaction between juglone at the concentration range of 10–110 µM and bovine serum albumin (BSA) or human serum albumin (HSA) at the constant concentration of 11 µM was investigated by fluorescence and UV absorption spectroscopy under physiological-like condition. Performing the experiments at different temperatures showed that the fluorescence intensity of BSA/HSA was decreased in the presence of juglone by a static quenching mechanism due to the formation of the juglone–protein complex. The binding constant for the interaction was in the order of 103 M−1, and the number of binding sites for juglone on serum albumins was determined to be equal to one. The thermodynamic parameters including enthalpy (ΔH), entropy (ΔS) and Gibb’s free energy (ΔG) changes were obtained by using the van’t Hoff equation. These results indicated that van der Waals force and hydrogen bonding were the main intermolecular forces stabilizing the complex in a spontaneous association reaction. Moreover, the interaction of BSA/HSA with juglone was verified by UV absorption spectra and molecular docking. The results of synchronous fluorescence, UV–visible and CD spectra demonstrated that the binding of juglone with BSA/HSA induces minimum conformational changes in the structure of albumins. The increased binding affinity of juglone to albumin observed in the presence of site markers (digoxin and ibuprofen) excludes IIA and IIIA sites as the binding site of juglone. This is partially in agreement with the results of molecular docking studies which suggests sub-domain IA of albumin as the binding site.
TL;DR: Poor nutritional status in patients with head and neck squamous cell carcinoma is associated with tumor progression and survival and prognostic value of nutritional and hematological markers in patients who received definitive treatments is examined.
Abstract: Objectives/Hypothesis
Poor nutritional status in patients with head and neck squamous cell carcinoma (HNSCC) is associated with tumor progression and survival This study examined the prognostic value of nutritional and hematological markers in patients with HNSCC who received definitive treatments
Study Design
A prospective observational cohort study
Methods
This study included 338 consecutive patients who underwent surgery and/or radiotherapy/chemoradiotherapy for treatment-naive HNSCC Body weight and nutritional and hematological parameters were regularly measured before and after treatment Univariate and multivariate analyses using Cox proportional hazards models were performed to identify factors associated with disease-free survival (DFS), cancer-specific survival (CSS), and overall survival (OS)
Results
Body weight, serum total protein and albumin levels, and hematological variables significantly decreased after treatment Univariate analyses illustrated that age, tumor site, T and N classifications, overall stage, pretreatment serum albumin (<35 g/dL) and hemoglobin (<12 g/dL) levels, and neutrophil-lymphocyte ratio were significantly associated with DFS, CSS, and OS (all P < 05) Multivariate analyses identified age, tumor site, N classification, and pretreatment albumin levels as independent predictors of DFS, CSS, and OS (all P < 05) Patients with low serum albumin levels prior to treatment experienced approximately sixfold increases in the risks of tumor progression and cancer-specific and overall mortality compared to the findings in their counterparts
Conclusions
Our results suggest that pretreatment serum albumin levels predict DFS, CSS, and OS in patients who received definitive treatment for HNSCC These findings might help to predict treatment outcome and guide nutritional intervention in patients with HNSCC
Level of Evidence
2b Laryngoscope, 2017
TL;DR: It is indicated that higher levels of albumin and uric acid are related to lower risks of breast cancer and cancer mortality and further studies are needed to assess whether the observed associations are causal.
Abstract: It has long been proposed that albumin, bilirubin and uric acid may inhibit cancer development due to their anti-oxidative properties. However, there is a lack of population-based studies on blood levels of these molecules and cancer risk. Associations between pre-diagnostic serum albumin, bilirubin and uric acid and the risks of common cancers as well as cancer death in the EPIC-Heidelberg cohort were evaluated by multivariable Cox regression analyses. A case–cohort sample including a random subcohort (n=2739) and all incident cases of breast (n=627), prostate (n=554), colorectal (n=256), and lung cancer (n=195) as well as cancer death (n=761) that occurred between baseline (1994–1998) and 2009 was used. Albumin levels were inversely associated with breast cancer risk (hazard ratioQuartile 4 vs Quartile 1 (95% CI): 0.71 (0.51, 0.99), Plinear trend=0.004) and overall cancer mortality (HRQ4 vs Q1 (95% CI): 0.64 (0.48, 0.86), Plinear trend<0.001) after multivariable adjustment. Uric acid levels were also inversely associated with breast cancer risk (HRQ4 vs Q1 (95% CI): 0.72 (0.53, 0.99), Plinear trend=0.043) and cancer mortality (HRQ4 vs Q1 (95% CI): 0.75 (0.58, 0.98), Plinear trend=0.09). There were no significant associations between albumin or uric acid and prostate, lung and colorectal cancer. Serum bilirubin was not associated with any cancer end point. The present findings indicate that higher levels of albumin and uric acid are related to lower risks of breast cancer and cancer mortality. Further studies are needed to assess whether the observed associations are causal.
TL;DR: Low serum albumin concentration (<3.5g/dL) worsens prognosis of patients with stable CHD, and is associated with an increased risk of all-cause mortality and hard CV events.
TL;DR: Studies on the interaction of selected boron clusters and their derivatives with serum albumin, the most abundant protein in mammalian blood, showed that metallacarboranes have the strongest interaction with albumin among the tested clusters.
Abstract: Boron clusters are polyhedral boron hydrides with unique properties, and they are becoming increasingly widely used in biology and medicine, including for boron neutron capture therapy (BNCT) of cancers and in the design of novel bioactive molecules and potential drugs. Among boron cluster types, icosahedral boranes, carboranes, and metallacarboranes are particularly interesting, and there is a need for basic studies on their interaction with biologically important molecules, such as proteins. Herein, we report studies on the interaction of selected boron clusters and their derivatives with serum albumin, the most abundant protein in mammalian blood. The interaction of boron clusters with albumin was examined by fluorescence quenching, circular dichroism, dynamic and static light scattering measurements and MALDI-TOF mass spectrometry. Our results showed that metallacarboranes have the strongest interaction with albumin among the tested clusters. The observed strength of boron cluster interactions with albumin decreases in order: metallacarboranes [M(C2B9H11)2]- > carboranes (C2B10H12) >> dodecaborate anion [B12H12]2-. Metallacarboranes first specifically interact with the binding cavity of albumin and then, with increasing compound concentrations, interact non-specifically with the protein surface. These findings can be of importance and are useful in the development of new bioactive compounds that contain boron clusters.
TL;DR: Preoperative serum albumin level was an important prognostic factor for overall survival and recurrence-free survival in patients with resected non-small cell lung cancer.
TL;DR: A decreased concentration of serum albumin ≥10 g/L on POD 1 was associated with a threefold increased risk of overall postoperative complications and may thus be used to identify patients at risk.
Abstract: Objective To test postoperative serum albumin drop (ΔAlb) as a marker of surgical stress response and early predictor of clinical outcomes. Design Prospective cohort study (NCT02356484). Albumin was prospectively measured in 138 patients undergoing major abdominal surgery. Blood samples were collected before surgery and on postoperative days 0, 1 2 and 3. ΔAlb was compared to the modified estimation of physiologic ability and surgical stress (mE-PASS) score and correlated to the performances of C reactive protein (CRP), procalcitonin (PCT) and lactate (LCT). Postoperative outcomes were postoperative complications according to Clavien classification and Comprehensive Complication Index (CCI), and length of hospital stay (LoS). Setting Department of abdominal surgery in a European tertiary centre. Participants Adult patients undergoing elective major abdominal surgery, with anticipated duration ≥2 hours. Patients on immunosuppressive or antibiotic treatments before surgery were excluded. Results The level of serum albumin rapidly dropped after surgery. ΔAlb correlated to the mE-PASS score (r=0.275, p=0.01) and to CRP increase (r=0.536, p Conclusions Early postoperative decrease of serum albumin correlated with the extent of surgery, its metabolic response and with adverse outcomes such as complications and length of stay. A decreased concentration of serum albumin ≥10 g/L on POD 1 was associated with a threefold increased risk of overall postoperative complications and may thus be used to identify patients at risk.
TL;DR: It is indicated that low serum albumin levels correlate with increased parameter measures of HCC aggressiveness, in addition to their role as a monitor of systemic inflammation.
Abstract: BackgroundSerum albumin levels have been shown to have prognostic significance in hepatocellular carcinoma (HCC), as part of an inflammatory index. The aim of this study was to examine the possible relationship of serum albumin levels to parameters of HCC aggressiveness.MethodsA large HCC patient cohort was retrospectively examined, and the possible relationships of albumin levels to tumor diameter, multifocality, portal vein thrombosis (PVT) and α-fetoprotein levels were examined.ResultsHCC patients with lower serum albumin levels had significantly larger maximum tumor diameters, greater prevalence of PVT, increased tumor multifocality and higher α-fetoprotein levels, than HCC patients with higher albumin levels. A correlation was found between levels of these tumor parameters and serum albumin levels.ConclusionsThese results indicate that low serum albumin levels correlate with increased parameter measures of HCC aggressiveness, in addition to their role as a monitor of systemic inflammation. Decreased ...
TL;DR: A low serum albumin is independently associated with an increased risk of developing of persistent organ failure and death in acute pancreatitis and may also be useful for the prediction of the severity of acute Pancreatitis.
Abstract: Background and Aims. To investigate the association between serum albumin levels within 24 hrs of patient admission and the development of persistent organ failure in acute pancreatitis. Methods. A total of 700 patients with acute pancreatitis were enrolled. Multivariate logistic regression and subgroup analysis determined whether decreased albumin was independently associated with persistent organ failure and mortality. The diagnostic performance of serum albumin was evaluated by the area under Receiver Operating Characteristic (ROC) curves. Results. As levels of serum albumin decrease, the risk of persistent organ failure significantly increases ( ). The incidence of organ failure was 3.5%, 10.6%, and 41.6% in patients with normal albumin and mild and severe hypoalbuminaemia, respectively. Decreased albumin levels were also proportionally associated with prolonged hospital stay ( ) and the risk of death ( ). Multivariate analysis suggested that biliary etiology, chronic concomitant diseases, hematocrit, blood urea nitrogen, and the serum albumin level were independently associated with persistent organ failure. Blood urea nitrogen and the serum albumin level were also independently associated with mortality. The area under ROC curves of albumin for predicting organ failure and mortality were 0.78 and 0.87, respectively. Conclusion. A low serum albumin is independently associated with an increased risk of developing of persistent organ failure and death in acute pancreatitis. It may also be useful for the prediction of the severity of acute pancreatitis.
TL;DR: Information is given on the substrate specificity of albumin and the possibility of its affiliation to certain classes in the nomenclature of enzymes is considered, which could help in the development of new types of antidotes.
Abstract: The albumin molecule, in contrast to many other plasma proteins, is not covered with a carbohydrate moiety and can bind and transport various molecules of endogenous and exogenous origin. The enzymatic activity of albumin, the existence of which many scientists perceive skeptically, is much less studied. In toxicology, understanding the mechanistic interactions of organophosphates with albumin is a special problem, and its solution could help in the development of new types of antidotes. In the present work, the history of the issue is briefly examined, then our in silico data on the interaction of human serum albumin with soman, as well as comparative in silico data of human and bovine serum albumin activities in relation to paraoxon, are presented. Information is given on the substrate specificity of albumin and we consider the possibility of its affiliation to certain classes in the nomenclature of enzymes.
TL;DR: In NMO, increased CSF MMP-2, likely induced by interleukin-6 signaling, may disrupt the BBB and enable serum anti-AQP-4 antibodies migration into the central nervous system (CNS).
Abstract: Background:Inflammation in neuromyelitis optica (NMO) is triggered by a serum antibody against the aquaporin-4 (AQP4). This process requires antibody penetration of the blood–brain barrier (BBB), but the mechanisms for BBB disruption in NMO remain unknown.Objective:We examined whether changes in cerebrospinal fluid (CSF) and serum matrix metalloproteinases (MMPs), tissue inhibitors of metalloproteinases (TIMPs), and cytokines are associated with BBB disruption in NMO.Methods:The concentrations 9 MMPs, 4 TIMPs, and 14 cytokines were measured by multiplex assay in CSF and serum samples from 29 NMO patients, 29 relapsing-remitting multiple sclerosis (MS) patients, and 27 patients with other neurological disorders. We also performed immunohistochemistry for MMP-2 and TIMP-1 expression in post-mortem brain tissues from NMO patients.Results:NMO patients exhibited significantly elevated MMP-2, TIMP-1, interleukin-6, and MMP-2/TIMP-2 ratio in CSF (but not sera) than the other groups. The CSF/serum albumin ratio, ...
TL;DR: Higher dietary protein intake represented by nPCR and its changes over time appear to be associated with increased serum albumin levels and greater survival among incident hemodialysis patients.
Abstract: Background and objectives There are inconsistent reports on the association of dietary protein intake with serum albumin and outcomes among patients on hemodialysis. Using a new normalized protein catabolic rate (nPCR) variable accounting for residual renal urea clearance, we hypothesized that higher baseline nPCR and rise in nPCR would be associated with higher serum albumin and better survival among incident hemodialysis patients. Design, setting, participants, & measurements Among 36,757 incident hemodialysis patients in a large United States dialysis organization, we examined baseline and change in renal urea clearance–corrected nPCR as a protein intake surrogate and modeled their associations with serum albumin and mortality over 5 years (1/2007–12/2011). Results Median nPCRs with and without accounting for renal urea clearance at baseline were 0.94 and 0.78 g/kg per day, respectively (median within-patient difference, 0.14 [interquartile range, 0.07–0.23] g/kg per day). During a median follow-up period of 1.4 years, 8481 deaths were observed. Baseline renal urea clearance–corrected nPCR was associated with higher serum albumin and lower mortality in the fully adjusted model (Ptrend Conclusions Among incident hemodialysis patients, higher dietary protein intake represented by nPCR and its changes over time appear to be associated with increased serum albumin levels and greater survival. nPCR may be underestimated when not accounting for renal urea clearance. Compared with the conventional nPCR, renal urea clearance–corrected nPCR may be a better marker of mortality.
TL;DR: The mechanism of interaction between cephalosporin antibiotic-ceftazidime (CFD) and human serum albumin (HSA) is explored by spectroscopic and molecular docking studies and confirms that CFD increases the alpha helical secondary structure as well as altered the environment around tryptophan and tyrosine.
TL;DR: These domains bind serum albumin of different species with nanomolar affinities, and have significantly improved pharmacokinetic properties both in mouse and cynomolgus monkey compared to non-serum albumin-binding DARPin® domains, indicating that pharmacokinetics properties in the range of monoclonal antibodies can be achieved with DARPin®, drug candidates.
Abstract: A long systemic half-life is key for therapeutic proteins. To that end we have generated serum albumin-binding designed ankyrin repeat domains. These domains bind serum albumin of different species with nanomolar affinities, and have significantly improved pharmacokinetic properties both in mouse and cynomolgus monkey compared to non-serum albumin-binding DARPin® domains. In addition, they exhibit high thermal stability and long storage stability, which is an essential feature for their use in drug development. Covalently linking a serum albumin-binding DARPin® domain to domains with other target specificities results in improvements of multiple orders of magnitude in exposure and terminal half-life, both in mouse and cynomolgus monkey. Pharmacokinetic assessment of such constructs revealed terminal half-life values ranging from 27 h to 80 h in mouse, and from 2.6 days to 20 days in cynomolgus monkey. Extrapolation by allometric scaling on these findings suggests terminal half-life values of 5-50 days in human, indicating that pharmacokinetic properties in the range of monoclonal antibodies can be achieved with DARPin® drug candidates. Such serum albumin-binding DARPin® domains are thus valuable tools for the generation of multi-functional drugs with an extended in vivo half-life.