Showing papers on "Serum albumin published in 2014"

Albumin Replacement in Patients with Severe Sepsis or Septic Shock

Abstract: BACKGROUND Although previous studies have suggested the potential advantages of albumin administration in patients with severe sepsis, its efficacy has not been fully established. METHODS In this multicenter, open-label trial, we randomly assigned 1818 patients with severe sepsis, in 100 intensive care units (ICUs), to receive either 20% albumin and crystalloid solution or crystalloid solution alone. In the albumin group, the target serum albumin concentration was 30 g per liter or more until discharge from the ICU or 28 days after randomization. The primary outcome was death from any cause at 28 days. Secondary outcomes were death from any cause at 90 days, the number of patients with organ dysfunction and the degree of dysfunction, and length of stay in the ICU and the hospital. RESULTS During the first 7 days, patients in the albumin group, as compared with those in the crystalloid group, had a higher mean arterial pressure (P = 0.03) and lower net fluid balance (P<0.001). The total daily amount of administered fluid did not differ significantly between the two groups (P = 0.10). At 28 days, 285 of 895 patients (31.8%) in the albumin group and 288 of 900 (32.0%) in the crystalloid group had died (relative risk in the albumin group, 1.00; 95% confidence interval [CI], 0.87 to 1.14; P = 0.94). At 90 days, 365 of 888 patients (41.1%) in the albumin group and 389 of 893 (43.6%) in the crystalloid group had died (relative risk, 0.94; 95% CI, 0.85 to 1.05; P = 0.29). No significant differences in other secondary outcomes were observed between the two groups. CONCLUSIONS In patients with severe sepsis, albumin replacement in addition to crystalloids, as compared with crystalloids alone, did not improve the rate of survival at 28 and 90 days. (Funded by the Italian Medicines Agency; ALBIOS ClinicalTrials.gov number, NCT00707122.)

Unraveling the mysteries of serum albumin—more than just a serum protein

Abstract: Serum albumin is a multi-functional protein that is able to bind and transport numerous endogenous and exogenous compounds. The development of albumin drug carriers is gaining increasing importance in the targeted delivery of cancer therapy, particularly as a result of the market approval of the paclitaxel-loaded albumin nanoparticle, Abraxane®. Considering this, there is renewed interest in isolating and characterizing albumin-binding proteins or receptors on the plasma membrane that are responsible for albumin uptake. Initially, the cellular uptake and intracellular localization of albumin was unknown due to the large confinement of the protein within the vascular and interstitial compartment of the body. Studies have since assessed the intracellular localization of albumin in order to understand the mechanisms and pathways responsible for its uptake, distribution and catabolism in multiple tissues, and this is reviewed herein.

Interactive Association of Drugs Binding to Human Serum Albumin

Abstract: Human serum albumin (HSA) is an abundant plasma protein, which attracts great interest in the pharmaceutical industry since it can bind a remarkable variety of drugs impacting their delivery and efficacy and ultimately altering the drug's pharmacokinetic and pharmacodynamic properties. Additionally, HSA is widely used in clinical settings as a drug delivery system due to its potential for improving targeting while decreasing the side effects of drugs. It is thus of great importance from the viewpoint of pharmaceutical sciences to clarify the structure, function, and properties of HSA-drug complexes. This review will succinctly outline the properties of binding site of drugs in IIA subdomain within the structure of HSA. We will also give an overview on the binding characterization of interactive association of drugs to human serum albumin that may potentially lead to significant clinical applications.

Prevention of vascular inflammation by nanoparticle targeting of adherent neutrophils

Abstract: Inflammatory diseases such as acute lung injury and ischaemic tissue injury are caused by the adhesion of a type of white blood cell--polymorphonuclear neutrophils--to the lining of the circulatory system or vascular endothelium and unchecked neutrophil transmigration. Nanoparticle-mediated targeting of activated neutrophils on vascular endothelial cells at the site of injury may be a useful means of directly inactivating neutrophil transmigration and hence mitigating vascular inflammation. Here, we report a method employing drug-loaded albumin nanoparticles, which efficiently deliver drugs into neutrophils adherent to the surface of the inflamed endothelium. Using intravital microscopy of tumour necrosis factor-α-challenged mouse cremaster post-capillary venules, we demonstrate that fluorescently tagged albumin nanoparticles are largely internalized by neutrophils adherent to the activated endothelium via cell surface Fcɣ receptors. Administration of albumin nanoparticles loaded with the spleen tyrosine kinase inhibitor, piceatannol, which blocks 'outside-in' β2 integrin signalling in leukocytes, detached the adherent neutrophils and elicited their release into the circulation. Thus, internalization of drug-loaded albumin nanoparticles into neutrophils inactivates the pro-inflammatory function of activated neutrophils, thereby offering a promising approach for treating inflammatory diseases resulting from inappropriate neutrophil sequestration and activation.

Circulating angiopoietin-like 4 links proteinuria with hypertriglyceridemia in nephrotic syndrome

Abstract: The molecular link between proteinuria and hyperlipidemia in nephrotic syndrome is not known. We show in the present study that plasma angiopoietin-like 4 (Angptl4) links proteinuria with hypertriglyceridemia through two negative feedback loops. In previous studies in a rat model that mimics human minimal change disease, we observed localized secretion by podocytes of hyposialylated Angptl4, a pro-proteinuric form of the protein. But in this study we noted high serum levels of Angptl4 (presumably normosialylated based on a neutral isoelectric point) in other glomerular diseases as well. Circulating Angptl4 was secreted by extrarenal organs in response to an elevated plasma ratio of free fatty acids (FFAs) to albumin when proteinuria reached nephrotic range. In a systemic feedback loop, these circulating pools of Angptl4 reduced proteinuria by interacting with glomerular endothelial αvβ5 integrin. Blocking the Angptl4-β5 integrin interaction or global knockout of Angptl4 or β5 integrin delayed recovery from peak proteinuria in animal models. But at the same time, in a local feedback loop, the elevated extrarenal pools of Angptl4 reduced tissue FFA uptake in skeletal muscle, heart and adipose tissue, subsequently resulting in hypertriglyceridemia, by inhibiting lipoprotein lipase (LPL)-mediated hydrolysis of plasma triglycerides to FFAs. Injecting recombinant human ANGPTL4 modified at a key LPL interacting site into nephrotic Buffalo Mna and Zucker Diabetic Fatty rats reduced proteinuria through the systemic loop but, by bypassing the local loop, without increasing plasma triglyceride levels. These data show that increases in circulating Angptl4 in response to nephrotic-range proteinuria reduces the degree of this pathology, but at the cost of inducing hypertriglyceridemia, while also suggesting a possible therapy to treat these linked pathologies.

Amyotrophic Lateral Sclerosis Outcome Measures and the Role of Albumin and Creatinine: A Population-Based Study

Abstract: Importance There is an urgent need to identify reliable biomarkers of amyotrophic lateral sclerosis (ALS) progression for clinical practice and pharmacological trials. Objectives To correlate several hematological markers evaluated at diagnosis with ALS outcome in a population-based series of patients (discovery cohort) and replicate the findings in an independent validation cohort from an ALS tertiary center. Design, Setting, and Participants The discovery cohort included 712 patients with ALS from the Piemonte and Valle d’Aosta Register for Amyotrophic Lateral Sclerosis from January 1, 2007, to December 31, 2011. The validation cohort comprised 122 patients with ALS at different stages of disease consecutively seen at an ALS tertiary center between January 1, 2007, and January 1, 2009. Main Outcomes and Measures The following hematological factors were investigated and correlated with survival: total leukocytes, neutrophils, lymphocytes, monocytes, glucose, creatinine, uric acid, albumin, bilirubin, total cholesterol, triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, creatine kinase, thyroid-stimulating hormones, and erythrocyte sedimentation rate; all analyses were performed separately by sex. The patient of the validation cohort also underwent bioelectrical impedance analysis for the calculation of fat-free mass. Result Of the 712 patients in the examined period in Piemonte and Valle d’Aosta, 638 (89.6%) were included in the study. Only serum albumin (men: ≤4.3 vs >4.3 mg/dL, P 4.3 mg/dL, P 0.82 mg/dL, P = .004; women: ≤0.65 vs >0.05 mg/dL, P = .004) and lymphocyte count (men: ≤1700 vs >1700/μL, P = .04; women: ≤1700 vs >1700/μL, P = .02) were significantly associated with ALS outcome in both sexes with a dose-response effect (better survival with increasing levels). These findings were confirmed in the validation cohort. Multivariable analysis showed that serum albumin (men: hazard ratio [HR], 1.39; 95% CI, 1.05-1.90; P = .02; women: HR, 1.73; 95 % CI, 1.35-2.39; P = .001) and creatinine (men: HR, 1.47; 95% CI, 1.11-1.95; P = .007; women: HR, 1.49; 95% CI, 1.07-2.05; P = .02) were independent predictors of survival in both sexes; no other hematological factor was retained in the model. In patients with ALS, serum albumin was correlated with markers of inflammatory state while serum creatinine was correlated with fat-free mass, which is a marker of muscle mass. Conclusions and Relevance In ALS, serum albumin and creatinine are independent markers of outcome in both sexes. Creatinine reflects the muscle waste whereas albumin is connected with inflammatory state. Both creatinine and albumin are reliable markers of the severity of clinical status in patients with ALS and can be used in defining prognosis at the time of diagnosis.

Cryptic Epitopes of Albumin Determine Mononuclear Phagocyte System Clearance of Nanomaterials

Abstract: While plasma proteins can influence the physicochemical properties of nanoparticles, the adsorption of protein to the surface of nanomaterials can also alter the structure and function of the protein. Here, we show that plasma proteins form a hard corona around synthetic layered silicate nanoparticles (LSN) and that one of the principle proteins is serum albumin. The protein corona was required for recognition of the nanoparticles by scavenger receptors, a major receptor family associated with the mononuclear phagocyte system (MPS). Albumin alone could direct nanoparticle uptake by human macrophages, which involved class A but not class B scavenger receptors. Upon binding to LSN, albumin unfolded to reveal a cryptic epitope that could also be exposed by heat denaturation. This work provides an understanding of how albumin, and possibly other proteins, can promote nanomaterial recognition by the MPS without albumin requiring chemical modification for scavenger receptor recognition. These findings also demonstrate an additional function for albumin in vivo.

Electrostatic Unfolding and Interactions of Albumin Driven by pH Changes: A Molecular Dynamics Study

Abstract: A better understanding of protein aggregation is bound to translate into critical advances in several areas, including the treatment of misfolded protein disorders and the development of self-assembling biomaterials for novel commercial applications. Because of its ubiquity and clinical potential, albumin is one of the best-characterized models in protein aggregation research; but its properties in different conditions are not completely understood. Here, we carried out all-atom molecular dynamics simulations of albumin to understand how electrostatics can affect the conformation of a single albumin molecule just prior to self-assembly. We then analyzed the tertiary structure and solvent accessible surface area of albumin after electrostatically triggered partial denaturation. The data obtained from these single protein simulations allowed us to investigate the effect of electrostatic interactions between two proteins. The results of these simulations suggested that hydrophobic attractions and counterion binding may be strong enough to effectively overcome the electrostatic repulsions between the highly charged monomers. This work contributes to our general understanding of protein aggregation mechanisms, the importance of explicit consideration of free ions in protein solutions, provides critical new insights about the equilibrium conformation of albumin in its partially denatured state at low pH, and may spur significant progress in our efforts to develop biocompatible protein hydrogels driven by electrostatic partial denaturation.

Structural studies of bovine, equine, and leporine serum albumin complexes with naproxen.

Abstract: Serum albumin, a protein naturally abundant in blood plasma, shows remarkable ligand binding properties of numerous endogenous and exogenous compounds. Most of serum albumin binding sites are able to interact with more than one class of ligands. Determining the protein-ligand interactions among mammalian serum albumins is essential for understanding the complexity of this transporter. We present three crystal structures of serum albumins in complexes with naproxen (NPS): bovine (BSA-NPS), equine (ESA-NPS), and leporine (LSA-NPS) determined to 2.58 A (C2), 2.42 A (P61), and 2.73 A (P212121) resolutions, respectively. A comparison of the structurally investigated complexes with the analogous complex of human serum albumin (HSA-NPS) revealed surprising differences in the number and distribution of naproxen binding sites. Bovine and leporine serum albumins possess three NPS binding sites, but ESA has only two. All three complexes of albumins studied here have two common naproxen locations, but BSA and LSA differ in the third NPS binding site. None of these binding sites coincides with the naproxen location in the HSA-NPS complex, which was obtained in the presence of other ligands besides naproxen. Even small differences in sequences of serum albumins from various species, especially in the area of the binding pockets, influence the affinity and the binding mode of naproxen to this transport protein. Proteins 2014; 82:2199–2208. © 2014 Wiley Periodicals, Inc.

Preoperative serum albumin level as a predictor of postoperative complication after spine fusion.

Abstract: STUDY DESIGN Retrospective cohort study. OBJECTIVE To investigate the association between preoperative baseline serum albumin and postoperative surgical complication. SUMMARY OF BACKGROUND DATA The prevalence of malnutrition in the hospitalized patient population has only been recently recognized. Preoperative hypoalbuminemia (serum albumin <3.5 g/dL) has been shown to be associated with increased morbidity and mortality rates. The prognostic implications and significance of hypoalbuminemia after spine fusion surgery remain unknown. In this study, we assess the predictive value of preoperative nutritional status (serum albumin level) on postoperative complication rates. METHODS The medical records of 136 consecutive patients undergoing spine fusion at Duke University Medical Center were reviewed. Preoperative serum albumin level was assessed on all patients and used to quantify nutritional status. Albumin less than 3.5 g/dL was recognized as hypoalbuminemia (malnourished). Patient demographics, comorbidities, and postoperative complication rates were collected. Patients were also stratified into 2 groups based on their cause, namely elective degenerative/deformity versus nonelective cases. The association between preoperative serum albumin level and postoperative complication was assessed via logistic regression analysis. RESULTS Overall, 40 (29.4%) patients experience at least 1 postoperative complication. Patients undergoing elective surgery had more complications based on preoperative albumin levels (malnourished patients: 35.7% vs. nourished patients: 11.7%, P = 0.03), whereas those undergoing nonelective surgery had similar complication rates (malnourished patients: 46.5% vs. nourished patients: 42.1%, P = 0.75). For patients undergoing elective spinal surgery, logistic regression with and without propensity score adjustment for risk factors, demonstrated that preoperative serum albumin level was a significant predictor of postoperative complications (OR: 4.21; 95% CI: 1.09-16.19; P = 0.04) and (OR: 4.54; 95% CI: 1.17-19.32; P = 0.04), respectively. CONCLUSION Preoperative hypoalbuminemia is an independent risk factor for postoperative complications after elective spine surgery for degenerative and deformity causes, and should be used more frequently as a prognostic tool to detect malnutrition and risk of adverse surgical outcomes. LEVEL OF EVIDENCE 2.

The pretreatment albumin to globulin ratio has predictive value for long-term mortality in nasopharyngeal carcinoma.

Abstract: Background Low serum albumin is predictive of poor survival in nasopharyngeal carcinoma (NPC). We evaluated the ability of the pretreatment albumin/globulin ratio (AGR) to predict long-term mortality in patients with NPC. Methods This retrospective study examined an unselected cohort of 694 patients with NPC who had documented pretreatment total serum protein and serum albumin levels (ALB). AGR was calculated as [AGR = ALB/(total serum protein - ALB)]. Survival analysis was used to evaluate the predictive value of AGR. Results Multivariate analysis demonstrated that a low pretreatment serum AGR (<1.4) was an independent predictor of poor OS (P = 0.029) and DMFS (P = 0.033). A low AGR was significantly associated with advanced stage disease (P<0.001), high white blood cell count (P = 0.033), high neutrophil count (P = 0.047), high total serum protein (P<0.001) and low ALB (P<0.001). Conclusion The pretreatment AGR may represent a simple, potentially useful predictive biomarker for evaluating the long-term prognosis of patients with undifferentiated NPC.

Role of Human Albumin in the Management of Complications of Liver Cirrhosis

Abstract: Albumin is a negatively charged, relatively small protein synthesized by liver cells. Is the most abundant protein in extracellular fluid and accounts for about 70% of the plasma colloid osmotic pressure. Therefore it plays a crucial role in regulating fluid distribution in the body. In addition, albumin possesses functional domains with important non-oncotic properties, such as potent anti-oxydant and scavenging activities, binding of highly toxic reactive metal species and a great amount of endogenous and exogenous substances. We have recently learned that albumin in cirrhosis undergoes a number of post-transcriptional changes that greatly impair its non-oncotic properties. The overall assessment of these changes clearly shows that the relative abundance of the native form of albumin is significantly reduced in hospitalized patients with cirrhosis and that these abnormalities worsen in parallel with the increasing severity of the disease. Thus, it is time to abandon the concept of serum albumin concentration and refer to the effective albumin concentration , that is the native intact albumin. Given the pathophysiological context in which we use human albumin in patients with cirrhosis, who are characterized by peripheral vasodilation and a low-grade but sustained inflammatory state, the use of albumin in patients with cirrhosis should aim at enhancing effective hypovolemia and exploiting its antioxidant and scavenging activities. The indications for the use of albumin in cirrhosis that clearly emerge from evidence-based medicine are represented by conditions characterized by an acute aggravation of effective hypovolemia and inflammation, such as such post-paracentesis circulatory dysfunction, spontaneous bacterial peritonitis, and hepatorenal syndrome. Other indications to the use of albumin that still require further studies are represented by bacterial infections other than spontaneous bacterial peritonitis, hepatic encephalopathy and long-term treatment of ascites, which has been debated for the last half-century.

Impact of pregnancy on vitamin D status: a longitudinal study.

Abstract: Nutritional requirements for vitamin D during pregnancy have been inadequately described, and there are conflicting data on the impact of gestation on vitamin D status. In the present study, we conducted a longitudinal analysis of total and free (unbound) serum 25-hydroxyvitamin D (25(OH)D), vitamin D-binding protein (DBP) and albumin concentrations in a random sample of thirty women from the Screening for Pregnancy Endpoints Ireland pregnancy cohort study at 15, 20, 24, 28, 32, 36 and 40 weeks of gestation and at 2 months postpartum. Concentrations of serum 25(OH)D, DBP and albumin were determined, and free 25(OH)D was calculated from the concentrations of total 25(OH)D, DBP and albumin. Serum albumin concentration decreased during pregnancy (P< 0·001), with a nadir at 36 weeks (P< 0·005), during which the concentration was approximately 80 % of the postnatal concentration. Serum DBP concentration increased during pregnancy and at 28 weeks of gestation, which was almost double the postnatal level (P< 0·001). Total and free 25(OH)D concentrations decreased (both P< 0·005) as pregnancy progressed, and both were lowest at 36 weeks of gestation. At 15 weeks, 10 and 63 % of the women had serum 25(OH)D concentration < 30 and 50 nmol/l, respectively, which increased to 53 and 80 % at 36 weeks of gestation. The time course of decreasing concentrations of 25(OH)D during gestation among women recruited during May-July, who delivered between October and November, and among those recruited in August-September, who delivered between February and March, was similar. The lower percentage of free 25(OH)D during pregnancy is mainly due to increased DBP.

Synthetic cationic antimicrobial peptides bind with their hydrophobic parts to drug site II of human serum albumin

Abstract: Background Many biologically active compounds bind to plasma transport proteins, and this binding can be either advantageous or disadvantageous from a drug design perspective. Human serum albumin (HSA) is one of the most important transport proteins in the cardiovascular system due to its great binding capacity and high physiological concentration. HSA has a preference for accommodating neutral lipophilic and acidic drug-like ligands, but is also surprisingly able to bind positively charged peptides. Understanding of how short cationic antimicrobial peptides interact with human serum albumin is of importance for developing such compounds into the clinics.

A pilot study to determine the dose and effectiveness of adrenocorticotrophic hormone (H.P. Acthar® Gel) in nephrotic syndrome due to idiopathic membranous nephropathy

Abstract: Background. H.P. Acthar® Gel is currently the only Food and Drug Administration therapy approved for the treatment of nephrotic syndrome. Active drug ingredients include structurally related melanocortin peptides that bind to cell surface G-protein-coupled receptors known as melanocortin receptors, which are expressed in glomerular podocytes. In animal models of membranous nephropathy, stimulation has been demonstrated to reduce podocyte injury and loss. We hypothesized that H.P. Acthar® Gel would improve symptoms of the nephrotic syndrome in patients with idiopathic membranous nephropathy. Methods. Twenty patients received a subcutaneous dose of 40 or 80 IU twice weekly. Changes in proteinuria, albumin, cholesterol profile, estimated glomerular filtration rate and serum anti-PLA2R antibodies were assessed at baseline and in response to treatment along with tolerance and safety. Results. Baseline characteristics included mean proteinuria (9.1 ± 3.4 g/day), albumin (2.7 ± 0.8 g/dL), estimated glomerular filtration rate (77 ± 30 mL/min) along with elevated total and low-density lipoprotein (LDL) cholesterol. By 12 months of follow-up, there was a significant improvement in proteinuria in the entire cohort, decreasing to 3.87 ± 4.24 g/day (P 50% decrease in proteinuria was noted in 65% of the patients with a trend toward better outcomes among patients who received greater cumulative doses. No significant adverse effects were documented. Clearing of serum anti-PLA2R antibodies prior to or in parallel with proteinuria improvement was noted in some, but not all patients. Conclusions. H.P. Acthar® Gel is a potential therapy for nephrotic syndrome secondary to idiopathic membranous nephropathy that deserves further study.

The association of preoperative serum albumin level and American Society of Anesthesiologists (ASA) score on early complications and survival of patients undergoing radical cystectomy for urothelial bladder cancer

Abstract: Objective To evaluate the impact of the preoperative American Society of Anesthesiologists (ASA) score and serum albumin level on complications, recurrences and survival rates of patients who underwent radical cystectomy (RC) for urothelial bladder cancer (UBC). Patients and Methods In all, 1964 patients underwent RC for UBC at our institution between 1971 and 2008. Preoperative serum albumin and ASA score were available in 1471 and 1140 patients, respectively. A complication was defined as any surgery related/unrelated event leading to lengthening hospital stay or re-admission. Endpoints were 90-day complication (90dC) rate, recurrence-free survival (RFS) and overall survival (OS). Results The median (range) follow-up was 12.4 (0.2–27.3) years. In all, 197 patients (13.4%) had a low albumin level (<3.5 g/dL) and 740 (64.8%) had a high ASA score (3 or 4). Low serum albumin and a high ASA score were associated with higher 90dC rate (42% vs 34%, P = 0.03 and 40% vs 28%, P < 0.001, respectively). On multiple logistic regression analysis, a high ASA score remained independently associated with increased 90dC rate (hazard ratio [HR] 1.52, P = 0.005) and decreased OS (HR 1.45, 95% confidence interval [CI] 1.13–1.86). A low serum albumin level was also independently associated with RFS (HR 1.68, 95% CI 1.16–2.43) and OS (HR 1.93, 95% CI 1.43–2.63). Conclusion A low serum albumin level was independently associated with cancer recurrence and decreased OS after RC. A high ASA score was also independently associated with decreased OS. These parameters potentially could be used as prognosticators after RC.

Preoperative serum albumin is associated with mortality and complications after radical cystectomy.

Abstract: Objective To determine the association between preoperative serum albumin and mortality and postoperative complications after radical cystectomy and urinary diversion. Patients and Methods We conducted a retrospective review of 1097 radical cystectomies performed for the treatment of bladder cancer between 1992 and 2005. All data were entered prospectively into a hospital-based complications database. We used multivariable logistic regression to assess the association between preoperative serum albumin and complications and mortality within 90 days of surgery, while controlling for preoperative patient and disease characteristics. Results Low preoperative serum albumin was identified in 14% of the cohort. Preoperative serum albumin was a predictor of postoperative complications (adjusted odds ratio [OR] per unit increase in albumin: 0.61, 95% confidence interval [CI] 0.42–0.90) and 90-day mortality (OR 0.33, 95% CI 0.14–0.75) when controlling for sex, race, age-adjusted Charlson score, body mass index, prior history of abdominal surgery, clinical stage, and neoadjuvant chemotherapy. As serum albumin decreased, the risk of complications and mortality increased. Conclusions In addition to age-adjusted Charlson score, low preoperative serum albumin is a significant predictor of complications and mortality after radical cystectomy. Serum albumin testing can be used to identify individuals at high-risk for morbidity and mortality. Keywords: hypoalbuminemia, postoperative complications, urinary bladder neoplasms INTRODUCTION Radical cystectomy (RC) for muscle-invasive bladder cancer is a major extirpative procedure that is associated with significant postoperative complications and mortality. Our group has reported complication rates of 64% and 30-day postoperative mortality rates of 1.5%.[1] Modifiable factors, such as nutrition status, are associated with postoperative outcomes in other major surgical procedures such as colorectal and cardiac surgery.[2, 3] Low preoperative serum albumin, in particular, as a surrogate marker for nutrition status, is a strong predictor of postoperative morbidity and mortality for procedures in multiple surgical disciplines; however, only a few small studies have focused on urologic surgery.[4–7] These prior studies have confirmed the association between preoperative serum albumin and mortality after RC, but an association between serum albumin and postoperative complications has not been investigated. The objective of this study was to define the relationship between preoperative serum albumin and 90-day complication and mortality rates in a large cohort of patients undergoing RC at a major tertiary cancer center.

Albumin Suppresses Human Hepatocellular Carcinoma Proliferation and the Cell Cycle

Abstract: Many investigations have revealed that a low recurrence rate of hepatocellular carcinoma (HCC) is associated with high serum albumin levels in patients; therefore, high levels of serum albumin are a major indicator of a favorable prognosis. However, the mechanism inhibiting the proliferation of HCC has not yet been elucidated, so we investigated the effect of serum albumin on HCC cell proliferation. Hep3B was cultured in MEM with no serum or containing 5 g/dL human albumin. As control samples, Prionex was added to generate the same osmotic pressure as albumin. After 24-h incubation, the expressions of α-fetoprotein (AFP), p53, p21, and p57 were evaluated with real-time PCR using total RNA extracted from the liver. Protein expressions and the phosphorylation of Rb (retinoblastoma) were determined by Western blot analysis using total protein extracted from the liver. For flow cytometric analysis of the cell cycle, FACS analysis was performed. The percentages of cell cycle distribution were evaluated by PI staining, and all samples were analyzed employing FACScalibur (BD) with appropriate software (ModFit LT; BD). The cell proliferation assay was performed by counting cells with using a Scepter handy automated cell counter (Millipore). The mRNA levels of AFP relative to Alb(-): Alb(-), Alb(+), and Prionex, were 1, 0.7 ± 0.2 (p < 0.001 for Alb(-)), and 1 ± 0.3, respectively. The mRNA levels of p21 were 1, 1.58 ± 0.4 (p = 0.007 for Alb(-) and p = 0.004 for Prionex), and 0.8 ± 0.2, respectively. The mRNA levels of p57 were 1, 4.4 ± 1.4 (p = 0.002 for Alb(-) and Prionex), and 1.0 ± 0.1, respectively. The protein expression levels of Rb were similar in all culture media. The phosphorylation of P807/811 and P780 of Rb protein was reduced in Alb(+). More cells in the G0/G1 phase and fewer cells in S and G2/M phases were obtained in Alb(+) than in Alb(-) (G0/G1: 60.9%, 67.7%, 61.5%; G2/M: 16.5%, 13.1%, 15.6%; S: 22.6%, 19.2%, 23.0%, Alb(-), Alb(+), Prionex, respectively). The same results were obtained in HepG2. Cell proliferation was inhibited in 5 g/dL albumin medium in both HepG2 cells and Hep3B cells in 24 h culture by counting cell numbers. The presence of albumin in serum reduces the phosphorylation of Rb proteins and enhances the expression of p21 and p57, following an increase in the G0/G1 cell population, and suppresses cell proliferation. These results suggest that albumin itself suppresses the proliferation of hepatocellular carcinoma.

In Vitro Hemocompatibility and Toxic Mechanism of Graphene Oxide on Human Peripheral Blood T Lymphocytes and Serum Albumin

Abstract: Graphene oxide (GO) has shown tremendous application potential as a biomedical material. However, its interactions with blood components are not yet well understood. In this work, we assess the toxicity of pristine GO (p-GO) and functionalized GO (GO-COOH and GO-PEI) to primary human peripheral blood T lymphocytes and human serum albumin (HSA), and also study the underlying toxic mechanism. Our results indicate that p-GO and GO-COOH have good biocompatibility to T lymphocytes at the concentration below 25 μg mL–1, but notable cytotoxicity above 50 μg mL–1. By contrast, GO-PEI exhibits significant toxicity even at 1.6 μg mL–1. Further investigations show that although p-GO does not enter into the cell or damage the membrane, its presence leads to the increase in reactive oxygen species (ROS), moderate DNA damage, and T lymphocyte apoptosis. Interestingly, little effect on T lymphocyte immune response suppression is observed in this process despite p-GO inflicting cell apoptosis. The toxic mechanism is that...

Optimization and evaluation of a thermoresponsive ophthalmic in situ gel containing curcumin-loaded albumin nanoparticles

Abstract: This study aimed to optimize and evaluate a thermoresponsive ophthalmic in situ gel containing curcumin-loaded albumin nanoparticles (Cur-BSA-NPs-Gel). Albumin nanoparticles were prepared via a desolvation method, and the gels were prepared via a cold method. The central composite design and response surface method was used to evaluate the effects of varying Pluronic® F127 and Pluronic® F68 concentrations on the sol–gel transition temperature, which is an indicator of optimum formulations. The optimized formulation was a free-flowing liquid below 30.9°C that transformed into a semi-solid gel above 34.2°C after dilution with simulated tear fluid. Results of the in vitro release and erosion behavior study indicated that Cur-BSA-NPs-Gel achieved superior sustained-release effects and that incorporation of albumin nanoparticles exerted minimal effects on the gel structure. In addition, in vivo ophthalmic experiments employing Cur-BSA-NPs-Gel were subsequently performed in rabbits. In vivo eye irritation results showed that Cur-BSA-NPs-Gel might be considered safe for ophthalmic drug delivery. The in vivo study also revealed that the formulation could significantly increase curcumin bioavailability in the aqueous humor. In conclusion, the optimized in situ gel formulation developed in this work has significant potential for ocular application.

Prevalence of and risk factors for reduced serum bicarbonate in chronic kidney disease

Abstract: Aim The prevalence of metabolic acidosis increases as glomerular filtration rate falls. However, most patients with stage 4 chronic kidney disease have normal serum bicarbonate concentration while some with stage 3 chronic kidney disease have low serum bicarbonate, suggesting that other factors contribute to generation of acidosis. The purpose of this study is to identify risk factors, other than reduced glomerular filtration rate, for reduced serum bicarbonate in chronic kidney disease. Methods This is a cross-sectional analysis of baseline data from the Chronic Renal Insufficiency Cohort Study. Multivariable logistic and linear regression models were used to relate predictor variables to the odds of low serum bicarbonate (<22 mM) compared with normal serum bicarbonate (22–30 mM) and the coefficients of Δ serum bicarbonate concentration. Results The prevalence of low serum bicarbonate at baseline was 17.3%. Lower estimated glomerular filtration rate had the strongest relationship with low serum bicarbonate. Factors associated with higher odds of low serum bicarbonate, independent of estimated glomerular filtration rate, were urinary albumin/creatinine ≥10 mg/g, smoking, anaemia, hyperkalaemia, non-diuretic use and higher serum albumin. These and younger age, higher waist circumference, and use of angiotensin converting enzyme inhibitors or angiotensin receptor blockers associated with negative Δ serum bicarbonate in linear regression models. Conclusions Several factors not typically considered to associate with reduced serum bicarbonate in chronic kidney disease were identified including albuminuria ≥10 mg/g, anaemia, smoking, higher serum albumin, higher waist circumference, and use of angiotensin converting enzyme inhibitors or angiotensin receptor blockers. Future studies should explore the longitudinal effect of these factors on serum bicarbonate concentration.

In Vivo Labeling of Serum Albumin for PET

Abstract: The purpose of this study was to develop a novel in vivo albumin-labeling method to allow PET of cardiac function after myocardial infarction and vascular leakage and increased permeability in inflammatory diseases and malignant tumors. Methods: To label albumin in vivo, we synthesized a NOTA (1,4,7-triazacyclononane-N,N′,N″-triacetic acid)-conjugated truncated form of Evans blue (NEB). 18F labeling was achieved by the formation of an 18F-aluminum fluoride (18F-AlF) complex, and 64Cu labeling was obtained by a standard chelation method. Sixty-minute dynamic PET imaging was performed on normal mice to evaluate the distribution of 18F-AlF-NEB, which was compared with in vitro–labeled mouse serum albumin (18F-fluorobenzyl-MSA). Electrocardiography-gated PET imaging was performed in a mouse model of myocardial infarction. Both dynamic and static PET scans were obtained in a mouse inflammation model induced by local injection of turpentine to evaluate vascular leakage. Tumor permeability was studied by dynamic and late-point static PET using 64Cu-NEB in a UM-22B xenograft model. Results: NEB was successfully synthesized, and 18F labeling including work-up took about 20–30 min, with a radiochemical purity greater than 95% without the need for high-performance liquid chromatography purification. Most of the radioactivity was retained in the circulation system at 60 min after injection (26.35 ± 1.52 percentage injected dose per gram [%ID/g]). With electrocardiography-gated PET, ventricles of the heart and major arteries were clearly visualized. The myocardial infarction mice showed much lower left ventricular ejection fraction than the control mice. Inflammatory muscles showed significantly higher tracer accumulation than the contralateral healthy ones. UM-22B tumor uptake of 64Cu-NEB gradually increased with time (5.73 ± 1.11 %ID/g at 1 h and 8.03 ± 0.77 %ID/g at 2 h after injection). Conclusion: The distribution and local accumulation of serum albumin can be noninvasively visualized and quantified by 18F-AlF-NEB and 64Cu-NEB PET. The simple labeling and broad applications make these imaging probes attractive for clinical translation.

A review on structure-affinity relationship of dietary flavonoids with serum albumins.

Abstract: Flavonoids are a class of plant secondary metabolites and among thousands of flavonoids few are considered as dietary flavonoids. Serum albumin (SA), the most abundant protein in plasma, functions as the most important carrier of vital drugs, including dietary flavonoids. The binding affinity of dietary flavonoids to SA is demonstrated to be governed by structure–affinity relationship (SAR) and its bioavailability. The present review summarizes the interactions of flavonoids categorized as flavanol, flavonol, flavone, isoflavone, flavanones, and anthocyanidins with SAs (bovine serum albumin and human serum albumin) in light of SAR. The key findings are: (1) the position and degree of hydroxylation highly influence the affinity of flavonoids to SAs, (2) glycosylation decreases and substitution of methoxy group increases the affinity of flavonoids for SAs, (3) catechin gallates have higher binding affinity to SAs than catechins and gallocatechins, (4) inorganic metal ions modulate the binding affinity of fl...

Binding of ascorbic acid and α-tocopherol to bovine serum albumin: a comparative study

Abstract: Binding of ascorbic acid (water-soluble antioxidant) and α-tocopherol (lipid-soluble antioxidant) to bovine serum albumin (BSA) has been studied using isothermal titration calorimetry (ITC), in combination with fluorescence spectroscopy, UV-vis absorption spectroscopy and Fourier transform infrared (FT-IR) spectroscopy. Thermodynamic investigations reveal that ascorbic acid/α-tocopherol binding to BSA is driven by favorable enthalpy and unfavorable entropy, and the major driving forces are hydrogen bonding and van der Waals forces. For ascorbic acid, the interaction is characterized by a high number of binding sites, which suggests that binding occurs by a surface adsorption mechanism that leads to coating of the protein surface. For α-tocopherol, one molecule of α-tocopherol combines with one molecule of BSA and no more α-tocopherol binding to BSA occurs at concentration ranges used in this study. Fluorescence experiments suggest that ascorbic acid has predominantly a “sphere of action” quenching mechanism, whereas, for α-tocopherol, the quenching mechanism is “static quenching” and due to the formation of a ground state complex. Additionally, as shown by the UV-vis absorption, synchronous fluorescence spectroscopy, and FT-IR, ascorbic acid and α-tocopherol may induce conformational and microenvironmental changes of BSA.