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Effect of Oral Branched-Chain Amino Acids on Serum Albumin Concentration in Heart Failure Patients with Hypoalbuminemia: Results of a Preliminary Study.
Uchino, Y, Watanabe, M, Takata, M, Amiya, E, Tsushima, K, Adachi, T, Hiroi, Y, Funazaki, T, Komuro, I
American journal of cardiovascular drugs : drugs, devices, and other interventions. 2018;(4):327-332
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Abstract
BACKGROUND We conducted a randomized, controlled trial to determine whether supplementation with oral branched-chain amino acids (BCAAs) improves serum albumin and clinical outcomes in heart failure (HF) patients with hypoalbuminemia. METHODS AND RESULTS We randomly assigned 18 in-hospital HF patients with serum albumin < 3.5 g/dL to receive oral BCAA granules (LIVACT®) for 28 days during their hospital stay or until discharge (BCAA group; N = 9) or to receive no supplementation (controls; N = 9), in addition to recommended HF therapy. The primary endpoints were changes from baseline in serum albumin and cardiothoracic ratio (CTR). Sixteen patients completed the study. The mean (± standard deviation) period of BCAA supplementation was 18.4 ± 8.4 days. Serum albumin significantly increased in the BCAA group [mean difference vs baseline, 0.44 g/dL; 95% confidence interval (CI) 0.13-0.76; P = 0.014] and did not change in controls (0.18 g/dL; 95% CI - 0.05 to 0.40; P = 0.108). CTR significantly decreased in the BCAA group (- 2.3%; 95% CI - 3.8 to - 0.8; P = 0.014) and did not change in controls (- 1.0%; 95% CI - 2.3 to 0.3; P = 0.111). CONCLUSION In-hospital HF patients with hypoalbuminemia supplemented with BCAAs showed increased serum albumin and decreased CTR. Clinical trial registration number UMIN000004488 [ http://www.umin.ac.jp/ctr/index.htm ].
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Volume of Plasma Expansion and Functional Outcomes in Stroke.
Miller, JB, Lewandowski, C, Wira, CR, Taylor, A, Burmeister, C, Welch, R
Neurocritical care. 2017;(2):191-195
Abstract
BACKGROUND Plasma expansion in acute ischemic stroke has potential to improve cerebral perfusion, but the long-term effects on functional outcome are mixed in prior trials. The goal of this study was to evaluate how the magnitude of plasma expansion affects neurological recovery in acute stroke. METHODS This was a secondary analysis of data from the Albumin in Acute Stroke Part 2 trial investigating the relationship between the magnitude of overall intravenous volume infusion (crystalloid and colloid) to clinical outcome. The data were inclusive of 841 patients with a mean age of 64 years and a median National Institutes of Health Stroke Scale (NIHSS) of 11. In a multivariable-adjusted logistic regression model, this analysis tested the volume of plasma expansion over the first 48 h of hospitalization as a predictor of favorable outcome, defined as either a modified Rankin Scale score of 0 or 1 or a NIHSS score of 0 or 1 at 90 days. This model included all study patients, irrespective of albumin or isotonic saline treatment. RESULTS Patients that received higher volumes of plasma expansion more frequently had large vessel ischemic stroke and higher NIHSS scores. The multivariable-adjusted model revealed that there was decreased odds of a favorable outcome for every 250 ml additional volume plasma expansion over the first 48 h (OR 0.91, 95 % CI, 0.88-0.94). CONCLUSIONS The present study demonstrates an association between greater volume of plasma expansion and worse neurological recovery.
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Asymmetric dimethylarginine (ADMA) in human blood: effects of extended haemodialysis in the critically ill patient with acute kidney injury, protein binding to human serum albumin and proteolysis by thermolysin.
Sitar, ME, Kayacelebi, AA, Beckmann, B, Kielstein, JT, Tsikas, D
Amino acids. 2015;(9):1983-93
Abstract
Free, non-protein bound asymmetrically guanidine-dimethylated arginine (ADMA) is an endogenous inhibitor of nitric oxide (NO) synthesis. Human erythrocytic membrane comprises considerable amounts of large (>50 kDa) ADMA-containing proteins. Location in the erythrocyte membrane and identity and physiological functions of ADMA-containing proteins are unrevealed. In healthy subjects, the concentration of free ADMA in heparinised plasma is almost identical to that of serum. We hypothesised that the robustness of free ADMA concentration in human blood is due to a remarkable resistance of erythrocytic ADMA-containing proteins against proteases. In vivo, we investigated the course of the concentration of ADMA in serum and EDTA plasma of a critically ill patient with acute kidney injury during extended haemodialysis. In vitro, we studied the effects of thermolysin, a useful experimental proteolytic enzyme of erythrocyte membrane proteins, on erythrocytic ADMA. The protein binding (PB) of ADMA to human serum albumin (HSA) was also determined. In these studies, ADMA was measured by a previously reported, fully validated GC-MS/MS method. We measured almost identical ADMA concentrations in plasma and serum samples of the patient. During dialysis, the circulating ADMA concentration decreased slowly and moderately indicating removal of this substance, which was however much less than expected from its low molecular weight (202 Da) and high water solubility. After dialysis, circulating ADMA concentration increased again, a phenomenon called rebound, and ADMA reached higher levels compared to the baseline. The PB value of ADMA to HSA was about 30 %. This surprisingly high PB value of ADMA to HSA may be an explanation for the rather poor dialysance of ADMA. Washed human erythrocytes suspended in phosphate-buffered physiological saline were found not to release appreciable amounts of free and ADMA-containing proteins. The lack of effect of coagulation or anticoagulation on the concentration of circulating free ADMA in humans is likely to be due to a remarkable resistance of ADMA-containing proteins in the erythrocyte membrane against proteases in vivo in humans. Our study suggests that free ADMA is released in the circulating blood at relatively high rates. The considerable PB of ADMA to HSA is likely to add to the apparently poor dialysability of ADMA. Other contributing factors could be redistribution of free ADMA between plasma and erythrocytes in favour of plasma ADMA and parallel formation of free ADMA from erythrocytic ADMA-containing proteins during haemodialysis.
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The effect of the systemic inflammatory response on plasma vitamin 25 (OH) D concentrations adjusted for albumin.
Ghashut, RA, Talwar, D, Kinsella, J, Duncan, A, McMillan, DC
PloS one. 2014;(3):e92614
Abstract
BACKGROUND Plasma 25-hydroxyvitamin D (25(OH) D) deficiencies are associated with several diseases. The magnitude of systemic inflammatory response, as evidenced by C-reactive protein (CRP), is a major factor associated with lower 25(OH)D. Other aspects of the systemic inflammatory response may be important in determining plasma 25 (OH)D concentrations. AIM: To examine the relationship between plasma 25(OH)D, CRP and albumin concentrations in two patient cohorts. METHODS 5327 patients referred for nutritional assessment and 117 patients with critical illness were examined. Plasma 25 (OH) D concentrations were measured using standard methods. Intra and between assay imprecision was <10%. RESULT In the large cohort, plasma 25 (OH) D was significantly associated with CRP (r(s) = -0.113, p<0.001) and albumin (rs = 0.192, p<0.001). 3711 patients had CRP concentrations ≤ 10 mg/L; with decreasing albumin concentrations ≥ 35, 25-34 and <25 g/l, median concentrations of 25 (OH) D were significantly lower from 35 to 28 to 14 nmol/l (p<0.001). This decrease was significant when albumin concentrations were reduced between 25-34 g/L (p<0.001) and when albumin <25 g/L (p<0.001). 1271 patients had CRP concentrations between 11-80 mg/L; with decreasing albumin concentrations ≥ 35, 25-34 and <25 g/l, median concentrations of 25 (OH) D were significantly lower from 31 to 24 to 19 nmol/l (p<0.001). This decrease was significant when albumin concentration were 25-34 g/L (p<0.001) and when albumin <25 g/L (p<0.001). 345 patients had CRP concentrations >80 mg/L; with decreasing albumin concentrations ≥ 35, 25-34 and <25 g/l, median concentrations of 25 (OH) D were not significantly altered varying from 19 to 23 to 23 nmol/l. Similar relationships were also obtained in the cohort of patients with critical illness. CONCLUSION Plasma concentrations of 25(OH) D were independently associated with both CRP and albumin and consistent with the systemic inflammatory response as a major confounding factor in determining vitamin D status.
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Association of serum albumin concentration with mortality, morbidity, CD4 T-cell reconstitution among tanzanians initiating antiretroviral therapy.
Sudfeld, CR, Isanaka, S, Aboud, S, Mugusi, FM, Wang, M, Chalamilla, GE, Fawzi, WW
The Journal of infectious diseases. 2013;(9):1370-8
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Abstract
BACKGROUND Prospective studies of serum albumin concentration measurement as a low-cost predictor of human immunodeficiency virus (HIV) disease progression are needed for individuals initiating antiretroviral therapy (ART) in resource-limited settings. METHODS Serum albumin concentration was measured at ART initiation for 2145 adults in Tanzania who were enrolled in a trial examining the effect of multivitamins on HIV disease progression. Participants were prospectively followed for mortality, morbidity, and anthropometric outcomes at monthly visits (median follow-up duration, 21.2 months). Proportional hazard models were used to analyze mortality, morbidity, and nutritional outcomes, while generalized estimating equations were used to analyze CD4(+) T-cell counts. RESULTS Individuals with hypoalbuminemia (defined as a serum albumin concentration of <35 g/L) at ART initiation had a hazard of death that was 4.52 times (95% confidence interval, 3.37-6.07; P < .001) that of individuals with serum albumin concentrations of ≥ 35 g/L, after multivariate adjustment. Hypoalbuminemia was also independently associated with the incidence of pulmonary tuberculosis (P < .001), severe anemia (P < .001), wasting (P = .002), and >10% weight loss (P = .012). Secondary analyses suggested that serum albumin concentrations of <38 g/L were associated with increased mortality and incident pulmonary tuberculosis. There was no association between serum albumin concentration and changes in CD4(+) T-cell counts (P = .121). CONCLUSIONS Serum albumin concentrations can identify adults initiating ART who are at high risk for mortality and selected morbidities. Future research is needed to identify and manage conditions that reduce the serum albumin concentration.
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Monitoring of the human serum albumin carbonylation level through determination of guanidino group content.
Aćimović, JM, Jovanović, VB, Srećković, VD, Penezić Romanjuk, AZ, Mandić, LM
Analytical biochemistry. 2013;(2):162-7
Abstract
Carbonylation of the protein amino, guanidine, and thiol groups with α-oxoaldehydes (which are produced in higher quantities in diabetes, uremia, oxidative stress, aging, and inflammation) is one of the important causes of vascular complications. For monitoring of the human serum albumin (HSA) carbonylation level, a spectrophotometric method based on the formation of colored adduct between guanidine group and thymol-sodium hypobromite reagent in the alkaline medium was investigated. Beer's law is obeyed in the concentration range of Arg and protein guanidine groups from 1 to 40 mM. Precision of the method (relative standard deviation) was in the range of 0.9 to 2%. Accuracy was examined by the standard addition method (recovery ~100%). The method was applied for monitoring of the carbonylation level of HSA with methylglyoxal in vitro and of HSA isolated (using affinity chromatography) from sera of 21 patients with type 2 diabetes and 12 healthy persons. The content of guanidine groups in HSA isolated from diabetics (19.64 ± 1.07 mM/mM albumin) was significantly lower (P < 0.001) in comparison with a control group (21.87 ± 1.02 mM/mM albumin). The method is simple and fast, has good accuracy and precision, and is suitable for clinical practice as well for in vitro protein carbonylation experiments.
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Defining metabolic acidosis in patients with septic shock using Stewart approach.
Mallat, J, Michel, D, Salaun, P, Thevenin, D, Tronchon, L
The American journal of emergency medicine. 2012;(3):391-8
Abstract
PURPOSE The aim of this study was to define the nature of metabolic acidosis in patients with septic shock on admission to intensive care unit (ICU) using Stewart method. We also aimed to compare the ability of standard base excess (SBE), anion gap (AG), and corrected AG for albumin and lactate (AGcorr) to accurately predict the presence of unmeasured anions (UA). PATIENTS AND METHODS Thirty consecutive patients with septic shock were prospectively included on ICU admission. Stewart equations modified by Figge were used to calculate the strong ion difference and the strong ion gap (SIG). RESULTS Most patients had multiple underlying mechanisms explaining the metabolic acidosis. Unmeasured anions and hyperchloremia were present in 70% of the patients. Increased UA were present in 23% of patients with normal values of SBE and [HCO3-]. In these patients, plasma [Cl-] was significantly lower compared with patients with low SBE and increased UA (103 [102-106.6] vs 108 [106-111] mmol/L; P=.01, respectively). Corrected AG for albumin and lactate had the best correlation with SIG (r²=0.94; P<.0001) with good agreement (bias, 0, and precision, 1.22) and highest area under the receiver operating characteristic curve (0.995; 95% confidence interval, 0.87-1) to discriminate SIG acidosis. CONCLUSIONS Patients with septic shock exhibit a complex metabolic acidosis at ICU admission. High UA may be present with normal values of SBE and [HCO3-] as a result of associated "relative" hypochloremic alkalosis. Corrected AG for albumin and lactate offers the most accurate bedside alternative to Stewart calculation of UA.
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Influence of ezetimibe monotherapy on ischemia-modified albumin levels in hypercholesterolemic patients.
Kotani, K, Caccavello, R, Sakane, N, Miyamoto, M, Gugliucci, A
Pharmacological reports : PR. 2011;(5):1248-51
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Abstract
Ischemia-modified albumin (IMA) is considered to be a novel biochemical marker for ischemic and atherosclerotic conditions. This study aimed to investigate the influence of ezetimibe monotherapy on circulating IMA levels in hypercholesterolemic patients. A total of 31 patients (mean age 65.7 years) received 10 mg of ezetimibe daily during a 12-week treatment period. The levels of low-density lipoprotein cholesterol and IMA were significantly reduced after ezetimibe treatment. The adjusted regression analyses revealed that the changes in the IMA levels were not significantly correlated with those of the other atherosclerotic risk markers, such as body mass index, blood pressure, glucose and lipid panels. The significant reduction of the IMA levels following ezetimibe treatment, which was independent of the reduction of low-density lipoprotein cholesterol levels, suggests that ezetimibe may improve the oxidative stress burden in hypercholesterolemic patients.
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Effect of intravenous iron administration frequency on AOPP and inflammatory biomarkers in chronic hemodialysis patients: a pilot study.
Anraku, M, Kitamura, K, Shintomo, R, Takeuchi, K, Ikeda, H, Nagano, J, Ko, T, Mera, K, Tomita, K, Otagiri, M
Clinical biochemistry. 2008;(14-15):1168-74
Abstract
OBJECTIVES Intravenous iron administration (IVIR) is effective for correcting anemia in hemodialysis (HD) patients, but it also enhances the generation of hydroxyl radicals. Previously we demonstrated that IVIR increases oxidized serum albumin levels in HD patients. However, the effect of IVIR frequencies on the oxidative stress has never been studied before. Therefore, we compared the two IVIR schedules recommended by the Japanese Society for Dialysis Therapy guideline 2004 by measuring oxidized albumin in chronic HD patients. DESIGN AND METHODS Twenty-two HD patients were divided into two IVIR protocol groups (group I: 40 mg of iron 3 times a week for 4 weeks, group II: 40 mg of iron once a week for 3 months). These protocols differ in IVIR frequency, but receive the same amount of iron (total 520 mg). We compared these two regimens by determining the levels of hemoglobin, serum ferritin, advanced oxidation protein products (AOPP), and oxidized albumin at 0, 4, 8, 12, 16, and 20 weeks. RESULTS Both patient groups resulted in a similar and significant increase in hemoglobin levels, whereas group I markedly induced AOPP and oxidation of serum albumin than group II at 4 weeks (P<0.05). AOPP and oxidation of serum albumin was also gradually declined by 20 weeks, while the oxidized albumin and AOPP in group II was not significantly changed during the entire experimental period. Transferrin saturation and serum ferritin levels were also increased in group I compared with group II at 4 weeks (P<0.001). In addition, we found a strong positive correlation between oxidized albumin and serum ferritin levels (r=0.615, P<0.05), suggesting the possibility that the accumulation of iron stores has a causative role in the progression of oxidative stress in HD patients treated with IVIR. CONCLUSIONS The results of this study indicate that lower frequency IVIR protocol is recommended to reduce IVIR-induced oxidative stress in HD patients.
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Significant association of serum albumin with severity of retinopathy and neuropathy, in addition to that of nephropathy, in Japanese type 2 diabetic patients.
Iwasaki, T, Togashi, Y, Terauchi, Y
Endocrine journal. 2008;(2):311-6
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OBJECTIVE The aim of this study was to determine the association between serum albumin and the severity of microvascular complications and presence of coronary artery disease in type 2 diabetic patients. PATIENTS AND METHODS The presence of diabetic complications was assessed in a total of 130 Japanese patients with type 2 diabetes mellitus. Retinopathy was classified as absent, simple or proliferative diabetic retinopathy. Neuropathy was considered to be present when the patient showed absence of Achilles tendon reflex, and also evaluated by measuring the median motor nerve conduction velocity (MNCV) in the nerve conduction study. RESULTS In relation to retinopathy, there were 83 patients with no retinopathy (absent), 26 with simple retinopathy and 21 with proliferative retinopathy. There was a significant difference in the serum albumin level between the "absent" group and the other two groups. In relation to nephropathy, there were 68 patients with no evidence of nephropathy, 49 with microalbuminuria and 13 with proteinuria. The results of logistic regression analysis with adjustment for three variables (age, gender, serum CRP) revealed that serum albumin was independently related to proliferative retinopathy and proteinuria. In relation to neuropathy, serum albumin was found to be significantly related to the absence of Achilles tendon reflex, MNCV, and MFWL. The results of multiple regression analysis with adjustment for three variables (age, gender, serum CRP) revealed that serum albumin was independently related to MNCV and MFWL. CONCLUSIONS Serum albumin was significantly associated with the severity of retinopathy and neuropathy.