Showing papers on "Serum albumin published in 1995"
TL;DR: It was concluded that the progression of renal failure is associated with a spontaneous decrease in DPI, especially below a CrCl of 25 mL/min, and that most nutritional indices in CRF patients worsen as CrCl and DPI decrease.
Abstract: Malnutrition at the initiation of dialysis is a strong predictor of subsequent increased mortality on dialysis. Few studies have documented the relationship between the progression of renal failure and spontaneous dietary protein intake (DPI) and other indices of malnutrition. In this prospective study, renal function was sequentially measured by creatinine clearance (CrCl) and DPI by 24-h urine collection; simultaneously, multiple sequential biochemical nutritional indices, including serum albumin, transferrin, prealbumin, and insulin-like growth factor-I (IGF-I) concentrations, were measured. The study involved 90 patients (46 men and 44 women) with chronic renal failure (CRF) of various causes monitored in an outpatient clinic. Dietary interventions were minimal. The mean duration of follow-up was 16.5 +/- 11.8 months. The results show that the mean (+/- SD) DPI was 1.01 +/- 0.21 g/kg per day for patients with CrCl over 50 mL/min and decreased to 0.85 +/- 0.23 g/kg per day for patients with CrCl between 25 and 50 mL/min. The DPI further decreased to a level of 0.70 +/- 0.17 g/kg per day for patients with CrCl between 10 and 25 mL/min and was 0.54 +/- 0.16 g/kg per day for patients with CrCl below 10 mL/min. This trend was statistically significant (P < 0.001). A similar statistically significant trend was observed for serum cholesterol, transferrin, and total creatinine excretion (all P < 0.01). A mixed model analysis indicated that for each 10 mL/min decrease in CrCl, DPI decreased by 0.064 +/- 0.007 g/kg per day, transferrin decreased by 16.7 +/- 4.1 mg/dL, weight decreased by 0.38 +/- 0.13% of initial weight, and IGF-I decreased by 6.2 +/- 1.9 ng/mL. It was concluded that the progression of renal failure is associated with a spontaneous decrease in DPI, especially below a CrCl of 25 mL/min, and that most nutritional indices in CRF patients worsen as CrCl and DPI decrease. Dietary protein restriction should be used cautiously in CRF patients when CrCl falls below 25 mL/min.
385 citations
TL;DR: It is concluded that chronic metabolic acidosis causes negative nitrogen balance and decreases albumin synthesis in humans and may be mediated, at least in part, by a suppression of insulin-like growth factor-I, free thyroxine and tri-iodothyronine.
Abstract: Chronic metabolic acidosis has been previously shown to stimulate protein degradation To evaluate the effects of chronic metabolic acidosis on nitrogen balance and protein synthesis we measured albumin synthesis rates and urinary nitrogen excretion in eight male subjects on a constant metabolic diet before and during two different degrees of chronic metabolic acidosis (NH4Cl 21 mmol/kg body weight, low dose group, and 42 mmol/kg body weight, high dose group, orally for 7 d) Albumin synthesis rates were measured by intravenous injection of [2H5ring]phenylalanine (43 mg/kg body weight, 75 atom percent and 15 atom percent, respectively) after an overnight fast In the low dose group, fractional synthesis rates of albumin decreased from 99 +/- 10% per day in the control period to 84 +/- 07 (ns) in the acidosis period, and from 83 +/- 13% per day to 63 +/- 11 (P < 0001) in the high dose group Urinary nitrogen excretion increased significantly in the acidosis period (sigma delta 634 mmol in the low dose group, 2,554 mmol in the high dose group) Plasma concentrations of insulin-like growth factor-I, free thyroxine and tri-iodothyronine were significantly lower during acidosis In conclusion, chronic metabolic acidosis causes negative nitrogen balance and decreases albumin synthesis in humans The effect on albumin synthesis may be mediated, at least in part, by a suppression of insulin-like growth factor-I, free thyroxine and tri-iodothyronine
360 citations
TL;DR: Analysis of the kinetic data indicated that the rate-limiting step was the reaction of NO with oxygen, and the reaction rate of the nitrosating species N2O3 with thiols is competitive with its rate of hydrolysis.
357 citations
TL;DR: Data from this study support the hypothesis that the pharmacological activity of MPA is a function of unbound drug concentration.
Abstract: Mycophenolate mofetil, the prodrug form of the immunosuppressive agent mycophenolic acid (MPA), is currently in clinical trials evaluating its effectiveness in transplant recipients. In this study, we validated an ultrafiltration system for the reliable measurement of free MPA. Using this technique, we evaluated factors that might be important in modulating the free fraction of this drug. Human serum albumin (HSA), high concentrations of the primary glucuronide metabolite of MPA, and sodium salicylate significantly affected MPA binding. For HSA the mean +/- SE binding capacity (Bmax) and the dissociation constant (Kd) were 1095 +/- 34 mumol/L and 12.98 +/- 0.93 mumol/L, respectively. The dose for 50% inhibition (IC50) of inosine monophosphate dehydrogenase isoform II by MPA increased 5.4-fold as the concentration of HSA added to the enzyme reaction mixture increased from 0 to 50 g/L (0-724 mumol/L). Furthermore, the IC50 MPA concentration for phytohemagglutinin A-stimulated human peripheral blood mononuclear cells increased 4.8-fold when incubations were performed in the presence of 10 g/L (145 mumol/L) HSA vs no added HSA. These data support the hypothesis that the pharmacological activity of MPA is a function of unbound drug concentration.
320 citations
TL;DR: Whether certain nutritional indices and the acute‐phase protein response are prognostic factors independent of disease stage for patients with unresectable pancreatic cancer are determined.
Abstract: Background. Current methods to predict survival duration of patients with pancreatic cancer are limited. The aim of this study was to determine whether certain nutritional indices and the acute-phase protein response are prognostic factors independent of disease stage for patients with unresectable pancreatic cancer. Methods. Variables at the time of diagnosis of 102 patients with unresectable pancreatic cancer were entered into a Cox's proportional hazards model. Included in the analysis were the serum concentration of C-reactive protein (CRP) and albumin, the extent of weight loss, age, sex, and disease stage (International Union Against Cancer criteria). Results. A multivariate analysis in which each factor was adjusted for the influence of the other factors revealed the patient age, disease stage, serum albumin, and serum CRP to be independent predictors of survival. The presence of an acute-phase protein response was the most significant independent predictor of survival duration. The median survival of those with an acute-phase protein response (CRP > 10 mg/L, n = 45) was 66 days compared with 222 days for those with no acute-phase protein response (n = 57, P = 0.001, Mann-Whitney Utest). Conclusion. The acute-phase protein response is a useful prognostic indicator for patients with unresectable pancreatic cancer. Moreover, the metabolic disturbances associated with an acute-phase protein response of patients with pancreatic cancer may be a worthwhile therapeutic target. Cancer 1995 ;75 :2077-82.
302 citations
TL;DR: The results show that the increase of IL-6 levels in CSF and serum is followed by a profound acute-phase response in patients with TBI, and it is hypothesized that IL- 6 produced in the central nervous system may play a role in initiating the acute- phase response.
Abstract: Patients with severe traumatic brain injury (TBI) show a profound acute-phase response. Because interleukin-6 (IL-6) is an important mediator of these pathophysiological changes, IL-6 levels were monitored in the cerebrospinal fluid (CSF) and serum of 20 patients with severe isolated TBI. All patients received indwelling ventricular catheters for intracranial pressure monitoring and for release of CSF when intracranial pressure exceeded 15 mmHg. CSF and blood samples were drawn daily for up to 14 days. The CSF/serum albumin ratio (QA) served as a parameter of blood brain barrier dysfunction. Differential blood counts as well as the acute-phase proteins C-reactive protein, alpha 1-antitrypsin, and fibrinogen were recorded. IL-6 was detected in all CSF samples and reached values of up to 31,000 pg/mL, while serum levels remained significantly lower (alpha < or = .01) and never exceeded 1,100 pg/mL the entire study period. A correlation between CSF and serum IL-6 was found initially after the trauma and corresponded to a severe dysfunction of the blood brain barrier (r = .637, p = .001). Maximum IL-6 concentrations in serum correlated with peak levels of acute-phase proteins (C-reactive protein, alpha 1-antitrypsin, and fibrinogen). With regard to blood cell count, an initial leukocytosis combined with a borderline lymphocytopenia was observed. Thrombocytes decreased to a subnormal level during the first few days, but reached supranormal numbers by the end of the study period. Our results show that the increase of IL-6 levels in CSF and serum is followed by a profound acute-phase response in patients with TBI. Because cytokine concentrations are significantly lower in serum compared with CSF, we hypothesize that IL-6 produced in the central nervous system may play a role in initiating the acute-phase response.
277 citations
TL;DR: The phase angle alpha was the best single predictive factor for survival among all 12 parameters (comparison of the respective Cox models with the likelihood ratio test) and the ECM/BCM ratio, Xc, BCM, serum cholesterol, number of CD4+ cells, and serum albumin had significant prognostic influence on survival.
Abstract: In patients with AIDS, short-term survival has been related to body weight, body composition, and serum nutritional parameters, but their prognostic impact at earlier stages of the HIV infection is not known. With an individual follow-up period of 1,000 days, we investigated the prognostic relevance of electrical tissue conductivity [resistance R, reactance Xc, phase angle alpha, extracellular mass (ECM), body cell mass (BCM)] measured by bioelectrical impedance analysis, of the CD4+ cell count, and of serum parameters indicating malnutrition in 75 HIV-infected male patients at Walter Reed stages 3-5. After initial recording, 29 patients (38.7%) died from AIDS during this period. Among 12 parameters estimated with a semiparametric Cox regression model adjusted for therapy (pentamidine, azidothymidine), the phase angle alpha (parameter estimate: -1.043, 95% confidence interval of -0.61 to -1.47; p < or = 0.0001), the ECM/BCM ratio, Xc, BCM, serum cholesterol, number of CD4+ cells, and serum albumin had significant prognostic influence on survival, whereas age, body weight, body mass index, resistance, serum protein, and serum triglycerides did not. In a model with four covariates (CD4+ cells, phase angle, pentamidine, azidothymidine), the prognostic impact of the CD4+ cell count (parameter estimate: -0.549) was lower compared with the phase angle alpha (parameter estimate: -0.799; p < or = 0.0001) and did not gain statistical significance (p = 0.0626). The phase angle alpha was the best single predictive factor for survival among all 12 parameters (comparison of the respective Cox models with the likelihood ratio test).(ABSTRACT TRUNCATED AT 250 WORDS)
251 citations
TL;DR: It is suggested that biochemical measures associated with visceral and somatic protein depletion are predominant long-term mortality risk factors in patients maintained on hemodialysis and CAPD.
239 citations
TL;DR: It is concluded that protein-bound dinitrosyl-iron complexes detected in high concentrations in certain tissues provide a reservoir of S-nitrosating species, e.g. low molecular dinitron-iron-di-L-cysteine complexes.
239 citations
TL;DR: A dose-response relationship between the amount of displaceable NO delivered and the extent of inhibition of neointimal proliferation at 2 wk is revealed and local administration of a stable protein S-nitrosothiol inhibits intimal proliferation and platelet deposition after vascular arterial balloon injury.
Abstract: Endothelium-derived relaxing factor is important for vascular homeostasis and possesses qualities that may modulate vascular injury, including vasodilation, platelet inhibition, and inhibition of smooth muscle proliferation. S-nitrososerum albumin is a naturally occurring adduct of nitric oxide (NO) with a prolonged biologic half-life and is a potent vasodilator and platelet inhibitor. Given the avidity of serum albumin for subendothelial matrix and the antiproliferative effects of NO, we investigated the effects of locally delivered S-nitroso-bovine serum albumin (S-NO-BSA) and a polythiolated form of bovine serum albumin (pS-BSA) modified to carry several S-nitrosothiol groups (pS-NO-BSA) on neointimal responses in an animal model of vascular injury. Locally delivered S-NO-BSA bound preferentially to denuded rabbit femoral vessels producing a 26-fold increase in local concentration compared with uninjured vessels (P = 0.029). pS-NO-BSA significantly reduced the intimal/medial ratio (P = 0.038) and did so in conjunction with elevations in platelet (P < 0.001) and vascular cGMP content (P < or = 0.001). pS-NO-BSA treatment also inhibited platelet deposition (P = 0.031) after denuding injury. Comparison of BSA, S-NO-BSA, pS-NO-BSA, and control revealed a dose-response relationship between the amount of displaceable NO delivered and the extent of inhibition of neointimal proliferation at 2 wk (P < or = 0.001). Local administration of a stable protein S-nitrosothiol inhibits intimal proliferation and platelet deposition after vascular arterial balloon injury. This strategy for the local delivery of a long-lived NO adduct has potential for preventing restenosis after angioplasty.
234 citations
TL;DR: Microalbuminuria is an independent marker of systemic transvascular albumin leakiness in clinically healthy subjects and was independent of age, sex, smoking status, blood pressure, body size, plasma volume, plasma albumin concentration and concentrations of blood glucose, serum insulin and serum lipids.
Abstract: 1. In epidemiological studies microalbuminuria, i.e. slightly elevated urinary albumin excretion rate, predicts increased atherosclerotic vascular morbidity and mortality. This study aimed to test the hypothesis that microalbuminuria in clinically healthy subjects is associated with a systemic transvascular albumin leakiness. In animal experiments the outflux of albumin and lipids to the arterial wall are highly correlated, and both are elevated in atherosclerosis.
2. All participants were recruited at random from a population-based epidemiological study, where the upper decile of urinary albumin excretion rate was 6.6 μg/min. Twenty-seven patients with persistent microalbuminuria (urinary albumin excretion rate 6.6–150 μg/min), and 56 age- and sex-matched control subjects with persistent normoalbuminuria (UAER ≤ 6.6 μg/min) were studied.
3. The systemic transvascular albumin leakage was measured as the fractional disappearance rate of 125I-labelled albumin from the total plasma compartment in 1 h after intravenous injection.
4. The fractional disappearance rate of albumin from the plasma compartment was higher in the microalbuminuric than in the normoalbuminuric group [5.8 (95% confidence interval 5.3–6.2; n = 27) versus 5.0 (4.6–5.5; n = 56)%/h, P < 0.05]. The positive correlation between urinary albumin excretion rate on continuous scale (logarithmically transformed) and the fractional disappearance rate of albumin from the plasma compartment [slope 0.4 (95% confidence interval 0.1–0.7; n = 83), r = 0.29, P < 0.005] was independent of age, sex, smoking status, blood pressure, body size, plasma volume, plasma albumin concentration and concentrations of blood glucose, serum insulin and serum lipids.
5. In conclusion, microalbuminuria is an independent marker of systemic transvascular albumin leakiness in clinically healthy subjects. This finding may partly explain the increased atherosclerotic vascular morbidity and mortality in microalbuminuric subjects. It is suggested that the observed transvascular leakiness, in addition, may cause increased lipid insudation to the arterial walls.
TL;DR: Analysis of amino acid modification, gel filtration chromatographic, and electrophoretic characteristics of bovine and human serum albumins irreversibly modified by methylglyoxal and by glucose-derived advanced glycation endproducts suggested that AGE formed from glucose-modified proteins and AGE-like compounds formed from methyl glyoxal- modified proteins may both be signals for recognition and degradation of senescent macromolecules.
Abstract: The amino acid modification, gel filtration chromatographic, and electrophoretic characteristics of bovine and human serum albumins irreversibly modified by methylglyoxal (MG-SA) and by glucose-derived advanced glycation endproducts (AGE-SA) were investigated. Methylglyoxal selectively modified arginine residues at low concentration (1 mM); at high methylglyoxal concentration (100 mM), the extent of arginine modification increased and lysine residues were also modified. Both arginine and lysine residues were modified in AGE-SA. Analytical gel filtration HPLC of serum albumin derivatives suggested that the proportion of dimers and oligomers increased with modification in both low and highly modified MG-SA and AGE-SA derivatives relative to unmodified serum albumins. In SDS-PAGE analysis, dimers and oligomers of low-modified MG-SA were dissociated into monomers, but not in highly modified MG-SA. MG-SA had increased anodic electrophoretic mobility under nondenaturing conditions at pH 8.6, indicating an increased net negative charge, which increased with extent of modification; highly modified MG-SA and AGE-SA had similar high electrophoretic mobilities. MG-SA derivatives were fluorescent: the fluorescence was characteristic of the arginine-derived imidazolone N delta-(5-methyl-4-imidazolon-2-yl)ornithine, but other fluorophores were also present. AGE-SA had similar fluorescence, attributed, in part, to glucose-derived imidazolones. AGE formed from glucose-modified proteins and AGE-like compounds formed from methylglyoxal-modified proteins may both be signals for recognition and degradation of senescent macromolecules.
TL;DR: This study demonstrates that transient, survivable disruption (wounding) of the cardiac myocyte plasma membrane is a constitutive event in vivo and proposes that contraction-induced cardiac myocytes wounding releases aFGF and bFGF, which then may act as autocrine growth-promoting stimuli.
Abstract: The heart hypertrophies in response to certain forms of increased mechanical load, but it is not understood how, at the molecular level, the mechanical stimulus of increased load is transduced into a cell growth response. One possibility is that mechanical stress provokes the release of myocyte-derived autocrine growth factors. Two such candidate growth factors, acidic and basic fibroblast growth factor (aFGF and bFGF, respectively), are released via mechanically induced disruptions of the cell plasma membrane. In the present study, we demonstrate that transient, survivable disruption (wounding) of the cardiac myocyte plasma membrane is a constitutive event in vivo. Frozen sections of normal rat heart were immunostained to reveal the distribution of the wound event marker, serum albumin. Quantitative image analysis of these sections indicated that an average of 25% of the myocytes contained cytosolic serum albumin; ie, this proportion had suffered a plasma membrane wound. Wounding frequency increased approximately threefold after beta-adrenergic stimulation of heart rate and force of contraction. Heparin-Sepharose chromatography, enzyme-linked immunosorbent assay, growth assay coupled with antibody neutralization, and two-dimensional SDS-PAGE followed by immunoblotting were used to demonstrate that both aFGF and bFGF were released from an ex vivo beating rat heart. Importantly, beta-adrenergic stimulation of heart rate and force of contraction increased FGF release. Cell wounding is a fundamental but previously unrecognized aspect of the biology of the cardiac myocyte. We propose that contraction-induced cardiac myocyte wounding releases aFGF and bFGF, which then may act as autocrine growth-promoting stimuli.
TL;DR: The adsorption of bovine serum albumin (BSA) onto hydroxyapatite (HA) has been studied as a function of protein concentration, pH and ionic strength, with results indicating that both electrostatic and hydration effects are important.
TL;DR: It is demonstrated that the amount of β2-glycoprotein I associated with liposomes, as quantitated by an enzyme-linked immunosorbent assay, is correlated with their clearance rates; moreover, the circulation residency time of cardiolipin-containing liposome is extended in mice pretreated with anti-β2- Glycop protein I antibodies.
TL;DR: Calorimetric experiments show strong perturbations of acyl chains of phospholipids by HA, predicting that disruptive effects of VLCFA on cell membrane structure and function may explain the neurological manifestations of ALD patients.
Abstract: Adrenoleukodystrophy (ALD) is an inherited disorder of fatty acid metabolism marked by accumulation of very long chain saturated fatty acids (VLCFA), especially the 26-carbon acid, hexacosanoic acid (HA), in membranes and tissues We have studied interactions of 13C-enriched HA with model membranes (phospholipid bilayer vesicles) and bovine serum albumin (BSA) by 13C NMR spectroscopy to compare properties of HA with those of typical dietary fatty acids In phospholipid bilayers the carboxyl group of HA is localized in the aqueous interface, with an apparent pKa (74) similar to other fatty acids; the acyl chain must then penetrate very deeply into the membrane Desorption of HA from vesicles (t1+2 = 3 h) is orders of magnitude slower than shorter chain fatty acids In mixtures of vesicles and BSA, HA partitions much more favorably to phospholipid bilayers than typical fatty acids BSA binds a maximum of only 1 mole of HA at one binding site Calorimetric experiments show strong perturbations of acyl chains of phospholipids by HA We predict that disruptive effects of VLCFA on cell membrane structure and function may explain the neurological manifestations of ALD patients These effects will be further amplified by slow desorption of VLCFA from membranes and by the ineffective binding to serum albumin
TL;DR: The results suggest that IL-6 may be a mediator of various reactions including an inflammatory response in lung cancer patients and in patients with benign lung diseases.
Abstract: Serum interleukin 6 (IL-6) levels were measured in 75 patients with lung cancer and in 20 patients with benign lung diseases. IL-6 was detectable in 29 patients with lung cancer (39%), but was not detectable in any of the patients with benign lung diseases. Serum C-reactive protein levels and plasma fibrinogen levels were significantly higher and serum albumin concentration was significantly lower in lung cancer patients with detectable serum IL-6 levels than in those without detectable serum IL-6 levels and in patients with benign lung diseases. On the other hand, no significant difference was observed in blood platelet counts in these three groups. Moreover, serum IL-6 levels were not significantly different in lung cancer patients with or without clinically demonstrated distant metastasis. These results suggest that IL-6 may be a mediator of various reactions including an inflammatory response in lung cancer patients.
TL;DR: It is shown that albumin is an important blood component responsible for inducing astrocyte proliferation and generates maintained trains of calcium spikes inAstrocytes, and that neither activity depends on blood coagulation.
Abstract: Cells in the central nervous system are normally prevented from coming into contact with albumin and other protein components of blood by the existence of a tight blood-brain barrier. Astrocytes and other glial cells proliferate to form glial scars when the blood-brain barrier is breached. In this report we show that albumin is an important blood component responsible for inducing astrocyte proliferation. Albumin also generates maintained trains of calcium spikes in astrocytes. Neither activity depends on blood coagulation, as albumins from both serum and plasma are approximately equally effective. Methanol extraction of albumin abolishes both actions, and recombination of the methanol-extracted factor with extracted albumin restores full activity indistinguishable from that of native albumin. The factor is sensitive to lipase, and the solvent extraction profile is that of a polar lipid.
TL;DR: In healthy elderly subjects, f−(HMA) was significantly lower than in healthy young male subjects, indicating that HSA in the elderly becomes more oxidized than in the young subjects, thus securing a certain redox buffer capacity with age.
TL;DR: The use of proteins as chiral selectors in CE is reviewed in this article, where the performance of packed-capillary electrochromatography with protein phases is compared with free-solution systems.
TL;DR: Zonal elution and high-performance affinity chromatography studies indicated that R- and S-ibuprofen had one common binding site on the immobilized HSA column and at least one other major binding region.
TL;DR: Human serum albumin prepared by blood fractionation for clinical purposes was found to degrade when stored at or above 30 degree C, and an intact aspartyl-alanyl dipeptide, purified from degraded albumin solutions, differed substantially from a synthetic dipeptic on amino acid analysis, N-terminal sequencing and NMR.
Abstract: Human serum albumin prepared by blood fractionation for clinical purposes was found to degrade when stored at or above 30 degree C. Mass spectrometry and N-terminal sequencing of the protein identified degradation corresponding to the loss of the first two residues, aspartic acid and alanine. The reaction was shown to be dependent upon temperature and the N-terminal alpha-amino group. In addition, comparison with serum albumins derived from other species showed that the instability of the N-terminus was specific to the human albumin sequence. An intact aspartyl-alanyl dipeptide, purified from degraded albumin solutions, differed substantially from a synthetic dipeptide on amino acid analysis, N-terminal sequencing and NMR. It is suggested that the released dipeptide may be cyclic, implying a novel cleavage mechanism.
TL;DR: It is suggested that HGF accelerates both the hepatic regeneration and function in vivo, and that rhHGF is clinically expected to be a potent therapeutic agent in hepatectomy and liver injury.
Abstract: The effects of recombinant human hepatocyte growth factor (HGF) on liver growth and function of normal and partially hepatectomized rats have been examined. HGF was continuously administered into the jugular vein because it was rapidly eliminated from the plasma (t1/2 alpha; approximately 4.5 min) and degraded. In normal rats, the labeling index of hepatocytes was increased about 6 times by the administration of HGF. HGF also decreased the prothrombin time and increased the hepaplastin and serum albumin content. In 70%-hepatectomized rats, HGF stimulated liver regeneration and increased the level of blood proteins such as hepaplastin in a dose-dependent manner. The stimulation of serum protein level seemed to result from not only the increase of hepatic cell number but also the direct effect of HGF on the protein production in hepatocytes, because HGF rapidly enhanced the protein synthesis prior to the increase of cell number and increased the mRNA content of albumin in the liver in vivo. In addition, a combination of heparin with HGF further accelerated the effects of HGF described above, possibly due to the decrease of HGF clearance. These findings suggest that HGF accelerates both the hepatic regeneration and function in vivo, and that rhHGF is clinically expected to be a potent therapeutic agent in hepatectomy and liver injury.
TL;DR: A 6-week regimen of subcutaneous rhIL-6 results in a rapid dilution anemia, caused by an acute and significant increase in plasma volume and followed by hypoferremia, which is reversible after the cessation of rhil-6 treatment.
TL;DR: The present limited data indicated that the four uremic toxins caused inhibition to any endo- or exogenous substances on HSA, and the binding parameter of CMPF was found to have the strongest affinity (10(7)M-1) among all the uremi toxins studied.
Abstract: The interaction of uremic toxins including indole-3-acetic acid (IA), indoxyl sulfate (IS), hippuric acid (HA) and 3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid (CMPF) with human serum albumin (HSA) has been investigated by three methods of fluorescent probe displacement, ultrafiltration and equilibrium dialysis. The binding parameter of CMPF was found to have the strongest affinity (10(7)M-1) among all the uremic toxins studied. Competitive experiment based on the method of Kragh-Hansen suggested that IA, IS and HA bind to site II, whereas CMPF binds to site I. The present limited data indicated that the four uremic toxins caused inhibition to any endo- or exogenous substances on HSA.
TL;DR: Paired sera and cervicovaginal secretions from 30 women infected with human immunodeficiency virus (HIV) type 1 (before AIDS) were analyzed for Igg and IgA antibodies to HIV and for IgG, IgA, and human serum albumin, suggesting a local synthesis of both isotypes.
Abstract: Paired sera and cervicovaginal secretions (CVS) from 30 women infected with human immunodeficiency virus (HIV) type I (before AIDS) were analyzed for IgG and IgA antibodies to HIV and for IgG IgA and human serum albumin Subjects were compared with 30 age-matched healthy controls In HIV-infected women cervicovaginal immunoglobulins were markedly increased and IgG predominated An increased immunoglobulin transudation was implicated since cervicovaginal albumin levels were 23-fold above those of normal controls Furthermore IgG excretion by reference to albumin was increased 19-fold whereas the IgA secretion tended to decrease suggesting a possible enhanced local IgG synthesis Mean IgG and IgA anti-HIV antibody titers were respectively 30- and 12-fold higher in serum than in CVS but their mean specific activities were higher in CVS than in serum suggesting a local synthesis of both isotypes The IgA antibody response to HIV remained poor compared with the strong IgG response (authors)
TL;DR: S-ODNs are likely to interact and displace other therapeutic agents that bind to albumin, particularly those binding at site I, and suggest cooperative binding and/or the presence of secondary binding sites on the S-ODN.
Abstract: Phosphorothioate oligonucleotides (S-ODNs) have the ability to modulate gene expression selectively and thus have potential therapeutic capabilities. This potential led us to investigate the protein binding characteristics of selected S-ODNs. We evaluated S-ODN interactions with bovine serum albumin (BSA) and human serum albumin (HSA) in vitro. The equilibrium dissociation constants Km for the binding of a 20 mer S-ODN with BSA and HSA range between 1.1-5.2 x 10(-5) and 2.4-3.1 x 10(-4) M, respectively. The Km for an unrelated 15 mer S-ODN binding with HSA ranges between 3.7 and 4.8 x 10(-5) M. Studies with a fluorescently labeled 27 mer S-ODN suggest cooperative binding (Hill slope = 1.67) and/or the presence of secondary binding sites on the S-ODN. HSA or BSA linked to Sepharose was incubated with a 15, 20, or 24 mer S-ODN followed by the addition of selected drugs known to be highly protein bound (nifedipine, warfarin, midazolam, probenecid, indomethacin, and mitoxantrone). Up to 30% of S-ODN was displaced by warfarin in competition binding assays. Conversely, HSA-bound warfarin was incubated with a variety of oligonucleotides, including RNA and genomic dsDNA. Maximum displacement of warfarin-bound HSA was observed following incubation with 5'-cholesterol-conjugated 20 mer S-ODN. In summary, S-ODNs are likely to interact and displace other therapeutic agents that bind to albumin, particularly those binding at site I.
TL;DR: The dissociation constants for the binding of the four compounds to human serum albumin were determined by fluorescence quenching titrations, and all four were found to have much lower affinities for albumin than the parent compound gossypol.
Abstract: 1,1'-Dideoxygossypol (DDG), 1,1'-dideoxygossylic acid (DDGA), 8-deoxyhemigossypol (DHG), and 8-deoxyhemigossylic acid (DHGA) were synthesized and tested for their ability to inhibit the replication of HIV in vitro. The EC50 for DDGA was < 1 microM, and its threshold cytotoxicity was approximately 20 microM. DDG was less effective than DDGA against HIV and showed considerable toxicity at 5 microM. DHGA was ineffective against HIV and had very low cytotoxicity. DHG showed some anti-HIV activity, but the threshold cytotoxicity was 5 microM. The dissociation constants for the binding of the four compounds to human serum albumin were determined by fluorescence quenching titrations, and all four were found to have much lower affinities for albumin than the parent compound gossypol.
TL;DR: Perfluoropropane-exposed sonicated dextrose albumin is an ultrasound contrast agent that can visually identify myocardial perfusion abnormalities from a peripheral venous injection.