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At least 19 recordsLinked to original sources
PubMed1986

Acetaldehyde adducts with serum proteins: effect on diazepam and phenytoin binding.

The in vitro effects of acetaldehyde treatment on the binding of phenytoin and diazepam to human serum albumin (HSA) and human serum proteins (HSP) have been investigated. The incorporation of acetaldehyde into proteins following incubation with different concentrations of [1,2-14 C]-acetaldehyde (0.5, 25, 100 mmol/l) was carried out. The proteins were then dialyzed so that only the stable adduct was retained. Binding of phenytoin and diazepam was then studied. Scatchard plot analysis showed a slight decrease (p less than 0.01 for HSP and 25 mmol/l acetaldehyde) in the number of binding sites for phenytoin when the acetaldehyde/protein ratio was increased. The affinity constant was also increased (p less than 0.01) with 100 mmol/l acetaldehyde. No change could be demonstrated in the number of diazepam binding sites on HSA; an increase in the binding capacity of HSP was shown following incubation with 25 mmol/l acetaldehyde. The fraction of drug bound at therapeutic levels has been also calculated for both drugs. An increase for diazepam but no change for phenytoin can be observed before or after treatment of proteins with acetaldehyde.

Acetaldehyde↗
PubMed2003

Capillary zone electrophoresis of serum proteins: effects of changed analytical conditions.

Analytical conditions in a system for capillary zone electrophoresis (Beckman Paragon CZE 2000) were originally selected to allow serum protein separation into five discrete protein zones, corresponding to those of conventional clinical electrophoresis. To improve the system's performance, new analytical conditions have been made available. We compared the two sets of conditions ("new" = y; "old" = x) for possible variations of results caused by the change. One hundred thirteen serum samples, covering wide intervals of values, were assayed on two twin instruments working under the old and the new conditions; results were assessed statistically and graphically. Possible clinical significance of differences was checked by comparison with the biological variation-based quality specifications for bias. Statistically significant (y-x) differences were observed for the alpha1-, alpha2- and beta-globulin zones; clinically significant differences were observed for all the zones, with the exception of the gamma-globulin zone. Therefore, old/new regression equations were calculated, whose reliability was assured by the wide interval of values, by the large sample size, and by the low dispersion of single values around the mean concordance estimates. Such equations may be used to convert "old" into "new" reference values, and for the intercomparison of patient results obtained under different analytical conditions.

Albumins↗
PubMed1989

[Displacing effect of serum protein binding on intestinal absorption of sulfadimethoxine].

The displacing effect of serum protein binding on the intestinal absorption of sulfadimethoxine (SDM) in rabbits was examined by using N4-acetylsulfadimethoxine (N4-AcSDM), a major metabolite of SDM, as a displacing drug. N4-AcSDM markedly decreased the in vitro serum protein binding of SDM, while many drugs including phenylbutazone and salicylic acid did not display such a marked decreasing-effect. The intravenous administration of N4-AcSDM clearly decreased the in situ intestinal absorption of SDM. As expected, the intravenously administered N4-AcSDM enhanced the serum concentration of unbound SDM in the common jejunal vein. However, the intravenously administered N4-AcSDM caused no change in the transfer of SDM across the intestinal membrane. These results indicate that the displacement of serum protein binding can become one of factors decreasing the intestinal absorption of SDM.

Animals↗
PubMedDate not supplied

Novel water-soluble bacteriochlorophyll derivatives for vascular-targeted photodynamic therapy: synthesis, solubility, phototoxicity and the effect of serum proteins.

New negatively charged water-soluble bacteriochlorophyll (Bchl) derivatives were developed in our laboratory for vascular-targeted photodynamic therapy (VTP). Here we focused on the synthesis, characterization and interaction of the new candidates with serum proteins and particularly on the effect of serum albumin on the photocytotoxicity of WST11, a representative compound of the new derivatives. Using several approaches, we found that aminolysis of the isocyclic ring with negatively charged residues markedly increases the hydrophilicity of the Bchl sensitizers, decreases their self-association constant and selectively increases their affinity to serum albumin, compared with other serum proteins. The photocytotoxicity of the new candidates in endothelial cell culture largely depends on the concentration of the serum albumin. Importantly, after incubation with physiological concentrations of serum albumin (500-600 microM), WST11 was found to be poorly photocytotoxic (>80% endothelial cell survival in cell cultures). However, in a recent publication (Mazor, O. et al. [2005] Photochem. Photobiol. 81, 342-351) we showed that VTP of M2R melanoma xenografts with a similar WST11 concentration resulted in approximately 100% tumor flattening and >70% cure rate. We therefore propose that the two studies collectively suggest that the antitumor activity of WST11 and probably of other similar candidates does not depend on direct photointoxication of individual endothelial cells but on the vascular tissue response to the VTP insult.

Bacteriochlorophylls↗
PubMed1979

Effect of serum protein binding on sulfisoxazole distribution, metabolism, and excretion in rats.

This investigation determined the effect of serum protein binding on the kinetics of sulfisoxazole distribution, metabolism, and excretion. Adult rats, whose serum free fraction of sulfisoxazole (at a total concentration of 81 +/- 6 micrograms/ml) was 0.05-0.24, received a rapid intravenous injection of 20 mg/kg. Sulfisoxazole concentrations in plasma declined biexponentially with time. There were pronounced and reproducible interindividual differences in the total, metabolic, and renal sulfisoxazole clearances, each positively correlated with the serum free fraction of sulfisoxazole. The renal sulfisoxazole clearance had a component unaffected by serum protein binding. The apparent central compartment volume increased with an increasing serum free sulfisoxazole fraction, but the latter had not apparent effect on the first exponential term of the biexponential equation describing sulfisoxazole elimination kinetics in rats. Serum protein binding was a major determinant of intersubject differences in sulfisoxazole excretion and biotransformation kinetics.

Animals↗
PubMed1990

Effects of serum proteins on estrogen action in the perfused rat liver.

To determine the effects of serum proteins on the biologic activity of estrogens, we perfused isolated livers from ovariectomized female rats with oxygenated Krebs-Henseleit-bicarbonate buffer (KHBB), with and without 4% human serum albumin (4% HSA), with and without added estrogens, or with charcoal-stripped human serum (CSHS) with and without added estradiol. At the end of the perfusions, the cytosolic and nuclear estrogen receptors were measured by an exchange assay. When added to KHBB, estradiol 10(-9) or 10(-8) M or estrone 10(-8) M did not cause any significant increase in the percent of receptors measured in the nucleus. When the livers were perfused with KHBB containing 4% HSA and estradiol 10(-9) to 10(-7) M or estrone 10(-8) M, there was an increase in nuclear receptors. Perfusion with estradiol 10(-8) M in CSHS resulted in significantly less receptor in the nucleus than after estradiol in KHBB plus 4% HSA. We conclude that the presence of 4% HSA in the perfusion medium increases the biologic activity of estradiol and estrone on the isolated rat liver, and this increase is inhibited in the presence of sex hormone-binding globulin. The exact mechanism by which HSA increases the biologic activity is uncertain, but may be due in part to better diffusion of estrogen through the liver.

Animals↗
PubMed1987

Effect of serum proteins on estrogen-mediated receptor translocation in the superfused rat uterus.

In order to examine the effects of serum proteins on the biologic activity of estrogens, we superfused uteri from ovariectomized rats with Krebs-Ringer phosphate buffer (KRP), 4% human serum albumin (HSA) in KR or charcoal-stripped human plasma (HP), alone or with estradiol (E2), estrone (E1) or estriol (E3), 5 x 10(-10), 10(-9) and 10(-8) M. Following superfusion, the uteri were homogenized and the cytosol and nuclear receptors were measured by an exchange technique. Since we could detect no significant difference in the percent of receptors in the nucleus when the time of superfusion was varied from 30-120 min, all studies were done using a 30 min superfusion at a flow rate of 0.6 ml/min. In control studies using KRP alone (n = 12) 23.8 +/- 1.8 (mean +/- SEM) of the receptors were present in the nucleus at the end of the 30 min superfusion. Addition of E1, E2 or E3 5 x 10(-10) M resulted in a significant increase compared to controls in the percent of receptors in the nucleus. The percent of nuclear receptors was significantly greater for E2 and E3 (46.5 +/- 3.2% and 43.6 +/- 1.8%) compared to E1 (34.0 +/- 0.9%). Superfusions of uteri with either E2 or E3 at 10(-9) M or 10(-8) M resulted in a significantly greater percent of nuclear receptors compared to equimolar infusions of E1. When uteri were superfused with E1 at 5 x 10(-10), 10(-9) or 10(-8) M or with E3 at 5 x 10(-10) or 10(-9) M in HSA or HP the percent of nuclear receptors was not different compared to the respective infusion of equimolar concentrations of E1 or E3 in KR. However, superfusions of E2 5 x 10(-10), 10(-9) or 10(-8) M in HSA or HP resulted in a significant decrease in the percent nuclear receptors compared to the percent after equimolar superfusions of E2 in KR. Superfusions of E2 in HSA or HP resulted in the same percent of receptors in the nucleus. The percent of receptors in the nucleus increased with increasing concentrations of E2, but at each concentration the percent of receptors was the same with HA as with HP. Using the percent of nuclear receptors as an index of biological activity, E1 has less activity than either E2 or E3. Interaction with serum proteins does not modulate the activities of either E1 or E3, except at the concentration of 10(-8) M for E3.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1978

Binding of aminoglycoside antibiotics to human serum proteins. III. Effect of experimental conditions.

The binding of several aminoglycoside antibiotics to human serum proteins was studied under varying experimental conditions. The protein binding was determined by means of equilibrium dialysis and, with sisomicin and gentamicin, also by the ultracentrifuge method in the presence and in the absence of Ca++ and Mg++ ions. The technical experimental procedure (dialysis, ultrafiltration, ultracentrifugation) has no effect on protein binding contrary to the physico-chemical conditions (varying concentrations of Ca++ and Mg++ ions). Under experimental conditions closely conforming to physiological conditions, the aminoglycosides of the kanamycin and neomycin series are not bound by the serum proteins, independent of the assay method used, whereas streptomycin is bound under these conditions. In the absence of divalent cations all the aminoglycosides studied were bound by the serum proteins to varying degrees; the fewer the OH groups contained in the aminoglycoside molecule the greater the rate of protein binding. At equal protein concentration, the albumin fraction of the serum has as great a binding capacity for sisomicin as gamma globulin. Alpha-1 and beta-1 globulin, however, are unable to bind sisomicin.

Aminoglycosides↗
PubMed2005

Underestimates and overestimates of total thyroxine concentrations caused by unwanted thyroxine-binding protein effects.

The first evidence of unwanted serum protein effects on analogue-based total thyroxine (T4) determinations came from a study that varied serum protein concentrations while total T4 concentrations were constant. The present study approached this issue by varying total T4 concentrations while protein concentrations were constant. Four analogue-based total T4 immunoassays were applied to solutions that contained either free T4 without binding protein, a T4-binding protein without T4, or protein-bound T4. When total T4 concentrations were 3-12 microg/dL, the assays reported total T4 determinations that ranged from none detected to 23 microg/dL. These T4 determinations reflected the protein to which T4 was bound, in addition to the level of T4. Total T4 was underrepresented when T4 was unbound, or thyroxine-binding globulin (TBG) bound. Total T4 was overrepresented when T4 was albumin-bound, or transthyretin-bound. There were substantial disparities among assays applied to the same total T4 solutions. These assays reported no detectable T4 when applied to T4-binding protein solutions without protein-bound T4. Nonetheless, T4-binding proteins contributed to the underestimates and overestimates of protein bound T4. Different forms of protein bound T4 were quantified differently, evidence that protein-T4 complexes persist during quantification. We attribute the unexpected total T4 values to a combination of incomplete protein-bound T4 release from T4-binding proteins during quantification, and variably inaccurate quantifications of the protein-bound T4 that remained.

Albumins↗
PubMed1999

Temperature effect on serum protein binding kinetics of phenytoin in monotherapy patients with epilepsy.

The effects of temperature on the binding kinetics of phenytoin (PHT) to serum proteins were determined in patients with epilepsy. Serum samples examined in the study were obtained from 59 patients (31 male, 28 female) with epilepsy on PHT monotherapy. Their age ranged from 3 to 64 years (mean (SD), 23.3 (16.3) years). Protein binding of PHT was evaluated by ultrafiltration under current routine laboratory conditions (25 +/- 3 degrees C) or at a temperature of 37 degrees C. The in vivo binding parameters of PHT to serum proteins were determined using a binding equation derived from the Scatchard equation for a one-site binding model. Significant differences were observed in serum concentrations of unbound PHT between paired data (P < 0.05). The mean association constant (K) of PHT to serum proteins is 0.011 microM-1 at 25 +/- 3 degrees C and 0.006 microM-1 at 37 degrees C, while mean total concentration of binding sites (n(Pt)) is 1002 microM for 25 +/- 3 degrees C and 1112 microM for 37 degrees C. Significant differences were observed in the binding kinetics of PHT to serum proteins for the different temperature conditions of ultrafiltration (P < 0.05). Our study confirms that binding affinity for PHT-serum protein interaction is approximately 45% lower at 37 degrees C than at 25 +/- 3 degrees C and consequently, binding potential (K.n(Pt)) is approximately 39% lower at 37 degrees C than at 25 +/- 3 degrees C.

Adolescent↗
PubMed1975

Seasonal and nutritional effects on serum proteins and urea concentration in the reindeer (Rangifer tarandus tarandus L.).

1. The effects of seasonal conditions and nutrition on serum proteins and serum urea concentrations were studied in female reindeer and reindeer calves in Finland. With the exception of one group in winter, the reindeer were roaming wild in the forests. This one group was kept in captivity, out of doors, on a comparatively high nutritional plane. One group lived wild during the winter in very poor nutritional conditions. 2. A very clear seasonal variation in the serum protein and urea concentration was found. The serum protein concentration was low in late winter and increased rapidly during the summer, being high in the autumn. The serum urea concentration was also low in the winter and high in the summer. In the autumn, however, the serum urea concentration was again low. 3. Changes in the serum protein concentration were normally associated with the serum globulins. Only in the very poor-nutrition group did the albumin content decrease significantly. As a result of the large changes in the concentration of serum globulins, there were also considerable changes in the albumin: globulin ratio. 4. The serum protein concentration was much lower in the reindeer calves than in the adult reindeer. The concentration of globulins in particular was much lower than in the adults.

Animal Nutritional Physiological Phenomena↗
PubMed1991

Effect of serum protein binding on the entry of lidocaine into brain and cerebrospinal fluid in dogs.

To test the hypothesis that lidocaine passage into the central nervous system is a function of free rather than total lidocaine concentration, we examined the effect of serum protein binding on the distribution of lidocaine into brain and cerebrospinal fluid (CSF) in dogs. Six of the 13 dogs studied were pretreated with rifampin to induce a 4-fold increase (P = 0.019) in serum concentration of alpha 1-acid glycoprotein, which is a major binding protein for lidocaine. The dogs were anesthetized and prepared surgically to obtain samples of cortical brain tissue or CSF from the cisterna magna. Lidocaine at a dose of 3 mg/kg was infused intravenously over 15 s. Arterial blood and brain cortex or CSF were sampled serially during a 60-min interval and analyzed for lidocaine content. Unbound or free fraction of lidocaine in serum was measured by equilibrium dialysis. Rifampin pretreatment led to a significant decrease in average serum free fraction of lidocaine, from 0.24 +/- 0.08 to 0.080 +/- 0.030 (P less than 0.001). Total lidocaine concentration in serum was higher, but free lidocaine concentration was lower in the rifampin group. Equilibration of lidocaine between serum and brain or CSF was reached by 10 min after lidocaine administration. Rifampin-pretreated dogs had consistently lower partition ratios of lidocaine between brain and serum or between CSF and serum. A strong and positive correlation between time-averaged brain to serum or CSF to serum ratios and serum free fractions were observed (r = 0.92, P less than 0.001 for brain; r = 0.90, P less than 0.01 for CSF).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1981

Aortic transmural serum protein transport: effect of concentration, time, and location.

The diffusive transport of certain 125I-labeled purified serum proteins, canine (C), human (H), and porcine (P) serum albumin (A), as well as human high-density lipoprotein (HDL), into the isolated deendothelialized intimal-medial thoracic aortic preparation was measured as a function of protein concentration (c0), intimal surface exposure time (T), and location (z) along the vessel at 21 degrees C. Selected proteins were studied in each of 11 canine preparations and 1 porcine preparation. The resulting uptake (M, nmol/cm2) was measured by direct gamma counting of specially excised fixed tissue specimens, and the transmural concentration distributions [c(xi), nmol/cm3] were calculated from electron probe X-ray microanalysis of the silver distributions across specially prepared microautoradiographs. The results showed 1) that the processes associated with the diffusive transport of CA, HA, PA, and HDL into the intimal-medial system are independent of c0, i.e., uptake is proportional to c0, 2) that the uptake of CA for short times appeared to be linear with T 1/2, 3) that the apparent wall-plasma partition coefficient for albumin rangers between 0.1 and 0.2, 4) that the apparent tissue albumin diffusion coefficient is approximately 2.7 X 10(-8) cm2/s, 5) that the transport processes for HA and CA are indistinguishable, 6) that the processes for the transport of HDL are two times slower than those for HA or CA, and 7) that the transport rate for albumin tends to decrease with z.

Animals↗
PubMed1995

Inhibition of protein tyrosine kinase alters the effect of serum basic protein I on triacylglycerols and cholesterol differently in normal and hyperapoB fibroblasts.

We studied whether the stimulatory effect of human serum basic protein I (BP I) on the formation of cell triacylglycerols and cholesterol may be mediated through protein tyrosine kinase in normal fibroblasts, and whether there was a deficiency in such a process in cells from subjects with hyperapobetalipoproteinemia (hyperapoB). Genistein, a highly specific inhibitor of tyrosine kinase phosphorylation, was used as a probe. When BP I (428.0 nmol/L) alone was added to F-12 medium without genistein, the mean mass of cell triacylglycerols doubled in six normal cell lines from healthy subjects, an effect that was decreased by 50% in six cell lines from subjects with hyperapoB (P = .007). The addition of genistein with BP I to normal cells decreased the stimulation of triacylglycerol formation by BP I by about 50% (P = .008), whereas genistein had little effect in the BP I-treated hyperapoB cells. The effect of genistein on the stimulation of triglyceride and cholesterol production by BP I was shown to be both time and concentration (92.5 nmol/mL medium nadir) dependent. In normal fibroblasts. BP I stimulated the rate of incorporation of both [14C]acetate (P = .0001) and [3H]mevalonolactone (P = .002) into unesterified cholesterol, an effect that was markedly deficient in the hyperapoB cells (P = .0001 for [14C]acetate and P = .0002 for [3H]mevalonolactone). In normal but not hyper-apoB cells, genistein inhibited the significant stimulation by BP I of the rates of both [14C]acetate (P = .0001) and [3H]mevalonolactone (P = .04) incorporation into unesterified cholesterol.(ABSTRACT TRUNCATED AT 250 WORDS)

Apolipoproteins B↗
PubMed1999

Effect of serum proteins on osteoblast adhesion to surface-modified bioactive glass and hydroxyapatite.

Previous studies indicate that modification of the surface of porous bioactive glass promotes osteoblast function. We hypothesize that bone formation on treated bioactive glass is due to the selective adsorption of serum attachment proteins. To test this hypothesis, we examined the profile of proteins adsorbed to treated bioactive glass and compared these proteins with those adsorbed to untreated bioactive glass and porous hydroxyapatite. Porous bioactive glass was treated with Tris-buffered electrolyte solution to generate a calcium phosphate-rich surface layer and then immersed in tissue-culture medium containing 10% serum. Proteins adsorbed to the ceramic surfaces were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western blot analysis. Porous hydroxyapatite bound a higher amount of total protein than did the other substrates. However, surface-modified porous bioactive glass adsorbed more fibronectin than did hydroxyapatite. The effect of serum-protein adsorption on osteoblast adhesion to bioactive glass and hydroxyapatite was also evaluated. Cell adhesion to porous bioactive glass that was surface-modified and serum-treated was significantly greater than to porous bioactive glass that was either surface-modified or serum-treated. Furthermore, cell adhesion to porous bioactive glass treated to form the dual layer of calcium phosphate and serum protein was significantly higher than adhesion to porous hydroxyapatite with adsorbed serum protein. Results of the study strongly suggest that adsorption of serum fibronectin to the surface of modified porous bioactive glass coated with calcium phosphate may be responsible for enhanced osteoblast adhesion.

Absorption↗