Α1-acid Glycoprotein Levels Research Articles

Relation between pancreatic islet cellular infiltration and plasma fibrinogen or alpha 1-acid glycoprotein levels in spontaneously and streptozotocin-diabetic rats: an increase in these protein levels is not necessary for inducing microcirculatory erythrocyte velocity alteration.

Plasma levels of fibrinogen, alpha 1-acid glycoprotein (AG) and albumin, pancreatic insulitis quantitative scores, and erythrocyte velocity in the mesoappendix microvessels were measured in BB diabetic (BBD) and streptozotocin-diabetic rats (WSTZ) in order to answer the following questions: (a) Does hyperfibrinogenemia or increase in AG plasma level occur in BBD and WSTZ rats, and if so, are these alterations secondary to the hyperglycemia or to an inflammatory process such as insulitis? (b) Is there a decrease in microcirculatory flow in the BBD and WSTZ rats, and if so, is it secondary to the hyperfibrinogenemia and/or the hyperglycemia? Insulitis was present in the BBD rats after 5 weeks of disease (with a score of 2.9 +/- 0.1 vs. 1.4 +/- 0.6 in the normoglycemic controls), but absent in WSTZ rats after 5 months of disease (1.2 +/- 0.06 vs. 1.1 +/- 0.06). Increase in fibrinogen and AG plasma levels was observed in the BBD rats only and appears linked to the insulitis. The major acute phase protein AG level is increased in BBD rats already on the first day of appearance of glycosuria. In the WSTZ rats, without insulitis, chronic hyperglycemia alone did not induce an increase in fibrinogen and AG plasma levels. A decreased microcirculatory erythrocyte velocity has been found in both BBD and WSTZ rats. Thus an increase in fibrinogen or AG plasma levels is not necessary for inducing a decrease in erythrocyte velocity. Hyperglycemia is probably the main factor responsible for the decrease in microcirculatory flow in the BBD and WSTZ rats.

Increased Erythrocyte and Protein Binding of Codeine in Patients with Sickle Cell Disease

Erythrocyte binding and plasma protein binding of codeine in sickle cell patients and healthy controls were determined. A reversed-phase HPLC procedure was used for codeine analysis. Codeine was extracted from alkalinized plasma, separated on a CN column, and assayed by fluorescence detection. The erythrocyte–buffer partition coefficient was significantly higher in sickle cell patients (1.72 ± 0.21) than in healthy controls (1.25 ± 0.14). No time dependence of partitioning was observed. The fraction of codeine bound to plasma proteins, determined by ultrafiltration, was significantly higher in sickle cell patients (66.0% ± 8.6%) than in healthy controls (30.5% ± 2.7%). No concentration dependence of erythrocyte or protein binding was observed. Further studies were performed to elucidate the binding mechanisms. From a ghost cell binding study it was concluded that the major binding sites for codeine are in the cell membrane. A decrease in codeine binding was observed in the presence of bilirubin. Codeine binding to α1-acid glycoprotein was found to be minimal. The levels of α1-acid glycoprotein and other glycoproteins in sickle cell patients and healthy controls were measured by glycoprotein electrophoresis. The results showed no significant difference between the two groups. Plasma protein electrophoresis was performed for the two groups. The results showed a significant difference in γ-globulin levels between sickle cell patients and healthy controls. Codeine is known to bind to γ-globulin, a fact that may explain in part the observed increase in the plasma protein binding of codeine in sickle cell patients. Because only the free fraction of the drug can cross biological membranes and is considered to be pharmacologically active, the increase in codeine binding in sickle cell patients may be a reason for the observed decreased response to normal doses of codeine in this population.

Clinical Pharmacokinetics of Theophylline and Levels of α1-Acid Glycoprotein in Smokeless Tobacco Users

Elimination half-life and apparent volume of distribution of theophylline were determined in ten healthy volunteers who used smokeless tobacco (snuff or chewing tobacco) regularly but did not smoke cigarettes. Serum concentrations of the acute phase reactant alpha 1-acid glycoprotein (AAG) were also measured. The elimination half-life of theophylline was 9.32 +/- 3.40 hours (mean +/- standard deviation), the apparent volume of distribution was 0.45 +/- 0.03 L/kg, and AAG concentrations were 63.8 +/- 15.76 mg/dL. All these values are comparable to values reported for nonsmokers. These results suggest that nonsmoking users of ST should be considered to be tobacco nonusers for purposes of planning theophylline dosing and monitoring strategies.

Clinical pharmacokinetics of imipramine and desipramine in alcoholics and normal volunteers.

Recently detoxified men with alcohol dependence (n = 15) and healthy volunteers (n = 14) were administered oral and intravenous imipramine and desipramine. Alcoholics had significantly greater total body clearance of imipramine (0.93 vs. 0.48 L/hr/kg; P less than 0.05) and desipramine (1.00 vs. 0.62 L/hr/kg; P less than 0.05) than did control subjects. Intrinsic clearance of unbound imipramine was greater in the alcoholic group (19.80 vs. 6.56 L/hr/kg; P less than 0.05), as was the intrinsic clearance of unbound desipramine (14.52 vs. 9.05 L/hr/kg; P less than 0.05). The mean elimination half-life for imipramine was significantly decreased in alcoholics (8.7 vs. 19.9 hours after intravenous infusion and 10.9 vs. 19.6 hours after oral administration; P less than 0.05). The mean elimination half-life for desipramine was decreased in alcoholics after intravenous infusion (16.5 vs. 22.4 hours; P less than 0.05). Unbound fractions of drug in plasma were decreased in the alcoholic group for both imipramine and desipramine after both routes of administration. alpha 1-Acid glycoprotein levels were elevated in the alcoholic group whereas total protein and albumin levels did not differ between groups. These findings suggest that recently detoxified alcoholics may require higher doses of imipramine than do nonalcoholic subjects. Desipramine clearance was affected to a lesser degree than imipramine, suggesting that from a pharmacokinetic standpoint it may be the preferred drug for the treatment of alcoholics with depression. Periodic monitoring of plasma levels may be required for recently abstinent alcoholics treated with antidepressants.

α-Antitrypsin and α1-Acid Glycoprotein Levels in the Cord Blood and Amniotic Fluid of Infants with Respiratory Distress Syndrome

Summary: α1-Antitrypsin, a proteinase inhibitor, was previously shown to be decreased in the cord blood and elevated in the amniotic fluid of infants with RDS. The low cord α1-antitrypsin in RDS may be the result of either decreased production or increased catabolism or loss of the protein by the fetus. To determine whether there is a specific preferential decrease in α1-antitrypsin in the cord blood of infants with RDS, we have compared the reduction in blood levels of α1-antitrypsin with that of a low molecular weight protein which has no antiproteinase activity, α1-acid glycoprotein (mol wt = 41,000). If a molecular sieve type of leakage is basic mechanism responsible for the low α1-antitrypsin in the cord blood of infants with RDS, then α1-acid glycoprotein might be decreased at least to a comparable degree in the cord blood. Both proteins were measured by the radial immunodiffusion method hi 36 cord blood specimens, 13 of which had matching amniotic fluids which were also studied. There was a significant lowering of the cord blood α1-acid glycoprotein in preterm infants with RDS (12.4 ± 1.3) compared to those without RDS (21.1 ± 4.3) (P < 0.05). When the same specimens were analyzed for α1-antitrypsin, the difference between preterm infants with RDS and those without RDS did not reach statistical significance (P = 0.12). These findings support the hypothesis the serum proteins are decreased in RDS mainly because of diffuse capillary leakage. Speculation: The results of this study suggest that in utero hypoxia or other factors associated with low Apgar scores and abnormal blood gases result hi increased capillary permeability. A detectable decrease in the concentration of one or more cord serum proteins, especially those of low molecular weight, may be a sensitive indicator of fetal distress and increased capillary permeability.

IDENTIFICATION OF DONAGGIO REACTION POSITIVE SUBSTANCES AND INCREASE OF α1-ACID GLYCOPROTEIN IN URINE AFTER EXHAUSTIVE EXERCISE

The Donaggio reaction positive substances from the urine after hard work were identified.These substances obtained from deproteinized urine by heat at pH 5.0 and having the high titer of Donaggio reaction were composed of α-glycoproteins, which were shown to be α1-globulin and small amounts of α2-globulin by means of cellulose-acetate electrophoresis.This α1-globulin nearly composed of serum α1-acid glycoprotein and one of the α2-globulin was composed of serum α2-HS globulin, both of which were shown by immuno double diffusion and by single radial immunodiffusion. The results of im-munodiffusion indicated that the other α1-glycoproteins were not contained, such as tryptophan-poor α1-glycoprotein, α1-antitrypsin, and α1-antichymotrypsin.The levels of α1-acid glycoprotein in urine before and after running, which were measured by single radial immunodiffusion, paralleled the Donaggio-titer.Serum mucoprotein purified by perchloric acid from human serum contained Donaggio positive substances.From these results, we can conclude that Donaggio positive substances were composed of at least two sorts of mucoprotein, α1-acid glycoprotein as a major part and α2-HS globulin as a minor.

Serum alpha-1 acid glycoprotein concentration in pregnancy and with oral contraception

With the use of the technique of single radial immunodiffusion, α1-acid glycoprotein levels were found to be decreased in the sera of pregnant women and in the sera of women ingesting oral contraceptives. Lower levels were detected in cord sera which, in turn, were more marked in the premature infant. As this protein is known to bind progesterone and to be elevated in the presence of tissue destruction or inflammation, sera from premature and toxemic patients were analyzed, but no significant differences in α1-acid glycoprotein concentration were noted when compared to the level encountered in normal term pregnancies.