Biomedical subjects

S Petrén

Publications and source records attributed to S Petrén.

9 recordsLinked to original sources

PubMed1999

Serum and cerebrospinal fluid concentrations of melatonin: a pilot study in healthy male volunteers.

Melatonin was determined in serum and cerebrospinal fluid (CSF) obtained from 13 healthy males lumbar-punctured in the sitting position without preceding bed rest. There was a significant correlation between the levels of melatonin in serum and the CSF. The serum concentration was lower than that in the CSF, a finding that calls in question the theory that melatonin is mainly released from the pineal gland into the bloodstream. In conclusion, serum levels of melatonin in healthy male volunteers, mirror the CSF concentrations when lumbar puncture is carried out using the described technique.

Adult↗

PubMed1999

Hydroxypropyl-beta-cyclodextrin inhibits spray-drying-induced inactivation of beta-galactosidase.

The single-step, fast spray-drying process may represent a valuable alternative to the multistep, time-consuming freeze-drying process in the area of formulation and processing of biopharmaceuticals. In this study, we tested the use of sucrose and hydroxypropyl-beta-cyclodextrin (HP-beta-CD) as stabilizing excipients in the spray-drying of a model protein, beta-galactosidase. The solutions were processed using a Büchi 190 cocurrent Mini Spray Dryer at an outlet temperature of 61 +/- 2 degrees C. The powders were redissolved and analyzed for catalytic activity, aggregation, chemical decomposition, and thermal susceptibility as observed by high-resolution calorimetry. Spray-drying significantly inactivated beta-galactosidase. Spray-drying beta-galactosidase in the presence of sucrose did not prevent inactivation. However, after spray-drying beta-galactosidase in the presence of HP-beta-CD, or HP-beta-CD and sucrose, full catalytic activity was exhibited on reconstitution. Furthermore, the reconstituted product was unchanged in terms of molecular weight, charge, and thermal stability. These findings are consistent with a hypothesis that the change responsible for inactivation of beta-galactosidase was mainly a monomolecular, noncovalent change, i. e., the formation of incorrect structures, that arose from surface denaturation. This study clearly demonstrates that cyclodextrins can be useful stabilizing excipients in the preparation of spray-dried protein pharmaceuticals.

2-Hydroxypropyl-beta-cyclodextrin↗

PubMed1990

Increased isotransferrin ratio and reduced erythrocyte and platelet volumes in blood from thermoplastic industry workers.

Ten women (aged 31-61 years) and five men (aged 20-59 years) occupationally exposed to welding fumes of polyacetate containing diethylphthalate in a thermoplastic industry were studied. They had been employed 1-33 years (median: 11 years). Seven women (aged 35-55) and eight men (aged 26-73) acted as unexposed controls. The exposed persons showed increased isotransferrin ratio in blood serum and reduced volumes of erythrocytes and platelets in blood.

Adult↗

PubMed1989

The N-acetylneuraminic acid content of five forms of human transferrin.

Five isoforms of human serum transferrin were separated by isoelectric focusing and their N-acetylneuraminic acid content was determined. The forms differed in isoelectric point by about 0.1 of a pH unit with the structural differences situated in the carbohydrate parts. Each form had one sialic acid molecule (NANA) less than the next most acidic form. GLC-MS showed that the most abundant form with isoelectric point 5.5 had two two-branched carbohydrate chains, each having the galactoses covered by terminal sialic acid. The form with isoelectric point 5.4 had one three-branched and one two-branched carbohydrate chain, and all branches terminated with a sialic acid residue. The form with isoelectric point 5.6 had a terminal galactose on one of its two two-branched carbohydrate chains. Comparison of the sialic acid content of the five transferrin forms and their carbohydrate structures showed that some of the forms expose terminal galactose without attracting the asialoglycoprotein receptors on hepatocytes.

Carbohydrate Sequence↗

PubMed1988

Concentration differences in isoforms of transferrin in blood from alcoholics during abuse and abstinence.

At least five different forms of iron-saturated transferrin (Tf) from blood plasma can be separated by isoelectric focusing. These transferrin forms differ in the carbohydrate parts, especially the amount of sialic acid. The increased relative concentration of the form with isoelectric point 5.7 (Tf5.7) has been shown to be a good indicator for liver effects caused by alcohol abuse. However, in alcoholics during abstinence the newly formed transferrin has a higher sialic acid content than most of the transferrin already present in the blood. This indicates that the elevated concentration of Tf5.7 with a low sialic acid content, found in alcoholics is not due to a defect at sialylation, but most probably caused by an impaired uptake of sialic acid-deficient transferrin by the hepatocytes due to membrane dysfunction.

Adult↗

PubMed1987

Differences among five main forms of serum transferrin.

Five forms of human serum transferrin with different isoelectric points were purified by isoelectric focusing in agarose gels. They constitute a set of main transferrin forms in serum of healthy individuals. Their relative proportions are changed in serum from alcoholic individuals, where the more basic of these forms are increased. Tryptic peptides of all forms were compared by high performance liquid chromatography (HPLC) patterns (fingerprint analysis). Two major differences were detected between corresponding tryptic peptides of the five transferrin forms. Some minor differences were also noticed. The corresponding peptides were purified from the main form and analyzed for total composition and amino acid sequence. The peptides with the major differences between the forms were found to be the two with the glycosylation attachment at positions 413 and 611. A minor peptide difference between the transferrin forms contains a product that is explained by incomplete stoichiometry in cleavage of the peptide bond at positions 217-218. Successive loss of sialic acid is compatible with the presence of different transferrin forms, and our results indicate that the main differences between the serum transferrin forms from healthy and alcoholic individuals are in successive changes of the carbohydrate chains attached at positions 413 and 611.

Amino Acid Sequence↗

PubMed1987

Studies of transferrin in serum of workers exposed to organic solvents.

Earlier studies have shown that determination of the serum concentration of different forms of transferrin (isotransferrins) may be used to detect hepatic effects caused by alcohol abuse. The isotransferrin variant with an isoelectric point of 5.7 has been compared with the total amount of serum transferrin in order to study hepatic effects caused by occupational exposure to organic solvents. Eighteen workers from a paint industry were tested before and after their holiday and compared with two different groups, a total of 60 subjects. The solvent workers had significantly higher values both before and after their holiday. This suggests that the effects on the liver caused by organic solvents are similar to those caused by alcohol abuse and that this is a long term effect. The level of exposure to organic solvents was below the Swedish threshold limit values.

Adult↗

PubMed1984

Increased concentrations of a transferrin variant after alcohol abuse.

Isoelectric focusing in agarose gel has been used for separation of different molecular forms of transferrin (Tf) in sera and plasma from alcoholics and controls. One special form of transferrin with isoelectric point 5.7 (= Tf5.7) was quantified by using zone immunoelectrophoresis assay (ZIA). This method was also used for quantification of total transferrin (Tftot). Significant differences in the ratio Tf5.7/Tftot between the groups were obtained and the diagnostic sensitivities, specificities and predictive values of positive tests were 100, 97, 93.8%, respectively. Thus the results showed that this principle seems to be much better for detection of alcoholic abuse than currently used assays as gamma-glutamyltransferase, etc. Samples taken on days following hospitalization showed that the Tf5.7 values decreased over a two-week period of abstinence. Possible explanations for the abnormal quotient after ethanol abuse are discussed.

Adult↗

PubMedDate not supplied

Separation of different forms of transferrin by isoelectric focusing to detect effects on the liver caused by xenobiotics.

Several genetic variants and also isoforms of transferrin differing in carbohydrate structure can be separated by polyacrylamide or agarose gel isoelectric focusing. Numerous blood plasma or serum samples can be analyzed in parallel in each gel. Studies of the heterogeneity of transferrin have already revealed many results of importance to different fields of human medicine. Gene typing can give important and useful information for paternity determination and in forensic medicine. The gene type C 2 seems to have increased frequency in certain malfunctions. Futhermore, functional abnormalities of liver cells can be revealed by determination of the concentrations of transferrin isoforms differing mainly in their carbohydrate parts. The isoforms can be quantified with zone immunoelectrophoresis assay. Thus valuable information can be obtained about important modulated regulations of cell and membrane functions, even when these are disturbed by disease and xenobiotics. The information may be useful e.g. in the detection of individuals suffering from toxic effects, to identify toxic agents and exposure conditions. Studies of house painters revealed that exposure to different types of paints had an effect on transferrin. Determination of the concentration of the isotransferrin with pI 5.7 in blood samples from alcoholics can be used as a marker for the detection of liver dysfunction and for the monitoring of therapy treatments. In addition, by analyzing the isotransferrins a rare genetic abnormality can be detected.

Alcoholism↗