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D Pantelić

Publications and source records attributed to D Pantelić.

At least 19 recordsLinked to original sources

Regulation of plasma acute-phase protein and albumin levels in the liver of scalded rats.

At 12 h after scalding of rats a doubling of the hepatocyte nuclear DNA content, which arose from the presence of additional complete genomes and not from amplification of genes coding for the major acute-phase proteins or albumin, was observed. Examination of relative transcription rates per control DNA mass revealed that alpha 1-acid-glycoprotein and cysteine-proteinase-inhibitor genes remained constitutive, alpha- and gamma-fibrinogen and haptoglobin genes underwent transcriptional activation for 290 and 339% respectively, whereas the relative transcription rate of albumin decreased to 65% of the control level. Along with these changes, the alpha 1-acid glycoprotein, cysteine-proteinase inhibitor and the fibrinogen mRNA concentrations increased about 500%, haptoglobin mRNA 250%, whereas the albumin mRNA concentration fell to 86% of the control. The regulation of the mRNA levels was assessed by comparing the relative change in transcription rates expressed per control DNA content with the relative changes of mRNA concentrations. We arrived at the conclusion that the concentrations of alpha 1-acid-glycoprotein and cysteine-proteinase-inhibitor mRNAs were predominantly regulated by a post-transcriptional mechanism, albumin mRNA by a transcriptional mechanism, and the fibrinogen and haptoglobin mRNAs by a combination of both. The degree of change of the serum levels of the examined proteins was similar to that of their mRNA concentrations and was the result of the complete use of the available RNA templates in protein synthesis.

Acute-Phase Proteins

Acute-phase response to scalding: changes in serum properties and acute-phase protein concentrations.

The time course of changes in the concentrations of individual acute-phase proteins (APRs) in the plasma was examined in the model of rats exposed to a single (sublethal) and repeated (fatal) scalding. These data were interrelated with the rate of survival, plasma volume, corticosterone level, and immunosuppressive potency of the serum. The infliction of a sublethal scalding composing 20% body surface area resulted in an initial 50% reduction of the plasma volume and a severalfold increase of the corticosterone level and immunosuppressive activity of the serum. A subsequent normalisation of these deviations proceeded in parallel with an increased rate of APR synthesis. An early infliction of a second scald was fatal. It led to a 60% reduction of the plasma volume, a lack of plasma APRs, and an additional enhancement of the immunosuppressive activity of serum.

Acute-Phase Proteins

Thermal injury-induced expression of acute-phase proteins in rat liver.

Relative changes in acute-phase protein and albumin mRNAs from the liver of rats exposed to sublethal and lethal scaldings were examined by hybridization and cell-free translation. Infliction of a sublethal scalding comprising 20 per cent of the total skin area resulted in a seven-fold increase of alpha 1-acid glycoprotein (AGP), alpha 1-cysteine protease inhibitor (CPI) and the alpha- and gamma-fibrinogens' (Fb) mRNAs, whereas the level of haptoglobin (Hp) mRNA increased three times. The simultaneous infliction of two such sublethal scaldings were lethal and accompanied by a significant decrease in the concentration of AGP while the levels of CPI. Hp and Fb mRNAs remained similar to those observed after a single 20 per cent injury. A 4 h time delay between the two scaldings was also fatal and followed by an additional increase in Hp mRNA concentration whereas the levels of the other mRNAs were close to those observed after a single 20 per cent scalding. These results demonstrated that the fatal effect of the second scalding was not related to any inhibition of acute-phase reactants mRNA synthesis in the liver.

Acute-Phase Proteins

Effect of non-lethal scalding on the amount of DNA and RNA in rat liver.

The quantities of DNA and RNA were measured in rat liver homogenate, supernatant and nuclei after scalding. Maximal increases of nuclear DNA and RNA were found 12 h after thermal injury. The RNA content in the rat liver supernatant and homogenate reached its maximum at 24 and 48 h, respectively. The results obtained in this study show that the thermal injury resulted in an activation of the genetic apparatus in rat liver cells. These findings correspond well with a significant role of the liver in post-traumatic metabolism.

Animals

Structural and biochemical aspects of liver cell nuclear organization in normal and scalded rats.

The response of rat liver nuclei to thermal injury was studied at the ultrastructural and biochemical levels using nuclei isolated in the presence of either Mg2+ or polyamines and metal chelators. The extent of chromatin condensation, as revealed by electron microscopy, increased in the order: nuclei in situ, Mg-stabilized nuclei, polyamine-stabilized nuclei. In addition, we observed that thermal injury caused an increase in the number of nuclear pores, an enlargement of nucleoli and an accumulation of ribonucleoprotein material. Along with this, greater amounts of protein, DNA and RNA were retained in nuclei from scalded rats. The salt-resistant residue from Mg-stabilized nuclei was a spherical proteinaceous structure of the nuclear matrix, whereas that of the polyamine-stabilized nuclei was amorphous and deprived of three major constituents of the spherical matrix, the 60-70 X 10(3) Mr lamina proteins. However, exposure of the polyamine-stabilized nuclei to Ca2+ and Mg2+ rendered the 60-70 X 10(3) Mr proteins salt-insoluble and thus enabled the extraction of a spherical residual nuclear structure. This structure was highly enriched in DNA, RNA and non-histone proteins and, hence, more like dehistonized nuclei than the minimal residual nuclear structure. It retained 70% of DNA in the controls but virtually all the DNA in scalded rats. This difference was interpreted to reflect activation-related changes in chromatin organization.

Animals

Thermal trauma-induced changes in the synthesis of rat serum proteins.

Infliction of non-lethal scalding was found to cause an increase in the rate of incorporation of 35S-methionine into albumin and globulin fractions of rat serum proteins, the the increase being remarkably higher for alpha- and beta-globulins than for albumin and gamma-globulins The most pronounced enhancement was associated with the 60- and 70-kd constituents of beta-globulins, the 34-, 55- and 136-kd polypeptides of alpha-2-globulins and the 50-, 60-, 125- and 145-kd polypeptides of alpha-1-globulins. The response of serum proteins to the heat shock was similar, though the changes were significantly less pronounced.

Alpha-Globulins

[Albumin and its therapeutic use - part I].

Albumin is most abundant and most studied protein of the circulation. Its biosynthesis is closely dependent on the nutrition, amino acid supply, hormonal millieu, environment, osmotic equilibrium, diseases and some other factors. Albumin is synthetized in the liver on a polyscmes and delivered into the blood streem. Degradation of albumin is practically still unknown and is one of many biological puzzles. Albumin prepared for therapeutic use almost contains dimers, oligomers and polymers which are very important, because they are one of the parameters for evaluation of albumin products quality.

Humans

[Albumin and its therapeutic use - Part II].

Albumin is the most effective oncotic agent and has wide clinical application. In the resuscitation of injured patients with hypovolemic shock (during war and peace) the use of supplemental albumin is purported to be more effective in restoring plasma volume, increasing cardiac output, preventing pulmonary oedema and maintaining organ perfusion than resuscitation without supplemental albumin. Most important in a study of albumin are criterias for appropriate use because it was sometimes unjustified. Therapeutic use of albumin should not be dictated by arbitrary or pragmatic restriction but rather by rational prescribing from physicians well educated in its use.

Adult