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Biomedical subjects

M Georgieva

Publications and source records attributed to M Georgieva.

At least 19 recordsLinked to original sources

Induction of apoptosis by electrotransfer of positively charged proteins as Cytochrome C and Histone H1 into cells.

Cytochrome C (Cyt. C) is a mitochondrial protein inducing apoptosis when it is accumulated in the cytosol by a currently unknown mechanism, but regulated by the bcl-2 family of proteins. The linker Histone H1 is another basic protein with highly conservative structure, composition, and equal molecular weight, not changed during the evolution. An attempt was made to understand better the apoptotic processes by electroloading of leukemic cells, such as K562, HL-60, and SKW3, and human lymphocytes with positively charged proteins, such as Cyt. C, Histone H1, and methylated BSA albumin (mBSA). The triggering apoptotic processes followed by MTT test, FACS analysis, and DNA fragmentation after the electrotransfer of these proteins into the cells were observed. Histone H1 and mBSA induce the release of Cyt. C from rat liver mitochondria. Cytochrome C release was higher when mitochondria were in "high-energy" state. It is supposed that release of Cyt. C from mitochondria is due to the mechanical rupture of the outer mitochondrial membrane, rich in negatively charged groups, predominately due to cardiolipin. The reason for the morphological rupture of the outer mitochondial membrane could be the rigidification and segregation of the membrane and the destroyed membrane asymmetries of both monolayers in the presence of positively charged proteins at higher linear charges such as Histone H1. We suggested that Histone H1, at a given moment of activated signaling for apoptosis, could be not transported to the nucleus and could lead to the release of Cyt. C from the mitochondria in the cytoplasm. It is temping to speculate that Histone H1 has other physiological extranuclear functions involved in apoptosis.

Animals↗

Determination of platinum(IV) by UV spectrophotometry.

A simple, rapid and sensitive spectrophotometric procedure for the determination of platinum has been elaborated. Pt traces were determined in the form of the PtCl(6)(2-) complex in hydrochloric acid solution whose concentration varies from 0.01 to 2 mol L(-1) by measuring the absorbance at 260 nm. The detection limit is 4.7 x 10(-7) mol L(-1), the linearity range from 2 x 10(-6) mol L(-1) to 7 x 10(-6) mol L(-1), and the correlation coefficient is r=0.9990. No significant interferences were observed from a majority of the investigated ions, such as Zn(II), Pb(II), Mn(II), Cd(II), Co(II) and Ni(II) with the exception of Cu(II), Sb(III), Fe(III), Pd(II), Sn(II) and I(-) ions. The method was successfully applied for the determination of Pt traces in different solid samples and the recovery from inorganic materials was studied.

Journal Article↗

[Urinary ascites and perirenal urinoma - a renoprotective "Complication" of posterior urethral valves].

We report on a male newborn with urinary ascites and perirenal urinoma due to calyceal rupture caused by bladder outlet obstruction and posterior urethral valves. Despite the presence of left-sided high-grade reflux, the "pop-off" mechanism occurred in the non-refluxing right kidney. Impressive normalization of the upper urinary tract anomalies and renal function occurred after surgical treatment of the valves and removal of obstruction.

Ascites↗

Improvement of posttranslational bottlenecks in the production of penicillin amidase in recombinant Escherichia coli strains.

Using periplasmic penicillin amidase (PA) from Escherichia coli ATCC 11105 as a model recombinant protein, we reviewed the posttranslational bottlenecks in its overexpression and undertook attempts to enhance its production in different recombinant E. coli expression hosts. Intracellular proteolytic degradation of the newly synthesized PA precursor and translocation through the plasma membrane were determined to be the main posttranslational processes limiting enzyme production. Rate constants for both intracellular proteolytic breakdown (k(d)) and transport (k(t)) were used as quantitative tools for selection of the appropriate host system and cultivation medium. The production of mature active PA was increased up to 10-fold when the protease-deficient strain E. coli BL21(DE3) was cultivated in medium without a proteinaceous substrate, as confirmed by a decrease in the sum of the constants k(d) and k(t). The original signal sequence of pre-pro-PA was exchanged with the OmpT signal peptide sequence in order to increase translocation efficiency; the effects of this change varied in the different E. coli host strains. Furthermore, we established that simultaneous coexpression of the OmpT pac gene with some proteins of the Sec export machinery of the cell resulted in up to threefold-enhanced PA production. In parallel, we made efforts to increase PA flux via coexpression with the kil gene (killing protein). The primary effects of the kil gene were the release of PA into the extracellular medium and an approximately threefold increase in the total amount of PA produced per liter of bacterial culture.

Bacterial Proteins↗

Genotoxic effect of substituted phenoxyacetic acids.

The potential toxic and mutagenic action of 2,4-dichlorophenoxyacetic acid has been studied in different test systems, and the obtained results range from increased chromosomal damage to no effect at all. We reexamined the effect of this herbicide by simultaneous using three tests based on yeast, transformed hematopoietic, and mouse bone marrow cells. The results obtained demonstrated that 2,4-dichlorophenoxyacetic acid has cytotoxic and mutagenic effects. The positive response of yeast and transformed hematopoietic cells was verified in kinetics and dose-response experiments. The analysis of metaphase chromosomes indicated a statistically proved induction of breaks, deletions, and exchanges after the intraperitoneal administration of 2,4-dichlorophenoxyacetic acid in mice. The study of phenoxyacetic acid and its differently chlorinated derivatives showed that cytotoxicity and mutagenicity are induced by chlorine atoms at position 2 and/or 4 in the benzene ring. The mutagenic effect was abolished by introduction of a third chlorine atom at position 5. Thus 2,4,5-trichlorophenoxyacetic acid was found to have very weak, if any mutagenic effect; however, the herbicide preserved its toxic effect.

2,4,5-Trichlorophenoxyacetic Acid↗

Effect of diphenylhydramine on the Tyr-MIF-1 antinociception in rats.

Tyr-MIF-1 is a representative of the MIF's family of endogenous peptides. It has been isolated from bovine hypothalamus and human parietal cortex that suggests its involvement in nociception. Tyr-MIF-1 can bind to the mu-receptors as well as to its specific non-opiate receptors in the brain. Data in the literature rise the idea that histamine (HA), a well known nociceptive agent, and Tyr-MIF-1 might have a common pathway in their effects on nociception. We tested that possibility by investigation of the combined action of diphenhydramine (DPH, an H (1) -antagonist) and Tyr-MIF-1 on nociception. The changes in the nociceptive effects were examined in the male Wistar rats by the Randall-Sellito paw-pressure (PP) and the tail-flick (TF) tests. Tyr-MIF-1 in a dose of 1 mg/kg exerted strong naloxone-reversible analgesic effects. DPH (100 microg/kg, i.p.) had an antinociceptive action, too. The co-administration of Tyr-MIF-1 and DPH enhanced the antinociceptive effect, as compared to DPH (PP) and to TYR-MIF-1 alone (TF). These effects were reversed when methylene blue (MB, 500 microg/rat) was applied 1h before the combination. However, naloxone (1 mg/kg, i.p.) only slightly affected the antinociceptive effect of DPH and TYR-MIF-1, compared to that of MB. The results obtained confirmed the hypothesis that cyclic nucleotides are involved in the realization of nociceptive effects of both HA and Tyr-MIF-1.

Analgesics↗

Incidence of dental caries /Is/ on milk molars /M1,M2/ in 3-8 year-old children from Plovdiv.

The incidence of dental caries /Is/ on deciduous molars in 1216 children aged 3 to 8 from Plovdiv has been studied. The results showed highest Is in the fissures of m1 and m2 and lowest Is on the smooth surfaces. The incidence of dental caries is getting higher with statistically significant differences in the lower jaw up to the 6th year and in the upper jaw up to 7th year of age. Is in the lower jaw is higher than that of the upper jaw only in the fissures.

Bulgaria↗

Influence of reserpine on iron absorption in rats.

The aim of our investigations was to define the influence of reserpine on iron absorption in rats. Iron absorption was determined in vivo at the 24th hour and in situ in a tied-off intestinal segment. Five-days treatment with reserpine (1 mg/kg b.wt) led to suppressed bone marrow erythropoiesis, manifested a considerable decrease in reticulocyte count and in a percentage of 59Fe-incorporation into newly formed erythrocytes. Increased plasma iron and decreased plasma ferritin levels were found. Iron absorption was found to be significantly increased, in spite of the suppressed erythropoiesis. The major conclusions of the experiments are, that reserpine interferes with the regulation of iron metabolism and erythropoiesis.

Animals↗

Oral hygiene and gingiva status in school children aged 7 to 14 from Plovdiv.

An assessment of the oral hygiene and periodontal health was made in 1596 school children (777 boys and 819 girls) aged 7-14 years from randomly selected classes and schools in Plovdiv, Bulgaria. The oral hygiene status of the school children assessed by the plaque indexes (PLI) of J. Greene and J. Vermillion, and that of J. Silness and H. Löe was found to be rather poor. The relative share of subjects with plaque index of 0.00 to 1.00 was found to increase with age for both sexes. The relative share of children with chronic catarrhal gingivitis was 42.61 +/- 2.34 indicating the necessity of active prophylaxis and treatment of the disease. A tendency was observed towards an increase of the disease incidence in comparison with data obtained in a 1983 study. A correlation between the hygiene status and chronic gingival inflammation in 14-year-old school children was found.

Adolescent↗

New patterns of bulk DNA repair in ultraviolet irradiated mouse embryo carcinoma cells following differentiation.

Mouse embryocarcinoma stem cells differentiate in culture, given the appropriate induction. We examined whether these cells could provide information about the regulation of nucleotide excision repair in relation to differentiation by measuring the rate-limiting incision step, the removal of cyclobutane dimers and (6-4) photoproducts from the genome as a whole and the effect of the bacteriophage T4 endonuclease (denV) gene on repair in differentiated cells. It was found that differentiation is accompanied by a marked decline in the early incision ability after UV irradiation (sixfold for P19, fourfold for PCC7 and twofold for F9), and we measured, in parallel, the loss of two common UV photoproducts [cyclobutane dimers and (6-4) photoproducts] from P19 cells. After differentiation, the excellent overall cyclobutane dimer repair capacity of proliferating cells (84% removal in 24 h) is lost (no removal in 24 h), while removal of (6-4) photoproducts, although normal at 24 h (94%), is much slower than in undifferentiated P19 at 3 h (no removal versus 64%). The presence of the denV gene greatly stimulates the repair of cyclobutane dimers in undifferentiated P19 cells (94% removal at 3 h versus 40%) and also in differentiated cells (50% removal at 24 h versus no removal). The denV gene also stimulates the early repair of (6-4) photoproducts in both differentiated and undifferentiated cells.

Animals↗

[Citric acid biosynthesis by Aspergillus niger strain IM-13 on a nutrient medium with methanol].

The dynamics of citric acid biosynthesis and some morphological changes of Asp. niger IM-13 in culture media containing starch hydrolysate and 3% methanol were traced. The culture developed in filamentous form and little fine pellets. Deformed hyphae with characteristic extensions were observed. The changes in Asp. niger IM-13 metabolism were studied by comparing the biomass accumulation, the utilization of reducing substances, the citric acid biosynthesis, pH and the protein content of the control and the experimental variants. A suppression of growth in the period from the 48th hour of cultivation up to the end of the process, suppression of protein synthesis in the micelium and increased synthesis of citric acid were established.

Aspergillus niger↗