Therapeutic drug monitoring using oral samples collected with the OraSure device.
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Biomedical subjects
Publications and source records attributed to F Bartos.
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Scleroplastic surgery is known to encounter the pathogenetical agent when the progressive myopia develops. In the first part, the implemented surgical approaches as well as up-to-date surgical techniques are presented. The experimental part is reserved for the selection of material which is necessary to perform scleroplasties. Both the allogenic and xenogenic grafts have been studied for histocompatibility on 20 rabbits. Following materials were used: 2 types of collagenic sponge, native and deproteinated human sclera, modified dura mater as well as both the native and devitalized sclera from rabbits. The best results were obtained with allogenic sclera, deproteinated xenogenic sclera and collagenic sponge. The application of other materials is discussed.
Female Wistar rats were pretreated with I ml of carbon tetrachloride/kg of body weight or with olive oil. All the rats were given this dose of CCl4 20 or 40 days later. Liver regeneration as evaluated by 3H-thymidine incorporation into liver DNA and by the number of mitotic hepatocytes was markedly impaired in CCl4-pretreated rats when compared with olive oil-pretreated controls. DNA labelling reached only 83 and 59% and mitotic index 35 and 58% of control values, respectively, at 20-day and 40-day time intervals. The variables characteristic of liver damage did not parallel the changes in cell division. About 20% of hepatocytes were necrotic both in the CCl4-pretreated and in the control rats. The activity of serum alanine aminotransferase was higher in the CCl4-pretreated rats. Only serum aspartate aminotransferase activities were somewhat lower when compared to controls. Similarly, serum aminotransferases were much less affected by the pretreatment than the markers of regeneration when two low doses of CCl4 (0.125 ml/kg) were given to rats 20 days apart. The activities of microsomal enzymes aniline hydroxylase and pethidine demethylase were equal in control and in experimental rats 20 days after CCl4 pretreatment which indicated that the effects of CCl4 were not mediated by an overall decrease in cytochrome P-450 enzymes. In summary, a single pretreatment of rats with CCl4 induced changes in liver that lasted for 40 days and impaired liver regeneration when another dose of CCl4 was applied.
Various doses of carbon tetrachloride (0.625 mmol to 10 mmol CCl4/kg body weight) were administered to female Wistar rats. Liver damage after a single treatment was evaluated by serum aminotransferase levels and by the extent of necrotic areas in parenchyma. Liver regeneration was evaluated by 3H-thymidine incorporation into liver DNA and by the number of dividing hepatocytes. Mitotic index of hepatocytes rose in parallel with the specific activity of DNA and with the extent of necrosis. However, the activities of serum aminotransferase AST and ALT increased much more rapidly and did not correlate either with necrosis or with regeneration rate. Increased membrane permeability in morphologically intact cells, increased synthesis of the enzymes by the liver as well as the leakage from necrotic cells are discussed as possible causes of the high aminotransferase activities in serum.
The effects of alpha-elastin (1) on the morphogenetic systems of the chick embryo were studied by means of the CHEST (chick embryotoxicity screening test). The subgerminal administration of doses of 0.3 mg and larger induced a growth retardation of the caudal morphogenetic systems (CMS). The administration of single effective doses of 1 subgerminally on the second day and intraamniotically on the third and fourth d of embryogenesis verified the beginning of the direct embryotoxicity range between the doses of 0.3 and 1 mg per embryo. It presents in the theoretical extrapolation for mammals the dose limits between 1 and 10 g.kg-1 of maternal weight. Embryotoxic manifestations (body wall defects, growth retardation and embryolethality) were induced predominantly in the embryos treated on d 2 with the very high doses only. Their frequency was rare. It has been concluded that 1 could be a safe potential natural drug carrier in clinical practice.
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It is very difficult to meet all prerequisites for the optimization of the tuberculostatic action of thiobenzamides. On the one hand, a strongly polarized C=S bond of the thiocarbamido group is necessary, and on the other hand, the value of the Hammett constant must be positive (to prevent hepatotoxicity). The conjugated system can be extended to reduce the excitation energy of the eta-eta electronic transition. However, the lipophilicity should not be overincreased (to avoid the risk of increased antimitotic activity and acute toxicity). Of the culture media, the Sauton system seems to be best suited since it is the most simple. However, the culture medium according to Sula comes closest to in vivo conditions as it contains proteins and is devoid of surfactants.
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Open wounds were incised in the dorsal skin of female Wistar rats. Solutions of Salmonella typhosa endotoxin (0.25 micrograms to 25 micrograms/ml saline) were applied 3 times a day on granulation tissue formed in the wounds. 5 days of treatment with the lowest endotoxin concentration resulted in 25% increase of the weight of the tissue, a more than 30% increase of DNA content and a 25% increase of hydroxyproline content in the tissue. Further elevation of these values could be obtained by increasing endotoxin concentration by tenfold or hundredfold but these changes were not very pronounced.
Fetal mouse liver and normal human bone marrow cell cultures were used for studies on the inhibition of erythroid colony formation (CFU-E) by sera from anemic patients with end-stage renal failure and the polyamine spermine. Sera from each of eight predialysis uremic anemic patients with end-stage renal failure produced a significant (P < 0.001) inhibition of erythroid colony formation in the fetal mouse liver cell cultures when compared to sera from normal human volunteers. In vivo or in vitro dialysis of the uremic sera with a 3,500-dalton exclusion limit membrane removed the inhibitor from uremic sera. The uremic serum dialysate provided by the membrane fractionation was significantly inhibitory in the erythroid cell cultures. When this dialysate was applied to gel filtration chromatography (Bio-Gel P-2) the inhibitor was found to be in the same molecular weight range as [(14)C]spermine. The polyamine spermine produced a dose-related inhibition of erythroid colony formation (CFU-E) in fetal mouse liver and normal human bone marrow cultures. Thus, the following evidence is provided that the in vitro inhibitor of erythropoiesis found in chronic renal failure patients' sera is identical with the polyamine spermine: (a) the inhibitor and radiolabeled spermine appeared in identical Bio-Gel P-2 effluent fractions; (b) when spermine was added to normal human sera at concentrations reported in sera of uremic patients, and studied in both the fetal mouse liver cell culture and normal human bone marrow cultures, a dose-related inhibition of erythroid colony (CFU-E) formation was noted; and (c) the inhibitory effects of crude uremic serum, uremic serum dialysate, and fractions of uremic serum dialysate from a Bio-Gel column, on erythroid colony formation were completely abolished by the addition of a specific rabbit antiserum to spermine.
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A protein that binds spermine specifically was separated from normal rabbit serum by affinity chromatography. Immunoelectrophoresis, the Ouchterlony immunodiffusion test, and gradient gel electrophoresis indicated that this protein has immunoglobulin characteristics and consists of several populations of antibodies to spermine. These were sequentially released from Sepharose-spermine gel by step-wise elution with solutions ranging in pH from 4 to 1. The binding constants varied from 5.0 x 10(8) to 11.1 x 10(8) liters per mole. These globulins did not react with monoacetylputrescine, L-ornithine, L-lysine, and histamine. Negligible cross-reactivity was detected with spermidine, putrescine, N8-monoacetylspermidine, cadaverine, and diaminopropane. Since perturbations in polyamine metabolism have been identified in several diseases, the study of extracellular polyamine homeostasis may reveal an important regulatory function for this protein.
Different methods of sample preparation for determination of di- and polyamines (putrescine, spermidine, spermine) and their conjugates in serum, plasma, and urine are discussed. Higher polyamine values obtained after hydrolysis of serum or plasma acidic extracts suggest the presence of polyamine conjugates. Additional polyamines might be bound to proteins and released by hydrolysis of the crude samples. Biological studies of bound polyamines in health and disease will require procedures for quantitative analysis. For the pertinent measurements, radioimmunoassays employing antibodies developed against isolated polyamine conjugates may prove useful.
Highly specific antibody to spermine was produced in the rabbits by immunization with a spermine-thyroglobulin conjugate of high molar ratio (740:1). Cross-reactivity with spermidine was 1.4-2.2 percent and negligible with putrescine and other compounds of similar structure. The average affinity constant of five pools of antispermine rabbit antisera was Ka = 1.8 +/- 0.2 X 10(8) liter/mole.
The significance of raised polyamine (P.A.) levels in chronic-dialysis patients is unknown. Since these biologically active substances have hormone-like properties and promote cell-growth in plant and animal tissues, it is possible that they stimulate proliferation of arterial smooth-muscle cells (S.M.C.)--a central process in atherogenesis--and thereby contribute to the rapidly accelerated cardiovascular disease observed during dialysis. Such a role for P.A. is supported by tissue-culture studies, which show not only that P.A.-rich serum from dialysis patients stimulates S.M.C. growth, but also that this mitogenic effect is lost when P.A. are selectively removed from uraemic serum and restored by their addition. Although these observations provide new insights into possible mechanisms of atherogenesis, they are not surprising in view of the many known biological actions of P.A.