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Biomedical subjects

T Trnovec

Publications and source records attributed to T Trnovec.

At least 37 records · Page 2Linked to original sources
PubMed1997

Effects of blockade of Kupffer cells by gadolinium chloride on hepatobiliary function in cold ischemia-reperfusion injury of rat liver.

The mechanisms of liver injury from cold storage and reperfusion are not completely understood. The aim of the present study was to investigate: 1) whether the inactivation of Kupffer cells (KCs) by gadolinium chloride (GadCl) modulates cold ischemia-reperfusion injury of rat liver; and 2) whether cold storage of rat liver involves injury to biliary epithelial cells (BECs). Hepatobiliary function was assessed using an isolated perfused rat liver model. Compared with control livers, in livers subjected to cold storage at 4 degrees C in Euro-Collins solution (EC) for 18 hours or in University of Wisconsin solution (UW) for 48 hours, portal flow was lower and resistance significantly higher, taurocholate (TC) and bromosulfophthalein (BSP) elimination were markedly impaired, bile flow was reduced, and lactate dehydrogenase (LDH) leakage into the perfusate was increased. Pretreatment of rats with GadCl, a selective KC toxicant, abrogated disturbances of the microcirculation in both models, but it did not influence viability and functional parameters of the liver. Most of the parameters studied in livers stored in UW solution for 18 hours were not significantly different from those found in control livers. As to biliary activity of gamma-glutamyl transferase (GGT), as an index of BEC integrity, it was increased with increasing time of cold storage. The reabsorption of glucose from the bile decreased with longer storage time. The results suggest the following: 1) that cold ischemia-reperfusion injury of rat liver is mediated by KC-dependent (hepatic microcirculation) and -independent (parenchymal cell function) mechanisms; and 2) that cold storage of rat liver induces functional impairment of BECs.

Animals↗
PubMed1997

Relationship between plasma fenofibric acid levels and the effect of micronized fenofibrate on cholesterol, low-density-lipoprotein cholesterol and apolipoprotein B in patients with primary hypercholesterolemia.

OBJECTIVE: We examined the relationship between plasma levels of fenofibric acid, the active metabolite of fenofibrate, and differences in concentrations of plasma lipids, in subjects with primary type IIA or IIB hyperlipoproteinemia (HLP). SUBJECTS AND METHODS: Twenty-nine patients (13 with type IIA and 16 with type IIB HLP) were treated with a single daily 200-mg dose of micronized fenofibrate for 3 months, after which the plasma levels of fenofibric acid were determined by HPLC after an overnight fast. RESULTS: In the type IIA HLP phenotype, statistically significant correlations were found between fenofibric acid levels and changes in total cholesterol, LDL-C and apo-B at all three control visits, with the highest correlation coefficients at V3 visit (total cholesterol r = 0.85. LDL-C r = 0.68, apo-B r = 0.85). In type IIB HLP, statistical significance was confirmed only when performing an analysis of pooled values for total cholesterol and LDL-C (r = 0.42, r = 0.34, respectively). The high correlation between plasma fenofibric acid levels and its effect on beta lipoprotein changes might reflect the effect of fenofibrate on the catabolism of plasma LDL by the LDL receptor, since that type of relationship is typical of drugs which directly influence the target compartment without an effect on intermediary steps of metabolism. An explanation for the different levels of correlations in type IIA and IIB patients might be found in their different metabolic defects. The fact that fenofibrate's impact on VLDLs is such an important part of its effect on lipoprotein metabolism supports the concept that the effect of circulating fenofibric acid is less pronounced on the LDL receptor in type IIB HLP.

Adult↗
PubMed1996

Increase in magnesium plasma level after orally administered trimagnesium dicitrate.

Magnesium plasma concentrations were measured in healthy probands before and after administration of trimagnesium dicitrate by the oral and intravenous routes. There was a notable circadian fluctuation of the plasma concentration with a peak in the evening hours. After oral administration of 12 and 24 mmol magnesium, a long-lasting, statistically significant increase in plasma magnesium concentration measured as the increase in area under the curve (AUC) between 0 and 12 h, of 3.1% and 4.6%, respectively, was found. After intravenous administration of 4 and 8 mmol magnesium, AUCs increased by 9.5% and 16.1%, respectively. The decline in the plasma magnesium concentration after i.v. administration was compatible with a three-compartment model with a terminal half-time of about 8 h. Although no absolute value of the oral bioavailability of trimagnesium dicitrate could be determined from the data, our results may be important in helping to elucidate the influence of magnesium preparations on the plasma magnesium concentration. By comparing the effects of different preparations, it should be possible to estimate the relative oral bioavailability and the bioequivalence of these preparations.

Administration, Oral↗
PubMed1996

ISO 14000: Origin, Structure, and Potential Barriers to Implementation.

The ISO 14000 is likely to become the international standard for environmental management. At present, it is an evolving series of individual voluntary standards and guideline reference documents that provide business management with the structure for managing environmental impacts. These encompass environmental management systems, environmental audits, eco-labeling, environmental performance evaluations, life-cycle assessment, and environmental aspects in product standards. The authors present the rationale for the ISO 14000 and the steps in its evolution so far, as well as its present provisions and their implications and its position with regard to regulatory agencies. Particular attention is paid to the consequences of voluntary disclosure and correction of violations. Hanley & Belfus, Inc. Int J Occup Environ Health 1077-3525 2 2 1996 April/June Perspectives on Rural Environmental Health in Central Europe 125 134 EN Tomas Trnovec Burton C. Kross CIREH-Room 352, International Center, University of Iowa, Iowa City, IA 52242, USA. Emil Ginter Life expectancy is about five to seven years less in Central European countries than in comparable countries in Western Europe. Environmental and occupational health risk factors, along with the socioeconomic and political conditions that have prevailed in this region for the past 40 years, are suspected contributing factors to this condition. The initial impression among observers was that environmental pollution by industry was the primary source of contamination leading to human health effects. Current thinking by the authors recognizes that combinations of personal habits, local environmental emissions (home heating), and occupational risk factors are more likely to be influencing the health of this region, particularly in rural areas. A predictive model for standard mortality rates determined that only three potential risk factors were statistically significant: consumption of alcoholic beverages, consumption of citrus fruits, and consumption of cereals. Additional emphasis should be placed on defining risk factors in rural areas of Central Europe, and designing intervention strategies to address these factors.

Journal Article↗
PubMed1996

Selective uptake of the anticancer drug bendamustine by liver and kidney tissues following its intravenous administration to mice.

Distribution of 14C-bendamustine following intravenous (i.v.) administration to mice was examined by whole body autoradiographic (WBAR) and quantitative techniques. The WBAR study showed that 14C-bendamustine-derived radioactivity was distributed extremely unevenly at each time interval investigated. After 5 min of administration the highest density of radioactive material was found in the liver and in the kidney. At all time intervals investigated the brain remained free of the label. In a detailed quantitative distribution study it was found that 14C-bendamustine-derived radioactivity was also unevenly distributed throughout the mouse tissues. At 5 min postdosing the level of 14C was by one order higher in the liver and in the kidney in comparison to the lungs, heart, spleen, and muscle. The results of both WBAR and quantitative tissue distribution studies suggest that bendamustine was selectively taken up from the blood by liver and kidney tissues. Because of this pharmacokinetic property, dose modification should be taken into consideration when administering the drug to patients suffering from hepatobiliary and kidney disorders.

Animals↗
PubMed1996

Role of hepatovasculature in warm ischaemia-reperfusion injury of rat liver.

Liver haemodynamics were studied after warm (37 degrees C) ischaemia of isolated rat livers for periods of 30 s (Group 1), 30 min (Group 2), and 60 min (Group 3) using a constant pressure system with a recirculating blood-free perfusate. Portal flow recovered to basal values within 6 min in livers from Group 1, whereas it was significantly reduced in Group 2 during the initial 15 min and in Group 3 during the first 33 min of reperfusion. Thus, the recovery of liver flow was proportional to the duration of ischaemia. By using the same mode of liver perfusion, the effect of norepinephrine on portal resistance was also studied in normal livers. At the beginning of reperfusion, the values of portal resistance in ischaemic livers were comparable to the values of portal resistance mediated by norepinephrine at concentrations between 10(-7) and 10(-6) mol/l in normal livers. The results suggest that vasoconstriction of the hepatovasculature may be a contributing factor to the reperfusion injury of the liver following warm ischaemia.

Animals↗
PubMed1995

Stereoselective binding of isradipine to human plasma proteins.

Isradipine (PN 200-110) is a highly potent calcium entry blocker with an asymmetrically substituted dihydropyridine ring (methyl- and isopropylester, respectively). The binding of the (+)-(S)-isradipine and (-)-(R)-isradipine to isolated human serum albumin (HSA, 30 mumol/l) and alpha 1-acid glycoprotein (AAG, 10 mumol/l) has been studied in vitro over a wide range of isradipine concentrations (0.06-20 mumol/l) using high-performance liquid chromatography (HPLC). HPLC experiments revealed that both isradipine enantiomers were bound to one class of high-affinity binding sites on the AAG molecule (n(S) = 0.83 +/- 0.05, Ka(S) = (1.33 +/- 0.25) x 10(6) l/mol, n(R) = 0.85 +/- 0.07, Ka(R) = (1.17 +/- 0.44) x 10(7) l/mol). The (R)-enantiomer also exhibited an interaction with the secondary low-affinity binding sites (n'Ka'(R) = (2.66 +/- 0.65) x 10(4) l/mol). In contrast, the pharmacologically more potent (+)-(S)-enantiomer was more strongly bound to HSA than its optical antipode (n(S) = 1.07 +/- 0.07, Ka(S) = (1.76 +/- 0.26) x 10(5) l/mol, nKa(R) = (3.62 +/- 0.06) x 10(4) l/mol). In general, the resulting binding characteristics of individual isradipine enantiomers showed stereoselectivity, but this was opposite for the two most important plasma binding proteins. The process of accumulation of isradipine by human platelets in the therapeutically relevant range (10-80 ng/ml) at 37 degrees C was devoid of stereoselectivity.

Binding Sites↗
PubMed1995

Uptake, reflux, and excretion of bromosulfophthalein in ischaemia-reperfusion injury of rat liver.

The uptake, reflux and excretion of bromosulfophthalein (BSP) were studied on a model of total warm ischaemia for 30 min (group 1) or 60 min (group 2) followed by reperfusion for 45 min in the isolated perfused rat liver of unfasting rats. In group 1, the BSP hepatic uptake was comparable to control livers (30 s ischaemia plus 45 min reperfusion), but was significantly reduced in group 2. The reflux of BSP from liver to perfusate in group 1 and group 2 resulted in the appearance of secondary concentration time peaks of BSP in the reservoir perfusate. This result suggests that ischaemia-reperfusion induced a qualitative change in BSP pharmacokinetics. Excretion of the dye into bile was significantly impaired in group 2 only. The leakage of lactate dehydrogenase into the perfusate was increased moderately in both group 1 and group 2 in comparison to the controls, suggesting a low degree of liver parenchymal injury. In conclusion, the results of this investigation showed that BSP pharmacokinetics were not only undergoing quantitative changes but also a qualitative change in the model of ischaemia-reperfusion injury of the liver obtained from fed rats and may thus serve as a highly sensitive indicator of liver viability.

Animals↗
PubMed1994

Determination of chlorinated phenols and cresols in human urine using solid-phase extraction and gas chromatography.

A method is described for the isolation, derivatization, separation and determination of chlorinated phenols and cresols in urine. After acid hydrolysis, solid-phase extraction on Separcol SI C18 was used. Quantification was based on the internal standard method using 2,6-dibromophenol. Before GC determination the isolated compounds were derivatized with pentafluorobenzyl bromide. The separation of interfering substances followed on a Ekosorb column using elution with dichloromethane-toluene (15:85). The recovery of the method ranged from 72.3 +/- 9.9 to 109.9 +/- 6.3% and the limit of determination varied from 0.0005 to 0.002 micrograms ml-1. Using this method, 52 persons from occupationally and non-occupationally exposed groups were examined for the presence of chlorinated compounds in urine. The levels of chlorinated phenols and cresols were several times higher in the group of occupationally exposed workers, especially for 2,4-dichlorophenol.

Chemical Industry↗
PubMed1994

Modeling of the saturable time-constrained amoxicillin absorption in humans.

Amoxicillin pharmacokinetics was modeled using a two-compartment disposition model and a saturable time-constrained absorption model with a storage compartment. The absorption model parameters estimated by the nonlinear regression are: a rate constant of the systemic input, ksys, (median: 1.31 h-1, range: 0.79-7.01 h-1), a maximal absorption rate, Vmax (median: 1407 mg/h, range: 703-4181 mg/h), an account corresponding to the half maximal rate, Kma, (median: 1077 mg, range: 235-4376 mg), time of the absorption cessation, Tabs, (median: 1.72 h, range: 0.82-4.53 h) and absorption lag time. Tlag, (median: 0.085 h, range: 0-0.123 h). It was shown, that the first-order absorption parallel to the saturable process is negligible in the dose range studied. The model described well the dependence of areas under concentration-time curves on the dose determined in several earlier studies. It was used also to predict the fraction of the amoxicillin dose absorbed for different doses. Simulations performed over a wide dose range (50-10000 mg) demonstrated that the fraction absorbed decreases nonlinearly from 90% at 50 mg to 22% at 10000 mg and strongly depends on the duration of the absorption period.

Absorption↗
PubMed1994

Comparative effects of a Mg-enriched diet and different orally administered magnesium oxide preparations on ionized Mg, Mg metabolism and electrolytes in serum of human volunteers.

OBJECTIVE: To determine whether: 1) short-term dietary elevation in magnesium (Mg) intake could alter serum ionized Mg (IMg2+), total Mg (TMg); % ionized Mg (% IMg2+) and other cations; and 2) different formulated preparations of Mg oxide (MgO) in the presence and absence of phosphate could alter serum IMg2+, TMg, % IMg2+ and other cations in Mg-loaded subjects. METHODS: A randomized, triple cross-over study was performed on a rigorously defined group of normal male volunteers. Eighteen males were administered diets containing four to five times the United States recommended daily allowance (USRDA) of Mg followed by a randomization of three different MgO preparations, in the presence or absence of phosphate, containing equimolar amounts (12.34 mmol) of elemental Mg. Forty age-matched volunteers served as reference range controls. Specific ion selective electrodes were utilized to measure IMg2+, ionized calcium (ICa2+), sodium (Na+) potassium (K+) and hydrogen ion concentration (H+). Measurement of urinary excretion of Mg as well as TMg were determined by atomic absorption spectroscopy. RESULTS: Diets enriched with different oral formulations of Mg given for 6 days result in significant elevations in serum IMg2+ and % IMg2+ but not TMg, ICa2+, K+ or H+ in normal subjects. Although such Mg-loaded subjects demonstrate significant elevation in urinary excretion of Mg, no further changes in IMg2+, TMg or any of the serum cations were produced by ingestion of either of the three MgO preparations. Subjects showing normally low basal levels of serum IMg2+, (< or = 0.54 mM/L), could easily have their serum IMg2+ level manipulated by diets enriched with Mg, whereas subjects having average normal or high normal IMg2+ levels did not have their IMg2+ elevated significantly with either diets enriched with Mg or with exogenous MgO. CONCLUSION: These results indicate that since serum IMg2+ and % IMg2+, but not TMg, can be altered by dietary intake, previous or future findings which may indicate no change in TMg by diet may not reflect changes in biologically-active Mg.

Adolescent↗
PubMed1994

Dose-ranging study of NG-nitro-L-arginine pharmacokinetics in rats after bolus intravenous administration.

1. NG-nitro-L-arginine (10, 30 and 100 mg/kg) was administered intravenously to the male Wistar rat. Plasma was collected over 48, 72 and 120 h and was analysed for the drug by hplc. Pharmacokinetic parameters were calculated using a non-compartmental method. 2. Drug concentration-time profiles of individual rats after all doses studied exhibited secondary peaks, while geometric mean concentration-time curves showed plateaus. 3. NG-nitro-L-arginine plasma concentrations divided by dose almost coincided. Pharmacokinetic parameters were not dose-dependent in the range of 10-30 mg/kg, but changed after 100 mg/kg of NG-nitro-L-arginine indicating some decline from linearity. 4. NG-nitro-L-arginine is a low-extracted drug in rat as the total clearance was low (0.05-0.07 l/h/kg). Half-life and mean residence time were found to be long (17-30 and 23-40 h, respectively). Despite its low lipophilicity, NG-nitro-L-arginine exhibited large steady-state and terminal volumes of distribution (1.4-2.2 l/kg and 1.4-2.4 l/kg, respectively). Together with the double peak phenomenon, these results may be explained by assuming NG-nitro-L-arginine is involved in a recirculation process in the body.

Animals↗
PubMed1994

The use of physiologically based models to simulate enantioselective differences in pharmacokinetics.

The majority of synthetic drugs are chiral and are usually administered as racemates. However, body proteins can recognize the steric configuration, and the pharmacological activity and pharmacokinetics of enantiomers usually differ. The key parameters that determine the overall enantioselectivity in disposition are those quantifying protein binding and biotransformation of drugs. Physiologically based models (PBMs) are effectively applied to predict pharmacokinetics of drugs using those parameters. In this work we used PBM to evaluate a range of changes in the model-independent pharmacokinetic parameters (total clearance, mean residence time, volume of distribution, half-life) with changing relative fraction of enantiomers unbound in the blood (range 1-8) and relative intrinsic hepatic clearance (range 1-10). A pharmacokinetic interaction between enantiomers was also simulated and it was shown that experiments with separate administration of pure enantiomers and of a racemate are equally important to avoid biases in pharmacokinetic parameter estimates due to interactions between enantiomers. Concentration-effect relationships were analyzed for the case of one enantiomer being active, and it was demonstrated that hysteresis as well as proteresis may appear depending on the differences in hepatic intrinsic clearances of enantiomers or fractions unbound in blood. The great predictive potential of physiologically based models in stereopharmacokinetics was thereby demonstrated.

Computer Simulation↗
PubMed1994

Factors influencing isradipine and amlodipine binding to human plasma lipoproteins.

The objectives of this study were to determine the distribution of isradipine among individual plasma lipoproteins ex vivo in healthy volunteers (n = 8) and in hypercholesterolaemic patients (n = 12), and to investigate the mechanisms involved in the interaction of isradipine and amlodipine with isolated lipoprotein fractions in vitro. The distribution study ex vivo demonstrated the different relative affinity of isradipine for the plasma lipoproteins: high-density lipoprotein (HDL) > low-density lipoprotein (LDL) > very low-density lipoprotein (VLDL). Isradipine binding correlated linearly with the cholesterol levels in LDL and VLDL; however, binding to HDL did not correlate with the cholesterol level in this fraction. The total binding affinity of isradipine to isolated LDL was markedly higher compared with amlodipine; total binding affinity (nKa) of isradipine vs amlodipine was (1.60 +/- 0.08) x 10(7) l/mol vs (4.14 +/- 0.33) x 10(6) l/mol, respectively. Binding to HDL was also higher with isradipine --nKa = (1.04 +/- 0.04) x 10(5) l/mol--compared with that of amlodipine: nKa = (3.82 +/- 0.18) x 10(4) l/mol. There was no significant competitive binding effect of cyclosporin A (CyA) on isradipine binding to individual lipoprotein fractions. It is likely that, in addition to the structure of surface apoproteins, the factors determining the interaction of calcium antagonists with plasma lipoproteins also include the plasma level of each lipoprotein fraction as well as the lipophilicity of the drug.

Amlodipine↗
PubMed1993

Biological environmental specimen banking in Slovakia.

Biological environmental specimens, including samples of human tissues, were stored for 5-10 years after solubilizing by mineralization in boiling nitric acid. The sampling procedure, transport treatment and storing was standardized. Documentation identifying the sample and its origin were used. Data on toxic metals in dust-fall, in the individual components of the environment as soil, air, ground and surface water, plants, animals, food and human tissues (liver, kidney, lung, brain, heart and plasma) are reported for the 6 most heavily contaminated regions of Slovakia. In some areas xenobiotics in the environment seriously affected the flora and fauna, including man. Banking of specimens has been stressed as the necessity for future analyses.

Animals↗
PubMed1993

The use of a nonlinear absorption model in the study of ascorbic acid bioavailability in man.

A two-compartment disposition model of ascorbic acid (AA) pharmacokinetics with saturable and time-constrained intestinal absorption was developed. The model was fitted to pharmacokinetic data obtained after oral administration to nine healthy volunteers of two effervescent dosage forms differing in AA content: Celaskon 60 mg (CK60) and Celaskon 500 mg (CK500). It was demonstrated that in the case of CK500 less than 30% of the dose was absorbed as compared with CK60. Parameters of the AA nonlinear absorption kinetics were assessed by simultaneous fitting of mean concentration-time data for both doses and placebo. The relatively short duration of absorption found (3.2 h) can explain the failure of past attempts to increase the AA bioavailability using sustained-release dosage forms. Model simulation showed that the ingestion of 60 mg with 3-4 h intervals is optimal for maximal bioavailability of AA.

Adult↗
PubMed1993

Health and chemical environment in Czecho-Slovakia, international cooperation context.

This review provides a record of the present situation with regard to public health and environmental degradation and its underlying causes in Czecho-Slovakia, taking into account "ways of life," which is a synonym for its two components: environment and behavior. It gives attention to the priorities which include air and water pollution and food contamination. "Environmental protection" includes the human health protection from air, water, land, and groundwater pollution, ecological protection and natural resource preservation, use of pesticides, food and consumer product safety, and safety associated with the introduction of new chemicals into commerce. Further, this review focuses on the fundamental building blocks for a new environmental policy and management system (Constitution Act, 1991; Environmental Law, 1991; Chemical Act, in preparation; standards regarding chemicals, etc.). With regard to the international concern about the dangers of chemicals for humanity and the natural environment, attention is drawn to the collaboration of Czecho-Slovakia in chemical safety with WHO, IRPTC, and OECD. An important task is to determine what scientific research is needed and to educate administrators, politicians, and the general public in chemical safety.

Adolescent↗