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R Marko

Publications and source records attributed to R Marko.

18 recordsLinked to original sources
PubMed1998

Uranium in urine--normalization to creatinine.

"Spot samples" of urine are routinely used to monitor occupational exposure to uranium and other toxic heavy metals, such as mercury, lead, and cadmium. In the present work, it was shown that diurnal variations in the uranium concentration in different urine samples from the same individual could be quite large. However, these variations were in correlation to the creatinine level of the same samples, with values of R = 0.72-0.99, for the five subjects studied here. Thus, it is proposed here that uranium concentrations in "spot" urine samples be expressed in terms of ng uranium g(-1) creatinine rather than ng uranium L(-1). Once the 24-h creatinine level is estimated for the individual based on weight, height and age, the adjusted values can be used for determination of the internal dose of uranium.

Circadian Rhythm↗
PubMed1998

Uptake of ingested uranium after low "acute intake".

The uptake of uranium, ingested as a soluble compound, was studied by monitoring the uranium level in urine by inductively coupled plasma mass spectrometry and through measurement of an isotopic tracer. The high sensitivity of this method allows measurement of uranium levels in urine samples from each voiding, therefore more detailed biokinetic studies are possible. To simulate low "acute intake," five volunteers with "normal" levels (5-15 ng L(-1)) of uranium in urine ingested a grapefruit drink spiked with 100 microg of uranium (235U/238U = 0.245%) as uranyl nitrate, and the level of uranium in their urine after ingestion was monitored. Two techniques were applied to estimate the extent of exposure: a) uranium levels above the normal level for each volunteer; and b) the deviation from natural isotopic ratio. Results were normalized relative to the creatinine concentration, which served as an indicator of urine dilution, to reduce effects due to diurnal changes. The results clearly indicate that currently accepted bio-kinetic models overestimate the time between ingestion of dissolved uranium and its excretion in urine, the maximum of which was found to be around 6-10 h. The uptake fraction was in agreement with recent studies, i.e., 0.1-0.5% of the ingested uranium for four of the subjects but above 1.5% for the fifth, and well below the 5% reported in International Commission on Radiation Protection Publication 54. Finally, partial results from the isotope dilution study indicate that uranium absorbed through the intestine interchanges with uranium retained in body organs. The time scale of this process is quite short, and the acute exposure led to a minimum in the isotopic ratio within hours, while recovery back to natural abundance due to low chronic exposure takes several days.

Adult↗
PubMed1996

Inductively coupled plasma mass spectrometry as a simple, rapid, and inexpensive method for determination of uranium in urine and fresh water: comparison with LIF.

A simple method, based on inductively coupled plasma mass spectrometry, for determination of uranium in urine at levels that indicate occupational exposure, is presented. Sample preparation involves a fifty-fold dilution of the urine by nitric acid (2% HNO3) and no other chemical treatment or separation. The analysis itself is completed in under 3 min. The analytical procedure is fully automated so that a technician may perform over 100 analyses per day. With proper control of the blank contribution, a lower limit of detection of 3 ng L(-1) in the original urine sample was achieved. Uranium concentrations in the range 6-30 ng L(-1) were found in urine samples of people that are not occupationally exposed. The validity of the results was demonstrated through measurement of standards, controlled uranium addition experiments and, at higher concentrations, by comparison with results obtained by an independent method based on laser induced fluorescence. The laser induced fluorescence technique was found to be sufficient for detection of occupational exposure at an action level of 1.5 microg L(-1). Use of internal standards, indium, and thallium, improved quantification by about 10%, but was not deemed necessary for routine analysis. The inductively coupled plasma mass spectrometry is also ideally suited for monitoring uranium in fresh water and drinking water, as no sample dilution is required and the lower limit of detection is below 0.15 ng L(-1).

Humans↗
PubMed1992

Electrophysiological actions of a new antiarrhythmic drug, bisaramil, on isolated heart preparations.

Electrophysiological effects of bisaramil--a new antiarrhythmic drug under clinical trial--were investigated on isolated heart preparations, at a concentration range of 2.3-23 x 10(-6) M. Bisaramil dose dependently decreased the maximum rate of depolarization (Vmax), action potential amplitude (APA) and overshoot (OS) both in auricle and in papillary muscle of guinea-pig heart. There was no significant and obvious effect on the duration of the action potential and the resting membrane potential was also unchanged. Bisaramil slowed the spontaneous frequency of pacemaker cells in rabbit sinus node preparation due to its inhibitory effect on slow diastolic depolarization (SDD). Bisaramil was able to inhibit slow Ca(2+)-action potentials induced by isoprenaline on K(+)-depolarized papillary muscle. Results obtained with transmembrane current measurements revealed that bisaramil inhibited both fast Na(+)-current and slow Ca(2+)-current in frog sinoauricular fibres at the same concentration. Bisaramil with a mixed mode of the action seems to be a very promising drug.

Animals↗
PubMed1991

[Electrophysiologic study of the anti-arrhythmic mechanism of action of phosphocreatine in acute myocardial ischemia and reperfusion].

To determine the possible application of exogenous phosphocreatine (ePC) to protect the ischemic myocardium from reperfusion abnormalities in cardiac rhythm, the antiarrhythmic and antifibrillatory activities of the agent were studied in an acute myocardial ischemia model and reperfusion-induced cardiac damage. It was shown that ePC produced a pronounced antifibrillatory effect in acute coronary occlusion and subsequent reperfusion. The agent substantially increased the threshold of electric ventricular fibrillation and the frequency of spontaneous defibrillation. The highest activity was shown by ePC in ischemic myocardial reperfusion. The agent suppressed both rapid inward Na+ current and slow inward Ca2+ current. The effects of ePC on transmembrane ion currents suggest that the agent has a unique electrophysiological mechanism of action involving the properties of Classes I and IV antiarrhythmics, making ePC promising in clinical application in patients with impaired conduction and automatism.

Acute Disease↗
PubMed1990

Trends and developments in radioprotection: the effect of nicotinamide on DNA repair.

Recent studies point to the naturally occurring molecules in expression of radiation damage and in protection. DNA repair was shown to be one of the parameters that can be modified to attain improved protection. The need for a natural compound that can enhance DNA repair in order to improve cellular protection focused our attention on nicotinamide (NA). The effects of addition of NA, a precursor for NAD+ synthesis, on the DNA repair capacity following gamma and ultraviolet irradiations were studied in several repair-proficient and repair-deficient cell lines. The addition of low concentrations of NA (less than 3 mM) resulted in increased repair synthesis in the repair-proficient cells. Addition to repair-deficient cells resulted in decreased repair synthesis. Cells which repair damage from one type of radiation, and not from another, responded accordingly to the presence of NA. However, addition of high concentrations of NA to repair-proficient cells resulted in decreased repair synthesis. Thus, nicotinamide can improve the repair capacity in a concentration-dependent manner, but it clearly requires the existence of functional repair processes.

Animals↗
PubMed1989

Inhibition of human lymphocyte stimulation by visible light and phthalocyanine photosensitization: mitogen and wavelength dependency.

Mitogenic stimulation of human peripheral blood lymphocytes is inhibited by phthalocyanine photosensitization using visible light. The mechanism of inhibition was studied using stimulating agents differing in their mode of action. Stimulation by the plant lectin phytohemagglutinin (PHA) was the least sensitive to inhibition by photosensitization, followed by the tumor promoter phorbol myristate acetate (PMA) and the calcium ionophore A23187. Mitogenic stimulation could also be inhibited by light only, but higher fluences were needed. The order of efficacy was blue greater than red greater than green light, and the response to A23187 was least affected, followed by an increased inhibition of the response to PHA and PMA stimulation. Possible targets and mechanisms for these effects are discussed.

Calcimycin↗
PubMed1988

Combined action of phthalocyanine photosensitization and gamma-radiation on mammalian cells.

The response of Chinese hamster cells and human lymphocytes to the combined action of photosensitization by chloroaluminium phthalocyanine tetrasulfonate and gamma-radiation was studied using colony-forming ability and [3H]thymidine incorporation following mitogenic stimulation respectively, as endpoints. The action of both treatments was usually additive regardless of the sequence of application. However, in human lymphocytes irradiated at low temperature, the photosensitization interacted synergistically with the subsequent ionizing radiation; in this experiment the initial photosensitization reduced the yield of micronuclei produced by gamma-radiation.

Animals↗
PubMed1987

Modification of the cardiac transmembrane potentials and currents by polyamines.

Spermine up to 10(-5) M increased the resting potential (RP) and maximum rate of rise (Vmax) of the action potential (AP) and accelerated the initial (20, 50%) repolarization in isolated guinea-pig and cat atria. These effects were not modified by pindolol (4 X 10(-7) M) or atropine (3 X 10(-7) M) but were prevented by indomethacin (10(-6) M). The right papillary muscle of guinea-pig only showed the acceleration of repolarization while the other parameters were not changed. Spermine did not influence the inward membrane currents under voltage clamp conditions in frog sinoatrial fibers. Spermidine up to 10(-5) M increased RP, Vmax and the duration of AP in guinea pig papillary muscle. RP, Vmax and AP duration were moderately enhanced by spermidine in guinea pig atrium and were not changed in cat atrium. Spermidine was found to stimulate the inward membrane current. Its stimulatory effect was confined to the fast component of the inward current. Neither spermidine nor spermine were able to induce the Ca2+-dependent slow AP in 25 mM K+-depolarized atrium. It is suggested that polyamines influence cardiac membrane events which are responsible for AP and ionic currents.

Animals↗
PubMed1987

Effect of light fluence rate on mammalian cells photosensitization by chloroaluminium phthalocyanine tetrasulphonate.

Phthalocyanines are photosensitizers evaluated for use in photodynamic therapy of cancer. As such, the dependence of the bioresponse on the light fluence rate may be of clinical importance. The effect of the fluence rate of white light from 0.165 to 3.3 kJ m-2 min-1 was studied in Chinese hamster cells and human lymphocytes, using as endpoints colony-forming ability and inhibition of [3H]thymidine incorporation following mitogenic stimulation and dye-photoactivation, respectively. Using Chinese hamster cells exposed to photoexcited chloroaluminium phthalocyanine tetrasulphonate in PBS solution, cytotoxicity was diminished as the fluence rate was reduced. In human lymphocytes changing the fluence rate between 0.33 and 3.3 kJ m-2 min-1 affected the response in a way similar to that of Chinese hamster cells. Human lymphocytes, when exposed to incremental increasing light fluences, 4 h after a conditioning dose, were able to recover from phthalocyanine-induced photodamage, as evidenced by the reappearance of a shoulder on the dose-effect curve. This recovery process during a protracted light exposure, could explain the reduced sensitivity to phthalocyanine photosensitization, compared to exposure at high fluence rates.

Animals↗
PubMed1986

[Electrophysiologic research on the anti-arrhythmia properties of bonnecor--a new dibenzazepine derivative].

A new dibenzepin derivative, bonnecor, showed marked antiarrhythmic and antifibrillation properties in anesthetized cats. One and 2 mg/kg doses of the drug reduce cardiac assimilation of imposed ventricular electric stimuli, increase ventricular fibrillation threshold with a strong and lasting effect and prevent arrhythmias and fibrillation due to 10-minute occlusion and subsequent reperfusion of the anterior descending branch of the left coronary artery. Experimental holding of atrial trabecular membrane potential in a frog, in conditions of a double saccharose bridge, showed bonnecor, in 5 X 10(-7) and 1 X 10(-6) g/ml concentrations, to inhibit rapid sodium inflow and slow calcium inflow. It is expected that bonnecor can be used clinically to control critical arrhythmias and prevent sudden cardiac death.

Animals↗
PubMed1983

[Effect of nonachlazine on transmembrane ionic currents in the frog atrial trabeculae].

The effect of the antianginal drug nonachlazine displaying antiarrhythmic properties on transmembrane ionic currents in the frog atrial fibers was studied in experiments on isolated trabeculae of the frog atria. The transmembrane ionic currents were measured by a voltage clamp technique based on a double sucrose gap arrangement. Nonachlazine (1.03 X 10(-5) mol/l) decreased the amplitude of the fast inward current whatever the magnitude of membrane potential. The drug inhibited the slow inward current and prevented the adrenaline-increased permeability of the slow sodium-calcium channel if external sodium ions were replaced by choline chloride. Nonachlazine (1.03 X 10(-5) mol/l) diminished the amplitude of the inward ionic current in a calcium-free medium as well. The stimulatory effect of prostacycline (2 X 10(-7) mol/l) on the fast inward ionic current was inhibited by nonachlazine. The data obtained suggest that the antiarrhythmic effect of nonachlazine might be linked with the inhibition of the fast sodium inward current and the slow calcium inward current.

Animals↗
PubMed1982

Drugs affecting the calcium-dependent slow depolarization mechanism of the cardiac cell membrane.

Transmembrane action potentials were recorded from isolated electrically paced cat and guinea pig left auricles in Tyrode solution and in the presence of 25 mM K+ or tetrodotoxin (TTX). The overshoot (OS) was increased, and the plateau of the action potential (AP) was shortened by epinephrine (5 X 10(-6)M) and by celluline-A (an organic calcium complex obtained from frog skin). The maximum rate of depolarization (Vmax) was enhanced by serotonin (5-HT) (10(-6)M), prostaglandin F2 alpha (2.8 X 10(-6)M), and by celluline-A. After inactivation of the fast sodium channel by TTX (10(-5)M) or by partial depolarization (25 mM K+ Tyrode) of electrically driven cat and guinea pig left auricle, catecholamines (epinephrine and isoproterenol, 4 X 10(-7) to 5 X 10(-6)M), histamine (10(-6) to 10(-5)M), and celluline-A restored the electrical and mechanical activity. Prostaglandins (PGE1, PGF2 alpha, 1.4 X 10(-8)-2.8 X 10(-6)M), 5-HT (10(-6)-5 X 10(-6)M), and 4-aminopyridine (1.5 X 10(-4)M) were ineffective in such conditions. The beta-adrenergic blocking agent pindolol (4 X 10(-7)M) prevented only the effect of catecholamines; the H1 receptor blocker mepyramine (10(-5)M) antagonized only that of histamine, and D-600 (2 X 10(-6)M), a selective Ca channel blocker, prevented the restoring effect of catecholamines, histamine, and celluline-A.

4-Aminopyridine↗
PubMedDate not supplied

Effect of dopamine on the inward membrane currents of the sinoauricular fibers of the frog heart.

Dopamine increased the slow inward current in the cardiac preparation after blocking (with tetrodotoxin) or eliminating (with Na+-free perfusion) of the "fast Na+ channel". Dopamine was, however, ineffective, if the "slow channel" was blocked (by MnCl2 or D-600) or eliminated (by Ca2+ free perfusion). This adrenaline-like effect of dopamine was prevented by beta-adrenergic blockade (pindolol) and was not modified by previous depletion of tissue catecholamine stores (pretreatment with reserpine). Our data suggest that dopamine affects cardiac electrogenesis through beta-adrenergic receptors and any dopamine-induced noradrenaline release may be only of secondary importance beside this direct agonistic effect.

Animals↗