Effect of Beer Consumption on Methylation and Redox Metabolism.

To investigate the influence of beer consumption on levels of homocysteine (HCY), vitamin B6, B12, folic acid (FA), dimethylglycine (DMG), betaine (BET) and other selected markers. One hundred and sixteen male volunteers were enrolled in the study. A one-month period of alcohol abstinence was followed by a one month when participants drank 830 mL of alcoholic beer every day. After that phase, one month of alcohol abstinence followed. At the beginning and after every phase blood samples were taken and analysed. Ninety-three participants completed the study. After the phase of alcohol consumption, uric acid (UA) (p<0.0001), antioxidative capacity (AOC) (p=0.02), superoxide dismutase (SOD) (0.025), glutathione reductase (GRH) (0.0001), total cholesterol (p<0.0001), HDL-cholesterol (p<0.0001), Apolipoprotein-AI (ApoAI) (p<0.0001), LDL-cholesterol (p<0.039) and Apolipoprotein B (ApoB) (p<0.009) increased, while vitamin B12 (p=0.0001) and fibrinogen (p<0.0001) decreased. Other tested parameters (DMG, BET, vitamin B6 and FA) did not show any significant changes. UA changes and changes in AOC were statistically significantly correlated (r=0.52, p<0.0001). HCY, DMG and BET levels did not show any statistically significant changes after beer consumption, whereas some markers of redox metabolism increased (UA, AOC, SOD and GRH). A statistically significant correlation denotes the dependence of UA and AOC changes in connection with beer consumption.

Synthetic isothiocyanate indole-3-ethyl isothiocyanate (homoITC) enhances sensitivity of human ovarian carcinoma cell lines A2780 and A2780/CP to cisplatin.

Isothiocyanates (ITCs), popular chemopreventive agents present in cruciferous vegetables, prove growth-inhibiting and apoptosis-inducing activities in cancer cell lines in vitro. Our study presents a new synthetic ITC derivate indol-3-ethyl isothiocyanate (homoITC) as an effective modulator of cellular proliferation and inducer of apoptosis with potential utility as an anticancer drug or a sensitizer to routinely used chemotherapeutic agent cisplatin (cis-Pt).
We analyzed the growth inhibitory effects of homoITC in the human ovarian carcinoma cell line A2780 and its cisplatin-resistant variant A2780/CP using MTT-test and its apoptosis-inducing properties by flow cytometry and caspase 3 activation. Combination index (CI) values from Calcusyn software were used to characterize the interactions of homoITC and cis-Pt as synergistic (CI1). Significant synergistic effect in growth inhibition of homoITC (5 - 15 microM) and cis-Pt (2.5 - 10 microM) on A2780 parental cell line (CI from 0.42 to 0.85) was also observed on A2780/CP resistant subline (CI from 0.18 to 0.73) for 10-50 microM cis-Pt concentrations and the same concentrations of homoITC. Synergy in growth inhibition correlated with the potential of homoITC to stimulate apoptosis induced by cis-Pt.We conclude that homoITC may be worth of further studies assessing its value in the ovarian cancer treatment and elucidating mechanisms of its action.

[Effect of a dialysis solution with icodextrin on ultrafiltration and selected metabolic parameters in patients treated with peritoneal dialysis]. / Vliv podání dialyzacního roztoku s icodextrinem na ultrafiltraci a vybrané metabolické parametry nemocných lécených peritoneální dialýzou.

BACKGROUND: To date, peritoneal dialysis has been performed almost exclusively using dialysis solutions containing glucose as the osmotic agent. Use of these solutions is fraught with problems regarding adequate fluid removal from the body and is also associated with undesirable metabolic effects; hence the search for alternative osmotic agents. A dialysis solution with the glucose polymer icodextrin generates ultrafiltration on the principle of colloidal osmosis. The aim of the study was to establish the effect of icodextrin-base dialysis solution on the magnitude of ultrafiltration and evaluate selected metabolic parameters of patients treated by ambulatory peritoneal dialysis. METHODS AND RESULTS: A total of 9 patients whose glucose-based solution was replaced by an icodextrin-based solution during the night-time exchange were evaluated. A control group of 9 patients used glucose-solution during all exchanges. Night-time bag ultrafiltration, blood pressure, and the serum levels of lipids, insulin, leptin, maltose, and amylase were determined before icodextrin administration (time 0), at one-month intervals (time 1, 2, 3), and one month after study completion (time 4). In icodextrin-treated patients, ultrafiltration rose from 246.5 +/- 60.5 ml (mean +/- SEM) at time 0 to 593.1 +/- 87.4 ml; p < 0.01, at time 1, to 547 +/- 67 ml; p < 0.05, at time 2, and to 586.7 +/- 58.8 ml; p < 0.01, at time 3, the icodextrin administration led to a rise in maltose from 0.02 +/- 0.01 g/l at time 0 to 0.1 +/- 0.1 g/l; p < 0.01, at time 1, to 1.0 +/- 0.09 g/l; p < 0.01, at time 2, and to 1.1 +/- 0.09 g/l; p < 0.01, at time 3, with a fall to zero values at time 4 (NS). Icodextrin administration was followed by a decrease in leptinemia from 34.6 +/- 17.2 ng/ml at time 0 to 21.7 +/- 8.9 ng/ml; p < 0.05, at time 1, to 21.4 +/- 9.5 ng/ml; p < 0.05, at time 2, and to 15.9 +/- 24.1 ng/ml; p < 0.05 at time 4. Insulin and lipid levels were not affected. There was no change in the above parameters in the control group. Icodextrin-treated patients reduced their antihypertensive medication, but not statistically significantly. CONCLUSION: Icodextrin administration significantly increase ultrafiltration thus providing for effective control of hydration status without the need for high-level glucose-based dialysis solutions. The use of a glucose polymer-based dialysis solution is associated with a significant yet reversible rise in serum maltose. The decrease in leptin may signal a reduction in body weight after replacing glucose in dialysis solutions with icodextrin, or enhanced rates of leptin elimination as a result of ultrafiltration-induced convective transport.

Determination of amidepin in human plasma by reversed-phase high-performance liquid chromatography with fluorescence detection.

An isocratic reversed-phase high-performance liquid chromatographic method for the determination of amidepin has been developed. The method is based on the extraction of alkaline plasma with diethyl ether-dichloromethane, and the injection into the Supelcosil LC-18 column of the evaporated and reconstituted organic phase. After separation, detection is carried out by a fluorescence detector (excitation at 195 nm with no filter). The limit of detection is 10 ng/ml of plasma. The mean coefficient of variation is 12%. The plasma levels after oral administration and after intravenous administration are shown.

[Determination of Lonazolac in blood using liquid chromatography with fluorescence detection and use of this method in a comparison of Lonazolac-Irritren preparations]. / Stanovení Lonazolacu v plazme kapalinovou chromatografií s fluorescencní detekcí a aplikace metodiky pri srovnání prípravku Lonazolac-Irritren.

An analytical method was worked out to determine Lonazolac in human plasma based on precipitation of human plasma with a precipitating agent and methanol. This deproteinized plasma was analyzed by liquid chromatography with the use of a reverse phase and fluorimetric detection. The described method is sufficiently sensitive (the limit of detection under 0.1 microgram/ml of plasma) and precise (error of the method = 9%). The precision of the method, recovery from the plasma (100 +/- 3%) and stability in frozen plasma (minimally one month) are presented. Application of the method in a comparison of the newly developed Czechoslovak preparation Lonazolac and the foreign preparation Irritren is shown. Results are documented by the course of the levels of both preparations in dependence on time and principal pharmacokinetic parameters derived from the one-compartmental model.

[Determination of naphthidrofuryl and naphthidrofurylic acid in human plasma using RP-HPLC and fluorimetric detection]. / Nekteré aspekty stanovení naftidrofurylu a naftidrofurylové kyseliny v lidské plazme metodou RP-HPLC s fluorimetrickou detekcí.

An analytical method was developed for the determination of naphthidrofuryl and its principle metabolite--naphthidrofurylic acid in human plasma by the RP-HPLC method with fluorimetric detection. The analytical method is based on a single extraction with a 5 ml mixture ether: hexane (1:1 by volume), with salting out by means of potassium chloride after which the organic phase after centrifugation, evaporation and reconstitution is sprayed on the reverse phase of HPLC and the separated substances are determined fluorimetrically (excitation 271 nm, emission 240 nm). Lonazolac served as the internal standard. The mobile phase consisted of 72% methanol, 1% triethylamine, 0.6% phosphoric acid. Optimization of the composition of the mobile phase from the aspect of the amino base, dependence of the percent content of methanol in the mobile phase and dependence of the recovery of substances on the composition of the extracting reagent are presented. The limit of detection was 4 ng/ml of plasma for naphthidrofuryl. The stability of compounds (a minimum of 2 months) and interference of some other drugs are shown.

[Determination of isosorbide dinitrate in human plasma after the administration of a newly-developed Czechoslovak preparation]. / Stanovení isosorbiddinitrátu v lidské plazme po aplikaci vývojového Ceskoslovenského preparátu.

An analytical method of the assay of isosorbide dinitrate in the human plasma was developed. The analytical method is based on the extraction of the plasma with toluene and direct injection of the toluene phase on the packed column (3% SE 30) of a gas chromatographic apparatus. After separation, detection is carried out with a detector of electron capture. The reported method is rapid (period of analysis = 10 min), sensitive (limit of detection = 0.1 ng/ml of plasma) and sufficiently precise (error of the method, 12%). The precision of the method during the day and between days is presented. The application of the method is shown in a comparison of a Czechoslovak preparation in advance development with the foreign preparation Iso-Mack. The results after administration of 5 mg of the Czechoslovak and foreign sublingual form of the preparation in a group of ten volunteers are documented with the course of the levels in the individual experimental subjects and the principal pharmacokinetic derived from the one-compartmental model.

[Determination of nitroglycerin in human plasma using gas chromatography after the administration of dosage forms used in Czechoslovakia]. / Stanovení nitroglycerinu plynovou chromatografií v lidské plazme po aplikaci nekterých lékových forem pouzívaných v CSSR.

An analytical method was developed to determine nitroglycerin in human plasma. The analytical method is based on the extraction of plasma with hexane and the feeding of the packed collumn (10% OV 101) of the gas chromatographic apparatus with the concentrated hexane phase. After separation, detection is carried out by a detector of electron capture. The described method is sensitive (limit of detection = 50 pg/ml of plasma) and sufficiently precise (error of the method = 13%). The precision of the method during the day (+/- 12%) and between the days (+/- 8%) is presented, as well as the return of nitroglycerin from plasma (95%). An application of the method on comparing the pharmacokinetic parameters in two dosage forms used in Czechoslovakia is shown. The results after the administration of one mg of the sublingual and spray forms of nitroglycerin preparations are documented by the course of the levels in the individual experimental subjects and the principal pharmacokinetic parameters derived from the one-compartmental model.