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R Hrdina

Publications and source records attributed to R Hrdina.

28 records · Page 2Linked to original sources

[CADISO (Cardiovascular Diseases and Stability of the Organism): 10 years of integrated research on natural substances at the Charles University Pharmacy School in Hradec Králové].

The research project CADISO (Cardiovascular Diseases and Stability of the Organism--Phytotherapeutical Possibilities) is an alliance board associating approximately 20 professional institutions, its centre and coordinating laboratory being the Department of Pharmaceutical Botany and Ecology, Faculty of Pharmacy, Charles University, Hradec Králové. It aims at the prevention (additives in food industry) and therapy of diseases of the circulatory apparatus using phytotherapeutic agents and substances isolated from higher plants and fungi. The project is divided into three systems of investigation: ADAPRETE, i.e. the substances increasing the nonspecific resistance of the organism (adaptogenes of plant origin, immunostimulants), DIACORD, dealing with the substances acting on the cardiovascular system in a mediated way, i.e. treating the diseases the eventual action of which alters the heart and vessels (antihypercholesterolemics, antihyperlipidemics, antidiabetics, anti-oxidants and quenchers of free radicals, hepatoprotectives, anti-aggregating agents), and CORCORAN studying the taxons and substances isolated from them which act directly on the circulatory system (cardiotonic, anti-arrhythmic and vasodilating agents). To achieve a real purpose of the project, the linking-up of the phytochemical, pharmacological-toxicological, pharmaceutical-technological fields, production of raw materials and legislation is ensured.

Cardiovascular Diseases↗

[Cardiotoxicity of a selected group of drugs].

Drugs and other chemical substances can impair the heart in any of its functions--electrical activity, mechanical activity and metabolism, most frequently by a graded pharmacological action or a direct toxic effect, or immunological mechanisms (hypersensitive reaction). The drugs with the potentially greatest cardiotoxic effect on the function of the heart include beta 1-sympathomimetics, beta 1-blockers, cardiac glycosides, antidysrhythmics, inhalational general anaesthetics, methylxanthine, and anthracycline cytostatics. Other drugs, which are mainly of toxicological importance and which can act cardiotoxically, are halogenated hydrocarbons, ethanol, nicotine and heavy metals. A knowledge of the cardiotoxic action of the above-mentioned groups of drugs is essential for their safe use in clinical practice.

Drug-Related Side Effects and Adverse Reactions↗

Changes in the toxicity and therapeutic efficacy of daunorubicin linked with a biodegradable carrier.

The effects of the linkage of daunorubicin (DNR) and the synthetic biodegradable polymer polyhydroxyethyl-L-glutamine (PHEG) on general toxicity, therapeutic efficacy, and acute organ toxicity were investigated. General toxicity was assessed by means of mortality, or body weight changes of male CBA mice weighing 22-25 g after a single-dose i.p. administration of 5 or 2.5 mg/kg DNR, free or bound. Linked DNR at a larger lethal dose significantly increased mean survival time (18 versus 12 days). Surprisingly, free DNR at a smaller dose produced larger increases in body weight as compared with linked DNR. The linkage of DNR and PHEG did not markedly change the therapeutic activity in three murine hemoblastoses--plasmacytoma MOPS 406, leukemia P388 and hemoblastosis La. Acute (24 h) changes in cardio- and hepatotoxicity were studied on female Wistar rats weighing 208 +/- 5 g after a single dose of 5 mg/kg i.v. both free and linked DNR, as well as after an administration of the PHEG polymer alone (200 mg/kg i.v.). Free DNR caused a three-fold increase in creatine kinase (CK) activity, the identical dose of linked DNR caused only a 1.7-fold increase. Free DNR administration resulted in a decrease in heart rate, other tested drugs did not significantly change either blood pressure or heart rate. Free DNR did not change the kinetics of bromsulphalein (BSP) except for a decrease in extraction effectivity. Both linked DNR and polymer alone significantly changed some kinetic parameters of BSP. The results showed that the biodegradable polymer PHEG cannot be clinically used due to its hepatotoxic action. On the other hand, a decrease in total toxicity and cardiotoxicity resulting from the linkage of DNR and PHEG, the therapeutic efficacy being preserved, stimulates the efforts to find a suitable polymer carrier of anthracyclines without more serious side-effects.

Animals↗

[Metabolic and acid-base changes in intensive diuretic therapy in heart failure].

A group of 65 patients with advanced heart failure was examined with the aim to disclose changes in serum glucose, creatinine, potassium, chloride, and acid-base balance under the influence of intensive diuretic therapy. 50 patients were treated with ordinary furosemide and amiloride combination (average observation time 25 days), in 15 cases amiloride was replaced by captopril 75-150 mg/day (average observation 15.5 days). The results are as follows: 1. We found no rise of glycaemia in non-diabetics with either ordinary diuretic therapy or captopril. On the contrary: stress hyperglycaemia in the beginning of the therapy normalized in the course of it. 2. There was a significant rise of serum creatinine during the first two weeks of therapy with furosemide and amiloride. Reversal of this trend followed after captopril. 3. There was no fall in the average serum chloride concentration during ordinary diuretic therapy. Adding captopril to the regime brought about a rise in serum chloride. 4. Serum potassium had no tendency to fall either after furosemide and amiloride or furosemide and captopril. 5. The acid-base balance showed no shift towards metabolic alkalosis during an intensive but rational diuretic regime either with or without captopril. On the contrary: mild initial metabolic alkalosis had a tendency to normalize with proceeding cardiac compensation.

Acid-Base Equilibrium↗

Changes in cardiac output, hepatic and renal functions in rats with isoprenaline-induced heart damage.

A model of acute rat heart damage by a large single dose of isoprenaline (ISO) (100 mg.kg-1 s.c.) was assessed for its suitability to evaluate changes in drug kinetics in acute heart failure. Within 24h after the administration of the above dose the colorimetric dilution method revealed a decrease in cardiac output by more than 20% and mild increase in total peripheral resistance in anaesthetized female Wistar rats. At the same time, marked hypotension developed with a decrease in mean arterial blood pressure by nearly 20%. An acceleration of both depolarization and repolarization of the atrial and ventricular musculatures and a surprising bradycardia were demonstrated electrocardiographically. ECG failed to demonstrate any signs of myocardial ischaemia. Determination of bromsulphalein and inulin clearance values revealed decreased liver and kidney function. Mild anaesthesia-induced respiratory and metabolic acidosis was improved by ISO administration. The described model at least partially corresponds to the manifestations of acute heart failure with hypotension in man.

Animals↗

Is DH-ergotoxine the best gerontologicum from the ergot source? Experimental comparison with individual components.

The effect of DH-ET (dihydroergotoxine = 33% DH-ergocornine (DH-ECO) + 33% DH-ergocristine (DH-ECS) + + 33% DH-ergokryptine (DH-alfa-ECP: DH-beta-ECP = 2:1 and that of the single DH-derivatives on the retention of 14C-uridine (14C-U) in three parts of the brain tissue, blood plasma and liver tissue was estimated (i.e. radioactivity four hours after ip. adm. of 74kBq X 100 g-1). In young male rats DH-ET and DH-ECO enhanced the retention of 14C-U especially in the parietal cortex In one year old males DH-ECS and DH-alfa-ECP had the greatest effect. As a model of undesired effects the influence on peripheral blood flow in the hind limb of urethanised rats was examined using the perfusion' technics. All substances in the dose of 1 microgram removed epinephrine induced vasoconstriction although they themselves in the dose of 100 micrograms enhanced the perfusion pressure, excepting DH-ECO. All substances diminished the liver blood pool in urethanised rabbits (as norepinephrine does), most efficient being DH-beta-ECP and DH-ECO. On the other hand these substances also slowed the velocity of blood stream. The highest toxicity (LD) of DH-ECS and the lowest one of DH-alfa-ECP was found by an infusion technique. All substances diminished heart frequency but had a variable effect on PQ and QT ECG intervals. Ranging all substances according to their desirable properties from the geriatric viewpoint an index for each substance was calculated. This was most advantageous in the case of DH-alfa-ECP and DH-ECS in contrast to DH-ET and DH-ECO.

Alzheimer Disease↗