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Biomedical subjects

V Simánek

Publications and source records attributed to V Simánek.

At least 37 records · Page 2Linked to original sources
PubMed2000

Chemoenzymatic preparation of silybin beta-glucuronides and their biological evaluation.

Chemoenzymatic glucuronidation of the optically pure silybin A (1) using ovine liver glucuronyl transferase afforded three beta-glucuronides of silybin, substituted at phenolic OH groups at the positions C-20 (2), C-7 (3), and C-5 (4) formed in the yields 27, 62.5, and 2.5%, respectively. Using these standards, it was shown that the main silybin conjugate in humans is its 20-beta-D-glucuronate (2), while the C-7 regioisomer (3) was formed in lower proportion. The rate of conjugation of (natural) silybin diastereomers 10S, 11S and 10R, 11R, and therefore also their metabolism in humans is rather different. The radical scavenging activity of 2 is considerably lower than that of its aglycone (1); however, the activity of 3 is higher than in the silybin. These findings corroborate the hypothesis that, at physiological pH, the exclusive target for one-electron oxidation of the silybin molecule is the o-methoxy-phenolic structure at C-19, C-20. This is first pharmacological study using optically pure silybin.

Chromatography, High Pressure Liquid↗
PubMed2000

Human hepatocyte--a model for toxicological studies. Functional and biochemical characterization.

Isolated human hepatocytes (HH) are an accepted model for in vitro experiments for testing liver function and xenobiotic metabolism. Preferred over more traditional animal hepatocyte model used in toxicological studies, it is the model of choice when substances undergoing biotransformation in man are investigated. The aim of this study was to optimize isolation and culture conditions for HH primary culture with regard to cell yield, viability, and metabolic activity, and to evaluate the suitability of donor samples for toxicology experiments. Cell viability, total cytochrome P450 (CYP) content, CYP3A4, CYP1A2 activity, and finally mixed ethoxycoumarin-O-deethylase (ECOD) activity were parameters measured in order to characterize the isolated HH. The quality of the primary cultures, stable and functional for a seven-day period following 24 hour stabilization, was assessed by lactate dehydrogenase (LDH) leakage and response to the model toxin tert-butylhydroperoxide (tBH) and to silybinin, a model cytoprotective substance. Based on HH obtained from livers of five multiorgan donors (average age 44.8 years, three males and two females), the individual variability of donors needs to be considered in evaluating cultures focussing on clinical liver tests. Greater sensitivity to toxins and silybinin was found in the hepatocyte culture from one donor with higher aminotransferase activity. In another case, higher serum bilirubin appeared to be linked to higher ECOD activity. Our conclusion is that values of clinical liver tests ought to suggest a healthy organ thus eliminating previous hepatocyte damage, the crucial factor of primary culture stability and functioning.

7-Alkoxycoumarin O-Dealkylase↗
PubMed2000

[300 videothoracoscopy procedures--personal experience].

Videothoracoscopy and video-assisted thoracic surgery are by now already standard therapeutic procedures in thoracic surgery. The authors submit their experience with the method after 300 thoracoscopic operation at the surgical clinic of the Faculty Hospital in Plzen from the end of 1993 to the beginning of 2000. The main indications for this mini-invasive procedure is the treatment of spontaneous pneumothorax, diagnostic biopsy in pulmonary dissemination of obscure etiology, diagnosis and treatment of pleural exudates and elimination of minor peripheral pulmonary lesions. The authors discuss different surgical procedures in the most frequent diagnoses, their advantages and risks, indication criteria, complications. Attention is also paid to the causes of 10% conversions. In case of treatment of a spontaneous pneumothorax the authors consider videothoracoscopy as the method of first choice, while in case of primary carcinoma of the lungs they recommend the classical procedure. Other possibilities for the wider application of thoracoscopy and its development in their own department include in particular traumatic thoracic surgery.

Humans↗
PubMed2000

[The bioartificial liver--an alternative in the treatment of acute liver failure].

One of the therapeutic approaches in acute liver failure is the use of an artificial system replacing hepatic function--bioartificial liver. Its application is the most perspective in fulminant liver failure during preparation for transplantation of the liver (so-called bridge to transplantation) or in case of a non-functioning hepatic graft, and to reduce the mortality and morbidity of patients with acute liver failure where transplantation is not indicated or where a suitable graft was not found. The authors discuss briefly the construction of these systems, analyze different indications of treatment and its results, obscure questions and perspectives of further development.

Humans↗
PubMed1999

Activities of silymarin and its flavonolignans upon low density lipoprotein oxidizability in vitro.

Silymarin, a standardized extract from Silybum marianum, inhibited in vitro the copper-induced oxidation of human LDL in a concentration-dependent manner. Silybin, a main flavonolignan of silymarin, appeared to be responsible for this LDL antioxidant effect. Silychristin and silydianin, other flavonolignans of silymarin, acted rather as pro-oxidants, but with regard to their content in silymarin, it did not contribute significantly to the reduction of the total LDL antioxidant capacity of silymarin.

Adult↗
PubMed1998

Silymarin inhibits the development of diet-induced hypercholesterolemia in rats.

To study the ability of silymarin, a standardized mixture of antioxidant flavonolignans from the medicinal plant Silybum marianum, and of silybin, the main flavonolignan of silymarin, to inhibit the development of diet-induced hypercholesterolemia the rats were fed high cholesterol diet (HCD). Silymarin or silybin were given as dietary supplements, and their influences on serum cholesterol levels were compared to those of probucol, an antioxidant hypocholesterolemic drug. Anticholesterolemic effect of silymarin was parallel to that of probucol, and dose-dependent at dietary drug concentrations of 0.1-0.5-1.0% (w/w). However, in contradistinction to probucol, silymarin caused an increase in high density lipoprotein (HDL)-cholesterol and a decrease in liver cholesterol content, changes considered to be of benefit. In addition to its anticholesterolemic effect silymarin partially prevented the HCD-induced decrease in liver reduced glutathione, an endogenous antioxidant. Silybin was not so effective as silymarin suggesting that either other constituent(s) of silymarin may be responsible for its anticholesterolemic effect or the bioavailability of silybin alone might be lower than that of silybin as a compound of silymarin.

Animals↗
PubMed1998

Effect of silymarin on serum cholesterol levels in rats.

Previously we have shown that perorally administered silymarin, a mixture of flavonolignans extracted from the seeds of Silybum marianum, possesses a hypocholesterolemic effect in rats fed high cholesterol diet enriched with fat. The aim of this paper was to complete the data concerning peroral and parenteral administration of silymarin. The rats fed standard laboratory diet did not respond to peroral administration of silymarin by decrease of serum cholesterol, but the mild increase in HDL cholesterol was found. Parenterally injected silymarin failed to reduce serum cholesterol both in rats fed high cholesterol diet and standard laboratory diet. The results suggest that silymarin could act either due to the fat-mediated improved bioavailability and/or by inhibiting of resorption of dietary cholesterol.

Administration, Oral↗
PubMed1995

Inhibition of copper/quinoprotein amine oxidases from Aspergillus niger by benzophenanthridine alkaloids.

Inhibition of copper/quinoprotein amine oxidases (EC 1.4.3.6), AO-I (dimer 2 x 75 kDa) and AO-II (monomer 80 kDa), from the fungus Aspergillus niger by benzophenanthridine alkaloids sanguinarine, chelerythrine, and fagaronine were studied. For both amine oxidases the alkaloids showed reversible noncompetitive inhibition of n-hexylamine oxidation with Ki 0.6, 0.9 and 2.8 mM for sanguinarine, chelerythrine, and fagaronine, respectively. The values of the inhibition constants corresponded to pKR+ values for the iminium ion/pseudobase equilibrium of the alkaloids. Since thio-compounds protected the enzymes against this inhibition, the inhibition effect was ascribed to the interaction with a sulfhydryl group essential for the enzymatic activity.

Alkaloids↗
PubMed1994

Induction of respiration-deficient mutants in Saccharomyces cerevisiae by chelerythrine.

Chelerythrine and sanguinarine, two structurally related benzo/c/phenanthridine alkaloids, prevented growth of yeast cells in medium containing either glucose or non-fermentable carbon sources. At concentrations permitting growth of the yeast Saccharomyces cerevisiae, chelerythrine, but not sanquinarine, induced cytoplasmic respiration-deficient mutants. The petite clones that were analysed exhibited suppressiveness and contained different fragments of the wild-type mitochondrial genome.

Alkaloids↗
PubMed1994

Effect of quaternary benzo[c]phenanthridine alkaloids sanguinarine, chelerythrine and fagaronine on some mammalian cells.

The effects of benzo[c]phenanthridine alkaloids sanguinarine (SA), chelerythrine (CHE), fagaronine (FA) and their dihydroderivates were tested on human leukocytes and lymphocytes, rat peritoneal mastocytes and primary cultured hepatocytes. The cytotoxicity of SA and CHE on hepatocytes is dose (35-100 microM) and time (1-3 h) dependent. Both alkaloids decrease chemiluminiscence of leukocytes and inhibit a creation of active E-rosets. The degranulation of mastocytes is inhibited only by CHE. Dihydroderivates of SA and CHE did not display any effect on studied cells, dihydrofagaronine exhibits a hepatotoxicity after 3 h.

Alkaloids↗
PubMed1993

Biochemical evaluation of colchicine and related analogs.

Transformation of ten colchicinoids by isolated rat liver microsomes resulted in the mixture of C-2, C-3, and C-10 O-demethylated metabolites. Colchicinoids administered i.p. to rats (2.5 mumol/kg) increased serum and liver activities of alkaline phosphatase and decreased liver microsomal demethylase activity as well as cytochrome P-450 content. The changes of acid phosphatase level were less pronounced. The aspartate and alanine aminotransferase activities were significantly increased only in colchicine treated rats. No relations between enzyme activity changes and colchicinoid hydrophobicities quantified by partition coefficients (log P) were found. However, the enzyme activity changes were related to the type of substitution at C-3, C-7, and C-10 of colchicinoids. Particularly, O-demethylation at C-3 resulted into the fall of alkaline phosphatase response. On the other hand, the microsomal demethylation and cytochrome P-450 content were related to the modification of the nitrogen substituent at C-7.

Animals↗
PubMed1993

Changes in colchicine and demecolcine content during vegetation period of colchicum autumnale L.

Colchicine and demecolcine were determined in raw and dried leaves, stems, mother and daughter corms of Colchicum autumnale L. in four stages of its ontogenesis. The colchicine content in raw material varies during plant growth. The content of both alkaloids decreases with drying. The HPLC method used is suitable both for the phytochemical analysis of Colchicum and for the toxicological evaluation in cases of intoxication by these plants.

Chromatography, High Pressure Liquid↗
PubMed1992

The effect of N-deacetylcolchiceine on serum lipoproteins in rats.

N-Deacetylcolchiceine (DAC) administered i.p. to rats decreased the level of serum cholesterol and apoB. It was accompanied by the fall of HDL-C due to the decrease of both HDL subfractions HDLa and HDLb, and by a rather weaker decrease of LDL-C. The levels of serum and lipoprotein triacylglycerols were not significantly affected. The "clearing reaction" to heparin in DAC rats differed from controls with regard to plasma cholesterol resulting in its accumulation in HDLa and LDL simultaneously with an increased activity of post-heparin lipoprotein lipase. These results suggest that the DAC accelerates the lipoprotein cholesterol metabolism.

Animals↗
PubMed1989

Antiphlogistics in periodontology.

In 146 individuals with inflammatory periodontal disease the authors verified the therapeutical effect of Sanchelin (the mixture of sanguinarine and chelerythrine in 0.05% concentration) in gel (4% hydrogel carboxymethylcellulose) applied into pockets and in aqueous solution administered in the intrapapillar route. The effect of Sanchelin in solution was compared with the effect of 2% hydrocortison in the same way of administration. The clinical condition of periodontium and the quality of oral hygiene was evaluated by means of indexes and papillae were examined histologically. The authors demonstrated that Sanchelin in gel is an effective drug in treatment of inflammatory periodontal disease. They observed lesser effectivity when intrapapillar administration of Sanchelin in solution was used.

Anti-Inflammatory Agents↗
PubMed1989

Electrochemical and thermal studies of some quaternary benzo(c) phenanthridine alkaloids.

The conditions of the electrochemical reduction and oxidation as well as those of thermal demethylation of quaternary benzo(c)-phenanthridine alkaloids namely chelerythrine (1), sanguinarine (2), and fagaronine (3) were studied. Differences in their electrochemical and thermal behavior are correlated with the results obtained from biotransformation studies with liver microsomal fraction.

Alkaloids↗