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Biomedical subjects

L Benes

Publications and source records attributed to L Benes.

At least 37 records · Page 2Linked to original sources
PubMed1999

Chemistry, physiology and pathology of free radicals.

The superoxide anion radical and other reactive oxygen species (ROS) are formed in all aerobic organisms by enzymatic and nonenzymatic reactions. ROS arise in both physiological and pathological processes, but efficient mechanisms have evolved for their detoxification. Similarly, reactive nitrogen intermediates (RNI) have physiological activity, but can also react with different types of molecules, including superoxide, to form toxic products. ROS and RNI participate in the destruction of microorganisms by phagocytes, as in the formation of a myeloperoxidase-hydrogen peroxide-chloride/iodide complex which can destroy many cells, including bacteria. It is known that the cellular production of ROS and RNI is controlled by different mechanisms. These free radicals can react with key cellular structures and molecules, thus altering their biological function. An imbalance between the systems producing and removing ROS and RNI may result in pathological consequences.

Animals↗
PubMed1999

Stobadine and heart mitochondria.

Previous work has shown, that stobadine-hydrochloride (-)cis-2,8-dimethyl-2,3,4,4a,5,9b-hexahydro-14-pyrido(4,3b) indole administered in a single dose 2 mg/kg of body weight reduces cardiotoxic effect of isoproterenol (1 mg/kg) as shown by lowered serum enzyme activities of AST, CPK, LDH and ALT. We studied the effect of stobadine in vivo on respiration, the level of ATP, malondialdehyde (MDA) and superoxiddismutase (SOD) in heart mitochondria. Serum enzyme activities of AST, CPK and LDH after stobadine application were significantly decreased. In mitochondria, respiration and activity of SOD were inhibited, level of MDA was increased and level of ATP was unchanged. The cardioprotective effect of stobadine is not linked to preservation of mitochondrial function. This effect is probably more complex and mediated on the level of the whole organism.

Animals↗
PubMed1999

Stobadine protects against ischemia-reperfusion induced morphological alterations of cerebral microcirculation in dogs.

Vascular diseases of the CNS are a major medical, social and economic problem. From the number of causes leading to nervous malfunction and damage, ischemia is most prominent. Thus, neuronal protection from ischemic damage may provide significant preventive and treatment potential. This study was designed to test possible protective effects of stobadine in a canine model of global cerebral ischemia. Seven minute ischemia was induced by four vessel ligation and maintained using a controlled systemic hypotension. Stobadine pretreated animals were infused with 2 mg/kg stobadine 30 minutes prior to ischemia, while control animals received vehicle. After a 24 hour reperfusion phase, animals were perfusion-fixed and evaluated using electron microscopy. Stobadine pretreated dogs showed much less damage to both endothelial lining and pericapillary structures of the blood-brain barrier. This included preservation of cellular shape of the endothelium, patency of microvessels, lack of intraluminal blebs material, near normal cytoplasmic osmiophilia, decreased thickness of endothelial basement membrane, significantly less edema of astrocyte end-feet, and preservation of fine mitochondrial structure compared to the control group. Ischemic neuronal changes were observed less frequently in the stobadine pretreated group. In summary, we conclude that stobadine protects both cerebral microcirculation and neurons from injury induced by global cerebral ischemia and reperfusion.

Animals↗
PubMed1999

Kinetics of hydrolysis of acetyl, valeroyl and nicotinoyl acyl derivatives of stobadine.

The present work deals with the kinetics of hydrolysis of the acyl derivatives of stobadine, an originally synthesized potential antiarrhythmic and antihypoxic drug, which was found to have also an excellent scavenging effect on reactive oxygen species. The acyl derivatives of stobadine, which possess high lipophilicity, represent model blood-brain barrier penetrating agents. It is assumed that the acyl derivatives of stobadine may act as prodrugs which are hydrolysed in different biological tissues to release the active drug. The decomposition of three acyl derivatives of stobadine was studied in acidic, basic and neutral buffer solutions at constant ionic strength (0.1 mol/L) at 25 degrees and 70 degrees C using UV spectrophotometric method. The pseudo first-order rate constants and the pH-rate profile for the degradation of acetyl-, valeroyl- and nicotinoyl-derivatives of stobadine were determined. Confirmation that stobadine was the first degradation product was provided by thin-layer chromatography.

Acetates↗
PubMed1997

Endoscopic stereotaxy--an eight year's experience.

During the 10th meeting of the WSSFN in Maebashi in 1989, we discussed 'endoscopic stereotaxy', and presented our preliminary results. This technique was first designed to optimize stereotactic biopsy, but it proved to be effective for other neurosurgical indications as well, including endoscopic stereotactic evacuation of intraparenchymal and intraventricular space-occupying cysts, endoscopic stereotactic cystoventriculostomy, third ventriculostomy, evacuation of brain abscess and intracerebral hematoma, and retrieval of adherent or free-floating ventricular catheters. Our results with endoscopic stereotaxy in different indications are encouraging, compared to conventional microsurgical techniques and pure stereotactic techniques. From 1989 to 1997 we have performed more than 400 stereotactic endoscopic procedures. The mortality rate is below 1%, the operative morbidity is below 3%.

Biopsy↗
PubMed1997

Gastroprotective effect of stereoisomeric cis- and trans-2-(1-pyrrolidinyl) and 2-(1-pyrrolidinylmethyl)cyclohexyl alkoxycarbanilates in rats.

The effect of cis- and trans-isomers of 2-(1-pyrrolidinyl) and of 2-(1-pyrrolidinylmethyl)cyclohexyl alkoxycarbanilates was tested in acute gastric injury induced by phenylbutazone and/or 96% ethanol administration in rats. In both models a more pronounced antiulcer and gastroprotective activity was observed after pretreatment with the trans-isomer of 2-(1-pyrrolidinyl)cyclohexyl ester of 3(n)-pentyloxycarbanilic acid. Its cis-isomer, by comparison, was less effective against ethanol-induced gastric injury and failed to prevent the gastric damage induced by phenylbutazone. After introducing a methylene group into the hydrophilic part of the molecule, there was a loss of stereospecific difference, with both stereoisomers exerting a similar gastroprotective activity.

Animals↗
PubMed1996

Effect of stobadine on gastric mucosal injury after ischaemia/reperfusion.

The ability of stobadine to prevent gastric mucosal injury was tested in rat gastric ischaemia induced by 30 min clamping of the coeliac artery with subsequent 30 min reperfusion. Serious injury of gastric mucosa (macroscopic and microscopic) and the increase of microvascular permeability was found after ischaemia/reperfusion in rats without stobadine. After oral pretreatment with stobadine (5 mg.kg-1, 30 min before surgery), the development of gastric mucosal lesions and changes of vascular permeability were significantly decreased.

Animals↗
PubMed1995

Local anesthetic effect of carbisocaine and its enantiomers.

The optically active isomers of carbisocaine [1-methyl-2-diethylaminoethyl ester of 2-(n)-heptyloxycarbonilic acid] were prepared. The blocking activity of equimolar concentrations of the carbisocaine and its corresponding enantiomers was tested on isolated rat sciatic nerves. There were no significant differences between the anesthetic action of racemic form and enantiomers, however, lower activity for the (--)-enantiomer was observed. The results may indicate negligible stereoselectivity of action of highly lipophilic local anesthetic carbisocaine in the excitable membrane.

Anesthetics, Local↗
PubMed1994

In vitro studies on the activity of japanese kampo herbal medicines Oren-Gedoku-To (TJ-15) and Toki-Shakuyaku-San (TJ-23) as scavengers of free radicals.

Oren-Gedoku-To (TJ-15) inhibited enzymatically (NADPH or CumOOH) and non-enzymatically (Fe-ascorbate) induced lipid peroxidation in rat liver microsomes as assessed by TBA-reactive product accumulation. Toki-Shakuyaku-San (TJ-23) had little effect on either system. The protective effect of TJ-15 against lipid peroxidation was not dependent upon the presence of microsomal drug-metabolizing activity and could not be fully accounted for by its action on microsomal electron transfer, as evaluated by studying the kinetics of cytochrome c reduction. Both TJ-15 and TJ-23 reduced the stable free radical 1,1-diphenyl-2-picrylhydrazyl (DPPH), indicating their free radical scavenging ability. The reactivity of TJ-15 was comparable with that of standard ascorbate, while the activity of TJ-23 was approximately 10 times lower. In a free solution TJ-15 and TJ-23 effectively scavenged OH* radicals, as indicated by the inhibition of ethylene production from 2-keto-4-methiolbutyric acid (KMBA), and O2*- anion radicals, as assessed by the inhibitory effect on the rate of nitro blue tetrazolium (NBT) reduction by the O2*- generating system xanthine/xanthine oxidase.

Animals↗
PubMed1994

Carbamate analogues of tocainide.

A series of the new aminoalkyl esters of chlor-, methyl- and alkoxy carbanilates was synthesized. All the compounds prepared were found to exhibit antiarrhythmic activities comparable with those of mexiletine.

Aconitine↗
PubMed1993

In vitro micronucleus test of the cardioprotective agent stobadine. A genotoxicological study.

The genotoxic effect of stobadine (1) was studied in vitro using the micronucleus test. Hamster and human fibroblastoid cells were used. In hamster cells, the highest concentration of 1 (1.10(-3) mol/l) caused a significant elevatin in the number of micronuclei, while in human cells no positive response was found for either of the concentrations used. Stobadine had no genotoxic effect on human fibroblastoid cells.

Animals↗
PubMed1992

Inhibition of cumene hydroperoxide-induced lipid peroxidation by a novel pyridoindole antioxidant in rat liver microsomes.

The ability of stobadine, a novel pyridoindole antioxidant, to inhibit lipid peroxidation induced by cumene hydroperoxide was investigated in rat liver microsomes. In the micromolar range stobadine effectively inhibited lipid peroxidation as measured by the formation of thiobarbituric acid reactive products. The peroxidation-related degradation of microsomal cytochrome P-450 was prevented by stobadine in the same pattern. Another line of evidence in support of the antioxidant action of stobadine was given by its inhibition of cumene hydroperoxide-induced oxygen consumption in microsomal incubations. Inhibition of lipid peroxidation was not a function of decreased bioactivation of cumene hydroperoxide, as stobadine did not affect the rate of cytochrome P-450 dependent cleavage of cumene hydroperoxide. Neither had stobadine any effect on cytochrome P-450 peroxidase function characterized by the rate of cumene hydroperoxide-dependent oxidation of TMPD, and no direct spectral interaction with microsomal cytochrome P-450 was observed in the micromolar region. We suggest that it is the ability of stobadine to scavenge alkoxyl and peroxyl radicals that is predominantly responsible for the observed antioxidant effect.

Animals↗
PubMed1992

Formation of stable free radicals from kampo medicines TJ-9, TJ-15, TJ-23, TJ-96, TJ-114 and their antioxidant effect on low density lipoproteins.

The Japanese herbal Kampo medicines TJ-9 (A), TJ-15 (B), TJ-23 (C), TJ-114 (D) and TJ-96 (E) were effective (2-5x less than alpha-tocopherol) in inhibiting a copper-induced peroxidation of low density lipoprotein. Kampo medicines dissolved in n-butanol formed stable free radical(s), detected by EPR spectroscopy as a single asymmetric line with g-value g = 2.005. The radical concentration increased in the order: C less than D approximately A approximately E less than B. When the Kampo medicines were oxidized in n-butanol by excess of PbO2 their radical concentration increased 7-15 fold and was in the order C less than D less than A approximately E much less than B. A relationship between the potency of the medicines to inhibit peroxidation of LDL and their ability to form stable free radicals upon oxidation was observed. The medicine which formed more radicals was more efficient in inhibiting peroxidation of LDL. In order to study whether Kampo medicines can reduce alpha-tocopherol radical, the alpha-tocopherol radical was generated by the reaction of alpha-tocopherol with UV irradiated di-tert-butylperoxide and by autooxidation of alpha-tocopherol in n-butanol (25 microliters ml-1) in air. In both systems vitamin-C greater than Kampo B decreased the concentration of the alpha-tocopherol radical and the EPR spectrum of Kampo B stable radical(s) appeared. The effect of other Kampo medicines was not clearly seen since their EPR spectra were superimposed with the spectrum of the alpha-tocopherol radical. The results indicate that Kampo medicines possess electron donor properties and ability to form stable radical(s). The results may contribute to understanding beneficial effects of Kampo medicines in diseases in which free radical damage is suggested.

Antioxidants↗
PubMed1992

[Local anesthetics. CVII. Local anesthetic effects of phenylcarbamates--the effect of connecting chain modification].

The preceding study of the effect of the branching of the connecting chain by the metoxymethyl-, ethoxymethyl- and propoxymethyl group on the alpha carbon on local anaesthetic activity was a stimulus for the preparation of 16 drugs of the group of 1-ethoxyethoxymethyl-2-(1-pyrrolidinyl-), 2-piperidino- and 2-(1-perhydroazepinyl) ethyl esters of o-, m- and p-alkoxyphenylcarbamic acids. The discontinuation of the substituent on the alpha carbon of the connecting chain by another oxygen atom (introduction of an ethoxyethoxymethyl group) has a positive effect on surface and infiltration anaesthesia. Of the prepared agents, 2-piperidino- and 2-(1-perhydroazepinyl-) derivatives with a hexyl or heptyloxy group in the o-position of the benzene ring were most effective; they exceeded the standards cocaine and procaine more than one hundred times. p-Derivatives were least effective; in some cases their indices of effectiveness did not achieve the effectiveness of the standards in both surface and infiltration anaesthesia under study. Acute toxicity of all drugs lies within the range of the toxicities of the standards.

Anesthetics, Local↗