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Biomedical subjects

V Bauer

Publications and source records attributed to V Bauer.

At least 19 recordsLinked to original sources
PubMed2001

Dietary supplementation of the pyridoindole antioxidant stobadine reduces vascular impairment in streptozotocin-diabetic rats.

We studied the influence of hyperglycemia lasting 1, 4, 6 and 8 months on the reactivity and ultrastructure of the aorta in Wistar rats. Moreover, the effect of the pyridoindole antioxidant stobadine ((-)-cis-2,8-dimethyl-2,3,4,4a,5,9b-hexahydro-1H-pyrido[4,3-b]indole) on the changes induced by the 8-month hyperglycemia were studied. Hyperglycemia was induced by streptozotocin (STZ, 55 mg/kg i.v.). In the functional study, responses to KCl, acetylcholine (ACh), noradrenaline (NA) and hydrogen peroxide were evaluated under isometric conditions. The first changes in aortic reactivity started after 1 month of hyperglycemia and were exhibited by significantly increased NA-induced contractions. Relaxant responses to acetylcholine were decreased, although not significantly. Prolongation of hyperglycemia to 4, 6 and 8 months did not cause any additional significant changes in responsiveness to NA. Decreased ACh-induced relaxation and increased contractile responses to H2O2 were observed in month 4. The functional responses were not substantially deteriorated by prolongation of hyperglycemia to 6 and 8 months. Ultrastructural examination of the diabetic aorta showed disturbances in normal tissue organization. An 8-month supplementation of stobadine in diabetic rats resulted in the protection of aortic function as well as its ultrastructure. These results suggest that abnormalities occurring in the aorta of diabetic rats might result from the damaging effects of oxygen free radicals.

Animals↗
PubMed2000

Effects of superoxide generating systems on muscle tone, cholinergic and NANC responses in cat airway.

To study the possible role of reactive oxygen species in airway hyperreactivity, we examined the effects of the superoxide anion radical (O(2)(-)) generating systems, pyrogallol and xanthine with xanthine oxidase, on muscle tone, excitatory and inhibitory neurotransmission in the cat airway. Smooth muscle contraction or non-adrenergic non-cholinergic (NANC) relaxation evoked by electrical field stimulation (EFS) were measured before or after O(2)(-) generating systems with or without diethydithiocarbamic acid (DEDTCA), an inhibitor of endogenous superoxide dismutase (SOD). Resting membrane potential or excitatory junction potential (EJP) were also measured in vitro. Both pyrogallol and xanthine/xanthine oxidase produced biphasic changes in basal and elevated (by 5-HT) muscle tone. After SOD pretreatment, both systems consistently produced a prolonged contraction, thereby indicating that O(2)(-) was converted to H(2)O(2) by the action of SOD and as a result the actions of O(2)(-) were lost but those of H(2)O(2) introduced. The O(2)(-) showed no significant effect on smooth muscle contraction or EJP evoked by EFS, however after DEDTCA pretreatment, it evoked initial enhancement followed by suppression of the contraction and EJP. DEDTCA pretreatment ameliorated the inhibitory action of pyrogallol and xanthine/xanthine oxidase on the NANC relaxation, probably because O(2)(-) could combine with endogenous NO to form peroxynitrite. These results indicate that the O(2)(-) generating systems have multiple actions, presumably due to the presence and simultaneous action of at least two different reactive oxygen species (O(2)(-) and H(2)O(2)). While H(2)O(2) seems to be responsible for elevation of muscle tone and augmentation of smooth muscle contraction by EFS, O(2)(-) inhibits muscle tone, cholinergic and NANC neurotransmission.

Animals↗
PubMed2000

Extraction and chromatographic separation methods in pharmacokinetic studies of Stobadine--an indole-related antioxidant and free-radical scavenger.

This overview provides comprehensive information on the most relevant results of Stobadine preclinical disposition studies. In order to investigate pharmacokinetic processes of the drug in rats, dogs and in human volunteers, several bioanalytical assays based on radiometric, spectrofluorometric, as well as chromatographic determination methods were developed and implemented. In small laboratory animals, the drug absorption, distribution, metabolism and elimination were investigated by administering 3H-labeled Stobadine. Spectrofluorometry was used alternatively for the determination of cold/unlabeled Stobadine in extracts of biomaterials sampled from larger animal species. The chromatographic separation methods proved, however, to be the most advantageous for determining details of the drug disposition and fate in the body.

Animals↗
PubMed2000

Effect of N-acetylcysteine on colitis induced by acetic acid in rats.

(1) To verify the proposed role of reactive oxygen species (ROS) in ulcerative colitis, the effect of an antioxidant N-acetylcysteine (NAC) was studied in acetic acid (AA)-induced colonic inflammation. (2) Depending on the dose used, NAC administered intracolonically was found to reduce the extent of colonic damage, along with a decrease in myeloperoxidase (MPO) activity, colonic wet weight and wet/dry weight ratio. (3) NAC attenuated the enhanced vascular permeability and prevented the depletion of colonic reduced glutathione (GSH) caused by AA administration. (4) The findings indicate that NAC may prove beneficial in the treatment of colitis.

Acetic Acid↗
PubMed2000

[Non-selective cationic current--the basis of depolarization in smooth muscle].

The activation of smooth muscle muscarinic receptors leads to its contraction. Electrophysiological and biochemical methods have gradually, over the time span of roughly 30-40 past years, helped to reveal this phenomenon's underlying processes. One element of this cascade of processes is the influx of cations into the smooth muscle cell--non-selective cationic current--causing depolarisation of the cell membrane and subsequent opening of voltage-operated calcium channels. This mini-review provides the reader with up-to-date knowledge on non-selective cationic current, supplemented with information on muscarinic receptors of smooth muscle, their coupling with effectors via G proteins, as well as on muscarinic modulation of calcium and potassium channels of smooth muscle. The conclusion is dedicated to pointing out the future trends of research in this area. (Tab. 2, Fig. 2, Ref. 82.)

Animals↗
PubMed2000

[Morphologic and clinical sequelae of focal ischemic lesions].

The diseases of vessels, mainly of those in brain are one of the most serious problems of the medical practice. The encephalomalacia or cerebral infarctions are usually caused by transient or permanent obstruction of the brain arteries lumen. Beside local dysfunction of vessels the obstructions could be based on embolic events originating in the heart. Such an obstructions are resulting in global and focal cerebral ischaemias. Arterial occlusion results in cerebral ischaemia and the lack of oxygen (anoxia) which leads to reversible or irreversible injury of the nervous cells in the ischaemic region. The local cell injury or cell death causes attraction of macrophages invading into the devitalized tissue within 72-96 hours after the beginning of the ischaemia. The aim of this study was to find out the correlation between asymptomatic or symptomatic course regarding localisation of the ischaemic lesions in the cerebral tissue. Our anatomical findings were collected from 318 autopsies, and reports on postmortem examinations during the period between September-December 1998. The grossing of the brain was carried out by using of Virchow's method. Atherosclerosis, hypertension, and diabetes mellitus were found to be the main risk factors for the production of focal cerebral ischaemia. Of those patients with focal cerebral ischaemia atherosclerosis had 87.5%, 44.3% were suffering from hypertension, and 25% from diabetes mellitus. The focal ischaemia analysed in this study originated from arterial stenosis or thromboembolic obstructions. We divided the lesions into 3 groups according to their size. The most frequently apparent lesions (72%) were the small cysts (0-10 mm in diameter)-lacunae. The majority of them (90%) was found in the basal ganglia. The second group consisted of postmalatic pseudocysts (10-30 mm in diameter), and the third group was represented by encephalomalatic lesions which were larger than 30 mm. Cerebral ischaemic lesions were present in 27.8% of the studied cases. Nevertheless, more than the half (56.8%) of the affected brains (postmalatic pseudocysts, lacunae and malaciae) belongs to the group of patients who were clinically asymptomatic. The asymptomatic lesions, having negative results in the patient's history, and the clinical course were localised mainly in the basal ganglia of both sides and in the frontal part of the right (nondominant) hemisphere.

Adult↗
PubMed1999

Reactive oxygen species induced smooth muscle responses in the intestine, vessels and airways and the effect of antioxidants.

Numerous experimental data confirm the importance of reactive oxygen species (ROS) in physiological activities of smooth muscles and in the pathogenesis of various diseases with altered function of smooth muscles. The present study shows that smooth muscles of the intestine, airways and vessels, as well as their epithelium, endothelium and innervations, might be important targets of the ROS action. We demonstrated differences among the actions of various ROS (endogenous, exogenous, produced enzymatically, non-enzymatically) as well as among their actions in different smooth muscle tissues. Our results indicate that ROS are involved in changes in muscle tone, membrane conductance, calcium homeostasis, calcium-dependent processes, as well as in eicosanoid and nitric oxide metabolism. The effects of antioxidative enzymes (superoxide dismutase, catalase), of several drugs of natural origin (e.g. Kampo Medicines) and synthetic agents (e.g. stobadine, nitrosopine, ACE inhibitors) suggest that smooth muscle tissues are useful models to study ROS action and drug intervention in ROS induced injuries.

Animals↗
PubMed1999

Protective effect of stobadine in experimental colitis.

To assess the possible role of reactive oxygen species in inflammatory bowel disease, the effect of the antioxidant and free radical scavenger stobadine was studied in acetic acid-induced experimental colitis. Stobadine administered locally into the colon was found to reduce the extent of colonic mucosal injury, abolish the increase in myeloperoxidase activity, attenuate the enhanced vascular permeability, and prevent the depletion of reduced glutathione. The attempt to reduce pharmacologically excessive free radical production and oxidative damage in the inflamed colonic mucosa may be regarded as a complementary treatment of ulcerative colitis.

Acetic Acid↗
PubMed1999

Reactive oxygen species as mediators of tissue protection and injury.

Extensive research efforts during the last three decades resulted in a large body of experimental evidence that suggests an important role of the disbalance between generation and elimination of the oxygen and xenobiotic derived free radicals in physiological and pathological processes. Reactive oxygen species (ROS) are generated in many metabolic pathways, and are entering the organisms from exogenous sources, dominantly via airways and gut. ROS induced injuries, e.g. thermal, chemical, radiation, ischaemia/reperfusion, inflammation, hyperoxia, etc., result in diseases like atherosclerosis, ulcerative colitis, autoimmune diseases, asthma, etc. The current paper is designed to provide an overview of the effects ROS may exert in various tissues. Because of the effective defense systems, the tolerance of viable human cells to ROS is relatively high. The oxidant stress induced dysfunction of various systems, such as the gut, airways, nervous, cardiovascular system, etc., involve both direct and indirect mechanisms. Understanding of these molecular mechanisms is essential for a rational antioxidant therapy.

Animals↗
PubMed1998

Gastric transmucosal potential difference: effect of antisecretory and gastroprotective drugs.

1. Ion transport and electrical resistance of the gastric mucosa are responsible for the generation of the transmucosal potential difference (PD), which is considered an index of mucosal integrity. 2. The aim of the present work was to study the effect of some antisecretory and gastroprotective agents on PD in stomachs damaged by ethanol. 3. Control PD values measured in anesthetized rats were 35 to 40 mV (mucosa negative). Oral administration of 96% ethanol or intragastric instillation of 20% ethanol induced an abrupt fall in PD from the basal values of 40.4+/-1.0 mV and 39.6+/-0.1 mV to 14.6+/-2.5 mV and 11.7+/-1.3 mV, respectively. 4. Oral and/or topical pretreatment with the antisecretory agents ranitidine and timoprazole, as well as with the gastroprotective agents PGE2 and pentacaine, but not with an aluminum- and magnesium-containing antacid and with sucralfate, reduced the maximal drop of PD caused by ethanol. 5. After the administration of concentrated ethanol, hemorrhagic lesions were formed in the glandular stomach. 6. With the exception of ranitidine, all the drugs tested prevented the development of lesions after ethanol administration. 7. The results indicate that the gastric barrier can be protected by various drugs that act through different mechanisms.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1997

Hypoxia-induced inhibition of calcium channels in guinea-pig taenia caeci smooth muscle cells.

1. The effects of hypoxia on whole-cell current in single smooth muscle cells and on a high K(+)-induced contraction of strips of the guinea-pig taenia caeci were studied. 2. In physiological salt solution (PSS) and K(+)-based pipette solution, hypoxia (PO2 = 20 mmHg) reversibly inhibited both the inward Ca2+ current (ICa) and outward Ca(2+)-activated K+ current (IK(Ca)) components of the whole-cell current. 3. In PSS and Cs(+)-based pipette solution, hypoxia reversibly suppressed ICa by 30 +/- 5% at 0 mV. 4. When Ba2+ was used as a charge carrier, the IBa was suppressed by hypoxia in a potential-dependent manner, with the maximum of 40 +/- 7% at +10 mV. Alterations of concentrations of EGTA, GDB beta S or ATP in the pipette solution did not change the inhibitory effects of hypoxia on ICa and IBa. 5. In PSS with 2 mM CaCl2 replaced by CoCl2, hypoxia did not affect the Ca2+ influx-independent potassium current. 6. In cells voltage clamped at -20 mV hypoxia reversibly inhibited the spontaneous transient outward currents. 7. The response of high K(+)-contracted taenia caeci to hypoxia was composed of an initial rapid relaxation followed by a small transient contraction and slow relaxation. The transient contraction was blocked by atropine (1-10 microM), while relaxations were unaffected by atropine and guanethidine (10 microM). 8. The results show that hypoxia reversibly inhibits ICa and secondarily suppresses IK(Ca) due to decreased Ca2+ influx through Ca2+ channels. 9. It is suggested that inhibition of ICa was responsible for the rapid relaxation, whereas transient contraction may have been due to release of acetylcholine from nerve terminals upon hypoxia.

Adenosine Triphosphate↗
PubMed1997

Hydrogen peroxide induced responses of cat tracheal smooth muscle cells.

1. The effects of hydrogen peroxide (H2O2) (10(-6)-10(-3) M) on membrane potential, membrane currents, intracellular calcium concentration, resting muscle tone and contractions elicited by electrical field stimulation (EFS) and carbachol were examined in cat tracheal strips and isolated smooth muscle cells. 2. H2O2 (10(-4) and 10(-5) M) enhanced the amplitude of contractions and excitatory junction potentials (e.j.p.) evoked by EFS without changing muscle tone and resting membrane potential of the tracheal smooth muscle, and enhanced the contraction induced by carbachol (10(-3) M). At an increased concentration (10(-3) M), H2O2 elevated resting muscle tone and marginally hyperpolarized the membrane in the majority of the cells. 3. In 51 out of 56 cells examined, H2O2 (10(-6)-10(-3) M) elicited an outward current at a holding potential of -40 mV and enhanced the frequency of the spontaneous transient outward current (STOC). In 20 cells the outward current was preceded by a small inward current. In the other cells, H2O2 elicited only an inward current or did not affect the background current. 4. In Ca2+ free solution the action of H2O2 on the resting muscle tone, STOCs, background current and on the current induced by ramp depolarization was significantly reduced. 5. H2O2 (10(-4) M) increased the intracellular ionized calcium concentration both in the absence and presence of external Ca2+. However, the effect developed faster and was of a higher amplitude in the presence of external Ca2+. 6. These results suggest that H2O2 increases intracellular Ca2+, with a subsequent augmentation of stimulation-evoked contractions, and enhances Ca2+ and voltage-sensitive potassium conductance.

Animals↗
PubMed1996

Effect of pentacaine and its derivatives on the contractile responses of smooth muscle in the guinea-pig stomach.

The effect of a carbanilic local anesthetic pentacaine [(+/-)-trans-2- (1-pyrrolidinyl)cyclohexyl ester of 3(n)-pentyloxyphenyl-carbanilic acid] and some of its derivatives [K-1905 [(+/-)-trans-2-diethylaminocyclopentyl ester of 3(n)-pentyloxyphenyl-carbanilic acid], K-2002 [(+/-)-trans-2-(1-pyrrolidinyl)cyclohexyl ester of 4(n)-pentyloxyphenyl-carbanilic acid], K-2006 [(+/-)-trans-2-(1-pyrrolidinyl)cyclopentyl ester of 4(n)-pentyloxyphenyl-carbanilic acid], and carbanilates P2 [(+/-)-trans-2-(1-pyrrolidinyl)cyclohexyl ester of 4-methoxy-carbonylphenyl-carbanilic acid], P3 [(+/-)-trans-2-(1-pyrrolidinyl)cyclohexyl ester of 3-methoxy-phenyl-carbanilic acid], and PeJ, the quaternized derivative of pentacaine), as well as that of oxethazaine was studied on longitudinal antral and circular fundic smooth muscle strips of the guinea-pig stomach. All the carbanilates studied relaxed the smooth muscle, attenuated the spontaneous smooth muscle contractions and shifted the acetylcholine, histamine, and BaCl2 cumulative concentration effect curves to the right, reducing their maximum. There was no direct relationship between their relaxing potency and the ability to reduce the action of different stimulants. For the effectiveness of the carbanilates studied, substitution in the lipophilic part of the molecule was more important than in the hydrophilic part and the meta position was more advantageous than the para position. Pentyloxy-derivatives (pentacaine, K-1905, K-2002 and K-2006) were more active than the methylcarbonyloxy (P2)- and methoxy (P3)-derivatives. Opening of the heterocyclic ring (K-1905) in the hydrophilic part of the molecule did not affect significantly the potency of the derivative studied, while quaternization (PeJ) significantly reduced the potency. It is suggested that the carbanilates studied may affect the smooth muscle responses via changes in the membrane fluidity and Ca2+ availability, and that these effects might be partly responsible also for their antiulcer activity.

Acetylcholine↗
PubMed1995

Effect of illuminated nifedipine, a potent antioxidant, on intestinal and vascular smooth muscles.

1. The effects of nifedipine (Nif) and its illuminated nitroso product nitrosopine (NTP) were investigated on lipid peroxidation, KCl elevated smooth muscle tension, and ionic currents of single smooth muscle cells. 2. Illumination of Nif at 400-700 nm within 24-48 h changed it completely to a potent antioxidant, NTP. 3. Nif relaxed the KCl-induced contractions of guinea-pig taenia caeci and rat aorta and reduced the amplitude of the evoked inward Ca2+ current of taenia caeci cells in a concentration-dependent manner. NTP (up to 100 microM) was ineffective in this respect. Pretreatment by NTP (10 microM) did not affect the actions of Nif. 4. The evidence suggests that NTP, generated by day-light illumination from Nif, exerts antioxidant activity but is devoid of voltage-dependent Ca2+ channel (VDC) blocking property and does not interfere with the action of Nif on the smooth muscle cell membrane VDC.

Animals↗
PubMed1995

Chronic toxicity and micronucleus assay of the new cardioprotective agent stobadine in rats.

A 26-week oral toxicity and micronucleus assays of the new cardioprotective drug stobadine (CAS 95751-51-2), in the form of dipalmitate salt (DP 1031) were performed in Wistar rats of both sexes. DP 1031 was administered daily orally in doses of 7.07, 23.60 and 70.07 mg/kg. Physical appearance and general behaviour of the treated animals were normal, with a small deviation (hypoactivity in the highest dose group at the start of experiment). Food and water consumption as well as body weight gain exhibited similar values in the control and experimental groups of animals. No drug-related changes were noted in the haematological, biochemical, histopathological and genotoxicological examinations. Neither sex differences nor dose-related changes were noted under these conditions.

Animals↗
PubMed1995

[Smooth muscle preparations as models for studies of drug effects on organs].

The action of drugs on processes in smooth muscles, in their innervation or mucosa results in changes in contractility of the gut, airways, vessels and urogenital system. Noteworthy insight has been gained into the basic common characteristics ot smooth muscles as well as into special properties of individual smooth muscle types whose fundamental properties have become adapted to a particular situation. This insight along with knowledge on the subcellular and cellular organization of smooth muscle cells and of their innervation, on the role of the mucosa, and introduction of sophisticated electrophysiological, biochemical, isotopic and morphological methods makes smooth muscle suitable for investigation of elemental physiological and pathophysiological processes and of targets of drug action. The complexity of the smooth muscle tissue allows to study the mechanisms of drug action on the peripheral cholinergic, adrenergic, nonadrenergic-noncholinergic nerves and their neuromediators, on the epithelial and endothelial cells and the biologically active substances which they release, on the membrane and subcellular receptors, receptor coupled processes, ion channels, enzymes, Ca2+ availability, etc. Since most of these mechanisms operate also in other tissues, the obtained results may characterize drug action in other systems as well.

Calcium Channels↗
PubMed1995

Involvement of different Ca2+ sources in changes of responsiveness of guinea-pig trachea to repeated administration of histamine and acetylcholine.

The role of Ca(i) and Ca(o) in changes of responsiveness of guinea pig tracheal smooth muscle strips to repeated applications of histamine and acetylcholine was investigated. Homologous desensitization to histamine developed when the airways were exposed to concentrations higher than 10(-5) mol/l, while sensitization to acetylcholine was recorded even when its highest concentration did not exceed 10(-5) mol/l. The maximum of the concentration response curves (CRC) was reduced upon repeated histamine, and enhanced upon repeated acetylcholine administration. There was, however, no significant difference in EC50 values for repeated CRCs of the stimulants. In Ca2+ free, EGTA (10(-4) mol/l) containing solution the second contraction elicited by single (10(-3) mol/l) or cumulative (10(-9)-10(-3) mol/l) histamine application was significantly smaller, while that elicited by acetylcholine did not differ significantly from the first one. In Ca(2+)-free, caffeine (10(-2) mol/l) and EGTA containing solution the contractile responses to repeated additions of Ca2+ (2.7 mmol/l) in histamine and acetylcholine (10(-3) mol/l) treated tracheae was decreased and unchanged, respectively. Addition of nifedipine (10(-6) mol/l) to this solution fully prevented Ca2+ in inducing contraction in histamine treated tracheae, while Ca2+ still induced contraction in acetylcholine treated tracheae. TMB-8 (10(-5) mol/l) was ineffective in blocking the remaining acetylcholine induced contractions. The present data suggest that contractions of the guinea pig trachea elicited by histamine and acetylcholine are due to release of intracellular Ca2+ from a caffeine sensitive store and to influx of Ca2+ from the extracellular space via voltage operated channels (VOC). Moreover, acetylcholine activated Ca2+ entry into guinea pig tracheal smooth muscle cells via the nifedipine insensitive mechanism, probably receptor operated channels (ROC). It is concluded that desensitization to histamine in the guinea pig trachea is most probably due to alterations in intracellular Ca2+ mobilization and Ca2+ influx via VOC. In contrast, sensitization to acetylcholine involved primarily enhanced Ca2+ influx via VOC and Ca2+ induced Ca2+ release.

Acetylcholine↗