Biomedical subjects

A Kohút

Publications and source records attributed to A Kohút.

At least 19 recordsLinked to original sources

PubMed2002

Allelic and haplotype frequencies of the p53 polymorphisms in brain tumor patients.

The polymorphisms of the tumor suppressor gene p53 in exon 4 (p53 BstUI) and in intron 6 (p53 MspI) have been suggested to be associated with the genetically determined susceptibility in diverse types of human cancer. In our hospital-based case-control study, we examined the allele and genotype incidence of these polymorphisms as well as their haplotype combinations in 60 brain tumor patients (27 males and 33 females) and 183 controls without malignancies. The genotype characteristics were determined by the PCR-based RFLP method using DNA extracted from peripheral blood. In this study we show that the p53 BstUI and the p53 MspI polymorphisms are not associated with increased risk of brain tumors. Thus, we conclude that the p53 BstUI and the p53 MspI polymorphic sites within the tumor suppressor gene p53 do not represent genetic determinants of susceptibility to brain tumors.

Adult↗

PubMed2001

Changes of gastric lipase activity after ethanol and indomethacin administration: influence of pretreatment with allopurinol, pentoxifylline and L-DOPA.

Gastric lipase (GL) plays an important role in emulsification and digestion of food fat. Lipids are components of the hydrophobic mucus and mucosa barrier. Damage of the gastric mucosa may therefore be related to changes in the lipid content and GL activity. In the present paper, we studied the effect of administration of a single dose of 96 % ethanol (E) and indomethacin 20 mg x kg(-1) (IND) on the activity of GL and on the concentrations of nonesterified fatty acids (NEFA) and triacylglycerols (TG) in the gastric mucosa of rats. Furthermore, we studied how these changes are affected by allopurinol (ALO), pentoxifylline (PX) and L-DOPA pretreatment 30 min before administration of E or IND. The effect of sialoadenectomy (SA) on these parameters was also evaluated. We found: 1) significant (p < 0.01) inhibition of GL activity after administration of E and IND and also ALO, as well as after pretreatment with ALO before E and PX before IND. L-DOPA administered alone stimulated GL activity, but its administration before IND significantly (p < 0.01) inhibited this enzymatic activity. GL activity was decreased to the threshold values in SA rats and after administration of E to SA animals. 2) NEFA concentrations were decreased after E and increased significantly (p < 0.01) after IND administration. A marked significant (p < 0.01) decrease in NEFA was found after PX and L-DOPA administration. The administration of ALO also lowered the concentration of NEFA. Pretreatment by drugs before E and IND resulted in a significant increase of NEFA in comparison with the drugs given alone (p < 0.05 for ALO + E; p < 0.01 for PX + IND). 3) TG were also decreased in all experimental groups in comparison with the control group, i.e. after E and IND, after ALO and SA and also after pretreatment by ALO before E. The concentration of TG decreased after PX, significantly (p < 0.05) after L-DOPA and after pretreatment by PX before IND. Pretreatment by ALO before E and L-DOPA before IND resulted in the increase of TG in comparison with drugs alone. Thus, these results suggest certain protective effect of pretreatment with ALO, PX and L-DOPA against the E- and IND-induced decrease in NEFA and TG during injury of the gastric mucosa. On the other hand, inhibition of GL activity was also apparent after administration of these drugs before E and IND, which suggest presence of a persisting impairment of lipid digestion in the stomach.

Allopurinol↗

PubMed1999

Reciprocal adaptive response of human peripheral lymphocytes induced by bleomycine or gamma rays.

The adaptive response and reciprocal adaptive response induced in vitro by exposure to low doses of gamma rays (0.05 Gy) or bleomycin (0.05 microg/ml) in human peripheral blood lymphocytes were assessed by the frequency of chromosome aberrations. Gamma rays (1.5 Gy) or bleomycin (1.5 microg/ml) were used as the challenge doses. In the experiments, blood samples from 5 healthy donors were investigated. It has been found that low doses of bleomycin and gamma rays induced a reciprocal adaptive response to high doses of gamma rays or bleomycin. Moreover, the results confirmed that the adaptive response did not correlate with the radiosensitivity of the peripheral blood lymphocytes.

Adaptation, Biological↗

PubMed1999

[Biochemical changes in apoptosis and methods for their determination (review)].

Apoptosis or programmed cell death is a physiological process which occurs at different biological states as well as at disease process. Morphologically it is characterized by the chromatine condensation and other changes with preserved integrity of plasmatic membrane. The major and most frequently studied biochemical characteristic of apoptosis is a DNA fragmentation. In our paper attention is directed to the early biochemical changes in cell membranes, i.g., the externalization of phosphatidylserine, hydrolysis of sphingomyeline on the ceramide and activation of phospholipases especially phospholipase A2. In one part we described the changes of cysteine proteases (caspases), which play a key role in the execution of apoptosis. These biochemical changes are associated with ceramide signalization of apoptosis. Briefly are presented also some dates about apoptosis induction with reactive oxygen radicals and the role of the arachidonic acid metabolites in this process. We consider the investigation and determination of these changes as important parameters of apoptosis at some diseases, e.g., cancer or degenerative diseases, and of their treatment.

Animals↗

PubMed1999

Effect of malotilate on ethanol-induced gastric mucosal damage in capsaicin-pretreated rats.

We studied the role of afferent sensory neurons in malotilate-mediated gastric mucosal protection. Intact and capsaicin sensory-denervated rats were used in the experiments. Gross gastric mucosal injury was assessed and evaluated as a main criterion of the gastroprotective effect of the tested substances. Besides malotilate, methyl-prostaglandin E2 was applied alone or in combination with malotilate to compare the effects and the mechanism of action of both substances. The results revealed that both malotilate as well as methyl-prostaglandin E2 exerted a significant protective action on 96% ethanol-induced gastric mucosal damage. However, there were no significant differences between intact and capsaicin-denervated rats. Only the use of 50% ethanol as a milder mucosal irritating agent resulted in significant differences in both groups of animals. We propose that malotilate (like methyl-prostaglandin E2) has a gastroprotective effect on ethanol-induced gastric mucosal injury. This effect is partly dependent on the sensory nervous system and the combination of both above substances has an additive effect.

Animals↗

PubMed1998

[Pharmacologic and toxicologic results in genetic polymorphisms (review)].

Paper provides a survey of the basic knowledge on the genetic polymorphism of enzymes involved in the metabolism of medicinal drugs and other xenobiotics. The major implications of this phenomenon have been described, namely the interindividual variability in the therapeutic effect of drugs differently metabolised by the polymorphically determined enzymes, or the interindividual variability in the susceptibility to neoplastic processes related to the polymorphically determined enzymes metabolising xenobiotics. Recent advances in the understanding of the molecular genetics of enzymes metabolising drugs and other xenobiotics (particularly cytochrome P-450, glutathione S-transferase, N-acetyltransferase, UDP-glucoronosyltransferases and others), help to understand the molecular basis of several genetic polymorphisms. Present article reviews the current status of studies on polymorphism of xenobiotics-metabolising enzymes and brings a discussion to their pharmacotherapeutical relevance and to their significance for identification of susceptible individuals/subgroups in the carcinogen exposed population.

Enzymes↗

PubMed1998

[Phospholipase A2: characteristics and function].

Phospholipase A2 (PLA2) hydrolyses membrane phospholipids (PL) and it may release arachidonic acid (AA)--the precursor of eicosanoids--from the sn-2 position. PLA2 and metabolites of its catalytic activity participate in many processes in the organism: metabolism of lipids, inflammation and immune reactions, membrane and tissue reparation, proliferation, and others. PLA2 as also an important element in the signal transduction. In the present article, PLA2 is characterised, classified into several types, and its mechanism of action together with its possible role in the disease processes are described. The attention is aimed at two forms of PLA2: The secretory (PLA2) of the type II which is associated with the inflammation injury, and the cytosolic PLA2 which is the main catalyst in the liberation of AA and which participates in the signal transduction. Other forms of PLA2 has been also described.

Arachidonic Acid↗

PubMed1998

Genetic polymorphism of glutathione S-transferases M1 and T1 as a risk factor in lung and bladder cancers.

A combined analysis of two polymorphic enzymes, glutathione S-transferase mu (GST M1) and q (GST T1) and their implication as cancer risk factors was performed in a case-control study of lung and bladder cancers. Using a multiplex polymerase chain reaction (PCR) based method, the frequency of the homozygous deleted GSTM1 and GSTT1 genotypes was examined in 117 lung cancer patients, 67 urinary bladder cancer patients, and in a community-based sample of 248 healthy, unrelated individuals. In both cancer groups the frequency of the GSTM1 null genotype was higher in comparison with that of the control group (59% and 59.7% vs. 49.6%), but this increase did not reach statistical significance (p > 0.05). After grouping by the smoking status, among smokers in both cancer groups (62.1% in lung cancer and 71.4% in the bladder cancer group, respectively) there were statistically significantly (p < 0.05) increased frequencies of the GSTM1 deletion genotype as compared to the control group (49.6%). Smokers with absence of the GSTM1 gene were at an approximately 1.7-fold higher risk for lung cancer (odds ratio--OR = 1.67, 95% confidence interval--CI 95% = 1.0-2.7, p = 0.04) and an approximately 2.5-fold higher risk for bladder cancer (OR = 2.54, CI 95% = 1.2-5.5, p = 0.02). As related to GSTT1, our study demonstrated an overall GSTT1 effect on bladder cancer risk. Individuals with absence of the GSTT1 gene were at an approximately 2.5-fold higher risk of developing bladder cancer. In the lung cancer cases, the frequency of the putatively high risk GSTT1 null genotype was not increased as compared with controls. No effect of smoking was found on risk of lung and bladder cancer associated with the GSTT1 0/0 genotype. In combined analysis, the obtained results suggested that individuals who were both GSTM1 null and GSTT1 null may be at increased risk because they lack both enzymes. The findings suggest that the GSTM1 null genotype may be associated with susceptibility to lung and urinary bladder cancer in dependence on the exposure to carcinogens in cigarette smoke and that the GSTT1 null genotype is not a critical factor in mediating the risk of lung cancer, but may be associated with an increased susceptibility to bladder cancer.

Aged↗

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↗

PubMed1996

Gastroprotective effect of malotilate in indomethacin- and ethanol-induced gastric mucosal damage.

Malotilate as a synthetic substance shares comparable hepatoprotective properties with various flavonoids. The gastroprotective effect of some flavonoids prompted us to ascertain the similar effectiveness of malotilate. The possible gastroprotectivity was examined in gastric mucosal damage in rats induced by indomethacin (20 mg.kg-1) or ethanol (96%). Oral pretreatment with malotilate (25, 50, 100, 200 and 400 mg.kg-1) reduced the extent of lesions induced by both indomethacin and ethanol. Histological analyses also revealed a mitigating effect on the severity of gastric mucosal lesions. Similar results were obtained in the group of rats pretreated with 5 mg.kg-1 indomethacin followed by oral administration of 96% ethanol. This finding suggests that the effect of malotilate on rat gastric mucosa is independent of endogenous prostaglandin production.

Animals↗

PubMed1994

Pentoxifylline-associated reduction of indomethacin-induced rat gastric mucosal injury is supported by decreased lipid peroxidation.

Pentoxifylline pretreatment protects rat gastric mucosa against indomethacin-induced damage. Lipid peroxidation after indomethacin treatment (determined as thiobarbituric acid reactants) was significantly reduced by a single dose of pentoxifylline. The same was true for pentoxifylline administration for 6 days. There is a relationship between reduced lipid peroxidation, decreased number of circulating activated neutrophils and diminished disposition for acute gastric mucosal lesions induced by indomethacin in pentoxifylline-pretreated rats.

Animals↗

PubMed1994

[The effect of long-term administration of levamisole and muramyl-dipeptide on phagocytic activity of polymorphonuclear leukocytes in relation to the age of rats].

The authors observed an immunostimulating effect of levamisole and MDP on fagocyting activity (FA) of neutrophile polymorphonuclear leucocytes in dependence on ageing in rats. They observed 3 age groups, namely 3, 12 and 18 month old animals. The substances were administered during a period of 30 days. It was found out that following both substances, FA elevation in 3 month old animals was significant after 15 days of medicament administration, though, in the 12 month old animals it supervened after 15 and also 30 days. In 18 month old animals following levamisole administration, a significant FA increase supervened only following 15 days; though after MDP administration, it supervened after 25 and also 30 days. It is remarkable that in this group, during administration of both medicaments, 38-50% of animals died. The study points out that age represents a factor which modifies the effect of immunostimulating substances. (Fig. 2, Ref. 16)

Acetylmuramyl-Alanyl-Isoglutamine↗

PubMed1993

[The effect of dopamine and PGI2 on indomethacin and alcohol-induced gastric lesions in rats of various ages in relation to gastric vascular permeability and HCl secretion].

Gastric lesions induced by indomethacin (20 mg.kg-1 i.p.) and ethanol (1 ml 95% intragastrically) were studied in rats after a 24 hour fast. The size of gastric lesions was correlated with gastric HCl secretion and with gastric vascular permeability (determined from the Evan's blue concentration in the gastric tissue after its i.v. administration). These parameters were also studied in rats pretreated with either PGI2 (5 micrograms.kg-1) or dopamine (0.5 mg.kg-1). It was found that in 12-months old rats the gastric lesions were significantly higher compared with the 3-month old group. PGI2 and dopamine significantly decreased gastric lesions in the 3-month rats but not in 12-month old rats. Both indomethacin and ethanol increased gastric vascular permeability in both age groups. It was observed that the decrease of gastric lesions after pretreatment with PGI2 and dopamine in the 3-month old rats was followed with decreased gastric vascular permeability and HCl secretion. On the other hand the increased susceptibility of the gastric mucosa due to indomethacin in the 12-month old rats was followed by a decrease of HCl secretion. PGI2 or dopamine had any effect on the 12-month old rats. These results show that susceptibility of gastric mucosa to PGI2 and dopamine is dependent on age. (Fig. 3, Ref. 31.)

Aging↗

PubMed1993

Effect of allopurinol and superoxide dismutase on indomethacin-induced gastric lesions in the rat.

Gastric lesions induced by indomethacin (20 mg.kg-1 i.p.) were studied in rats after a 24 hour fast. The size of the lesions was correlated with gastric vascular permeability (determined from the Evans blue concentration in the stomach tissue after its i.v administration) and with the rate of gastric emptying (determined from the phenol red concentration after its intragastric application). These changes were correlated with the prevention of gastric lesions by allopurinol (50 mg.kg-1) after a single dose or once daily for 3 days before indomethacin and by a single dose (15,000 U.kg-1) of superoxide dismutase (SOD). Indomethacin significantly increases the rate of gastric emptying concomitantly with gastric vascular permeability. The pretreatment of animals with allopurinol and SOD inhibits gastric lesions as well as gastric vascular permeability without changing gastric emptying which was increased after indomethacin administration. The inhibition of gastric lesion formation and gastric vascular permeability was more marked in rats pretreated with allopurinol for 3 days when compared with rats treated with a single dose of allopurinol only. These results support the suggestion that oxygen-derived free radicals contribute to the pathogenesis of indomethacin-induced gastric lesions.

Allopurinol↗

PubMed1992

Effect of sialoadenectomy on stomach lesions induced by indomethacin and ethanol in relation to gastric vascular permeability, the gastrin level and HCl secretion in rats.

Stomach lesions induced by indomethacin (20 mg.kg-1 i.p.) and ethanol (1 ml 95% intragastrically) were studied after a 24 hour fast in rats which had undergone sialoadenectomy. The size of the lesions was correlated with gastric HCl secretion, with gastric vascular permeability (determined from the Evans blue concentration in the stomach tissue after its i.v. administration) and with the serum gastrin level. These parameters were also studied in sialoadenectomized rats and in animals given epidermal growth factor (EGF) (50 lg.kg-1). It was found that sialoadenectomy significantly (p < 0.01) raised the incidence of stomach lesions after the administration of indomethacin and also after ethanol (p < 0.05). A significant increase in both basal and stimulated HCl secretion was found after sialoadenectomy. Both indomethacin and ethanol also increased gastric vascular permeability in rats not subjected to sialoadenectomy, but sialoadenectomy raised it significantly compared with the non-sialoadenectomized group. The serum gastrin levels fell after sialoadenectomy and the decrease was significant after the subsequent administration of indomethacin or ethanol. The administration of EGF to sialoadenectomized rats lowered the incidence of stomach lesions, inhibited HCl secretion and reduced vascular permeability. The lowered susceptibility of the gastric mucosa to the formation of lesions in sialoadenectomized rats given indomethacin or ethanol can be regarded as the outcome of the uptake of EGF.

Animals↗

PubMed1992

[The role of polymorphonuclear leukocytes in the development of gastric lesions induced by indomethacin and ethanol and the relation of vascular permeability].

The relationship between a reduced number of polymorphonuclear leukocytes (PMN), activated PMN/NBT (+) PMN/, permeability of gastric vessels, and disposition for the development of gastric lesions was studied following administration of indomethacin or ethanol in rats. Decrease in the number of circulating neutrophils and in the number of NBT (+) PMN after 3- or 6-day administration of methotrexate was found to diminish the disposition for the development of gastric lesions. Six-day administration of pentoxifylline resulted in a decreased number of NBT (+) PMN and in a diminished disposition for gastric mucosa injury induced by indomethacin, yet failed to reduce the occurrence rate of lesions after ethanol administration. No direct relationship was established between changes in gastric vascular permeability and decreased disposition for the development of gastric lesions after administration of methotrexate or pentoxifylline. (Fig. 3, Ref. 30.)

Animals↗

PubMed1992

The influence of prolonged cimetidine administration on serum gastrin levels and gastric acid secretion in rats.

The correlation between serum gastrin levels and gastric acid secretion during 4 weeks of cimetidine administration (once daily) was investigated. Serum gastrin levels and gastric acid secretion were estimated on the 7th, 14th, 21st and 28th day after cimetidine administration (25 mg.kg-1, intragastrically). At the mentioned time intervals gastric acid secretion stimulated by histamine and pentagastrin was also studied. It was found that on the 14th and 21st day after cimetidine administration serum gastrin levels were significantly elevated. Basal gastric acid secretion after cimetidine administration was significantly decreased at all the observed time intervals. Histamine-stimulated gastric acid secretion was increased on the 14th, 21st and 28th day after cimetidine administration. Hypoacidity was not followed at all time intervals by hypergastrinaemia (only on day 14 and 21 after cimetidine).

Animals↗

PubMed1991

Effect of stobadine on indomethacin- and ethanol-induced stomach lesions and gastric secretion.

Stobadine was found to inhibit the ulcerogenic activity of indomethacin in relation to the dose but was ineffective against the direct necrotizing action of ethanol. It also inhibited gastric acid secretion when administered intraduodenally. Although stobadine is considered to be a scavenger of free radicals, our results indicate that, under the given experimental conditions, it is rather the inhibition of gastric acid secretion that is responsible for its antiulcerogenic effect. The preliminary results do not allow the exclusion of other mechanisms for explaining its antiulcerogenic effect.

Animals↗