PubMed Health⌕ Search

Biomedical subjects

J Vácha

Publications and source records attributed to J Vácha.

At least 37 records · Page 2Linked to original sources
PubMed2001

Interactions of lymphotoxin alpha (TNF-beta), angiotensin-converting enzyme (ACE), and endothelin-1 (ET-1) gene polymorphisms in adult periodontitis.

BACKGROUND: Adult periodontitis is a complex multifactorial disease whose etiology is not well defined. To investigate whether the genes encoded within the HLA class III region may confer susceptibility to periodontitis, polymorphisms in the ET-1 and TNF-beta genes were analyzed together with the I/D polymorphism of the ACE gene. METHODS: We determined allele and genotype frequencies of the NcoI bi-allelic polymorphism of the TNF-beta gene, the I/D (insertion/deletion) polymorphism of the ACE gene, and the TaqI polymorphism of the ET-1 gene in 63 Caucasian patients with adult periodontitis and 95 orally healthy controls. RESULTS: We found a significant difference in a 3 locus combination of genotypes between patients and controls (P<0.05). In the next analyses, no significant differences were found in allele frequencies of single genes, but we did find a significant difference in the genotype distribution between cases and controls for TNF-beta (P<0.03). Differences were also observed for 2 locus combinations of ACE and TNF-beta genotypes (P<0.03), and the ET-1 and TNF-beta (P<0.05) genes. Evidence of deviation from Hardy-Weinberg equilibrium was observed in the periodontitis group for TNF-beta, with an absence of the B1B1 homozygotes in patients. CONCLUSIONS: This study is of an exploratory nature. Considering the number of significant results, however, at least a part of the observed associations may obviously be real and our findings suggest that interactions of the TNF-beta, ET-1, and ACE genes may be involved in susceptibility to adult periodontitis.

Adult↗
PubMed2001

Combination of drugs elevating extracellular adenosine with granulocyte colony-stimulating factor promotes granulopoietic recovery in the murine bone marrow after 5-fluorouracil treatment.

Combined administration of drugs elevating extracellular adenosine, namely dipyridamole and adenosine monophosphate, together with granulocyte colony-stimulating factor was shown to enhance granulopoietic recovery in the bone marrow of mice treated with 5-fluorouracil. Enhanced regeneration was found both at the level of hematopoietic progenitor cells for granulocytes and macrophages and in the compartment of morphologically recognizable granulocyte precursors. The results might have positive clinical impact. The adjunct use of drugs elevating extracellular adenosine might reduce the cost expenditure of therapy with granulocyte colony-stimulating factor.

Adenosine↗
PubMed2000

Single effects of apolipoprotein B, (a), and E polymorphisms and interaction between plasminogen activator inhibitor-1 and apolipoprotein(a) genotypes and the risk of coronary artery disease in Czech male caucasians.

To evaluate whether polymorphisms in genes whose products are involved in lipid metabolism and fibrinolysis alter the risk of coronary artery disease (CAD), allele frequencies of four genetic polymorphisms were ascertained by PCR-based methods in 175 Czech male patients with coronary artery disease and in 222 Czech men with no symptoms of CAD. The following polymorphisms were studied: apolipoprotein B (apo B) signal peptide insertion/deletion polymorphism, 5' apolipoprotein(a) [apo(a)] TTTTA repeat polymorphism, apolipoprotein E (apo E) varepsilon2, varepsilon3, varepsilon4 polymorphism, and plasminogen activator inhibitor-1 (PAI-1) 4G/5G promoter polymorphism. Apo B and apo(a) allele frequencies differed significantly between the CAD and the control groups (P<0.01 each), with higher frequencies of apo B deletion and apo(a) shorter repeat alleles in the CAD group. We did not observe any differences in allele frequencies of either PAI-1 or apo E polymorphisms but the genotype frequencies of apo E were slightly different between the two groups (P<0.05). In addition, we observed a gene-gene interaction between the PAI-1 and apo(a) polymorphisms with respect to the risk of CAD. None of the polymorphisms studied were associated with the severity of CAD or a history of myocardial infarction. Our findings support the idea that several polymorphisms in apolipoprotein genes may by themselves and/or in interaction with other polymorphisms contribute to risk factors for CAD in men.

Adult↗
PubMed2000

Influence of the joint treatment with granulocyte colony-stimulating factor and drugs elevating extracellular adenosine on erythropoietic recovery following 5-fluorouracil-induced haematotoxicity in mice.

The presented data address the problem of pleiotropic effects of granulocyte colony-stimulating factor (G-CSF) and suggest the ability of drugs increasing the level of extracellular adenosine to activate erythropoiesis when given jointly with G-CSF. To demonstrate these interactions, the effects of the drugs on the recovery from erythropoietic damage induced in mice by a single dose of 5-fluorouracil (5-FU) were investigated. Elevation of extracellular adenosine and thus activation of adenosine receptors was induced by joint administration of dipyridamole (DP), a drug inhibiting the cellular uptake of adenosine, and adenosine monophosphate (AMP), an adenosine prodrug. The drugs were injected in a 4-d treatment regimen starting 2 h after 5-FU injection. Both DP+AMP and G-CSF alone induced only weak effects. However, the combination of the three drugs produced significant elevation of erythrocytes in the peripheral blood which pertained in the posttreatment period. Stimulation of proliferation of erythroid progenitor cells (BFU-E) in femoral bone marrow and increased levels of reticulocytes in the peripheral blood were observed in the course of the 4-d treatment regimen. In addition, significantly decreased mean cell haemoglobin accompanying the elevated numbers of erythrocytes in the combination-treated mice was found. This effect could be interpreted as the result of a sublethal 5-FU-induced damage to erythroid progenitor and precursor cells forced to proliferate intensively by the combination therapy. The observed additivity and synergism of G-CSF with elevated extracellular adenosine in terms of erythropoiesis is an interesting finding with potential implications in clinical practice.

Adenosine↗
PubMed1999

Association of 3 gene polymorphisms with atopic diseases.

BACKGROUND: Various peptidases, including angiotensin-converting enzyme (ACE), inactivate some inflammatory peptides that are considered to influence the pathogenesis of atopic diseases. This enzyme is also involved in the conversion or activation of 2 bronchoconstriction mediators: angiotensin II from angiotensinogen and endothelin (ET), respectively. OBJECTIVE: We tested a hypothesis that asthma or other atopic diseases are associated with insertion/deletion ACE, M235T angiotensinogen, and TaqI ET-1 gene polymorphisms. METHODS: A case-control approach was used in the study. Healthy subjects (141 persons) were used as control subjects, and 231 patients with histories of atopic asthma, allergic rhinitis, atopic dermatitis, or a combination thereof were studied. ACE genotype was determined by PCR, angiotensinogen M235T and ET-1 by PCR, and restriction analysis by AspI and TaqI, respectively. RESULTS: We found the significant association of the insertion/deletion polymorphism of the ACE, as well as that of M235T polymorphism of the angiotensinogen genes, with the group of patients with atopic diseases ( P =.0025 and P =.0204, respectively). No difference was proved for the intron 4 (position 8000) polymorphism in the ET-1 gene when comparing the atopic patients with the control group (P =.1774). A significant difference was found between groups of patients with both asthma and rhinitis and patients without both respiratory atopic diseases (P =.0033). CONCLUSION: It follows that the examined polymorphisms in the genes for ACE, angiotensinogen, and ET-1 could participate in the etiopathogenesis of atopic diseases.

Adolescent↗
PubMed1999

Pretreatment with granulocyte colony-stimulating factor reduces myelopoiesis in irradiated mice.

The purpose of this study was to investigate effects of the treatment prior to irradiation with granulocyte colony-stimulating factor (G-CSF) on hematopoiesis in B10CBAF1 mice exposed to a sublethal dose of 6.5 Gy of 60Co gamma radiation. G-CSF was administered in a 4-day regimen (3 microg/day); irradiation followed 3 h after the last injection of G-CSF. Such a treatment was found to stimulate granulopoiesis, as shown by increased counts of granulocyte-macrophage progenitor cells (GM-CFC) and of granulocytic cells in the femoral marrow and spleen at the time of irradiation. However, postirradiation counts of GM-CFC and granulocytic cells in the marrow of mice pretreated with G-CSF were reduced up to day 18 after irradiation. Interestingly, the D0 values for marrow GM-CFC determined 1 h after in vivo irradiation were 1.98 Gy for controls and 2.47 Gy for mice pretreated with G-CSF, indicating a decreased radiosensitivity of these cells after drug treatment. The inhibitory effects of the pretreatment with G-CSF on the postirradiation granulopoiesis could be attributed to the phenomenon of "rebound quiescence" which can occur after cessation of the treatment with growth factors. Postirradiation recovery of erythropoiesis in the spleen of mice pretreated with G-CSF exhibited a dramatic increase and compensated for the decreased erythropoiesis in the marrow at the time of irradiation. This complexity of the hematopoietic response should be taken into account when administering G-CSF in preirradiation regimens.

Animals↗
PubMed1999

Granulocyte colony-stimulating factor and drugs elevating extracellular adenosine act additively to enhance the hemopoietic spleen colony formation in irradiated mice.

The effects of combined administration of two drugs elevating extracellular adenosine, namely dipyridamole (DP) and adenosine monophosphate (AMP), and granulocyte colony-stimulating factor (G-CSF) on hemopoietic stem cells in vivo were investigated. The experiments were performed on mice using the endogenous spleen colony formation in gamma-irradiated animals as an endpoint. The results have shown that DP and AMP act additively with G-CSF to enhance spleen colony formation and thus the erythroid repopulation of the spleen. These findings indicate that the signaling pathways of G-CSF and drugs elevating extracellular adenosine can interact at the level of primitive hemopoietic stem cells. The enhancement of hemopoiesis-stimulating effects of G-CSF by DP and AMP, which are low-priced and clinically available drugs, could improve the cost-effectiveness of the therapy with G-CSF.

Adenosine↗
PubMed1999

Association analysis of 24-h blood pressure records with I/D ACE gene polymorphism and ABO blood group system.

The purpose of this study was to analyze the association between 24-h blood pressure parameters, insertion/deletion polymorphism of the angiotensin I converting enzyme gene and the ABO blood group system in a sample of the general Czech population. Fourteen parameters describing the 24-h blood pressure readings were obtained by analyzing blood pressure records in 243 volunteers, 119 men and 124 women. These parameters were adjusted for sex and body mass index (BMI) by means of multiple regression test. All subjects were genotyped for the insertion/deletion polymorphism of angiotensin I converting enzyme (I/D ACE) gene and routinely examined for the blood group phenotype in the ABO system. An association was found between the interaction of I/D ACE gene polymorphism and ABO blood group system on the one hand and mean values of systolic (p=0.016) or mean arterial (p=0.027) blood pressures and the phase shift of 24-h BP rhythm (p=0.036) on the other hand. Among three I/D ACE variants the DD genotype was associated with the highest values of mean blood pressure in blood group A and AB carriers. The same genotype was associated with the lowest blood pressures in blood group B and O carriers. In subjects with the DD genotype, the earlier daily position of the maximum of 24-h BP rhythm was found in blood group B, AB and O carriers. On the contrary, blood group A was associated with the latest position of maximum of the 24-h BP rhythm in the DD genotypes.

ABO Blood-Group System↗
PubMed1998

Angiotensin I-converting enzyme and angiotensinogen gene interaction and prediction of essential hypertension.

To prove whether the interaction between insertion/deletion (I/D) angiotensin I converting enzyme (ACE) and M235T angiotensinogen (AGT) gene polymorphic alleles could contribute to causing essential hypertension, we examined subjects from the Czech Republic (365 Caucasians total; 202 normotensives and 163 hypertensives). Subjects were genotyped for insertion/deletion polymorphism of ACE (I/D ACE, intron 16) and for M235T polymorphism of angiotensinogen gene (AGT, exon 2) by means of the polymerase chain reaction (PCR) method. The case-control approach was used. Fisher's exact test followed by Holmes's test to overcome the problem of multiple comparisons were used for the statistical analysis of data. No association of single gene allelic variants with essential hypertension was found in our population. Having compared only double homozygote combinations, the association of the DDMM genotype with essential hypertension was proven (P = 0.0081). To the contrary, IITT (P = 0.0086) was found more frequently in normotensive subjects. We conclude that the interaction of the I/D ACE and M235T AGT polymorphic alleles can contribute to essential hypertension, despite the absence of single gene associations with the condition.

Adult↗
PubMed1998

Granulocyte colony-stimulating factor and drugs elevating extracellular adenosine synergize to enhance haematopoietic reconstitution in irradiated mice.

The activation of adenosine receptors has recently been demonstrated to stimulate haematopoiesis. In the present study, we investigated the ability of drugs elevating extracellular adenosine to influence curative effects of granulocyte colony-stimulating factor (G-CSF) in mice exposed to a sublethal dose of 4 Gy of 60Co radiation. Elevation of extracellular adenosine in mice was induced by the combined administration of dipyridamole, a drug inhibiting the cellular uptake of adenosine, and adenosine monophosphate (AMP), an adenosine prodrug. The effects of dipyridamole plus AMP, and G-CSF, administered either alone or in combination, were evaluated. The drugs were injected to mice in a 4-d treatment regimen starting on d 3 after irradiation and the haematopoietic response was evaluated on d 7, 10, 14, 18 and 24 after irradiation. While the effects of G-CSF on the late maturation stages of blood cells, appearing shortly after the completion of the treatment, were not influenced by dipyridamole plus AMP, positive effects of the combination therapy occurred in the post-irradiation recovery phase which is dependent on the repopulation of haematopoietic stem cells. This was indicated by the significant elevation of counts of granulocyte-macrophage progenitor cells (GM-CFC) and granulocytic cells in the bone marrow (d 14), of GM-CFC (d 14), granulocytic and erythroid cells (d 14 and 18) in the spleen, and of neutrophils (d 18), monocytes (d 14 and 18) and platelets (d 18) in the peripheral blood. These effects suggest that the repopulation potential of the combination therapy lies in a common multilineage cell population. The results of this study implicate the promising possibility to enhance the curative effects of G-CSF under conditions of myelosuppressive states induced by radiation exposure.

Adenosine↗
PubMed1997

[Clinical experience with Spersadex comp. gtt].

The preparation Spersadex comp. gtt. was tested on three groups of patients (60 patients, 109 eyes) in order to assess its effectiveness in indications outlined by the manufacturer. The preparation has a very favourable antimicrobial, and antiphlogistic action. It proved very effective also in the treatment of chlamydial infections and in the postoperative treatment the combination of the antiphlogistic effect and the antibiotic action proved very useful, though tested only in small groups of patients. Spersadex comp. gtt. is a very effective preparation, well tolerated by patients and it supplements in a useful way the range of eye drops by a new antibiotic-corticoid combination.

Adolescent↗
PubMed1997

Enhancement of haemopoietic spleen colony formation by drugs elevating extracellular adenosine: effects of repeated in vivo treatment.

The potential role of adenosine receptor signalling in the amplification of haemopoietic stem cells in vivo was investigated. Elevation of extracellular adenosine in mice was induced by the joint administration of dipyridamole, a drug inhibiting the cellular uptake of adenosine, and adenosine monophosphate, an adenosine prodrug. The response of haemopoietic stem cells to the drug treatment was measured by endogenous spleen colony-forming assay in sublethally gamma-irradiated animals. The combination of drugs was administered before irradiation either singly or repeatedly at 24 h intervals. The results demonstrated the possibility of enhancing the spleen colony formation by the drug treatment. The highest stimulatory effect on spleen colony counts and on the colony sizes occurred after 3-4 injections of the drugs. Higher spleen colony responses were observed under injection regimens terminated 3 h before irradiation, as compared to those terminated 24 h before the radiation exposure. The results are interpreted as an evidence of the expansion of the stem cell pool. A tolerance to this stimulatory action developed after more than 3 injections of the drugs.

Adenosine↗
PubMed1995

Synergistic effect of granulocyte colony-stimulating factor and drugs elevating extracellular adenosine on neutrophil production in mice.

Experimental evidence suggests that the activation of purinoceptors by extracellular adenosine can modulate proliferation and/or differentiation of hematopoietic cells. The present study was undertaken to investigate the potential interactions of this system of intercellular signaling with the effects of granulocyte colony-stimulating factor (G-CSF) on granulopoiesis in vivo. Elevation of extracellular adenosine in normal mice was induced by the joined administration of dipyridamole, a drug inhibiting the cellular uptake of adenosine, and adenosine monophosphate (AMP), an adenosine prodrug. The effects of dipyridamole, AMP, and G-CSF, administered either alone or in combinations, were evaluated. The agents were injected to mice in a 4-day regimen, and the hematologic endpoints were determined 24 hours after the completion of the treatment. It was shown that the effects of G-CSF, ie, increases in peripheral blood neutrophils, granulocyte-macrophage progenitor cells (GM-CFC), and morphologically determined granulocytic cells in femoral marrow and a decrease in the marrow erythroid cells, can be enhanced by the combination of dipyridamole plus AMP administered 30 minutes before G-CSF. Furthermore, it was ascertained that the stimulatory action of dipyridamole plus AMP was expressed particularly at lower doses of G-CSF (1.5, 3, and 4.5 micrograms/d). At higher doses of G-CSF (6 and 9 micrograms/d), the interactions were no more evident. When combining dipyridamole, AMP, and 3 micrograms of G-CSF, peripheral neutrophils increased approximately 3.9- to 4.5-fold compared with an approximate 2.2-fold increase induced by G-CSF alone. The results indicate the possible therapeutic potential of combination therapy with G-CSF and drugs increasing extracellular adenosine.

Adenosine↗
PubMed1995

Radioprotection of mouse hemopoiesis by dipyridamole and adenosine monophosphate in fractionated treatment.

The purpose of the studies reported here was to investigate the ability of the combined administration of dipyridamole and adenosine monophosphate, drugs known to elevate extracellular adenosine, to protect mice undergoing treatment with fractionated irradiation (five doses of 2 or 3 Gy each) given at 24-h intervals. Based on observations of hemopoietic recovery (endogenous hemopoietic spleen colony formation, marrow granulocyte-macrophage colony-forming cells, peripheral blood cells) after the completion of fractionated irradiation and on survival studies, it was demonstrated that the repeated administration of the drugs 60 min before each of the radiation fractions mitigates the hemopoietic injury and enhances the survival of mice irradiated with an additional "top-up" dose. It could be deduced that the single protective actions of the drugs retain their efficacy in repeated treatment and enhance the sparing effect of dose fractionation on hemopoiesis. Interestingly, the toxic side effects of the drugs tend to decrease when they are administered repeatedly, probably due to the development of tolerance to their cardiovascular action. This reduction in toxicity offers benefit with respect to the potential use of these hemopoiesis-protecting drugs in clinical radiotherapy.

Adenosine Monophosphate↗
PubMed1995

Radioprotective efficacy of dipyridamole and AMP combination in fractionated radiation regimen, and its dependence on the time of administration of the drugs prior to irradiation.

We have recently demonstrated that the combined administration of dipyridamole and adenosine monophospate to mice induces radioprotective effects in terms of postirradiation haemopoietic recovery in animals irradiated with a single dose. The aim of the present experiments was to investigate the radioprotective ability of the drug combination under conditions of fractionated radiation treatment. It has been shown that administration of drugs either 15 or 60 min before each of the five daily 3-Gy doses of gamma-radiation enhances haemopoietic recovery and survival of mice exposed to an additional "top-up" dose of 3.5 Gy. Furthermore, it has been ascertained that the regimen using administration of the drugs 60 min prior to irradiation is more effective than administration of the drugs 15 min prior to irradiation. Due to the evidence that administration of the drugs 15 min prior to irradiation protects the organism mainly via mechanisms of systemic hypoxia while the pretreatment 60 min before irradiation avoids the role of hypoxia and mainly induces cell proliferation effects, our results suggest a more effective protective role of mechanisms stimulating haemopoiesis under conditions of fractionated radiation. The data may provide a basis for more rational use of radioprotection in fractionated radiation regimens.

Adenosine Monophosphate↗