Biomedical subjects

G Horvath

Publications and source records attributed to G Horvath.

At least 19 recordsLinked to original sources

PubMed2006

Accumulation of tocopherols and tocotrienols during seed development of grape (Vitis vinifera L. cv. Albert Lavallée).

Tocopherols and tocotrienols are present in mature seeds. Yet, little is known about the physiological role and the metabolism of these compounds during seed development. Here we present data on tocopherol and tocotrienol accumulation during seed development in Vitis vinifera L. cv. Albert Lavallée (Royal). This species was chosen for its ability to synthesize both tocopherols and tocotrienols. It is shown here for the first time that during seed development there are significant differences in localization and accumulation kinetics of tocopherols and tocotrienols. Tocopherols are found homogeneously dispersed throughout all tissues of the seed, in concentrations ranging from 20 to 100 microg tocopherol per g dry weight. Tocopherol levels decrease gradually during seed development. In contrast, tocotrienols are only found in the endosperm of the seeds, accumulating in a sigmoid fashion during the maturation period of seed development. Tocotrienol levels were found to be (54+/-7.4) microg/g dry seed in 90-day-old seeds of V. vinifera L. Furthermore, tocotrienol biosynthesis is demonstrated in these seeds during tocotrienol accumulation and in an endosperm fraction isolated at 75 days after flowering.

Seeds↗

PubMed2006

Chromosomal alterations in 98 endometrioid adenocarcinomas analyzed with comparative genomic hybridization.

The aim of the present study was to investigate chromosomal alterations in a large set of homogeneous tumors, 98 endometrioid adenocarcinomas. We also wanted to evaluate differences in chromosomal alterations in the different groups of tumors in relation to stage, survival and invasive or metastatic properties of the tumors. Comparative genomic hybridization (CGH) was used to detect chromosomal alterations in tissue samples from 98 endometrioid adenocarcinomas. All chromosomes were involved in DNA copy number variations at least once in the tumor material, but certain changes were recurrent and rather specific. Among the specific changes, it was possible to identify 39 chromosomal regions displaying frequent DNA copy number alterations. The most frequent alteration was detected at 1q25-->q42, in which gains were found in 30 cases (30%). Gains at 19pter-->p13.1 were detected in 26 tumors (26%) and at 19q13.1-->q13.3 in 19 tumors (19%). Increased copy numbers were also detected at 8q (8q21-->q22 and 8q22-->qter), at a relatively high rate, in 17 cases (17%). Furthermore, gains at 10q21-->q23 and 10p were found in 14 (14%) and 13 cases (13%), respectively. The most common losses were found in the three regions 4q22-->qter, 16q21-->qter and 18q21-->qter, all of which were detected in eight of the 98 tumors (8%). We also detected differences between the tumors from deceased patients and from survivors. Gain at 1q25-->q42 was more commonly detected in the tumors from patients who died of cancer. We noted that the regions most affected differed in the different surgical stages (I-IV). The results of the CGH analysis identify specific chromosomal regions affected by copy number changes, appropriate objects for further genetic studies.

Carcinoma, Endometrioid↗

PubMed2006

Inhaled corticosteroids: effects on the airway vasculature in bronchial asthma.

Inhaled corticosteroids suppress airway inflammation and components of airway remodelling in bronchial asthma. In the tracheobronchial (airway) vasculature, these include the inhibition of inflammatory hyperperfusion, microvascular hyperpermeability, mucosal oedema formation, and the formation of new blood vessels (angiogenesis). Corticosteroids are now known to exert their effects on the airway vasculature through genomic and nongenomic mechanisms. Genomic actions involve the regulation of target genes, and suppress most of the vascular elements of inflammation and angiogenesis in the airway. In contrast, nongenomic actions are mediated by rapid cellular mechanisms, and induce transient vasoconstriction in the airway, thereby reversing inflammatory hyperperfusion. The vascular actions of corticosteroids contribute to controlling clinical symptoms of asthma primarily by influencing airway calibre in the lung periphery and airway hyperreactivity. In this review article, recent advances into the understanding of cellular mechanisms and the clinical implications of the interaction of inhaled corticosteroids and the airway vasculature in asthma are reviewed.

Administration, Inhalation↗

PubMed2006

Open-heart surgery and Jehovah's Witnesses.

The religious community of Jehovah's Witnesses holds that blood transfusion is against God's law. Therefore, surgical treatment of Jehovah's Witnesses is a great challenge for every surgeon, especially for cardiac surgeons because blood transfusion is frequently needed during such operations. In this study we summarize the experience with Jehovah's Witnesses who have undergone open-heart surgery in Debrecen from 1989 to 1999 due to various cardiac diseases. Applying a complex surgical procedure developed by the authors to minimize blood loss during operation, preserved blood products were omitted. Three patients out of twenty-four died during the postoperative period. The twenty-one longtime survivors showed significant improvement in their clinical stage during the mean follow up of 37.6 months. More and more operations are done successfully without blood or preserved blood products worldwide, so it could be said that nowadays surgical treatment of Jehovah's Witnesses has a lower risk than before.

Adult↗

PubMed2004

[Tissue engineering of bone. Integration and migration of human mesenchymal stem cells in colonized contructs in a murine model].

Tissue engineering opens up new ways for therapy of bone defects. Therefore, the aim of this study was to establish a mouse model to investigate local cell growth of human mesenchymal stem cells (hMSC) on the scaffold in vivo. Moreover, migration of cells to other organs should be excluded.hMSC (Cambrex, USA) were cultivated according to supplier's recommendations. After inoculation on cylindric scaffolds, one matrix cell construct and one scaffold without hMSC were implanted subcutaneously left and right paravertebrally in athymic nude mice. After 2, 4, 8, and 12 weeks constructs and organs were harvested for immunohistological evaluation and PCR. In conclusion, we found integration of scaffolds loaded with hMSC implanted ectopically. HMSC seeded on 3D scaffolds survived for a period of up to 12 weeks. In addition, we could not detect hMSC in any other organ of the host.

Animals↗

PubMed2003

Oxidative stress status in patients with diabetes mellitus: relationship to diet.

OBJECTIVE: To investigate the relationship between dietary intakes and in vivo oxidative stress (OS) status in diabetic patients. DESIGN: Case-control study. SETTING: Outpatient-Clinic and Laboratory Endocrinology, University Antwerp. SUBJECTS AND METHODS: A total of 30 patients (24 type 1 diabetes mellitus (T1DM)/6 type 2 diabetes mellitus (T2DM) were asked to complete a 2 weekdays+1 weekend day food consumption questionnaire during the week preceding their yearly diabetes control consultation, when samples were collected for the assay of oxidative stress (OS) (blood levels of antioxidants, peroxides, malondialdehyde (MDA) and minerals). Blood samples were also collected from 25 age- and sex-matched healthy controls. RESULTS: Diabetic patients had lower glutathione (5.80+/-1.15 vs 6.75+/-1.03 micromol/g Hb in the controls, P=0.002) and higher MDA (0.687+/-0.212 vs 0.545+/-0.101 micromol/l, P=0.002). Although the group average intakes were within the Belgian RDA, intakes of fat >35% energy, fibre <15 g/1000 kcal, fruit <2 portions and vitamin E <10 mg/day were seen in more than 20 patients. Blood antioxidants did not correlate with intakes of energy, fat, protein or fibres or of their respective antioxidant. Vitamins A and E correlated with serum lipids (r=0.58, P <0.0005 between serum alpha-tocopherol and cholesterol). Blood peroxide levels were only related to intakes of saturated fat and cholesterol (P<0.05). In diabetic subjects but not in controls (P<0.05) MDA was related to glutathione and uric acid. CONCLUSIONS: In diabetic patients, blood levels of antioxidants are not related to their dietary intakes but to serum lipids. Levels of oxidative damage products are only related to intakes of saturated fats and cholesterol and to levels of endogenous antioxidants.

Adult↗

PubMed2003

Molecular targets for steroids in airway vascular smooth muscle.

The actions of norepinephrine (NE) released from airway sympathetic nerves are partially terminated by the extraneuronal catecholamine uptake. Because various steroid hormones inhibit extraneuronal uptake, it could be responsible for the airway vasoconstriction caused by inhaled glucocorticosteroids (GSs) in vivo. Using bronchial arteries obtained from donor lungs rejected for transplantation, we showed that a plasma membrane-associated transporter is responsible for NE uptake by airway vascular smooth muscle. We identified this transporter, namely the extraneuronal monoamine transporter (EMT), by demonstrating its function and mRNA expression. Furthermore, we showed that the rapid, nongenomic inhibitory GS effect on EMT is likely mediated through the activation of specific K+ channels in the plasma membrane. We believe that our studies identified new molecular targets for GSs in modulating noradrenergic control of airway vascular tone.

Binding Sites↗

PubMed2001

Excitable gap in canine fibrillating ventricular myocardium: effect of subacute and chronic myocardial infarction.

INTRODUCTION: The existence of an excitable gap during ventricular fibrillation (VF) has been suggested in several prior studies. However, the effects of myocardial infarction on the presence and duration of an excitable gap during VF have not been evaluated. METHODS AND RESULTS: Electrophysiologic study was performed in normal dogs and in dogs with subacute and chronic infarction. Experimental infarction was produced by left anterior descending coronary ligation. The excitable gap was determined indirectly using either evaluation of intrinsic wavefronts during VF or from the shortest activation interval at individual sites using recordings from a 112-electrode plaque sutured to the epicardial surface of the left ventricle. The excitable gap also was correlated to local electrophysiologic and anatomic properties. The excitable gap using the wavefront propagation method and shortest activation method was significantly longer in subacute infarction dogs (48 +/- 17 msec and 37 +/- 18 msec, respectively) and chronic infarction dogs (41 +/- 14 msec and 35 +/- 14 msec, respectively) than normal dogs (32 +/- 13 msec and 30 +/- 11 msec, respectively; P < 0.05 normal vs subacute and chronic infarction dogs in both methods). The excitable gap occupied approximately 30% and 27% of the VF cycle length in all three groups using the wavefront propagation and shortest activation method, respectively. The excitable gap correlated better with local ventricular refractoriness determined using the wavefront propagation method than with the shortest activation method, but not at all with refractoriness determined using extrastimulus testing. Tissue necrosis was noted in subacute infarction dogs and fibrosis in chronic infarction dogs, but the gap was not highly correlated with anatomic changes. CONCLUSION: During VF, an excitable gap exists in both normal and infarcted canine ventricular myocardium. It is significantly longer in the presence of infarction. These finding have implications for understanding the pathophysiology of VF and targeting antiarrhythmic therapies.

Acute Disease↗

PubMed2001

Mice with a targeted disruption of the H1t gene are fertile and undergo normal changes in structural chromosomal proteins during spermiogenesis.

H1t is an H1 histone variant unique to late spermatocytes and early spermatids. Using gene targeting and embryonic stem cell technologies, we have produced mice with a disrupted H1t gene. Homozygous H1t-null mice have normal fertility and show no obvious phenotypic consequence due to the lack of this histone. Biochemical and immunohistochemical approaches were used to show that normal changes in chromosomal proteins occurred during spermatid development, including the appearance and disappearance of transition proteins 1 and 2. Both protamines 1 and 2 are present in normal amounts in sonication-resistant spermatid nuclei from H1t-null mice. Analysis of H1 histones by quantitative gel electrophoresis in enriched populations of pachytene spermatocytes and round spermatids showed that the lack of H1t is only partially compensated for by somatic H1s, so that the chromatin of these cells is H1 deficient. Because H1t is thought to create a less tightly compacted chromatin environment, it may be that H1-deficient chromatin is functionally similar to chromatin with H1t present, at least with respect to permitting spermatogenesis to proceed.

Alleles↗

PubMed2001

The synergistic antinociceptive interactions of endomorphin-1 with dexmedetomidine and/or S(+)-ketamine in rats.

UNLABELLED: Spinal administration of the endogenous mu-opioid agonist peptide, endomorphin-1, results in antinociception in rodents, but there are few data about its interaction with other antinociceptive drugs. We investigated the antinociceptive interactions at the spinal level of endomorphin-1 with the N-methyl-D-aspartate antagonist S(+)-ketamine, the alpha2-adrenoceptor agonist dexmedetomidine, or both in awake rats. Nociception was assessed by the tail-flick test. Dose-response curves were determined for endomorphin-1 (0.6-50 microg), for dexmedetomidine (0.1-10 microg), for mixtures of S(+)-ketamine (30 or 100 microg) with endomorphin-1 (2-18 microg) or of endomorphin-1 with dexmedetomidine in a fixed ratio (4:1), and for the triple combination of the three drugs after intrathecal administration. Endomorphin-1 and dexmedetomidine both produced dose-dependent antinociception. The coadministration of 100 microg S(+)-ketamine significantly enhanced the antinociceptive effect of 6 microg endomorphin-1. Isobolographic analysis of the combinations of endomorphin-1 and dexmedetomidine revealed a synergistic interaction between these drugs. The 80% effective dose for the triple combination was significantly less than that for either binary combination. These data indicate that S(+)-ketamine and dexmedetomidine, acting via different receptors, produce synergistic antinociceptive interaction with endomorphin-1 at the spinal level. Furthermore, the triple combination of an opioid agonist, an alpha2-adrenoceptor agonist, and an N-methyl-D-aspartate receptor antagonist shows potent antinociceptive activity. IMPLICATIONS: The coadministration of the N-methyl-D-aspartate antagonist receptor antagonist, S(+)-ketamine, or the specific alpha2-adrenoceptor agonist, dexmedetomidine, significantly enhances the antinociceptive effect of the endogenous mu-opioid agonist, endomorphin-1, at the spinal level. The triple combination of the three drugs causes a further improved antinociception.

Adrenergic alpha-Agonists↗

PubMed2001

Steroid sensitivity of norepinephrine uptake by human bronchial arterial and rabbit aortic smooth muscle cells.

We have shown that an inhaled glucocorticosteroid (GS) causes alpha(1)-adrenergic antagonist-blockable, rapid, and transient bronchial vasoconstriction in healthy and asthmatic subjects. Steroids inhibit norepinephrine (NE) uptake by non-neuronal cells, thereby increasing NE concentration at alpha-adrenergic receptor sites. This could explain the GS-induced bronchial vasoconstriction. We therefore studied expression of the steroid-sensitive extraneuronal monoamine transporter (EMT) and steroid sensitivity of NE uptake in human bronchial artery and rabbit aorta (as a substitute for the limited supply of human bronchial artery). NE uptake was measured using a semiquantitative, sucrose-potassium phosphate-glyoxylic acid fluorescence method that we newly adapted for use in single cells. Both human bronchial arteries and rabbit aorta expressed messenger RNA for EMT, and steroids blocked NE uptake into freshly dissociated human bronchial arterial and rabbit aortic smooth-muscle cells (SMCs). In the latter, inhibition of NE uptake by steroids was not altered, either by a protein synthesis inhibitor (cycloheximide) or by a transcription inhibitor (actinomycin D), and corticosterone made membrane-impermeant by conjugation to bovine serum albumin inhibited NE uptake equipotently. These data show that NE uptake into bronchial arterial and rabbit aortic SMCs is sensitive to steroids, possibly mediated by EMT, and suggest a mechanism for GS-induced bronchial vasoconstriction.

Animals↗

PubMed2000

[The effect of estradiol on human endometrial cancer. Experimental in vivo and in vitro studies].

In this article our findings concerning estradiol-induced changes in steroid receptor activation, cell kinetics and tumor growth regulation during in vivo and in vitro progression of human endometrial adenocarcinomas are reviewed. We found major changes such as alterations in estrogen receptor function and post-receptor alterations in tumor growth regulation. Our results suggest that although the development of these alterations is genetically determined, they may to some extent be modified by circulating estradiol levels. No biological changes were found, suggesting that the use of menopausal estrogen replacement therapy by women with non-diagnosed endometrial cancer may increase their death rate.

Adenocarcinoma↗

PubMed2000

Endomorphin-1 and endomorphin-2: pharmacology of the selective endogenous mu-opioid receptor agonists.

The recently discovered endogenous opioid peptides, endomorphins-1 and -2, appear to have properties consistent with neurotransmitter/neuromodulator actions in mammals. This review surveys the information gained so far from studies of different aspects of the endomorphins. Thus, the endomorphins have been found unequally in the brain; they are stored in neurons and axon terminals, with a heterogeneous distribution; they are released from synaptosomes by depolarization; they are enzymatically converted by endopeptidases; and they interact specifically and with high affinity with mu-opioid receptors. The most outstanding effect of the endomorphins is their antinociceptive action. This depends on both central and peripheral neurons. Additionally, the endomorphins cause vasodilatation by stimulating nitric oxide release from the endothelium. Their roles in different central and peripheral functions, however, have not been fully clarified yet. From a therapeutic perspective, therefore, they may be conceived at present as potent antinociceptive and vasodilator agents.

Analgesics, Opioid↗

PubMed2000

A new, convenient method for the preparation of 4-[18F]fluorobenzyl halides.

A convenient method suitable for automated preparation of 4-[18F]fluorobenzyl halides from no-carrier-added [18F]fluoride has been developed. 4-[18F]Fluorobenzaldehyde, synthesized from [18F]fluoride by aromatic nucleophilic substitution on 4-trimethylammoniumbenzaldehyde triflate, was first retained on a C18 cartridge and there efficiently reduced to 4-[18F]fluorobenzyl alcohol simply by flowing an aqueous solution of NaBH4. The conversion of 4-[18F]fluorobenzyl alcohol to 4-[18F]fluorobenzyl halide was investigated using PBr3, PI3, P2I4, Ph3PBr2 and Ph3PI2 in CH2Cl2. 4-[18F]Fluorobenzyl halides were purified by passing through a disposable silica cartridge. The conversion rapidly proceeded in radiochemical yields of nearly 90% at 40 degrees C with P2I4 and almost quantitatively at room temperature with Ph3PBr2. With this last reagent 4-[18F]fluorobenzyl bromide was obtained in overall radiochemical yields of 50-60% within 30 min from EOB.

Journal Article↗

PubMed2000

The curative and palliative potential of the monoclonal antibody MOv18 labelled with 211At in nude mice with intraperitoneally growing ovarian cancer xenografts--a long-term study.

The purpose of the present study was to investigate the therapeutic efficacy of 211At-labelled specific monoclonal antibody MOv18 in nude mice with intraperitoneal growth of the human ovarian cancer cell line OVCAR3. In the first part of the study the antibody was injected intraperitoneally when the cancer growth was microscopic. The injected activity was 485-555 kBq. The median survival for treated mice was 213 days compared to 138 days for untreated mice (p < 0.014, log-rank test). No obvious toxicity was seen. Thirty-three percent of the mice were apparently free of cancer after 7 months and were probably cured. In the second part of the study mice with macroscopic cancer and signs of ascites were injected intraperitoneally with the same 211At-labelled antibody (377-389 kBq). This treatment possibly delayed the production of ascites. Hopefully radioimmunotherapy with regionally administered 211At-labelled antibody will be of value in women with ovarian cancer as well.

Animals↗

PubMed2000

The effects of ketamine and its enantiomers on the morphine- or dexmedetomidine-induced antinociception after intrathecal administration in rats.

BACKGROUND: The spinal administration of some N-methyl-d-aspartate receptor antagonists results in antinociception and potentiates the effects of opioids and alpha2-adrenoceptor agonists, but ketamine and its enantiomers have not been examined. The present study investigated the interactions of racemic ketamine, R(-)-ketamine and S(+)-ketamine with morphine and with dexmedetomidine. METHODS: Intrathecal catheters were implanted into male Wistar rats. Three days later, the acute nociceptive sensitivity was assessed using the tail-flick test. Analgesic latencies were converted to the percentage maximum possible effect. The dose that yielded 50% of the maximum possible effect (ED50) and dose-response and time-course curves were determined for the ketamines (30-300 microg), morphine (0.1-3.0 microg), dexmedetomidine (0.3-10.0 microg), and mixtures of two doses of ketamines (30 or 100 microg) with different doses of morphine or dexmedetomidine for fixed-dose analysis. RESULTS: Neither racemic ketamine nor its enantiomers alone had a significant effect on the tail-flick test, with the exception of the highest dose of racemic ketamine, which caused motor impairment. Morphine and dexmedetomidine each produced dose-dependent antinociception, with ED50 of 1.7 microg (95% confidence interval: 1.04-2.32) and 4. 85 microg (3.96-5.79), respectively. A low dose (30 microg) of racemic ketamine or its enantiomers did not influence the ED50 of morphine significantly. Coadministration of 100 microg racemic ketamine or S(+)-ketamine, but not R(-)-ketamine, significantly enhanced and prolonged the antinociceptive effect of morphine. Both doses of racemic ketamine or its isomers significantly decreased the ED50 value for dexmedetomidine, although the higher dose of racemic or S(+)-ketamine had the highest potency. One-hundred micrograms of racemic ketamine or S(+)-ketamine also prolonged the effects of dexmedetomidine. CONCLUSIONS: These data indicate that racemic ketamine and S(+)-ketamine, but not R(-)-ketamine, exhibit similar effectiveness in potentiating the antinociceptive effects of both morphine and dexmedetomidine.

Adrenergic alpha-Agonists↗

PubMed2000

Effect of underlying heart disease on the frequency content of ventricular fibrillation in the dog heart.

Although prior studies have examined the frequency content of local electrogram characteristics during fibrillation, little is know about the effects of underlying heart disease on these parameters. This study was designed to compare the frequency content of local electrograms during VF in canine models of acute ischemia, subacute infarction, and chronic myocardial infarction (MI) to those in control animals to test the hypothesis that underlying heart disease can alter the basic characteristics of VF. VF was induced using burst pacing in three groups of mongrel dogs. Five dogs were evaluated 8 weeks after LAD occlusion MI, five were evaluated 5 days after experimental MI, and 5 had VF induced before (control) and immediately after LAD occlusion (ischemia). During VF, unipolar electrograms were recorded from 112 sites on the anterior LV and electrograms were evaluated 15 and 30 seconds after VF initiation in each group. Electrograms were analyzed by fast Fourier transform. No significant time dependent changes in VF characteristics were noted. The peak frequency was highest in control animals and 8-week MI, intermediate in 5-day MI, and lowest in acute ischemia (P < 0.01 for pairwise comparisons). In contrast, the fractional of energy within a bandwidth of 25% peak amplitude was highest in acute ischemia, (P < 0.001) and similar in the other three groups. Infarction decreased total energy by approximately 50%. In conclusion, the pressure of ischemia or infarction alters the frequency content of VF in a complex fashion. In addition to decreasing the peak frequency, the shape of the power spectral curve is altered in models of structural heart disease. These results suggest that the electrophysiological changes produced by infarction or ischemia alter the structural organization of ventricular fibrillation.

Animals↗

PubMed2000

Electrophysiological and anatomic heterogeneity in evolving canine myocardial infarction.

Although the heterogeneity of electrophysiological properties is increased after myocardial infarction, the degree of this heterogeneity has not been well quantitated and its relationship to the histological changes that occur after infarction has not been carefully examined. The purpose of the present study was to test the hypothesis that alterations in electrophysiological properties in healing canine infarction are related to particular histological changes. Experimental infarction was produced by left anterior descending coronary ligation. Six dogs were used as controls, six were studied 5 days following, and six were studied 8 weeks following infarction. Pacing thresholds, effective refractory periods, and activation-recovery times were determined at 112 sites on the anterior left ventricle using a multiple electrode plaque. Conduction velocity, conduction-heterogeneity index--a measure of conduction disturbance--and histology of the epimyocardium underlying the plaque were assessed. The effective refractory periods and activation-recovery times were greater in both infarction groups, most prominently in the subacute group. In subacute infarction, significant postrepolarization refractoriness was present. In healed infarction, conduction velocity was decreased and the conduction-heterogeneity index was increased compared to controls and subacute infarction. Dispersion of excitability and repolarization was associated with more extensive local scarring. Dispersion of myocardial fiber angles was associated with the conduction-heterogeneity index. Some but not all of the electrophysiological changes noted in the animals with infarction were also seen in sham operated animals. Thus, heterogeneity in repolarization and refractoriness is greatest in the subacute phase of myocardial infarction and is associated with the extent of local cell death. In contrast, disturbances in conduction are greatest in healed infarction and associated with disarray of myocardial fibers.

Animals↗