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Biomedical subjects

T Szabó

Publications and source records attributed to T Szabó.

At least 19 recordsLinked to original sources
PubMed1999

A non-pungent triprenyl phenol of fungal origin, scutigeral, stimulates rat dorsal root ganglion neurons via interaction at vanilloid receptors.

1. A [3H]-resiniferatoxin (RTX) binding assay utilizing rat spinal cord membranes was employed to identify novel vanilloids in a collection of natural products of fungal origin. Of the five active compounds found (scutigeral, acetyl-scutigeral, ovinal, neogrifolin, and methyl-neogrifolin), scutigeral (Ki=19 microM), isolated from the edible mushroom Albatrellus ovinus, was selected for further characterization. 2. Scutigeral induced a dose-dependent 45Ca uptake by rat dorsal root ganglion neurons with an EC50 of 1.6 microM, which was fully inhibited by the competitive vanilloid receptor antagonist capsazepine (IC50=5.2 microM). 3. [3H]-RTX binding isotherms were shifted by scutigeral (10-80 microM) in a competitive manner. The Schild plot of the data had a slope of 0.8 and gave an apparent Kd estimate for scutigeral of 32 microM. 4. Although in the above assays scutigeral mimicked capsaicin, it was not pungent on the human tongue up to a dose of 100 nmol per tongue, nor did it provoke protective wiping movements in the rat (up to 100 microM) upon intraocular instillation. 5. In accord with being non-pungent, scutigeral (5 microM) did not elicit a measurable inward current in isolated rat dorsal root ganglion neurons under voltage-clamp conditions. It did, however, reduce the proportion of neurons (from 61 to 15%) that responded to a subsequent capsaicin (1 microM) challenge. In these neurons, scutigeral both delayed (from 27 to 72 s) and diminished (from 5.0 to 1.9 nA) the maximal current evoked by capsaicin. 6. In conclusion, scutigeral and its congeners form a new chemical class of vanilloids, the triprenyl phenols. Scutigeral promises to be a novel chemical lead for the development of orally active, non-pungent vanilloids.

Animals↗
PubMed1999

High prevalence of silent celiac disease in preschool children screened with IgA/IgG antiendomysium antibodies.

BACKGROUND: Because of the different sensitivity and specificity of serologic tests, the search for silent celiac disease is usually performed with the combined or sequential use of several tests. Among these, the IgA-class endomysium antibody test has the highest specificity and positive predictive value, but it may overlook IgA-deficient patients. METHODS: To test a new one-step screening approach, serum samples from 427 apparently healthy, 3- to 6-year-old Hungarian children were investigated for IgA-class and IgG-class endomysium antibodies using monkey esophagus and human jejunum as substrates. RESULTS: Five new cases with flat mucosa were identified by strong endomysium antibody positivity and subsequent jejunal biopsy, yielding a celiac disease prevalence of 1:85. An additional child may have latent celiac disease (slight histologic changes at present). Two of the screening-detected celiac patients exhibited only IgG-class endomysium antibodies due to associated IgA-deficiency. Despite the young age of the screened population, antigliadin antibodies were positive in only three of the five celiac patients. CONCLUSIONS: Prevalence of celiac disease in the study population was much higher than expected on the basis of antigliadin antibody-based studies. The screening system used detected celiac cases in which there was IgA-deficiency and those in which there was not and also those negative for antigliadin antibodies. The findings suggest the importance of the primary testing of autoantibodies in future celiac disease screening policies.

Autoantibodies↗
PubMed1998

[Gastric and duodenal intramural hematoma: report of two cases].

Two cases of intramural hematoma arising in the duodenum and the stomach are reported. Both patients were male, aged 40 and 58 years, and suffered from chronic pancreatitis. Hematoma of the duodenal wall may have resulted from the acute exacerbation of the chronic pancreatitis in the first patient. As to the second case, continuous administration of Colfarit following myocardial infarction may have been causal to the gastric lesion. The initially suspected diagnosis in the first case, was pancreatic pseudocyst with obstruction of the duodenum while in the second case the gastric hematoma imitated a submucosus neoplastic process. The authors review clinical symptoms and therapeutic approaches of intramural hematomas of the proximal gastrointestinal tract. Literature data regarding etiology and therapy are presented.

Adult↗
PubMed1998

Functional and structural properties of Na+/K(+)-ATPase enzyme in neonatal erythrocytes.

BACKGROUND: The Na+/K(+)-pump is the main regulator enzyme of intracellular monovalent cation concentration. There are only limited data available concerning its structure and function in healthy neonates, in comparison with data available regarding its structure and function in children. PATIENTS AND METHODS: Samples of 100 microL of anticoagulated blood were taken from 53 healthy neonates (age under 6th postnatal day, median age 3.5 days) and 61 healthy children (median age 12.4 months, range 6-36 months,). The Na+/K(+)-ATPase activity, its sensitivity to ouabain (a digoxin-analogue substance) and the expression of Na+/K(+) ATPase subunit isoforms were determined. RESULTS: The enzyme activity (429.2 +/- 17.2 versus 295.5 +/- 10.2 U, P < 0 x 0.001) and I50 value for ouabain inhibition (1.50 +/- 0.10 versus 0.96 +/- 0.10 mumol L-1, P < 0.05) was higher in neonates. More alpha 1 subunits (relative density: 1.16 +/- 0.10 versus 0.75 +/- 0.03, P < 0.001) and higher alpha 1/ alpha 2 ratio (4.14 +/- 0.21 versus 2.02 +/- 0.16, P < 0.01) were detected. CONCLUSION: This is the first study demonstrating changes of Na+/K(+) -ATPase molecules not only in enzyme activity, but also on protein level. Our results might contribute to the understanding of the resistance of neonatal cell membranes toward the pharmacodynamic actions of cardiac glycosides.

Aging↗
PubMed1998

Compensation of endothelin-1-induced coronary vasoconstriction.

The vasodilator capacity of the coronaries was determined by the reactive hyperemia (RH) test in open-chest anesthetized dogs. The myocardial release of adenine nucleosides (adenosine and inosine) was measured by the HPLC-UV method. In group I (n = 9) after the control RH test, a bolus injection of endothelin-1 (ET-1; 1.0 nmol i.c.) was administered and was followed by a second RH test. In group II (n = 9), glibenclamide (GLIB) was infused continuously (1.0 mumol/min i.c.) and RH tests were performed during the control period and then before and after bolus injection of ET-1. In contrast to the significant reduction of the RH response after ET-1 in group I and after GLIB in group II, the nucleoside release into the coronary sinus during the first minute of the RH test was significantly higher (adenosine release 0.05 +/- 0.02 vs. 0.10 +/- 0.04 mumol, and 0.02 +/- 0.00 vs. 0.08 +/- 0.02 mumol; p < 0.05). Injection of ET-1 did not result in further RH reduction in GLIB-pretreated dogs (group II) but significantly increased nucleoside release. High doses of ET-1 activated the metabolic compensatory mechanisms of the myocardium and thereby increased the release of adenine nucleosides into the venous blood of the heart. However, whether these metabolites can exert any significant compensatory vasodilator effects appears doubtful.

Adenosine↗
PubMed1998

Increased monophasic action potential dispersion in endothelin-1-induced ventricular arrhythmias.

The aim of this study was to investigate the changes in monophasic action potentials (MAP) from different sites in the heart and to determine MAP dispersion during endothelin-1 (ET-1) infusion. Standard ECG, left ventricular anterior, right ventricular lateral, right ventricular septal, and right ventricular apical MAPs and intra-arterial blood pressure were monitored in seven anesthetized open-chest mongrel dogs. After radiofrequency atrioventricular node ablation, ventricular pacing (70/min) was performed and intracoronary ET-1 (60 pmol/min) was administered into the left anterior descending coronary artery. Both MAPd90 and MAPd90 dispersion increased significant during ET-1 infusion. The onset of spontaneous monomorphic and polymorphic sustained ventricular tachycardias (sVT) was observed in five dogs (around 40 min), and nonsustained VTs (nsVT) developed in another two dogs. The increases in MAP and MAP dispersion lasted until the appearance of polymorphic nsVTs and sVTs, but at the time of these VTs this difference decreased. At the termination of the experiments, ventricular fibrillation occurred in six cases. In four cases third-phase early afterdepolarizations were recorded. Our results suggest that increased MAP dispersion and development of EAD contribute to the arrhythmogenic action of ET-1, and these phenomena might explain the pathogenesis of a wide variety of ventricular arrhythmias with different morphology observed in this study.

Action Potentials↗
PubMed1998

Electrophysiological effects of intrapericardial infusion of endothelin-1.

Recently, extremely high levels of endothelin-1 (ET-1) were detected in the pericardial fluid of patients undergoing open-heart surgery. ET-1 has been suggested to have direct arrhythmogenic effect on myocardium. The aim of the present study was to examine the putative arrhythmogenic effect of intrapericardial infusion of ET-1 in anesthetized dogs (n = 15). In preliminary experiments, ET-1 (0.125-1.0 nmol/min, n = 7) was infused into the closed pericardial sack for 40 min. ET-1 induced non-sustained and/or sustained ventricular tachyarrhythmias in all but the lowest dose. For detailed arrhythmia analysis in addition to standard ECG ventricular endocardial and epicardial monophasic action potentials (MAP) were recorded. ET-1 (0.250 nmol/min, n = 7) induced mono- and polymorphic ventricular tachycardias, which degenerated into ventricular fibrillation in two instances. Moderate if any ischemic signs could be detected before the onset of arrhythmias. The arrhythmias spontaneously disappeared in all instances with the exception when ventricular fibrillation terminated the experiment. QT interval (260 +/- 23 ms vs. 317 +/- 31 ms, P < 0.05), and endo- and epicardial MAPD90 (at 300 ms cycle length) prolonged significantly (in average 182 +/- 12 ms vs. 224 +/- 25 ms, P < 0.05). Using MAP recording afterdepolarizations were detected in three instances. In control animals (n = 3) arrhythmias were not observed and all electrophysiological parameters remained unchanged. The present results show that intrapericardial administration of ET-1 can induce ventricular arrhythmias in dogs. The arrhythmogenic effect of ET-1 may be based on prolongation of MAP duration and development of afterdepolarizations. However, the elucidation of the precise mechanism needs further investigation.

Action Potentials↗
PubMed1997

[Systemic mastocytosis].

The systemic mastocytosis is a rare disorder, however, the authors recently diagnosed two cases causing diagnostic problems. The diagnosis was proved by bone marrow biopsy in both patients. The authors review the diagnostic pathway considering the pitfalls. According to their conclusion, the most important factor in the diagnosis of systemic mastocytosis is to think of the possibility of systemic mastocytosis.

Aged↗
PubMed1995

A new approach to the synthesis of the 5'-deoxy-5'-methylphosphonate linked thymidine oligonucleotide analogues.

A new synthetic method for the preparation of the 5'-deoxy-5'-methylphosphonate linked thymidine oligonucleotides (5'-methylenephosphonate analogues) was developed. The method is based on the use of a phosphonate protecting group, 4-methoxy-1-oxido-2-picolyl, enabling intramolecular nucleophilic catalysis which together with the condensing agent, 2,4,6-triisopropylbenzenesulfonyl chloride, secures fast and efficient formation of the 5'-methylenephosphonate internucleosidic bonds. The produced protected oligomers were treated with thiophenol and triethylamine to remove the phosphonate protecting groups, cleaved from the solid support using concentrated aqueous ammonia, and purified by HPLC. Several thymidine oligonucleotide analogues with the chain length of up to 20 nucleotidic units, in which all internal 5'-oxygen atoms have been replaced by methylene groups directly bound to phosphorus, were synthesised using this methodology.

DNA↗
PubMed1995

[Diagnostic errors in symptom-poor hyperthyroidism in the aged].

The diagnosis of hyperthyreoidism manifesting in the elderly meets difficulty in many cases. Lack of some characteristic symptoms observable in younger patients can be misleading. The authors summarize the data of ten clinical cases where the hyperthyreoidism appeared in occult form, reminding rather for heart disease or malignant tumours. The assay of thyroid hormones and the level of antithyreoglobulin and anti-thyreoid peroxidase antibodies was unavoidable in order to establish correct diagnosis. Though the early diagnosis and treatment may enhance the life expectancy of the patients and may considerably decrease the cardial and the consecutive cerebral complications. The authors analyse the reasons and possible pathomechanism of the formation of atypical hyperthyreoidism occurring in the elderly.

Age Factors↗
PubMed1995

Biochemical properties of the ligand-binding 20-kDa subunit of the beta-glucan receptors on human mononuclear phagocytes.

beta-Glucan receptors are present on mammalian leukocytes and initiate phagocytosis of particulate yeast beta-glucans, such as zymosan particles. Human monocytes and U937 cells express two membrane proteins of 180 and 160 kDa, each of which binds particulate yeast glucan through a 20-kDa polypeptide constituent. In this report, the structural composition of the two beta-glucan receptors and the biochemical properties of their polypeptide constituents were examined. The 180-kDa receptor was composed of three disulfide-linked polypeptides of 95, 60, and 20 kDa, whereas the 160-kDa receptor was a multimer of two polypeptides of 27 and 20 kDa. Unlike other receptor constituents, the 20-kDa polypeptide was nonglycosylated and focused at two distinct isoelectric points. Immunoblots of the focused polypeptides showed the two 20-kDa variants and the 95-kDa subunit to be constitutively tyrosine-phosphorylated, a feature not previously reported for receptors on human mononuclear phagocytes. Dephosphorylation of the receptor proteins resulted in the loss of antigenic phosphotyrosine without affecting the antigenicity of either 20-kDa variant for the anti-idiotypic antibody to beta-glucan receptors. Separate analysis of the 160-kDa receptor showed it contained both variants of the 20-kDa polypeptide. Thus, the 20-kDa subunit constituent of the two beta-glucan receptors is a functionally and chemically unique polypeptide with apparent microheterogeneity in its primary structure.

Amino Acids↗
PubMed1994

Blood pressure and heart rate reactivity to mental strain in adolescent judo athletes.

This exploratory investigation examined the association between maximal aerobic power (VO2max) and blood pressure (BP) and heart rate (HR) reactivity to mental challenge. Adolescent male judo athletes (n = 20) performed a 2-min mental arithmetic. Heart rate was recorded before, during, and after the arithmetic, and BP was recorded before and after the mental challenge. Blood pressure in the immediate stress-recovery period was not related to VO2max, but subjects having a higher maximal aerobic power showed faster HR recovery from mental stress than those having a lower VO2max. Subjects who showed earlier peak HR responses, during the stress episode, demonstrated lower average HR reactivity than subjects who attained the maximal HR response later in the stress period. The relationship between the interval to reach peak HR and the magnitude of reactivity deserves further attention. However, at present these findings should be viewed as tentative because of the uniqueness and size of the sample.

Adolescent↗
PubMed1993

Molecular and crystal structure of Sp-thymidin-3'-yl 4-thiothymidin-5'-yl methylphosphonate.

The molecular structure of one diastereomer of the dinucleoside methylphosphonate Tp(Me)sT (1) has been determined by X-ray diffraction methods. The crystal asymmetric unit contains one molecule of 1 and one methanol in an orthorhombic unit cell of dimensions a = 13.241(4), b = 13.844(3), c = 14.944(7) A, space group P2(1)2(1)2(1). Both pyrimidine bases in 1 are oriented anti relative to the 2'-deoxyribose rings, and the sugar conformations are 2E and 2(3)T in the 4-thiothymidine and thymidine moieties, respectively. The deoxyribose-phosphonate backbone has an extended conformation with the bases completely unstacked and almost parallel. The absolute configuration at the phosphorus center in 1 is Sp.

Carbohydrates↗