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Biomedical subjects

D Szabó

Publications and source records attributed to D Szabó.

At least 19 recordsLinked to original sources
PubMed2001

Ellipticine analogues and related compounds as inhibitors of reverse transcriptase and as inhibitors of the efflux pump.

Ten polycyclic derivatives related to ellipticine have been synthesised and tested for their intercalating, reverse transcriptase (RT) inhibitory and multidrug resistance efflux pump inhibitory properties. The intercalating activity and the RT inhibitory activity of the derivatives suggest that ellipticine analogues bind at an allosteric binding site on RT or that this inhibition could be controlled at the DNA level. The MDR efflux pump inhibitory activities of these derivatives, however, appears to be unrelated to the DNA binding ability.

Animals↗
PubMed2001

Emergence of extremely high penicillin and cefotaxime resistance and high-level levofloxacin resistance in clinical isolates of Streptococcus pneumoniae in Hungary.

Oxacillin disc diffusion tests revealed that 36.7% of 327 Hungarian Streptococcus pneumoniae strains from clinical specimens were not penicillin susceptible. Determination of the MICs of penicillin, cefotaxime and levofloxacin for these strains by Etest confirmed that 30 (9.2%), 19 (5.8%) and four to 11 (1.2-3.4%) were fully penicillin-, cefotaxime- and levofloxacin-resistant, respectively. Most had extremely high MICs. Lower respiratory tract strains were more resistant than those from the upper respiratory tract. Levofloxacin-resistant strains were either penicillin intermediate or resistant, but their MICs did not correlate strongly.

Anti-Infective Agents↗
PubMed2001

In vitro and in vivo activities of amikacin, cefepime, amikacin plus cefepime, and imipenem against an SHV-5 extended-spectrum beta-lactamase-producing Klebsiella pneumoniae strain.

The in vitro and in vivo effectiveness of amikacin, cefepime, and imipenem was studied using a high inoculum of an extended-spectrum beta-lactamase-producing Klebsiella pneumoniae strain. An in vitro susceptibility test at the standard inoculum predicted the in vivo outcome of amikacin or imipenem while it did not do so for cefepime due to the inoculum effect.

Amikacin↗
PubMed2000

Magnetic and Mössbauer Studies of Magnetite-Loaded Polyvinyl Alcohol Hydrogels.

Materials producing strain in a magnetic field are known as magnetoelastic or magnetostrictive materials. A new type of material that is able to produce giant strain in a nonhomogeneous magnetic field has been developed. In these magnetic-field-sensitive gels (ferrogels) fine colloidal particles having superparamagnetic behavior are incorporated into a highly swollen elastic polymer network. Magnetic properties of ferrogels have been investigated using electron microscopy, static magnetization measurements, and Mössbauer spectroscopy. Analysis of the data yielded information on the superparamagnetic behavior of ferrogels and made it possible to estimate the size distribution of the magnetic cores of magnetite particles made by chemical precipitation and built into a chemically cross-linked polyvinyl alcohol matrix. The results are interpreted on the basis of a core-shell model. Copyright 2000 Academic Press.

Journal Article↗
PubMed2000

beta-Lactam susceptibility patterns and investigation of cephalosporin hydrolysing beta-lactamases of Gram-negative extraintestinal clinical isolates.

Of more than 3500 isolates of enterobacteriaceae, 48-69% were resistant to aminopenicillins and 11-45% to amoxycillin+clavulanic acid. Resistance to second and third generation cephalosporins was present in 11-17 and 3-8% of Escherichia coli, 47-56 and 15-52% of Klebsiella-Enterobacter, 36-57 and 16-27% of Proteus, Providencia and Morganella isolates. Pseudomonas aeruginosa strains varied in their resistance to antipseudomonal beta-lactams. Isoelectric points, inhibitor profiles and substrate profiles of beta-lactamases extracted from representatives of the resistant strains indicated that the resistance was mainly due to the hyperproduction of chromosomally encoded AmpC beta-lactamases. This was confirmed by plasmid profile and PCR investigations. Extended-spectrum beta-lactamase and metallo-penicillinase producing strains were not found. One Pseudomonas maltophilia strain produced an oxacillinase.

Anti-Bacterial Agents↗
PubMed2000

Exciton coupling in the CD spectra of chiral spiro-lambda 4-sulfanes and related sulfonium salts.

Enantiomers of spiro-lambda 4-sulfanes 2-7 and related cyclic sulfonium salts 2c-7c have been obtained by stereospecific synthesis. Exciton splitting was observed in the CD spectra of spiro-lambda 4-sulfanes and sulfonium salts having both benzene and naphthalene-benzene rings. The absolute configurations were deduced from the sign of the couplet. Exciton couplets in the CD spectra of sulfonium salts and their parent lambda 4-sulfanes show the same sign which follows from the same orientation of the coupled electric transition moments due to their similar trigonal bipyramidal geometry. Based on the known stereomechanism of the formation of spiro-lambda 4-sulfanes and sulfonium salts as well as of their hydrolysis leading to the corresponding sulfoxides (2a-7a and 2b-7b), the absolute configurations of sulfoxides could also be deduced from the sign of exciton couplet in the CD spectra of related lambda 4-sulfanes and sulfonium salts.

Journal Article↗
PubMed1999

Anti-psychotic drugs reverse multidrug resistance of tumor cell lines and human AML cells ex-vivo.

Anti-psychotic drugs are used in cancer patients undergoing chemotherapy frequently and the concomitantly used drugs may alter the pharmacokinetics of each other. One reason for the alteration of pharmacokinetics may be the modulation of the function of P-glycoprotein, whose efflux pump occurs in resistant cancer cells, in human intestine and in the blood-brain barrier. For this reason we tested the effect of several anti-psychotic drugs on the multidrug-resistant pump, P-glycoprotein. We found that in the MDR gene transfected L121C MDR, L5178 MDR and in the KB-V-1 cells selected for resistance some antipsychotic drugs block the function of P-glycoprotein. Blood cells of two treatment-resistant leukemic patients also showed increased uptake of daunorubicin if treated ex vivo with the anti-psychotic drugs. Our results suggest that pharmacokinetic studies should be performed prior to concomitant clinical use of such drugs which block P-glycoprotein function.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1999

Molecular epidemiology of a cluster of cases due to Klebsiella pneumoniae producing SHV-5 extended-spectrum beta-lactamase in the premature intensive care unit of a Hungarian hospital.

Fifteen nosocomial cases of extended-spectrum beta-lactamase-producing Klebsiella pneumoniae occurred among 132 neonates in a premature intensive care unit in Hungary in June through November 1998. Fourteen strains were indistinguishable by molecular biological typing and harbored the same single conjugative extended-spectrum beta-lactamase-encoding plasmid that was spontaneously found in a Serratia marcescens strain in the same patient.

Anti-Bacterial Agents↗
PubMed1997

Extended-spectrum beta-lactamases: an actual problem of hospital microbiology (a review).

Although there is a variety of mechanisms of bacterial resistance to beta-lactam antibiotics, the most important one is production of beta-lactamases inactivating penicillins and cephalosporins. The classification of beta-lactamases is based on biochemical, enzymological (i.e. molecular structure, inhibitory property, substrate-profile, relative rate of hydrolysis) and immunological characters. Extended-spectrum beta-lactamases (ESBLs) can be derived from TEM or SHV enzymes. These enzymes have now been sequenced and it has been found that relatively few point mutations have occurred in the gene of the TEM and SHV type enzymes. These point mutations clustered in five areas of the gene. The amino acid mutations can alter the conformation, the active site and change the hydrance of beta-lactamase-cephalosporin binding capacity. So the enzyme is able to bind and hydrolyse the third generation cephalosporins. Successive mutation interacted radically increasing the binding capacity of enzymes and confer resistance to newer cephalosporins. The use of these drugs provides a strong selective pressure to develop these mutations. Sporadic nosocomial outbreaks due to strains producing an ESBL led to an epidemic problem in some hospitals resulting in a concurrent dissemination of genes, plasmids or strains. Clinical epidemiological importance and role of ESBLs and emergence of multiply resistance of bacteria of nosocomial importance are discussed in this brief.

Aminohydrolases↗
PubMed1996

Effects of joining peptide (1-18) and histamine on dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulphate (DHEAS) production of human adrenocortical cells in vitro.

Joining peptide 1-18 (JP 1-18), added alone in concentrations of 10(-13)-10(-7) M to collagenase-dispersed human adrenocortical cells, did not affect the basal production of corticosterone, cortisol, aldosterone, dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulphate (DHEAS). JP 1-18 potentiated the ACTH-stimulated production of steroids. When administered in combination with histamine (10(-8)-10(-3) M), JP 1-18 (10(-8) or 10(-10) M), enhanced the synthesis of DHEA and DHEAS. JP 1-18, together with histamine, may play a role in the regulation of DHEA and DHEAS production.

Adrenal Cortex↗
PubMed1996

Viscosity of rat adrenocortical lipids in different functional states: morphological characteristics.

Impaired adrenocortical steroidogenic activity is often concomitant with morphologically and physiologically altered lipids in the cells of the adrenal cortex. The physical state of these lipid droplets and the morphological characteristics of crystal-shaped bodies were studied in different functional states of adrenocortical cells. In the perinatal period when steroidogenesis is suppressed by a negative feedback mechanism, crystal-shaped bodies (i.e. rectangular, electron-lucent formations, either alone or in clusters, surrounded by lysosomal matrix or in close proximity of lysosomes) were frequently observed in the inner zona fasciculata and zona reticularis. In experimentally suppressed adrenocortical activity, following the administration of dexamethasone, aminoglutethimide or cycloheximide, almost identical crystal-shaped bodies were frequently observed in adrenocortical cells. These crystal-shaped bodies appear to be cholesterol, as revealed by the digitonin reaction at the electron microscopic level. Following stimulation of the zona fasciculata by ACTH treatment for 14 days, a marked increase in the fluidity of the lipid droplets was observed in the thermotropic phase transitions with the polarizing microscope. In contrast, following aminoglutethimide treatment, the fluidity of the lipid droplets decreased. The thermotropic phase transitions of normal and neoplastic human adrenal cells, namely adrenocortical tumours causing Conn's or Cushing's syndrome, were also investigated. When hormone biosynthesis was enhanced, the appearance of birefringence and multiple phase transitions of lipid droplets was demonstrable in the low-temperature range.

Adrenal Cortex↗
PubMed1993

Dopamine is taken up from the circulation by, and released from, local noradrenergic varicose axon terminals in zona glomerulosa of the rat: a neurochemical and immunocytochemical study.

The effect of supramaximal electric field stimulation on [3H]dopamine (DA) release by rat adrenal capsule-glomerulosa preparations was studied using a micro-volume perfusion system. When the tissues were preloaded with [3H]DA, a considerable amount of [3H]DA and [3H]noradrenaline (NA) were released in response to field stimuli. Reserpinization, calcium removal or tetrodotoxin blocking of Na+ influx all completely inhibited the stimulation-evoked release of DA/NA, indicating that the radioactivity released is of neuronal and vesicular origin. In the adrenal cortex, a substantial proportion of tyrosine hydroxylase and dopamine-beta-hydroxylase immunoreactive nerve fibres and varicosities were observed around the zona glomerulosa. DA-containing nerves were not seen in the adrenal cortex; however, the same immunocytochemical procedures clearly demonstrated dopaminergic nerve cells and fibres in the substantia nigra and the striatum respectively, and cells of the adrenal medulla. Like the NA release from noradrenergic varicosities in the zona glomerulosa, the DA release from noradrenergic endings is not subject to negative feedback modulation through DA2 receptors since apomorphine, a DA2-receptor agonist, and sulpiride, a selective DA2-receptor antagonist, failed to affect the release. After in-vivo i.v. administration of [3H]DA, the glomerulosa content of DA and NA and the in-vitro release of [3H]DA and [3H]NA of zona glomerulosa both increased, indicating that the local varicose axon terminals were able to accumulate DA from the circulation, convert it into NA and release it in response to neural activity. This local arrangement of noradrenergic axon terminals, able to take up DA from the circulation and release it or convert it into NA, provides the possibility of a fine tuning of local circulation and aldosterone synthesis in the zona glomerulosa.

Adrenal Cortex↗
PubMed1992

Effect of chronic ACTH treatment on the physical state of lipid droplets in rat adrenocortical cells.

A histophysical method has been adapted to determine the thermotropic phase transitions of adrenocortical lipid droplets using a polarizing microscope equipped with a cold/hot stage. Cryosections of freshly-removed, unfixed adrenals, derived from control (untreated), and 14 days ACTH-treated rats were examined. The lipid droplets in the zona fasciculata and zona reticularis of the untreated rats were birefringent at room temperature (22 degrees C). The birefringence of zona glomerulosa lipids selectively increased in the temperature range from -10 to -15 degrees C. In cryosections prepared from ACTH-treated rats, thermotropic phase transitions of the lipid droplets appeared at a temperature range between -30 and -40 degrees C in each cortical zone. The chemical analysis of the isolated lipids revealed that the relative amount of triglycerides in the zona fasciculata lipids increased, while that of free and esterified cholesterol decreased after chronic ACTH treatment. Present data suggest that the increased fluidity of lipid droplets promotes lipid mobilization in response to the enhanced demand of the chronically stimulated adrenocortical cells. Viscosity-dependent mobilization of free cholesterol from lipid droplets is not a rate-limiting process in adrenal steroidogenesis, but rather may represent an important control of the availability of precursor from lipid stores.

Adrenal Cortex↗
PubMed1992

Changes in adrenocortical lipid fluidity of hyperfunctioning human adrenals.

Lipid droplets, the storage places of cholesterol in adrenocortical cells, exhibit a relatively uniform appearance studied by the electron microscope but they are heterogeneous in respect of their optical polarizing properties. Optical birefringency was studied in cryosections of normal and hyperfunctioning adrenal cortex by a polarizing microscope, equipped with a cold/hot stage working in the temperature range from -40 to 40 degrees C. The majority of lipid droplets in normal adrenal cortex were optically anisotropic in each cortical zone at room temperature (22 degrees C) indicating a long-range molecular order of the lipid components. The lipids of the zona glomerulosa, in the cases of Conn's and Bartter's syndromes, became anisotropic when the temperature was lowered below ambient. The birefringency of the lipids of the zona fasciculata in the case of Cushing's disease was observed at temperatures below -10 degrees C indicating ordered packing of the components of lipid droplets at this temperature. Thus the lipids were more fluid in the hyperfunctioning, hormone-producing cells--this may represent an optimal precondition for their mobilization and processing by the hydrolyzing enzyme system. The changes in fluidity of the intracellular lipids can be attributed to different functional states in the adrenal cortex. Study of the thermotropic phase transitions of the lipid droplets by polarizing microscopy may be a useful additional method for the diagnosis of some adrenocortical diseases.

Adrenal Cortex↗
PubMed1992

Catecholamines released from local adrenergic axon terminals are possibly involved in fine tuning of steroid secretion from zona glomerulosa cells: functional and morphological evidence.

The effect of supramaximal electric field stimulation on [3H]noradrenaline (NA) release and hormone production by rat adrenal capsule-glomerulosa preparations was studied using a microvolume perfusion system. A substantial proportion (about 20%) of nerve endings (varicosities) were observed close to zona glomerulosa cells, and about half of them appeared to be catecholaminergic, as judged by the chromaffin reaction of the synaptic vesicles studied at electron microscopic level. In tissue, preloaded with [3H]NA, the release of NA in response to electrical stimulation was frequency-dependent. Reserpinization, calcium removal or inhibition of Na+ influx by tetrodotoxin completely blocked NA release by field stimulation, indicating that the release resulted from axonal activity and is of vesicular origin. Neither the alpha 2-adrenoceptor agonist xylazine nor the muscarine-receptor agonist oxotremorine affected the stimulation-evoked release of [3H]NA, suggesting that, in contrast with other neurones present in the central nervous system or in the peripheral autonomic nervous system but like those in the median eminence, these axon terminals contained few presynaptic modulatory receptors. The NA (10.20 +/- 1.79 (S.E.M.) micrograms/g, n = 9), adrenaline (24.38 +/- 5.50 micrograms/g, n = 9) and dopamine (0.35 +/- 0.09 micrograms/g, n = 6) contents of the preparations were high, as determined by high-performance liquid chromatography. Our observations that the release and content of NA is high, and that a substantial proportion of catecholaminergic axon terminals lie in close proximity to zona glomerulosa cells (median value of the distance 300 nm) or to smooth muscle cells of the vessels, suggest that NA released from local adrenergic neurones without being presynaptically modulated may play an important role in fine-tuning both steroid production and/or blood flow through the gland, itself a powerful modulator of the adrenocortical response. This local modulating effect of NA may be especially significant when sympathetic activity is enhanced.

Adrenal Cortex Hormones↗