Biomedical subjects

N Varga

Publications and source records attributed to N Varga.

8 recordsLinked to original sources

PubMed2005

Mechanisms of acrylamide formation: Maillard-induced transformation of asparagine.

The formation of acrylamide (AA) from L-asparagine was studied in Maillard model systems under pyrolysis conditions. While the early Maillard intermediate N-glucosylasparagine generated approximately 2.4 mmol/mol AA, the Amadori compound was a less efficient precursor (0.1 mmol/mol). Reaction with alpha-dicarbonyls resulted in relatively low AA amounts (0.2-0.5 mmol/mol), suggesting that the Strecker aldehyde pathway is of limited relevance. Similarly, the Strecker alcohol 3-hydroxypropanamide generated low amounts of AA (0.2 mmol/mol). On the other hand, hydroxyacetone afforded more than 4 mmol/mol AA, indicating that alpha-hydroxycarbonyls are more efficient than alpha-dicarbonyls in transforming asparagine into AA. The experimental results are consistent with the reaction mechanism proposed, i.e. (i) Strecker-type degradation of the Schiff base leading to azomethine ylides, followed by (ii) beta-elimination of the decarboxylated Amadori compound to release AA. The functional group in beta-position on both sides of the nitrogen atom is crucial. Rearrangement of the azomethine ylide to the decarboxylated Amadori compound is the key step, which is favored if the carbonyl moiety contains a hydroxyl group in beta-position to the N-atom. The beta-elimination step in the amino acid moiety was demonstrated by reacting under pyrolysis conditions decarboxylated model Amadori compounds obtained by synthesis.

Acetone↗

PubMed2000

Determination of the plant growth regulator chlormequat in food by liquid chromatography-electrospray ionisation tandem mass spectrometry.

A confirmatory method for the determination of trace levels of chlormequat in a variety of different food matrices was developed. It entails a single clean-up step over a solid-phase cation exchange resin and subsequent liquid chromatography-electrospray ionisation tandem mass spectrometry using a stable isotopically labelled internal standard. Mass spectral acquisition was done in selected reaction monitoring mode, selecting the transitions from both the 35Cl and the 37Cl isotope of chlormequat. Recoveries after extraction and clean-up, determined with radio-labelled chlormequat and averaged over the spiking range (16-65 microg kg(-1)) in four different commodities, were within 88-96%, with a coefficient of variation better than 8%. The method can be applied to pears, pear juice concentrates, fruit purées, and cereal products, with typical limits of detection for chlormequat estimated at 2-5 microg kg(-1). A survey of different food commodities revealed that chlormequat was detectable--albeit at very low levels--in many of the food samples analysed, with the highest concentration recorded in pears purchased in Switzerland and of South African origin (5.5 mg kg(-1)). Measurements were also conducted on two LC-MS instruments and demonstrate the versatility and robustness of the method and its applicability to instruments of different ion source design.

Calibration↗

PubMed2000

Asymmetric copper-catalyzed

The asymmetric copper-catalyzed generation and subsequent [2,3]-sigmatropic rearrangement of sulfur ylides is strongly dependent on the structure of the starting allyl sulfide. A series of alkyl and aryl substituted allyl sulfides (2a-i) were reacted with ethyl diazoacetate in the presence of copper triflate (CuOTf) and a C2-symmetric bis-oxazoline ligand (5a-c). The degree of asymmetric induction ranged from 2.8% for allyl methyl sulfide (2a) to 60% for (1S,2S,5R)-(+)-allyl menthyl sulfide (2d). The enantioselectivity of the reactions was also dependent on the electronic nature of the sulfide; allyl phenyl sulfide (2e) gave a 14% ee, whereas allyl p-methoxyphenyl sulfide (2i) produced only an 8% ee. The stereochemistry of 2d and (1R,2S,5R)-(+)-allyl menthyl sulfide (7) was assigned on the basis of NMR spectroscopic experiments.

Journal Article↗

PubMed1999

Evaluation of Escherichia coli DJ4309 expressing human P450 1A2 in mutagenicity testing of complex food mixtures.

Heterocyclic aromatic amines (HAAs) are potent bacterial mutagens and potential human carcinogens formed in heat processed proteins. The Ames test (strain TA98) is a useful mutagenicity test system to screen food products for these compounds. HAAs require activation to their genotoxic forms, and in the Ames test, a rat liver S-9 preparation is normally used. In order to better understand the mechanisms of mutagen activation with respect to human metabolism, new bacterial strains containing human cytochrome P450s and other metabolic enzymes have recently been developed. We have investigated the capacity of one of these strains, DJ4309 [Josephy et al., Chem. Res. Toxicol. 11 (1998) 70-74] as a screening tool for mutagens in food products. DJ4309 expresses the human P450 1A2, human NADPH cytochrome reductase and the bacterial acetyl CoA:arylamine N-acetyltransferase. This strain is as sensitive as the Ames system to the mutagenic effects of the heterocyclic aromatic amines 2-amino-3-methylimidazo[4,5-f]quinoline, 2-amino-3, 4-dimethylimidazo[4,5-f]quinoline and 2-amino-3,8-dimethylimidazo[4, 5-f]quinoxaline, but less sensitive to 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine. However, the mutagenicity of the arylamine 2-aminofluorene is considerably higher in DJ4309 than in the Ames test system. Meat extracts with a total HAA content ranging from less than 2 ng/g to 20 ng/g are efficiently detected by the Ames TA98 strain with rat liver S-9 activation. DJ4309 is less sensitive, with fewer revertants induced over the same dose range. Unknown compounds present in the meat extracts appear to inhibit the activity of the P450 1A2 enzyme in the DJ4309 strain. We have therefore demonstrated that although DJ4309 is a useful tool for mechanistic studies in chemical carcinogenesis, the screening of complex food matrices for HAAs by this bacterial strain must be conducted with caution.

Amines↗

PubMed1998

Activation of heterocyclic aromatic amines by rat and human liver microsomes and by purified rat and human cytochrome P450 1A2.

The dietary mutagens 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) are activated to genotoxins by rat and human liver cytochrome P450 (P450) 1A1- and 1A2-mediated N-oxidation. Immunoquantitation of 51 human liver samples revealed a wide range in P450 1A2 expression (10-250 pmol/mg of microsomal protein, median 71 pmol/mg), with 39% of the livers containing >100 pmol/mg of protein. There was no evidence for expression of P450 1A1 (<1 pmol/mg of protein). P450 1A2 levels were correlated to MeIQx and PhIP N-oxidation rates (r = 0.83, 0.73, respectively). In male Fischer-344 and Sprague-Dawley rats, hepatic P450 1A2 ranged from 5 to 35 pmol/mg of protein, while P450 1A1 was <1 pmol/mg. Animal pretreatment with 3-methylcholanthrene, beta-naphthoflavone, or polychlorinated biphenyls (PCB) resulted inasmuch as 340-fold and >1000-fold induction of P450 1A2 and 1A1, respectively, and a 220-fold increase in N-oxidation activity. Approximately 20% of the human samples were as active in N-oxidation and conversion of MeIQx to bacterial mutagens as microsomes of PCB-pretreated rats [3-4 nmol of NHOH-MeIQx formed min-1 (mg of protein)-1]. In contrast, microsomes from PCB-treated rats displayed higher rates of PhIP N-oxidation and activation to mutagens than the most active human liver microsomes [8-24 vs 2-4 nmol of HNOH-PhIP formed min-1 (mg of protein)-1]. Recombinant human P450 1A2 showed catalytic efficiencies of MeIQx and PhIP N-oxidation that were 10-19-fold higher than purified rat P450 1A2. Cytochrome P450 1A2 expression in rodent and human liver tissue varies greatly and there are considerable differences between the enzymes in the two species in the activation of some heterocyclic aromatic amines, which must be considered when assessing human health risk.

Animals↗

PubMed1996

Antimutagenicity and catechin content of soluble instant teas.

The antimutagenic properties of soluble instant teas were examined using the bacterial Ames assay. Inhibition of the numbers of revertants induced from a number of known mutagens indicates that aqueous extracts of instant teas have antimutagenic activity and antioxidative properties, and can inhibit nitrosation reactions. Despite a significant reduction in the amounts of major green tea catechins, quantified using reversed-phase HPLC with electro-chemical detection, no differences in antimutagenicity were observed between the instant teas, a black fermented tea and a green tea. Oxidation of polyphenolic compounds which occurs during the production of instant tea does not therefore decrease the antioxidant, free radical scavenging and antimutagenic properties. This suggests that catechins are not the only compounds responsible for the protective effects of teas.

Antimutagenic Agents↗

PubMedDate not supplied

Follow-up of minimal residual disease in acute childhood lymphoblastic leukemia by WT1 gene expression in the peripheral blood: the Hungarian experience.

The aim of the study was to investigate if monitoring WT1 gene expression in the peripheral blood is an appropriate approach to monitor the progression of childhood acute lymphoblastic leukemia (ALL). Forty-six patients have been enrolled into this study (24 ALL and 22 control, nonleukemic cases). The peripheral blood was tested for WT1 gene expression using a sensitive nested RT-PCR technique. The assay was sensitive enough to detect 10(2) leukemic cells among 10(6) normal leukocytes. In agreement with the literature 96% of childhood ALL (23/24) expressed WT1 independent of the prognostic factors of the disease. On the other hand, no WT1 gene expression was found in the peripheral blood of nonleukemic hematological diseases, except myelodysplasia. WT1 became negative in the peripheral blood of these patients at the end of the induction phase of the therapy in the majority of the cases (19/24), whereas clinical remission was achieved in all patients except one. WT1 gene expression changes in the peripheral blood was monthly monitored in 20 ALL patients for 1 year and in 16 cases during the second year (for a maximum of 21 months). Although continuous monitoring detected transient (1- to 3-month long) WT1 expression in the majority of the ALL cases (16/20), clinical relapse occurred in 2 cases only when the WT1 expression was maintained for 11-15 months. Follow up studies of the WT1 gene expression in the peripheral blood of WT1-positive childhood ALL may enable researchers to monitor MRD and detect a very low leukemic cell count (perhaps called "molecular relapse"). According to this study, the transient WT1 positivity for 1-3 months does not predict clinical relapse of childhood ALL, unlike a longer-lasting positivity.

Adolescent↗

PubMedDate not supplied

[Studies of the influenza epidemic of January-March, 1974].

In an epidemiologic, clinical and viral study of several influenza foci in some urban districts of Romania during January-March 1974, 23 influenza virus B Hong-Kong 8/73 strains were isolated. The dynamics of HAI serum antibodies confirmed the viral diagnosis. The epidemic ran a slow course, affecting especially the 14-25 years age group and had an evident benign clinical aspect.

Adolescent↗