PubMed Health⌕ Search

Biomedical subjects

Thomas Hofmann

Publications and source records attributed to Thomas Hofmann.

At least 55 records · Page 3Linked to original sources
PubMed2004

Systematic studies of structure and physiological activity of alapyridaine. A novel food-born taste enhancer.

By application of taste dilution analysis (+)-(S)-1-(1-carboxyethyl)-5-hydroxy-2-(hydroxymethyl)-pyridinium inner salt was recently successfully identified as a multimodal taste enhancer in beef bouillon. While being taste-less on its own, this so-called alapyridaine was found to intensify the human perception of sweet, salty, and umami taste. To gain information on the molecular requirements of this novel class of taste enhancer, a range of structurally related pyridinium betaines were synthesized, purified, and their physiological activities sensorially evaluated. Removal or modification of the hydroxyl and the hydroxymethyl group, respectively, induced a loss in bioactivity, thus indicating the 2-(hydroxymethyl)-5-hydroxypyridinium moiety as an essential structural element for taste enhancement. Regarding the amino substituent, neither the prolongation or removal of the alkyl chain or the carboxy function in the 1-(1-carboxy-2-ethyl)-moiety, nor the incorporation of an additional carboxy function led to any active derivative, thus demonstrating that also the structure of the nitrogen substituent is rather conserved for taste enhancement. But substitution of the methyl group by a benzyl group yielded a compound showing similar taste enhancing activities as found for alapyridaine. Interestingly, additional insertion of glycine between the 1-(1-carboxy-2-phenylethyl)-moiety and the pyridinium ring resulted in a compound eliciting comparable taste enhancing effects as shown for the compound lacking the glycine spacer. In contrast to these multimodal taste enhancers, substitution of the alanine moiety in alapyridaine by an arginine moiety revealed an one-dimensional taste enhancer exclusively increasing the human sensitivity for salty taste.

Alanine↗
PubMed2004

[Risk management of coronary artery disease--pharmacological therapy].

Treatment of coronary artery disease primarily aims at reducing the severity and frequency of cardiac symptoms and improving prognosis. Both goals can be achieved by the administration of beta-receptor blockers, which are now used as first-line therapy in these patients. Calcium channel blockers or nitrates should be given in the event of contraindications or severe intolerance to beta-receptor blocking therapy. Only long-acting calcium channel blockers should be used in this setting. Another indication for additional treatment with calcium channel blockers and nitrates is given when the efficacy of beta-blocker therapy is not sufficient to relieve symptoms. Nitroglycerin and nitrates are the drugs of choice for the treatment of the acute angina pectoris attack. Calcium channel blockers are used as first-line treatment in patients with vasospastic angina. In patients with syndrome X, nitrates as well as calcium channel blockers or beta-receptor blockers can be administered. In the absence of contraindications, every patient with coronary artery disease should be given aspirin. A daily dosage of 75 to 150 mg is sufficient to reduce the rate of future cardiac events. Clopidogrel should be given in every patient with intolerance or contraindications for aspirin. Increased plasma homocystein levels seem to be a risk factor for coronary artery disease. Homocystein levels can be reduced by dietary means as well as supplementation of folic acid or vitamin B complex. There is no evidence from controlled randomised studies that a decrease of homocystein is beneficial for the prognosis of patients with coronary artery disease.

Adrenergic beta-Antagonists↗
PubMed2004

Surgical revision of an uncommonly dislocated self-expanding Amplatzer septal occluder device.

Open heart surgery is the standard procedure for closure of ostium secundum atrial septal defects. Recently, percutaneous transcatheter procedures emerged as therapeutic alternatives for closure of both atrial septal defects and patent foramen ovale. Unfortunately, however, such percutaneous procedures may require surgical intervention for early or late complications. We report a case with emergent surgery for dislocation of the Amplatzer septal occluder into the aortic arch diagnosed 30 days after percutaneous closure of an atrial septal defect.

Aorta, Thoracic↗
PubMed2004

Three-dimensional color Doppler echocardiography for assessing shunt volume in atrial septal defects.

Background Three-dimensional color Doppler echocardiography has been used to assess cardiac blood flow in experimental settings. We tested whether this technique can be applied to assess transatrial shunt flow in patients with atrial septal defect in a clinical setting. Methods In 46 consecutive patients with atrial septal defects, shunt flow was assessed during cardiac catheterization using the Fick method and by conventional 2-D quantitative transesophageal Doppler echocardiography. The averaged values for shunt flow obtained by both methods were used as a reference. Transesophageal 3-D color Doppler echocardiography was performed for analysis of the 3-D flow velocity field of transatrial shunt flow. Shunt volume was calculated by application of the Gauss theorem. Results We found a close correlation between shunt volume (L/min) obtained by either 3-D color Doppler echocardiography or the reference methods ( r = 0.981, P < .001). Using 3-D color Doppler data to predict the reference values, 95% confidence limits were -11.5 to +11.6%. Conclusions Shunt flow in patients with atrial septal defects can be assessed in a clinical setting by transesophageal 3-D color Doppler echocardiography.

Adolescent↗
PubMed2004

Clinical application of enoxaparin.

Low-molecular-weight heparins have several important advantages over unfractionated heparin (UFH). Due to a longer plasma half life together with high bioavailability and a linear dose-response relationship, the drugs can be safely and effectively administered in the hospital or ambulatory settings without the need to monitor the anticoagulant effect. Enoxaparin (Lovenox), Aventis Pharma) is a low-molecular-weight heparin which has been studied in a variety of clinical situations. In general surgery the efficacy of enoxaparin to prevent venous thromboembolism is similar to UFH but the tolerability is better. In patients undergoing cancer, orthopedic or vascular surgery the efficacy of enoxaparin is significantly higher with similar rates of bleeding complications. The database for enoxaparin in nonsurgical patients is smaller compared with surgical groups. There is evidence that the efficacy of enoxaparin may be superior to UFH in patients with severe cardiac disease. Efficacy and safety of UFH and enoxaparin are similar for the treatment of deep vein thrombosis. However, enoxaparin can be safely administered by the patients at home which is not possible with UFH. In patients with acute coronary syndromes, enoxaparin has been shown to reduce the rate of deaths and serious cardiac events in comparison with UFH. Furthermore, exonaparin treatment has been shown to be cost-effective, and therefore is the therapy of choice in this setting. In addition, enoxaparin has been shown to be a safe and effective alternative to the combination of UFH and phenprocoumone therapy in patients undergoing electrical cardioversion for atrial fibrillation.

Anticoagulants↗
PubMed2004

Activation, subunit composition and physiological relevance of DAG-sensitive TRPC proteins.

The classical transient receptor potential (TRP) protein family consists of seven members which share a common gating mechanism contingent on phospholipase C activation. While some family members are thought to be activated subsequent to emptying of intracellular calcium stores, others appear to be gated by as yet undefined lipid messengers. TRPC 3, 6 and 7 form a structural and functional TRPC subfamily characterized by their sensitivity towards diacylglycerols (DAGs). TRPC6 is a non-selective cation channel that is activated by DAG in a membrane-delimited fashion, independently of protein kinase C. Depletion of internal Ca2+ stores is not required for TRPC6 activity. TRPC6 mRNA and protein are abundantly expressed in smooth muscle cells and DAG-evoked Ca2+ transients can be observed in primary myocytes derived from lung and blood vessels. Thus, TRPC6 is a promising candidate for as yet unidentified non-selective cationic channels in smooth muscle cells potentially involved in vasoconstrictor-activated cation influx and myogenic tone of resistance arteries. Recent systematic studies revealed that TRPC proteins assemble into heteromultimers predominantly within the confines of distinct TRPC subfamilies. The known principles of channel complex formation will be instrumental in assessing the physiological role of distinct TRPC proteins in living cells.

Animals↗
PubMed2003

Activity-guided identification of a chemopreventive compound in coffee beverage using in vitro and in vivo techniques.

The aim of the present study was to apply an activity-guided screening procedure to coffee brew to identify a key chemopreventive compound by means of in vitro antioxidant tests as well as cell culture experiments and to prove the in vivo activity of that compound by an animal feeding experiment. Solvent fractionation, followed by multiple-step ultrafiltration, revealed that the polar coffee compounds with molecular weights below 1 kDa show the major inhibitory effect on the in vitro peroxidation of linoleic acid as well as the predominant chemopreventive enzyme modulating activity on the NADPH-cytochrome c reductase (CCR) and glutathione S-transferase (GST) in human intestinal Caco-2 cells. To identify the chemical structure of the most active antioxidants and chemopreventive compounds, the polar compounds were further separated by HPLC techniques, followed by the activity-guided screening of the individual HPLC fraction. These experiments demonstrated 5-chlorogenic acid to be the most powerful antioxidant in vitro, whereas, in contrast, chemopreventive effects on the GST activity were found for the N-methylpyridinium ion, the structure of which was elucidated by LC-MS and NMR experiments and confirmed by synthesis. The in vivo activities of coffee beverage and N-methylpyridinium ions were tested in a 15-day feeding experiment on rats. In the liver, feeding of 4.5% coffee beverage resulted in increases of GST and UDP-GT activities by 24 and 40% compared to animals fed the control diet (p > 0.05), respectively. Plasma total antioxidant capacity and plasma tocopherol were elevated in animals fed the coffee beverage and the N-methylpyridinium-containing diet. In summary, the results demonstrating a strong in vitro antioxidant activity for coffee were confirmed by the feeding study. Surprisingly, feeding of N-methylpyridinium also resulted in an increased total antioxidant capacity in the plasma. The data indicate that the mode of action demonstrated for N-methylpyridinium in biological systems is different from that in foods.

Animals↗
PubMed2003

Identification of the taste enhancer alapyridaine in beef broth and evaluation of its sensory impact by taste reconstitution experiments.

An essential compound imparting the sweet taste to beef broth was investigated. Taste activity-guided fractionation of beef broth by ultrafiltration, gel permeation chromatography, and HPLC in combination with the recently developed comparative taste dilution analysis enabled the localization of a fraction possessing sweetness-enhancing activity upon degustation. Comparison of the chromatographic, spectroscopic, and sensory data with those of the synthetic reference compound led to the identification of the sweetness-enhancing N-(1-carboxyethyl)-6-(hydroxymethyl)pyridinium-3-ol inner salt, named alapyridaine, which was recently isolated from heated aqueous solutions of hexoses and l-alanine. After quantification of alapyridaine in beef broth, sensory analysis of synthetic beef taste recombinates spiked with synthetic alapyridaine in its "natural" concentration of 419 mug/L and comparison to the taste quality of a tastant recombinate lacking the alapyridaine revealed a significant increase in sweetness and umami character only when the alapyridaine was present in the recombinate. These data demonstrate for the first time that, in "natural" concentrations, the alapyridaine exhibited a pronounced effect on the overall taste quality of beef broth, in particular, on the sweet and umami character.

Alanine↗
PubMed2003

N-linked protein glycosylation is a major determinant for basal TRPC3 and TRPC6 channel activity.

The TRPC family of receptor-activated cation channels (TRPC channels) can be subdivided into four subfamilies based on sequence homology as well as functional similarities. Members of the TRPC3/6/7 subfamily share common biophysical characteristics and are activated by diacylglycerol in a membrane-delimited manner. At present, it is only poorly understood whether members of the TRPC3/6/7 subfamily are functionally redundant or whether they serve distinct cellular roles. By electrophysiological and fluorescence imaging strategies we show that TRPC3 displays considerable constitutive activity, while TRPC6 is a tightly regulated channel. To identify potential molecular correlates accounting for the functional difference, we analyzed the glycosylation pattern of TRPC6 compared with TRPC3. Two NX(S/T) motifs in TRPC6 were mutated (Asn to Gln) by in vitro mutagenesis to delete one or both extracellular N-linked glycosylation sites. Immunoblotting analysis of HEK 293 cell lysates expressing TRPC6 wild type and mutants favors a model of TRPC6 that is dually glycosylated within the first (e1) and second extracellular loop (e2) as opposed to the monoglycosylated TRPC3 channel (Vannier, B., Zhu, X., Brown, D., and Birnbaumer, L. (1998) J. Biol. Chem. 273, 8675-8679). Elimination of the e2 glycosylation site, missing in the monoglycosylated TRPC3, was sufficient to convert the tightly receptor-regulated TRPC6 into a constitutively active channel, displaying functional characteristics of TRPC3. Reciprocally, engineering of an additional second glycosylated site in TRPC3 to mimic the glycosylation status in TRPC6 markedly reduced TRPC3 basal activity. We conclude that the glycosylation pattern plays a pivotal role for the tight regulation of TRPC6 through phospholipase C-activating receptors.

Amino Acid Motifs↗
PubMed2003

Synthesis and sensory characterization of novel umami-tasting glutamate glycoconjugates.

Two glycoconjugates of glutamic acid, namely, the N-glycoside dipotassium N-(d-glucos-1-yl)-l-glutamate (1) and the corresponding Amadori compound N-(1-deoxy-d-fructos-1-yl)-l-glutamic acid (2), have been synthesized in yields of 35 and 52%, respectively, using new Maillard-mimetic approaches, and their chemical structures have unequivocally been elucidated by 1D- and 2D-NMR and MS experiments. Systematic sensory studies revealed that both glycoconjugates exhibit pronounced umami-like taste with recognition taste thresholds of 1-2 mmol/L, close to that of monosodium glutamate (MSG). Contrary to an aqueous solution of MSG, 1 does not show the sweetish and slightly soapy by-note, but evokes an intense umami taste. Aqueous solutions of 2 were described by the descriptors umami, seasoning, and bouillon-like. Added to a bouillon base, which did not contain any taste enhancers, both glycoconjugates imparted a distinct umami character similar to the control sample containing the same amount of MSG on a molar basis. To the best of our knowledge, these types of glycoconjugates in general and, in particular, N-glucosyl glutamate and N-deoxyfructosyl glutamate have never been reported as taste active compounds having umami-like properties. Therefore, 1 and 2 represent a new class of umami-type taste compounds showing properties similar to the umami reference compound MSG. Systematic (13)C NMR measurements revealed that 1 was fairly stable in aqueous solutions under alkaline conditions (pH 8-10) as well as in dry form. However, it rapidly hydrolyzes in neutral and acidic solutions, giving rise to glucose and glutamate. In contrast, glycoconjugate 2 was observed to be rather stable in aqueous solution as well as in the presence of human saliva.

Flavoring Agents↗
PubMed2003

Racemic and enantiopure synthesis and physicochemical characterization of the novel taste enhancer N-(1-carboxyethyl)-6-(hydroxymethyl)pyridinium-3-ol inner salt.

Convenient syntheses were developed to obtain on a multigram scale the novel taste enhancer N-(1-carboxyethyl)-6-(hydroxymethyl)pyridinium-3-ol 1, called alapyridaine, as a racemic mixture and as pure (+)-(S) and (-)-(R) enantiomers, respectively. 5-(Hydroxymethyl)-2-furaldehyde was used as key intermediate and was reacted with l-alanine under alkaline conditions to obtain racemic 1. Alternatively, reductive amination of 5-(hydroxymethyl)-2-furaldehyde with Raney-Ni/hydrogen and l- or d-alanine followed by mild oxidation led to (+)-(S)-1 and (-)-(R)-1, respectively. Racemization was promoted under alkaline and boiling conditions via a carbanion, the formation of which was facilitated by the electron-withdrawing effect of the iminium cation and the resonance-stabilizing capacity of the pyridinium moiety. Under these conditions, 1 was obtained in a 1:1 mixture of the phenol (1) and phenolate (1-H) forms as shown by X-ray diffraction. Racemic 1 formed monoclinic crystals of high molecular organization in which the phenol-type (RS)-1, the phenolate-type (RS)-1-H, sodium cations, and ethanol molecules are present. The crystal structure of [Na(1)(1-H).(C(2)H(6)O)] shows one-dimensional mu(2)-bridging-oxygen polymers stabilized by a three-dimensional network of ionic, hydrogen bond, and pi-stacking interactions with channels occupied by solvent molecules.

Alanine↗
PubMed2003

TRPM5 is a voltage-modulated and Ca(2+)-activated monovalent selective cation channel.

The TRPM subfamily of mammalian TRP channels displays unusually diverse activation mechanisms and selectivities. One member of this subfamily, TRPM5, functions in taste receptor cells and has been reported to be activated through G protein-coupled receptors linked to phospholipase C. However, the specific mechanisms regulating TRPM5 have not been described. Here, we demonstrate that TRPM5 is a monovalent-specific cation channel with a 23 pS unitary conductance. TRPM5 does not display constitutive activity. Rather, it is activated by stimulation of a receptor pathway coupled to phospholipase C and by IP(3)-mediated Ca(2+) release. Gating of TRPM5 was dependent on a rise in Ca(2+) because it was fully activated by Ca(2+). Unlike any previously described mammalian TRP channel, TRPM5 displayed voltage modulation and rapid activation and deactivation kinetics upon receptor stimulation. The most closely related protein, the Ca(2+)-activated monovalent-selective cation channel TRPM4b, also showed voltage modulation, although with slower relaxation kinetics than TRPM5. Taken together, the data demonstrate that TRPM5 and TRPM4b represent the first examples of voltage-modulated, Ca(2+)-activated, monovalent cation channels (VCAMs). The voltage modulation and rapid kinetics provide TRPM5 with an excellent set of properties for participating in signaling in taste receptors and other excitable cells.

Animals↗
PubMed2003

Structural and sensory characterization of compounds contributing to the bitter off-taste of carrots (Daucus carota L.) and carrot puree.

Sequential application of solvent extraction, gel permeation chromatography, and HPLC in combination with taste dilution analyses revealed that not a sole compound but a multiplicity of bitter tastants contribute to the bitter off-taste of cold-stored carrots and commercial carrot puree, respectively. Among these bitter compounds, 3-methyl-6-methoxy-8-hydroxy-3,4-dihydroisocoumarin (6-methoxymellein), 5-hydroxy-7-methoxy-2-methylchromone (eugenin), 2,4,5-trimethoxybenzaldehyde (gazarin), (Z)-heptadeca-1,9-diene-4,6-diin-3,8-diol (falcarindiol), (Z)-heptadeca-1,9-diene-4,6-diin-3-ol (falcarinol), and (Z)-3-acetoxy-heptadeca-1,9-diene-4,6-diin-8-ol (falcarindiol 3-acetate) could be identified on the basis of MS as well as 1D- and 2D-NMR experiments. Due to the low concentrations of <0.1 mg/kg and the high taste thresholds found for eugenin and gazarin, these compounds could be unequivocally excluded as important contributors to the bitter taste of carrots. Calculation of bitter activity values as the ratio of their concentration to their bitter detection threshold clearly demonstrated that neither in fresh and stored carrots nor in commercial carrot puree did 6-methoxymellein contribute to the bitter off-taste. In contrast, the concentrations of falcarindiol in stored carrots and, even more pronounced, in carrot puree were found to be 9- and 13-fold above its low bitter detection concentration of 0.04 mmol/kg, thus demonstrating that this acetylenic diol significantly contributes to the bitter taste of the carrot products investigated.

Alkynes↗
PubMed2003

Sensory activity, chemical structure, and synthesis of Maillard generated bitter-tasting 1-oxo-2,3-dihydro-1H-indolizinium-6-olates.

Thermal treatment of aqueous solutions of xylose, rhamnose, and l-alanine led to a rapid development of a bitter taste of the reaction mixture. To characterize the key compounds causing this bitter taste, the recently developed taste dilution analysis (TDA), which is based on the determination of the taste threshold of reaction products in serial dilutions of HPLC fractions, was performed to locate the most intense taste compounds in the complex mixture of Maillard reaction products. By application of this TDA, 26 fractions were obtained, among which seven fractions were evaluated with a high taste impact. LC/MS and NMR spectroscopy as well as synthetic experiments revealed the 1-oxo-2,3-dihydro-1H-indolizinium-6-olates 1-5 as the key compounds contributing the most to the intense bitter taste of the Maillard mixture. Calculation of the taste impact of these compounds based on a dose/activity relationship indicated that these five compounds already accounted for 56.8% of the overall bitterness of the Maillard mixture, thus demonstrating this class of 1-oxo-2,3-dihydro-1H-indolizinium-6-olates as the key bitter compounds. First synthetic studies on the relationship between the chemical structure and the human psychobiological activity of 1-oxo-2,3-dihydro-1H-indolizinium-6-olates revealed that substitution of the furan rings of 1 by 5-methylfuryl moieties (compounds 3-5) or by 5-(hydroxymethyl)furyl groups (compound 6) led to a significant increase of the bitter threshold. In contrast, the substitution of the oxygen atoms in the furan rings of 1 by sulfur atoms induced a significant decrease of the detection threshold of the 1-oxo-2,3-dihydro-1H-indolizinium-6-olate; for example, the thiophene derivative 7 showed the extraordinarily low bitter detection threshold of 6.3 x 10(-5) mmol/kg (water).

Alanine↗
PubMed2003

Discovery and structure determination of a novel Maillard-derived sweetness enhancer by application of the comparative taste dilution analysis (cTDA).

Application of a novel screening procedure, the comparative taste dilution analysis (cTDA), on the non-solvent-extractable reaction products formed in a thermally processed aqueous solution of glucose and l-alanine led to the discovery of the presence of a sweetness-enhancing Maillard reaction product. Isolation, followed by LC-MS and 1D- and 2D-NMR measurements, and synthesis led to its unequivocal identification as N-(1-carboxyethyl)-6-(hydroxymethyl)pyridinium-3-ol inner salt. This so-called alapyridaine, although being tasteless itself, is the first nonvolatile, sweetness-enhancing Maillard reaction product reported in the literature. Depending on the pH value, the detection thresholds of sweet sugars, amino acids, and aspartame, respectively, were found to be significantly decreased when alapyridaine was present; for example, the threshold of glucose decreased by a factor of 16 in an equimolar mixture of glucose and alapyridaine. Studies on the influence of the stereochemistry on taste-enhancing activity revealed that the (+)-(S)-alapyridaine is the physiologically active enantiomer, whereas the (-)-(R)-enantiomer did not affect sweetness perception at all. Thermal processing of aqueous solutions of alapyridaine at 80 degrees C demonstrated a high thermal and hydrolytic stability of that sweetness enhancer; for example, more than 90 or 80% of alapyridaine was recovered when heated for 5 h at pH 7.0, 5.0, or 3.0, respectively.

Alanine↗
PubMed2003

RAGE-mediated MAPK activation by food-derived AGE and non-AGE products.

Investigating the cellular effects of food compounds formed by heat treatment during processing, we recently demonstrated the expression of the receptor for advanced glycation endproducts (RAGE) and the p44/42 MAP kinase activation by casein-N(epsilon )-(carboxymethyl)lysine (casein-CML), a food-derived AGE, in the intestinal cell line Caco-2. In this work, we report a Caco-2 p44/42 MAP kinase activation by bread crust and coffee extract. After identification, quantification, and synthesis of two key compounds formed in association with the process-induced heat impact applied to bread dough and coffee beans, those compounds, namely the AGE pronyl-glycine and the non-AGE N-methylpyridinium, were also demonstrated for the first time to activate the p44/42 MAP kinase through binding to RAGE in Caco-2 cells. Blocking of RAGE by an antagonistic antibody and expression of C-terminally truncated RAGE resulted in a reduced Caco-2- and HEK-293-MAP kinase activation. These findings unequivocally point to a RAGE-mediated activating effect of chemically defined food-derived, thermally generated products, both, AGEs and non-AGEs, on cellular signal transduction pathways involved in inflammatory response and cellular proliferation.

Antibodies↗
PubMed2003

Maillard reaction products modulating the growth of human tumor cells in vitro.

We investigated the effect of a series of Maillard reaction products formed from carbohydrates under household heating conditions on the growth of human tumor cells in vitro. 4-Hydroxy-5-methyl-3-(2H)-furanone (1) was found to potently enhance the proliferation of human tumor cells. In contrast, the Maillard-type chromophores 2-(2-furyl)methylidene-4-hydroxy-5-methyl-2H-furan-3-one (2), 4-(2-furyl)-7-[(2-furyl)methylidene]-2-hydroxy-2H,7H,8aH-pyrano[2,3-b]- pyran-3-one (6), and 3-hydroxy-4[(E)-(2-furyl)methylidene]methyl-3-cyclopentene-1,2 dione (13) inhibited the growth of human tumor cells in vitro in the low micromolar range. GXF251L cells (gastric carcinoma), synchronized by serum deprivation, were retained in the G1-phase of the cell cycle after treatment with 2, 6, or 13 for 24 h. Concomitantly, a distinct sub-G1 peak was observed, indicative for apoptosis induction. DNA fragmentation was further investigated by ELISA using antibodies raised against histones and DNA. 2 induced a significant increase of fragmented DNA at concentrations > or = 30 microM. After treatment with compound 6, DNA fragmentation was observed at a higher concentration range (> or = 50 microM), whereas incubation with 13 resulted in a marked DNA fragmentation already at 20 microM. On the protein level, the activation of caspase 3, as an early marker for apoptosis induction, was determined. The results were almost identical to those obtained in the DNA fragmentation ELISA. In summary, Maillard reaction products potently modulating the growth of human tumor cells were identified. The Maillard-type chromophores 2, 6, and 13 were found to interfere with the proliferation of gastric carcinoma cells, causing cell cycle arrest and apoptosis induction.

Antineoplastic Agents↗