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PubMed1987

Actions of amiloride analogues on prostacyclin synthesis by rat aortic rings.

1 Fresh rat aortic rings were incubated in HEPES-buffered salt solutions (pH 8.0) in the presence or absence of amiloride analogues. The effect of these drugs on prostacyclin (PGI2) synthesis was determined by radioimmunoassay of the stable hydrolysis product 6-oxo-prostaglandin (PG)F1 alpha. 2 Amiloride and phenamil (potent inhibitors of epithelial Na+ transport) had no significant effect on basal or Ca2+-stimulated PGI2 synthesis. 3 Several analogues previously reported to inhibit Na+/Ca2+ exchange caused a dose-related increase in 6-oxo-PGF1 alpha production in media containing NaCl 120 mM and CaCl2 2.5 mM. 2',3'-Benzobenzamil was the most potent analogue with a maximum stimulation of 4.51 +/- 0.89 fold, and an EC50 of 3 x 10(-5) M. 4 Amiloride analogues bearing substituents on the 5-amino group of the pyrazine ring have been reported to inhibit Na+/H+ exchange more potently than Na+/Ca2+ exchange. Three of these compounds inhibited Ca2+-stimulated 6-oxo-PGF1 alpha production at concentrations that did not significantly influence basal 6-oxo-PGF1 alpha production.

6-Ketoprostaglandin F1 alpha↗

PubMed1988

Effects of non-sedative anxiolytic drugs on responses to GABA and on diazepam-induced enhancement of these responses on mouse neurones in cell culture.

1. Intracellular microelectrode recording techniques were performed on mouse spinal cord and cerebral hemisphere neurones grown in primary dissociated cell culture. The effects of several anxiolytics applied by local pressure ejection on responses to gamma-aminobutyric acid (GABA) evoked by iontophoresis were investigated. Responses to GABA were depolarizing since intracellular chloride ion concentration was increased by injection from potassium chloride (3M)-filled recording micropipettes and neurones were held at large negative membrane potentials (-70 to -90 mV). The agents studied were six 'non-sedative anxiolytics', CL 218,872 (3-methyl-6-(3-trifluoromethyl-phenyl)1,2,4-triazolo(4,3-b) pyridazine), PK 8165 (2-phenyl-4-(2-(4-piperidinyl)ethyl)-quinoline), PK 9084 (2-phenyl-4-(2-(3-piperidinyl)ethyl)-quinoline), CGS 9896 (2-(4-chlorophenyl)-2,5-dihydropyrazolo(4,3-c)quinoline-3(3H)-one) , ZK 91296 (ethyl 5-benzyloxy-4-methoxymethyl-beta-carboline-3-beta-carboxylate), buspirone (8-4-[4-(2-pyrimidinyl)-1-piperazinyl]butyl-8-azaspiro[4.5]decane- 7,9- dione), and two sedative anxiolytics, diazepam and zopiclone [( 6-(5-chloro-2-pyridyl)-6,7-dihydro-7-oxo-5H-pyrrolo[3,4-b]pyrazin- 5- yl]4-methyl-1-piperazinecarboxylate). 2. Direct effects on responses to GABA were studied for all drugs applied in varying concentrations. For the drugs which significantly altered responses to GABA, the effects of the benzodiazepine receptor antagonists Ro 15-1788 (ethyl-8-fluoro-5,6-dihydro-5-methyl-6-oxo-4H-imidazo(1,5a)-(1,4)benzodi azepine - 3-carboxylate) and CGS 8216 (2-phenylpyrazolo(4,3-c)-quinolin-3(5H)-one) were evaluated. For the drugs devoid of significant direct effect on responses to GABA, the influence on diazepam-induced enhancement of responses to GABA was evaluated. 3. Diazepam, zopiclone and CL 218,872 concentration-dependently and reversibly enhanced responses to GABA. Maximal enhancement was 82% for diazepam (500 nM), 64% for zopiclone (10 microM) and 20% for CL 218,872 (10 microM). PK 8165 effects varied with concentration, enhancing responses to GABA (up to 18%) at nM concentrations and reducing responses to GABA (up to 90%) at microM concentrations. CGS 9896, ZK 9126, PK 9084 and buspirone, in concentrations ranging from 1 nM to 10 microM, lacked significant direct effects on responses to GABA. 4. The enhancing effects of diazepam, zopiclone, CL 218,872 and PK 8165 were antagonized by Ro 15-1788. However, the reducing effect on responses to GABA of PK 8165 at microM concentrations was not antagonized by CGS 8216. CGS 9896 and ZK 91296 concentration-dependently blocked the diazepam-induced enhancement of responses to GABA. However, PK 9084 and buspirone did not antagonize the diazepam-induced enhancement of responses to GABA. 5. These results indicate that diazepam and zopiclone may be full agonists, CL 218,872 and PK 8165 are partial agonists, and CGS 9896 and ZK 91296 are pure antagonists at benzodiazepine receptors. On the other hand, PK 9084 and buspirone do not interact with benzodiazepine receptors.

Animals↗

PubMed1999

Update from Asia. Asian studies on cancer chemoprevention.

In Asia, nontoxic dietary products are considered desirable primary prevention vehicles for conquering cancer. As early as 1978, investigators in Korea carried out extensive long-term anticarcinogenicity experiments using the mouse lung tumor model and observed an anticarcinogenic effect of Panax ginseng C.A. Meyer extract in 1980. The results showed that natural products can provide hope for human cancer prevention. A newly established nine-week medium-term model using mouse lung tumors (Yun's model) could confirm the anticarcinogenicity of ginseng that varies according to its type and age. Subsequently, the ginseng was shown by epidemiological studies to be a nonorgan-specific cancer preventive agent associated with a dose-response relationship. The anticarcinogenic effects of vegetarian foods common at every dining table in Korea and some synthetics were also studied using Yun's nine-week model. In brief, ascorbic acid, soybean lecithin, capsaicin, biochanin A, Ganoderma lucidum, caffeine, and a novel synthetic 2-(allylthio)pyrazine decrease the incidence of mouse lung tumors, whereas fresh ginseng (4 years old), carrot, spinach, Sesamum indicum, beta-carotene, and 13-cis retinoic acid do not. This result regarding beta-carotene is consistent with the ineffective findings of the ATBC trial, the CARET trial, and the Physicians' Health Study. In 1983, a cancer chemoprevention study group was first established in Japan. Subsequently, (-)-epigallocatechin gallate, cryptoporic acid E, and sarcophytol A from natural products, and synthetic acyclic retinoid and canventol were shown to be anticarcinogenic or chemopreventive in human subjects. Despite the frequent consumption of tea wordwide as a beverage and current experimental evidence of anticarcinogenesis, including controversial results of epidemiological studies, more systematic clinical trials for confirmation of preventive activity of tea against cancer are needed. Placebo-controlled intervention trials of dietary fiber are under study in Japan. In the past decade, new triterpenoids were isolated from various natural sources, and its biological activities were investigated in Asia. In the late 1970s a comprehensive chemoprevention program was established at the Institute of Materia Medica, Chinese Academy of Medical Sciences. Since then, many retinoid compounds have been synthesized and screened in the search for chemopreventive cancer agents. The National Cancer Institute (USA) and China are jointly engaged in the two-nutrition intervention in Linxian, China. The results of joint study of the general population and of dysplasia in China should stimulate further research to clarify the potential benefits of micronutrient supplements. We need to clarify if there is a connection between the lower rates of cancer mortality in Korea and the frequent consumption of anticarcinogenic vegetables or traditional foods, including ginseng and Ganoderma lucidum. The constituents of the nontoxic stable dietary products promise to be the future hope for conquering cancers in the coming years.

Animals↗

PubMed1993

Sodium-dependent regulation of epithelial sodium channel densities in frog skin; a role for the cytoskeleton.

1. A weak electroneutral sodium channel blocker 6-chloro-3,5-diamino-pyrazine-2-carboxamide was used to perform noise analysis on isolated epithelium from Rana fuscigula to determine the cellular mechanism underlying autoregulation of Na+ channel densities in response to a reduction in the mucosal Na+ concentration. 2. The inherent transport rates of these tissues were generally lower than in other frog skins. The macroscopic sodium current, INa, averaged 10.71 microA/cm2 and was mainly determined by the number of open channels (N(o)) which averaged 21.6 million/cm2. The calculated mean channel open probability (beta') was 0.38, and corresponded very closely to values previously determined by patch clamp. 3. Reducing the mucosal Na+ from 110 to 10 mM caused large increases in the open channel density, which stabilized the Na+ transport rate. N(o) increased from a mean value of 26.6 to 64.3 million/cm2 within 2 min. 4. Autoregulatory changes were induced primarily by increasing beta' by about 60% and to a lesser extent by an increase in NT, the total number of open and closed channels. 5. We also examined the role of the cytoskeleton in the regulation of Na+ channel densities. Colchicine treatment, which disrupted microtubules, had no apparent effect on the ability of the tissues to autoregulate their Na+ channel densities. 6. The integrity of the microfilaments were essential for autoregulatory changes in N(o). After we had disrupted the microfilaments with cytochalasin B, we observed a marked reduction in the ability of the tissues to increase N(o). 7. The mean N(o) did not increase in response to a drop in mucosal Na+ despite the fact that beta' increased by 69%. We, therefore, assumed that cytochalasin B did not affect Na+ channels already present in the membrane but interfered with recruitment of new channels. Significantly, we did not observe any increase in NT. 8. In kidney and other tight epithelia, microfilaments are responsible for regulating the delivery of newly synthesized membrane proteins. We believe that our results with cytochalasin-treated tissues support the theory that autoregulatory changes in N(o) are also regulated by the recruitment of channels from a cytoplasmic pool.

Animals↗

PubMed2006

Pharmacological evidence for a functional serotonin-2B receptor in a human uterine smooth muscle cell line.

The present study investigated the serotonin-induced increase in phosphoinositide hydrolysis and mobilization of intracellular Ca2+ ([Ca2+]i) in human uterine smooth muscle cells (HUSMCs) to identify the serotonergic receptor positively coupled to phospholipase C in these cells. In phosphoinositide (PI) assays, serotonin (5-HT) and alpha-methyl-5-HT were potent, full agonists (EC50 = 20 and 4.1 nM, respectively), whereas the phenylethylamine, R-(-)-1-(4-iodo-2,5-dimethoxyphenyl)-2-aminopropane hydrochloride, was less active (EC50 = 63 nM). Proposed 5-HT2B-selective agonists, BW-723C86 [alpha-methyl-5-(2-thienylmethoxy)-1H-indole-3-ethanamine hydrochloride] and (+)-norfenfluramine, exhibited strong agonist potency and efficacy comparable with 5-HT (EC50 = 18 and 33 nM, respectively) and approximately 15-fold more potency than (-)-norfenfluramine (EC50 = 500 nM). 5-HT2C receptor agonists m-chlorophenylpiperazine and MK-212 [6-chloro-2-(1-piperaxinyl)pyrazine] were weak agonists in these cells, with potencies of 110 and 880 nM, respectively. A similar rank order of potency was observed in [Ca2+]i mobilization assays (r = 0.9, p < 0.005) in the HUSMC and with contraction of rat stomach fundus strips that contain a 5-HT2B receptor (r = 0.9, p < 0.001). Antagonist studies revealed that a 5-HT2B-selective antagonist, RS-127445 [2-amino-4-(4-fluoronaphth-1-yl)-6-isopropylpyrimidine] (Ki = 0.13 nM), was significantly more effective at inhibiting 5-HT-induced activity than a 5-HT2A antagonist, M-100907 (R-(+)-alpha-(2,3-dimethoxyphenyl)-1-[2-(4-fluorophenyl)ethyl]-4-piperidinemethanol]) (Ki= 914 nM) and the 5-HT2C antagonists RS-102221 (8-[5-(2,4-dimethoxy-5-(4-trifluoromethylsulfo-amido)phenyl-5-oxopentyl]-1,3,8-triazaspiro[4.5]decane-2,4-dione hydrochloride) (Ki = 2.5 microM) and SB-242084 (6-chloro-5-methyl-1-[6-92-methylpyridin-3-yloxy) pyridine-3-ylcarbamoyl] indoline) (Ki = 42.4 nM) in the HUSMC PI turnover assays. Taken together, these studies strongly suggest the presence of a functionally active 5-HT2B receptor subtype in HUSMCs. The physiological role of this receptor in these cells remains to be defined.

Calcium↗

PubMed2006

Pyrazinoic acid and its n-propyl ester inhibit fatty acid synthase type I in replicating tubercle bacilli.

The activity of different analogs of pyrazinamide on Mycobacterium tuberculosis fatty acid synthase type I (FASI) in replicating bacilli was studied. Palmitic acid biosynthesis was diminished by 96% in bacilli treated with n-propyl pyrazinoate, 94% in bacilli treated with 5-chloro-pyrazinamide, and 97% in bacilli treated with pyrazinoic acid, the pharmacologically active agent of pyrazinamide. We conclude that the minimal structure of pyrazine ring with an acyl group is sufficient for FASI inhibition and antimycobacterial activity.

Bacterial Proteins↗

PubMed1995

Activity of n-propyl pyrazinoate against pyrazinamide-resistant Mycobacterium tuberculosis: investigations into mechanism of action of and mechanism of resistance to pyrazinamide.

The mechanism of action of pyrazinamide (PZA) is not known. One hypothesis is that PZA functions as a prodrug of pyrazinoic acid. Susceptibility to PZA correlates with amidase activity of the Mycobacterium tuberculosis isolate in question. PZA-resistant isolates retain susceptibility in vitro to pyrazinoic acid and n-propyl pyrazinoate. Esters of pyrazinoic acid appear to circumvent the requirement for activation by mycobacterial amidase. The MICs of n-propyl pyrazinoate for M. tuberculosis isolates are lower than those of pyrazinoic acid. Further studies to assess the effects of modifications of the alcohol and pyrazine moieties of pyrazinoate esters on in vitro and in vivo antituberculosis activity are under way. This may lead to a candidate compound with enhanced activity against both PZA-susceptible and PZA-resistant M. tuberculosis isolates suitable for clinical development.

Amidohydrolases↗

PubMed1994

Photometabolism of Heterocyclic Aromatic Compounds by Rhodopseudomonas palustris OU 11.

Rhodopseudomonas palustris OU 11 (ATCC 51186; DSM 7375) isolated from a pond of chemical industry effluent could anaerobically photometabolize heterocyclic aromatic compounds belonging to the pyridine and pyrazine groups only after a period of adaptation on pyrazinoic acid of 5 to 6 weeks. Growth on heterocyclic compounds was light dependent. The effects of various concentrations of heterocyclic compounds on growth suggest that higher concentrations of these compounds inhibit growth and are toxic.

Journal Article↗

PubMed1996

Geosmin and Related Volatiles in Bioreactor-Cultured Streptomyces citreus CBS 109.60.

Streptomyces citreus CBS 109.60 produced geosmin and a complex pattern of other volatile compounds during cultivation in a 2.5-liter laboratory bioreactor. Volatiles were isolated from disrupted cells, from the culture medium, and from the waste air of the bioreactor by adsorption on Lewatit OC 1064MD. Quantitative and qualitative analyses were carried out using capillary gas chromatography and coupled gas chromatography-mass spectroscopy. S. citreus produced 56 volatile compounds, which were mainly terpenoids but also included aliphatic ketones, alcohols, esters, pyrazines, furan(on)es, and aromatic types during the growth phase. The major components were geosmin and a germacradienol. A biosynthetic pathway for geosmin including eudesmanolides is proposed.

Journal Article↗

PubMed1985

Biosynthesis of riboflavin in Bacillus subtilis: origin of the four-carbon moiety.

We studied the incorporation of [1-13C]ribose and [1,3-13C2]glycerol into the riboflavin precursor 6,7-dimethyl-8-ribityllumazine, using a riboflavin-deficient mutant of Bacillus subtilis. The formation of the pyrazine ring requires the addition of a four-carbon moiety to a pyrimidine precursor. The results show that C-6 alpha, C-6, C-7, and C-7 alpha of 6,7-dimethyl-8-ribityllumazine were biosynthetically equivalent to C-1, C-2, C-3, and C-5 of a pentose phosphate. C-4 of the pentose precursor was lost through an intramolecular skeletal rearrangement. Thus, the last steps in the biosynthesis of 6,7-dimethyl-8-ribityllumazine apparently involve the same mechanism in bacteria as in fungi.

Bacillus subtilis↗

PubMed1992

Screening tests for pathogenic corynebacteria.

AIM: To provide simple tests that would help in the identification of corynebacteria that produce diphtheria toxin. METHODS: A collection of 99 freshly isolated corynebacteria was assembled and the cultures identified by conventional tests confirmed by an identification kit. Modifications were made to procedures for preparation of the culture medium for the Elek test and to the test for detection of pyrazinamidase (pyrazine carboxylamidase) activity. These two together with an indicator medium for cystinase activity were applied to the collection of organisms. RESULTS: Cystinase was detected in all 61 members of the toxigenic species and none produced pyrazinamidase. In contrast, all but two of the 38 representatives of non-toxigenic species yielded pyrazinamidase and none formed cystinase. Of the 61 cystinase producing cultures (which were also pyrazinamidase negative), 21 gave a positive Elek test with the modified culture medium. A total of 30 of these 61 were tested for toxigenicity in guinea pigs and the results of the animal and plate tests concorded. At least seven cultures could have been reported as non-toxigenic if Elek tests based on media prepared in the conventional way had been the only test available. CONCLUSION: The three procedures described go some way towards meeting the needs of diagnostic laboratories for efficient procedures for distinguishing pathogenic corynebacteria.

Amidohydrolases↗

PubMed1989

Distinct epitopes on amiloride.

Most Na(+)-selective transport proteins are inhibited by the drug amiloride. Studies using amiloride analogues suggest that specific regions of amiloride might participate in binding to receptors on these transport proteins. To determine whether certain domains of this drug are recognized as distinct epitopes, amiloride was coupled to albumin through either its C-5 NH2-group on the pyrazine ring or through a terminal NH2-group of the guanidino moiety, and antibodies were raised against these amiloride-albumin conjugates. Studies of antibody binding to amiloride analogues identified the 3,5-diaminopyrazinyl, the guanidinocarbonyl, and the C-6 halo moieties as distinct epitopes, although the antibodies required the presence of both the 3,5-diaminopyrazinyl as well as the guanidinocarbonyl moiety for binding.

Amiloride↗

PubMed1991

Distinct epitopes on amiloride. II. Variably restricted epitopes defined by monoclonal anti-amiloride antibodies.

Specific regions of amiloride appear to participate in binding to receptors on amiloride-sensitive transport proteins. Previous studies characterizing epitopes on amiloride recognized by anti-amiloride antibodies have demonstrated that antibodies recognize specific domains on amiloride and that these epitopes are determined, in part, by the site on amiloride used to couple to carrier protein. The 3,5-diaminopyrazinyl and guanidinocarbonyl moieties were identified as distinct epitopes. Since Na(+)-selective transport proteins are sensitive to changes of the halide on the amiloride molecule, additional monoclonal anti-amiloride antibodies were raised to determine whether the C-6 halo group of amiloride could be identified as an important site for drug-antibody binding. The epitopes recognized by a series of three monoclonal antibodies raised against amiloride coupled to rabbit serum albumin through its C-5 NH2-group were defined. Two antibodies recognize extensive regions on the amiloride molecule, including both the acylguanidino and pyrazinyl groups. In addition, both antibodies are sensitive to changes in the C-6 halo group on amiloride. A third antibody was relatively insensitive to changes in the halide in the C-6 position of the pyrazine ring of amiloride and recognized a more restricted epitope on amiloride.

Amiloride↗

PubMed2006

Anticancer activity of BIM-46174, a new inhibitor of the heterotrimeric Galpha/Gbetagamma protein complex.

A large number of hormones and local agonists activating guanine-binding protein-coupled receptors (GPCR) play a major role in cancer progression. Here, we characterize the new imidazo-pyrazine derivative BIM-46174, which acts as a selective inhibitor of heterotrimeric G-protein complex. BIM-46174 prevents the heterotrimeric G-protein signaling linked to several GPCRs mediating (a) cyclic AMP generation (Galphas), (b) calcium release (Galphaq), and (c) cancer cell invasion by Wnt-2 frizzled receptors and high-affinity neurotensin receptors (Galphao/i and Galphaq). BIM-46174 inhibits the growth of a large panel of human cancer cell lines, including anticancer drug-resistant cells. Exposure of cancer cells to BIM-46174 leads to caspase-3-dependent apoptosis and poly(ADP-ribose) polymerase cleavage. National Cancer Institute COMPARE analysis for BIM-46174 supports its novel pharmacologic profile compared with 12,000 anticancer agents. The growth rate of human tumor xenografts in athymic mice is significantly reduced after administration of BIM-46174 combined with either cisplatin, farnesyltransferase inhibitor, or topoisomerase inhibitors. Our data validate the feasibility of targeting heterotrimeric G-protein functions downstream the GPCRs to improve anticancer chemotherapy.

Animals↗

PubMedDate not supplied

Kinetics of binding of [(3)H]glycine to transport proteins in channel catfish brain.

[(3)H]Glycine was observed to bind to channel catfish brain particles in a manner displaying saturation kinetics. The dissociation constant was calculated to be 7.38 +/- 2.11 microM. Though some binding occurred in the absence of Na(+) ions, the presence of such ions stimulated binding in a concentration-dependent manner. Similarly, chloride ions had a stimulatory effect on [(3)H]glycine binding. Several inhibitors of binding were identified, the most effective being beta-alanine, pipecolic acid, 2,3-pyrazine dicarboxylic acid and 3,5-pyrazole dicarboxylic acid. Each is a structural analogue of glycine. Harmaline, a known inhibitor of Na(+) binding, also inhibited glycine binding. A previous study had shown the presence of a sodium-dependent, active uptake system for glycine in synaptosomes derived from catfish brain. The present results suggest that the binding of [(3)H]glycine was to a glycine transporter and that the amino acid functions as a neurotransmitter in this species.

Amino Acid Transport Systems, Neutral↗

PubMed1993

Inhibitory effects of vasoactive intestinal peptide on superoxide anion formation by N-formyl-methionyl-leucyl-phenylalanine-activated inflammatory cells in vitro.

Effects of vasoactive intestinal peptide (VIP) on superoxide anion (O2-) formation by N-formyl-methionyl-leucyl-phenylalanine (fMLP)-activated inflammatory cells from healthy volunteers were investigated using 2-methyl-6-[p-methoxyphenyl]-3,7-dihydroimidazo [1,2-a]pyrazin-3-one (MCLA) as a chemiluminescence probe. VIP inhibited the maximal light intensity of MCLA-dependent luminescence in a dose-dependent manner by the activated peripheral blood neutrophils, mononuclear cells and also by the human monoblast cell line U937, the capacity of which for O2- formation was induced by pretreatment with interferon-gamma. 3 x 10(-6) M VIP also inhibited O2- formation by the activated peripheral blood eosinophils and alveolar macrophages obtained by bronchoalveolar lavage.

Eosinophils↗

PubMed1993

Cu-Zn superoxide dismutase activities in platelets from stable bronchial asthmatic patients.

Cu-Zn superoxide dismutase (SOD) activities in platelets from stable bronchial asthmatic patients were measured using 2-methyl-6-[p-methoxyphenyl]-3,7- dihydroimidazo[1,2-a]pyrazin-3-one as a chemiluminescence probe. Cu-Zn SOD activities in platelets from the asthmatics were significantly higher than those from normal healthy subjects. Platelet Cu-Zn SOD activities were significantly higher in atopic than in non-atopic asthmatics. There were no significant differences in platelet Cu-Zn SOD activities between aspirin-sensitive and aspirin-tolerant patients. These results suggest that an oxidant-to-antioxidant imbalance may play a role in the inflammatory situations in the airways of asthmatics.

Adult↗

PubMed1989

Protein reactions during food processing and storage--their relevance to human nutrition.

The main reactions of protein components during food processing and storage were presented and discussed. Since most data are available from the reactions of lysine with other food components these results are mainly demonstrated. Using furosine as indicator the formation and presence of the early Maillard products fructoselysine, lactuloselysine or maltuloselysine in several food systems was measured. Also lysinoalanine is mentioned. A further, recently detected compound, N-epsilon-carboxymethyllysine, appears to be also of biological and technological interest. Several foods contained up to 2,000 ppm carboxymethyllysine in the protein. Experiments with rats and human volunteers have shown that the fructoselysine moiety is poorly digested and absorbed and apparently not metabolized but soon excreted via the kidneys. While being on a normal diet the 20 volunteers excreted 3.3 +/- 1.4 mg fructoselysine per day, which indicates that our food contains always some of these products. Less is known about the absorption and excretion of lysinoalanine or carboxymethyllysine. These reactions cause undoubtedly drastic reductions in the availability of lysine and in this way also in the biological value (and in higher grades of damage additionally of the protein digestibility). Moreover some adverse effects-e.g. interference with the transport of other amino acids, increased renal losses of zinc and copper and cytomegaly in the pars recta of the outer medullary stripe of rat kidneys-were observed in connection with the products of the early or advanced Maillard reaction. These partially negative influences, however, appear not to be of significance under practical conditions. Compounds, possibly carcinogenic, are some degradation products of tryptophan and imidazoquinoline- or imidazoquinoxalin-2-amine derivatives (IQ compounds), which are formed during broiling of meat or fish by the reaction of Maillard products (pyridines or pyrazines and aldehydes) with creatinine.

Animals↗