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A Mortensen

Publications and source records attributed to A Mortensen.

At least 37 records · Page 2Linked to original sources
PubMed1997

Comparative mechanisms and rates of free radical scavenging by carotenoid antioxidants.

The comparative mechanisms and relative rates of nitrogen dioxide (NO2.), thiyl (RS.) and sulphonyl (RSO2.) radical scavenging by the carotenoid antioxidants lycopene, lutein, zeaxanthin, astaxanthin and canthaxanthin have been determined by pulse radiolysis. All the carotenoids under study react with the NO2. radical via electron transfer to generate the carotenoid radical cation (Car.+). In marked contrast the glutathione and 2-mercaptoethanol thiyl radicals react via a radical addition process to generate carotenoid-thiyl radical adducts [RS-Car].. The RSO2. radical undergoes both radical addition, [RSO2-Car]. and electron abstraction, Car.+. Both carotenoid adduct radicals and radical cations decay bimolecularly. Absolute rate constants for radical scavenging were in the order of approximately 10(7)-10(9) M(-1) s(-1) and follow the sequence HO(CH2)2S. > RSO2. > GS. > NO2.. Although there were some discernible trends in carotenoid reactivity for individual radicals, rate constants varied by no greater than a factor of 2.5. The mechanism and rate of scavenging is strongly dependent on the nature of the oxidising radical species but much less dependent on the carotenoid structure.

Antioxidants↗
PubMed1997

Relative stability of carotenoid radical cations and homologue tocopheroxyl radicals. A real time kinetic study of antioxidant hierarchy.

Real time detection following laser flash photolysis of transient carotenoid radical cations and tocopheroxyl radicals formed in chloroform and bleaching of the carotenoids has allowed interaction between carotenoids and tocopherols to be studied. It is found that alpha-, beta-, and gamma-tocopherol reduce all the carotenoid radical cations investigated whereas the delta-tocopheroxyl radical can be reduced by lycopene and beta-carotene. Astaxanthin, canthaxanthin, and beta-apo-8'-carotenal radical cations are scavenged rapidly by all four tocopherol homologues whereas the other carotenoid radical cations react much more slowly with the tocopherols. The results allow the antioxidant hierarchy to be established: alpha-tocopherol > lycopene approximately beta-tocopherol approximately gamma-tocopherol > beta-carotene > zeaxanthin approximately delta-tocopherol > lutein > echinenone >> canthaxanthin approximately beta-apo-8'-carotenal > astaxanthin.

Carotenoids↗
PubMed1997

Lymphoma induction by heterocyclic amines in E mu-pim-1 transgenic mice.

The usefulness of transgenic E mu-pim-1 mice bearing in their genome the pim-1 oncogene supplemented with an upstream immunoglobulin enhancer and a downstream murine leukaemia virus long terminal repeat, as sensitive test organisms was studied in two short-term carcinogenicity studies. The mice were fed standard diet Altromin 1314 supplemented either with 0.03% 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) for 7 months or with 0.03% 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) for 6 months. PhIP and IQ are heterocyclic amines formed during cooking of meat and fish and are mutagenic to bacteria and cultured mammalian cells. PhIP is a potent mouse lymphomagen, while IQ is a liver, lung and forestomach carcinogen in mice. We found that transgenic E mu-pim-1 mice are highly susceptible to PhIP induced lymphomagenesis but do not respond to IQ treatment. PhIP feeding of E mu-pim-1 mice not only increased the total number of T-cell lymphomas but also decreased the latency time compared to either transgenic or wild-type controls. The effect was most pronounced in the treated female E mu-pim-1 mice, which showed a higher incidence of PhIP induced T-cell lymphomas than transgenic males and a strongly reduced latency period after PhIP treatment compared to non-transgenic mice. Our results suggest that the transgenic E mu-pim-1 mouse may be a useful model for short-term carcinogenicity screening of potential genotoxic carcinogens having the lymphoid system as target tissue. Carcinogens that do not target this tissue, like IQ, however will not be recognised.

Animals↗
PubMed1997

Role of endothelium and nitric oxide in histamine-induced responses in human cranial arteries and detection of mRNA encoding H1- and H2-receptors by RT-PCR.

1. Histamine induces relaxation of human cranial arteries. Studies have revealed that the relaxant histamine H1-receptor predominates in human cerebral and the H2-receptor in temporal arteries, while H1- and H2-receptors are of equal importance in the middle meningeal artery. The purpose of the present study was to examine the role of the endothelium and nitric oxide in histamine-induced responses and to show the presence of mRNA encoding H1- and H2-receptors in human cranial arteries. 2. Electrophoresis of polymerase chain reaction (PCR) products from human cerebral, middle meningeal and temporal arteries, demonstrated products corresponding to mRNA encoding both H1- and H2-receptors in arteries with and without endothelium. The amplified PCR products were sequenced and showed 100% homology with the published sequences of these histamine receptors. 3. A sensitive in vitro system was used to study vasomotor responses to histamine. In precontracted cerebral, middle meningeal and temporal arteries with and without endothelium, histamine caused a concentration-dependent relaxation with Imax values between 87% and 81% and pIC50 values between 8.14 and 7.15. In arteries without endothelium the histamine-induced relaxation was significantly less potent (Imax values between 87% and 66% and pIC50 values between 7.01 and 6.67) than in cranial arteries with an intact endothelium. 4. This addition of histamine to arteries without endothelium and pretreated with the histamine H2-antagonist, cimetidine (10(-5) M), caused a concentration-dependent contraction of the cranial arteries with Emax values between 86% and 29% and pEC50 values between 7.53 and 6.77. This contraction was blocked by the histamine H1-receptor antagonist, mepyramine (10(-7) M), and even turned into a relaxation with Imax values between 84% and 14% and pIC50 values between 7.42 and 5.86. 5. The nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME, 3 x 10(-5) M) significantly inhibited the relaxant response to histamine in cerebral and temporal arteries (pIC50 values between 7.43 and 7.13). The combined treatment with L-NAME (3 x 10(-5) M) and cimetidine (10(-5) M) caused a further displacement of the concentration-response curve (pIC50 values between 7.14 and 6.57) and decreased the maximum relaxant responses in all three cranial arteries (Imax values between 62% and 39%). 6. In conclusion, this is the first study which show mRNA encoding histamine H1- and H2-receptors in human cranial arteries. The results indicate that histamine-induced relaxation of human cranial arteries is partially mediated via an endothelial H1-receptor coupled to the production of nitric oxide and partially via a H2-receptor associated with the smooth muscle cells. In addition, there is evidence for a contractile H1-receptor in the smooth muscle cells in these arteries.

Cerebral Arteries↗
PubMed1997

Short-term carcinogenicity testing of a potent murine intestinal mutagen, 2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine (PhIP), in Apc1638N transgenic mice.

Transgenic Apc1638N mice, heterozygous for a targeted frameshift mutation at codon 1638 of the endogenous adenomatous polyposis coli (APC) gene, are predisposed to develop multiple adenomas and adenocarcinomas along the intestinal tract and to a number of extra-intestinal lesions including, among others, mammary tumors. We have studied these mice in a short-term carcinogenicity test with 2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine (PhIP), a potent murine small intestinal mutagen and lymphomagen. Upon dietary administration of 0.03% PhIP in a short-term (6 months) study, a significantly increased number of small intestinal tumors as well as an increased number of aberrant crypt foci (ACF) were observed in male Apc+/Apc1638N mice compared with untreated transgenic mice. No differences in intestinal and mammary tumor multiplicity were observed between treated and control Apc+/Apc1638N females.

Animals↗
PubMed1997

Free radical transients in photobleaching of xanthophylls and carotenes.

Carotenoids in chloroform and carbon tetrachloride photobleach upon nanosecond laser flash photolysis in two steps: instantaneously and in a second-order reaction. The rate constant for second-order reaction (first-order in a solvent derived radical and first-order in (excess) carotenoid) is largest for carotenes (9.8.10(8) M-1 for beta-carotene), intermediate for hydroxylated carotenoids, and smallest for carbonyl containing carotenoids (1.0.10(8) M-1 S-1 for astaxanthin) in chloroform at 20 degrees C. Near infrared absorbing transients are formed concomitant with photobleaching in chloroform (not detected in carbon tetrachloride). A species formed instantaneously is tentatively identified as either a carotenoid/solvent adduct or an ion-pair. A second species is formed by decay of instantaneously formed species and is identified as the carotenoid radical action. This species is formed in a first-order reaction with a rate constant of approx. 5.10(4) S-1 and absorbing at longer wavelength than the precursor. The lifetime (second-order decay) of the intermediates appears to be longest for the carotenoids with the longest conjugated system. The results indicate that carotenes are better antioxidants than xanthophylls as the carotenes, at least in the present lipophilic solvents, react faster with free radicals.

Carbon Tetrachloride↗
PubMed1997

Real time detection of reactions between radicals of lycopene and tocopherol homologues.

Laser flash photolysis of lycopene in homogeneous chloroform solution together with tocopherol homologues results in rapid formation of the lycopene radical cation and slower formation of tocopheroxyl radicals. Time-resolved detection by absorption spectroscopy of decay of the lycopene radical cation, of formation of the tocopheroxyl radicals, and of bleaching of lycopene has shown that alpha-tocopherol is able to reduce the lycopene radical cation and thereby partially regenerate lycopene on a ms timescale. In contrast, lycopene is able to reduce the delta-tocopheroxyl radical, whereas an equilibrium exists between the lycopene radical cation and beta- or gamma-tocopherol. The relative stability of these antioxidant radicals is hence: alpha-tocopheroxyl > lycopene radical cation approximately beta-tocopheroxyl approximately gamma-tocopheroxyl > delta-tocopheroxyl.

Carotenoids↗
PubMed1996

Calcitonin gene-related peptide is released from capsaicin-sensitive nerve fibres and induces vasodilatation of human cerebral arteries concomitant with activation of adenylyl cyclase.

The vasomotor effects of calcitonin gene-related peptide (CGRP) analogues have been studied in circular segments of fresh human cerebral arteries obtained at neurosurgical operations using a sensitive in vitro system. Human alpha-CGRP, human beta-CGRP, rat alpha-CGRP and rat beta-CGRP induced strong and potent relaxation of precontracted circular vessel segments. The Imax (maximum relaxant effect) to human calcitonin was low and the pD2 (concentration for half maximum effect) 7.7 was much lower than that of CGRP. The CGRP-1, antagonist human alpha-CGRP8-37 blocked the response to human alpha-CGRP but not to human beta-CGRP, while the putative antagonist [Tyr]CGRP28-37 did not. Capsaicin (10(-15)-10(-8)M) caused relaxation of the cerebral arteries by 22% of precontraction. Pre-treatment with 10(-6)M human alpha-CGRP8-37 inhibited this relaxation. Human alpha-CGRP increased the cyclic AMP content of human cerebral arteries in a concentration-dependent manner. This increase in adenylyl cyclase activity was blocked by human alpha-CGRP8-37. The results suggest that CGRP-1 receptors coupled to adenylyl cyclase are present in human cerebral arteries.

1-Methyl-3-isobutylxanthine↗
PubMed1996

Short-term carcinogenicity testing of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) and 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) in E(mu)-pim-1 transgenic mice.

The usefulness of transgenic E(mu)-pim-1 mice over-expressing the pim-1 oncogene in lymphoid tissues, as sensitive test organisms was studied in a short-term carcinogenicity study. The mice were fed standard diet Altromin 1314 supplemented either with 0.03% 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) for 7 months or with 0.03% 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) for 6 months. PhIP and IQ are heterocyclic amines formed during cooking of meat and fish and are mutagenic to bacteria and cultured mammalian cells. PhIP is a potent mouse lymphomagen, while IQ is a liver carcinogen and also causes lung tumors and tumors of the forestomach in mice. We found that transgenic E(mu)-pim-1 mice are highly susceptible to PhIP induced lymphomagenesis but do not respond to the IQ treatment. PhIP feeding of E(mu)-pim-1 mice not only increased the total number of T-cell lymphomas but also decreased the latency time compared to either transgenic or wild-type controls. The effect was most pronounced in the treated female E(mu)-pim-1 mice, which showed a higher incidence of PhIP induced T-cell lymphomas than transgenic males and a strongly reduced latency period after PhIP treatment compared to non-transgenic mice. Our results suggest that the transgenic E(mu)-pim-1 mouse may be a useful model for short-term carcinogenicity screening of potential genotoxic carcinogens having the lymphoid system as target tissue. The carcinogen IQ which does not have the lymphoid system as a target was not recognized in this model.

Animals↗
PubMed1996

Modulation of cytokine expression by CD4+ T cells during coxsackievirus B3 infections of BALB/c mice initiated by cells expressing the gamma delta + T-cell receptor.

Two variants of coxsackievirus B3 have been used to investigate the pathogenesis of myocarditis in BALB/c mice. H3 virus induces moderate myocarditis and H310A1 virus induces minimal myocarditis, although both viruses infect and replicate in the heart. Cells expressing the gamma delta+ T-cell receptor composed 5 to 13% of the lymphocytes infiltrating the hearts of H3 virus-infected mice and belonged to either the CD4- CD8+ gamma delta+- or CD4- CD8- gamma delta+-cell population. Giving 5,000 gamma delta+ cells isolated from the hearts of H3 virus-infected mice to H310A1 virus-infected recipients restored myocarditis susceptibility in the recipient animals and shifted the pattern of cytokine production in the virus-immune CD4+-cell population from being predominantly interleukin-4 producing to being predominantly gamma interferon producing in the H310A1 virus-infected mice. Apoptosis was evident in the infiltrating lymphocyte population in the myocardia of H3 virus-infected mice by the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling assay and in splenic lymphocytes by DNA fragmentation in agarose gel electrophoresis and was confined to the CD4+ population. No apoptosis was observed in H310A1 virus-infected mice, but apoptosis was induced subsequent to gamma delta +-T-cell transfer. These results are consistent with the hypothesis that gamma delta+ T cells may help modulate cytokine responses during virus infections in vivo and that apoptosis might be involved in this modulation.

Animals↗
PubMed1996

Reproductive performance and changes in blood lipids in breeding females and in growing Watanabe heritable hyperlipidaemic and New Zealand White rabbits.

The aim of the study was to compare the reproductive performance of homozygous and heterozygous WHHL and NZW females, to record the changes in blood lipids due to gestation and lactation in the heterozygous WHHL and NZW females, and to investigate the changes in blood lipids from 4 to 11 weeks of age in homozygous and heterozygous WHHL and NZW rabbits. The conception rate of homozygous WHHL females was 14% lower than that of NZW and heterozygous WHHL females. The litter size and the weaning rate of homozygous WHHL females were significantly lower than in NZW and heterozygous WHHL females. In heterozygous WHHL and NZW females the total cholesterol was lower during the gestation and lactation while the triglycerides were higher during the gestation and were the lowest during lactation when compared to the levels at mating. In growing homozygous WHHLs of both sexes the total cholesterol did not change from 4 to 11 weeks of age. The triglycerides remained unchanged in males but decreased in females at 11 weeks of age. At this age the triglycerides were significantly lower in females than in males. In growing heterozygous WHHLs of both sexes the total cholesterol and triglycerides decreased with age. At 11 weeks of age the blood lipids were significantly higher in females than in males. The triglyceride levels in homozygous and heterozygous WHHL males and females were comparable at 4 and 6 weeks of age but significantly lower in heterozygous WHHLs at 11 weeks of age. In growing NZW rabbits of both sexes the blood lipids decreased significantly with age but no sex difference was recorded. The blood lipids in the heterozygous WHHLs of both sexes were higher than in NZWs during weaning. At 11 weeks of age the blood lipids of the males and triglycerides of the females of both strains were comparable. Only the total cholesterol remained higher in heterozygous WHHL females. The decrease with age in blood lipids in growing rabbits should be kept in mind when designing experiments beginning in animals younger than 3 months of age.

Aging↗
PubMed1996

Kinetics of photobleaching of beta-carotene in chloroform and formation of transient carotenoid species absorbing in the near infrared.

Upon laser flash photolysis of beta-carotene in chloroform instantaneous bleaching of beta-carotene and concomitant formation of near infrared absorbing species are observed. One species, absorbing with maximum at 920 nm, is formed during the laser pulse (10 ns) and is practically gone in one millisecond, the decay showing a bi-exponential behaviour. The second species, absorbing with maximum at 1000 nm, is formed from the species absorbing at 920 nm by first order kinetics with a rate constant of 4.9.10(4) s-1 at 20 degrees C. This second species decays by second order kinetics and is gone within a few milliseconds. An additional slow bleaching of beta-carotene and formation of the species absorbing at 920 nm is observed. This slow bleaching/formation of transient absorption is probably due to processes involving free radicals generated during the instantaneous bleaching. The species absorbing at 920 nm is suggested to be either (i) a free radical adduct formed from beta-carotene and chloroform or (ii) beta-carotene after abstraction of a hydrogen atom. The species absorbing at 1000 nm is most likely the radical cation. Formation and decay of the near infrared absorbing species and bleaching of beta-carotene are independent of whether oxygen is present or absent in the solutions.

Carotenoids↗
PubMed1996

Kinetics of parallel electron transfer from beta-carotene to phenoxyl radical and adduct formation between phenoxyl radical and beta-carotene.

Phenoxyl radicals generated by laser flash photolysis were found to react with beta-carotene with concomitant beta-carotene bleaching in two parallel reactions with similar rates: (i) formation of a beta-carotene adduct with a (pseudo) first order rate constant of 1-1.5 x 10(4) s-1 with absorption maximum around 800 nm, and (ii) formation of a beta-carotene radical cation with a (pseudo) first order rate constant of 2-3 x 10(4) s-1 with absorption maximum around 920 nm. Both beta-carotene radicals decay on a similar time scale and have virtually disappeared after 100 ms, the beta-carotene adduct by a second order process. Oxygen had no effect on beta-carotene bleaching or radical formation and decay. The reduction of phenoxyl radicals by beta-carotene may prove important for an understanding of how beta-carotene acts as an antioxidant.

Electron Transport↗
PubMed1995

(-)-anipamil retards atherosclerosis in Watanabe heritable hyperlipidemic rabbits.

Calcium antagonists have been reported to limit atherosclerosis in cholesterol fed rabbits. The purpose of this study was to examine the effect of the calcium antagonist (-)-anipamil on the spontaneous development of atherosclerosis in homozygote WHHL rabbits. From the age of 7 weeks, three groups of rabbits received 0 (control, n = 11), 1 mg/kg body weight (n = 11), or 10 mg/kg body weight (n = 12) of (-)-anipamil for 17 weeks. Serum cholesterol at start of the investigation was 18.8 +/- 1.2 (mean +/- SEM), 20.5 +/- 1.8, and 19.5 +/- 0.8 mM, respectively, in the three groups. No significant differences were found in serum lipids (i.e., VLDL, IDL, LDL, HDL) in the study period among the three groups. Plasma anipamil at the end of the study was 0.23 +/- 6, and 202 +/- 19 ng/ml, respectively, in the three treatment groups. The degree of atherosclerosis in the abdominal aorta was significantly lower (p < 0.02) in the 10 mg/kg body weight (-)-anipamil group compared with the two other groups. No significant difference was found in the thoracic aorta. It is concluded that (-)-anipamil retards development of atherosclerosis in the abdominal aorta in WHHL rabbits.

Animals↗
PubMed1994

Atherosclerosis in Watanabe heritable hyperlipidaemic rabbits. Evaluation by macroscopic, microscopic and biochemical methods and comparison of atherosclerosis variables.

The spontaneous development of atherosclerotic disease in 38 homozygous and 34 heterozygous Watanabe heritable hyperlipidaemic rabbits was evaluated by qualitative and quantitative light microscopy in aorta, coronary, pulmonary and renal arteries, by naked eye and macroscopic morphometric estimation of aortic atherosclerosis extent and by biochemical analysis of aortic cholesterol content. No noteworthy atherosclerosis was demonstrated within 19 months in heterozygous rabbits. In homozygous rabbits, atherosclerotic lesions were seen from the age of 4 months and progressed with age. All 19-month-old rabbits had severe atherosclerotic disease. As much as 64% of the variation in atherosclerosis extent/severity could be explained by serum cholesterol and age. A highly significant correlation between the various methods for quantitation of atherosclerosis extent and/or severity was demonstrated, suggesting that quantitative microscopy, macroscopic morphometry and determination of aortic cholesterol content may be equally valid as a measure of atherosclerosis in WHHL rabbits and are therefore interchangeable.

Animals↗
PubMed1993

Evidence for enhanced expression of c-fos, c-jun, and the Ca(2+)-activated neutral protease in rat liver following carbon tetrachloride administration.

The effects of CCl4 on hepatic c-fos and c-jun gene expression were examined, and the correspondence between intermediate-early gene expression and the expression of the Ca(2+)-activated neutral proteinase (mu and mCANP) characterized. Administration of CCl4 to rats resulted in a pronounced dose- and time-dependent increase in c-jun and c-fos mRNA levels (approximately 8 to 17-fold) as detected by either Northern blot or RT-PCR analyses. The expression of mu and mCANP following CCl4 treatment was monitored by Northern blot analysis and mu and mCANP mRNA levels were found to be elevated approximately 5- to 15-fold over the time period of 18 to 24 h. Experiments were performed to determine whether the Fos-Jun heterodimeric AP-1 transcription factor complex bound the AP-1-like binding motif present in the mCANP gene. Gel retardation assays using hepatic nuclear extracts from CCl4-treated animals revealed binding of a protein to the AP-1-like motif present in the mCANP gene and competition and supershift assays confirmed the specificity of AP-1 transcription factor binding. These results show that CANP gene expression is enhanced in response to oxidative cellular damage and that the AP-1 complex may be involved in the regulation of CANP gene expression.

Animals↗