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  1. Artikel ; Online: Single-dose pharmacokinetics, safety, and tolerability of the dual endothelin receptor antagonist aprocitentan in subjects with moderate hepatic impairment.

    Fontes, Magda S C / Dingemanse, Jasper / Halabi, Atef / Tomaszewska-Kiecana, Monika / Sidharta, Patricia N

    Scientific reports

    2022  Band 12, Heft 1, Seite(n) 19067

    Abstract: ... hepatic impairment and healthy subjects, with maximum plasma concentrations (C ...

    Abstract The effect of moderate hepatic impairment on the pharmacokinetics (PK), safety, and tolerability of the dual endothelin receptor antagonist aprocitentan was clinically investigated as 25% of aprocitentan is cleared through the liver. Aprocitentan is in clinical development for the treatment of resistant hypertension. This was an open-label, Phase 1 study. Subjects were recruited in two groups (i.e., moderate hepatic impairment (Child-Pugh B; n = 8) and matched healthy subjects (n = 9) and received a single oral dose of 25 mg aprocitentan. Thereafter, they were observed for 14 days. Due to personal reasons one healthy subject discontinued the study. The PK of aprocitentan were similar between subjects with moderate hepatic impairment and healthy subjects, with maximum plasma concentrations (C
    Mesh-Begriff(e) Humans ; Area Under Curve ; Endothelin Receptor Antagonists/adverse effects ; Liver Diseases/drug therapy ; Liver Diseases/metabolism ; Pyrimidines ; Sulfonamides
    Chemische Substanzen aprocitentan (MZI81HV01P) ; Endothelin Receptor Antagonists ; Pyrimidines ; Sulfonamides
    Sprache Englisch
    Erscheinungsdatum 2022-11-09
    Erscheinungsland England
    Dokumenttyp Clinical Trial, Phase I ; Journal Article
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/s41598-022-22470-z
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  2. Artikel ; Online: Multiple-Dose Pharmacokinetics, Safety, and Tolerability of Aprocitentan, a Dual Endothelin Receptor Antagonist, in Healthy Japanese and Caucasian Subjects.

    Fontes, Magda S C / Dingemanse, Jasper / Sidharta, Patricia N

    Clinical pharmacology in drug development

    2020  Band 10, Heft 7, Seite(n) 718–725

    Abstract: Aprocitentan is an orally active dual endothelin receptor antagonist currently in development for treatment of difficult-to-control (resistant) hypertension. In phase 1 and 2 studies, aprocitentan has been characterized predominantly in Caucasian ... ...

    Abstract Aprocitentan is an orally active dual endothelin receptor antagonist currently in development for treatment of difficult-to-control (resistant) hypertension. In phase 1 and 2 studies, aprocitentan has been characterized predominantly in Caucasian subjects. In this bridging, double-blind study, 20 healthy Japanese and Caucasian male and female subjects received 25 mg of aprocitentan or placebo once daily for 10 days and were monitored until 216 hours after the last dosing. The pharmacokinetics of aprocitentan were similar between ethnicities. At steady state, maximum plasma concentration was reached at 4 and 3 hours, and elimination half-life was 49.1 and 48.8 hours for Japanese and Caucasian subjects, respectively. The accumulation index was around 3 for both populations. Geometric means ratios for maximum plasma concentration and area under the plasma concentration-time curve during 1 dosing interval were around 1, with 90% confidence interval ranging from 0.87 to 1.30. Aprocitentan was safe and well tolerated in both groups. As no clinically relevant differences were found between Japanese and Caucasian subjects, it is unlikely that the pharmacokinetics of aprocitentan would differ significantly between Caucasian subjects and other ethnicities. Aprocitentan can therefore be administered at a dose level of up to 25 mg in any ethnicity without dose adjustment.
    Mesh-Begriff(e) Adult ; Area Under Curve ; Asians ; Double-Blind Method ; Endothelin Receptor Antagonists/administration & dosage ; Endothelin Receptor Antagonists/adverse effects ; Endothelin Receptor Antagonists/pharmacokinetics ; Female ; Half-Life ; Humans ; Male ; Pyrimidines/administration & dosage ; Pyrimidines/adverse effects ; Pyrimidines/pharmacokinetics ; Sulfonamides/administration & dosage ; Sulfonamides/adverse effects ; Sulfonamides/pharmacokinetics ; Whites ; Young Adult
    Chemische Substanzen Endothelin Receptor Antagonists ; Pyrimidines ; Sulfonamides ; aprocitentan (MZI81HV01P)
    Sprache Englisch
    Erscheinungsdatum 2020-10-15
    Erscheinungsland United States
    Dokumenttyp Clinical Trial, Phase I ; Journal Article ; Randomized Controlled Trial ; Research Support, Non-U.S. Gov't
    ZDB-ID 2649010-9
    ISSN 2160-7648 ; 2160-763X
    ISSN (online) 2160-7648
    ISSN 2160-763X
    DOI 10.1002/cpdd.881
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  3. Artikel ; Online: Single-dose pharmacokinetics, safety, and tolerability of the dual endothelin receptor antagonist aprocitentan in subjects with moderate hepatic impairment

    Magda S. C. Fontes / Jasper Dingemanse / Atef Halabi / Monika Tomaszewska-Kiecana / Patricia N. Sidharta

    Scientific Reports, Vol 12, Iss 1, Pp 1-

    2022  Band 7

    Abstract: Abstract The effect of moderate hepatic impairment on the pharmacokinetics (PK), safety, and tolerability of the dual endothelin receptor antagonist aprocitentan was clinically investigated as 25% of aprocitentan is cleared through the liver. ... ...

    Abstract Abstract The effect of moderate hepatic impairment on the pharmacokinetics (PK), safety, and tolerability of the dual endothelin receptor antagonist aprocitentan was clinically investigated as 25% of aprocitentan is cleared through the liver. Aprocitentan is in clinical development for the treatment of resistant hypertension. This was an open-label, Phase 1 study. Subjects were recruited in two groups (i.e., moderate hepatic impairment (Child–Pugh B; n = 8) and matched healthy subjects (n = 9) and received a single oral dose of 25 mg aprocitentan. Thereafter, they were observed for 14 days. Due to personal reasons one healthy subject discontinued the study. The PK of aprocitentan were similar between subjects with moderate hepatic impairment and healthy subjects, with maximum plasma concentrations (Cmax) reached at 4.0 h. There was no difference in Cmax, indicated by the geometric means ratio (90% confidence interval) of 1.03 (0.86–1.24). There was a lower apparent clearance, a similar apparent volume of distribution, a longer terminal half-life (56.4 h vs 48.3 h in healthy subjects), and an increase in area under the curve from zero to infinity of 23% in moderate hepatically impaired subjects compared to healthy subjects. There were no differences observed in plasma protein binding (range 98.7–99.0%). Aprocitentan was well tolerated, and headache was the only adverse event reported by one subject. In conclusion, there were no clinically relevant differences in PK between subjects with moderate hepatic impairment and healthy subjects. Based on these results, aprocitentan can be administered in subjects with mild and moderate hepatic impairment and dose adjustment is not required. Clinical Trial Registration ClinicalTrials.gov NCT04252495.
    Schlagwörter Medicine ; R ; Science ; Q
    Thema/Rubrik (Code) 150
    Sprache Englisch
    Erscheinungsdatum 2022-11-01T00:00:00Z
    Verlag Nature Portfolio
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  4. Artikel ; Online: Ventricular TLR4 Levels Abrogate TLR2-Mediated Adverse Cardiac Remodeling upon Pressure Overload in Mice.

    Kessler, Elise L / Wang, Jiong-Wei / Kok, Bart / Brans, Maike A / Nederlof, Angelique / van Stuijvenberg, Leonie / Huang, Chenyuan / Vink, Aryan / Arslan, Fatih / Efimov, Igor R / Lam, Carolyn S P / Vos, Marc A / de Kleijn, Dominique P V / Fontes, Magda S C / van Veen, Toon A B

    International journal of molecular sciences

    2021  Band 22, Heft 21

    Abstract: Involvement of the Toll-like receptor 4 (TLR4) in maladaptive cardiac remodeling and heart failure (HF) upon pressure overload has been studied extensively, but less is known about the role of TLR2. Interplay and redundancy of TLR4 with TLR2 have been ... ...

    Abstract Involvement of the Toll-like receptor 4 (TLR4) in maladaptive cardiac remodeling and heart failure (HF) upon pressure overload has been studied extensively, but less is known about the role of TLR2. Interplay and redundancy of TLR4 with TLR2 have been reported in other organs but were not investigated during cardiac dysfunction. We explored whether TLR2 deficiency leads to less adverse cardiac remodeling upon chronic pressure overload and whether TLR2 and TLR4 additively contribute to this. We subjected 35 male C57BL/6J mice (wildtype (WT) or TLR2 knockout (KO)) to sham or transverse aortic constriction (TAC) surgery. After 12 weeks, echocardiography and electrocardiography were performed, and hearts were extracted for molecular and histological analysis. TLR2 deficiency (
    Mesh-Begriff(e) Animals ; Blood Pressure ; Cardiomegaly/metabolism ; Cardiomegaly/pathology ; Cardiomegaly/physiopathology ; Heart Ventricles/metabolism ; Heart Ventricles/pathology ; Heart Ventricles/physiopathology ; Male ; Mice ; Mice, Knockout ; Toll-Like Receptor 2/genetics ; Toll-Like Receptor 2/metabolism ; Toll-Like Receptor 4/genetics ; Toll-Like Receptor 4/metabolism ; Ventricular Remodeling
    Chemische Substanzen Tlr2 protein, mouse ; Tlr4 protein, mouse ; Toll-Like Receptor 2 ; Toll-Like Receptor 4
    Sprache Englisch
    Erscheinungsdatum 2021-10-30
    Erscheinungsland Switzerland
    Dokumenttyp Journal Article
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms222111823
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  5. Artikel ; Online: Response to the letter from Warren et al.

    Takanari, Hiroki / Fontes, Magda S C / van der Heyden, Marcel A G / Vos, Marc A / van Veen, Toon A B

    Cardiovascular research

    2017  Band 113, Heft 14, Seite(n) 1799–1800

    Mesh-Begriff(e) Anti-Arrhythmia Agents ; Calcium-Calmodulin-Dependent Protein Kinase Type 2 ; Calmodulin ; Cell Communication ; Heart
    Chemische Substanzen Anti-Arrhythmia Agents ; Calmodulin ; Calcium-Calmodulin-Dependent Protein Kinase Type 2 (EC 2.7.11.17)
    Sprache Englisch
    Erscheinungsdatum 2017-10-16
    Erscheinungsland England
    Dokumenttyp Letter ; Comment
    ZDB-ID 80340-6
    ISSN 1755-3245 ; 0008-6363
    ISSN (online) 1755-3245
    ISSN 0008-6363
    DOI 10.1093/cvr/cvx200
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  6. Artikel ; Online: Optical ventricular cardioversion by local optogenetic targeting and LED implantation in a cardiomyopathic rat model.

    Nyns, Emile C A / Jin, Tianyi / Fontes, Magda S / van den Heuvel, Titus / Portero, Vincent / Ramsey, Catilin / Bart, Cindy I / Zeppenfeld, Katja / Schalij, Martin J / van Brakel, Thomas J / Ramkisoensing, Arti A / Zhang, Guoqi / Poelma, René H / Ördög, Balazs / de Vries, Antoine A F / Pijnappels, Daniël A

    Cardiovascular research

    2021  Band 118, Heft 10, Seite(n) 2293–2303

    Abstract: Aims: Ventricular tachyarrhythmias (VTs) are common in the pathologically remodelled heart. These arrhythmias can be lethal, necessitating acute treatment like electrical cardioversion to restore normal rhythm. Recently, it has been proposed that ... ...

    Abstract Aims: Ventricular tachyarrhythmias (VTs) are common in the pathologically remodelled heart. These arrhythmias can be lethal, necessitating acute treatment like electrical cardioversion to restore normal rhythm. Recently, it has been proposed that cardioversion may also be realized via optically controlled generation of bioelectricity by the arrhythmic heart itself through optogenetics and therefore without the need of traumatizing high-voltage shocks. However, crucial mechanistic and translational aspects of this strategy have remained largely unaddressed. Therefore, we investigated optogenetic termination of VTs (i) in the pathologically remodelled heart using an (ii) implantable multi-LED device for (iii) in vivo closed-chest, local illumination.
    Methods and results: In order to mimic a clinically relevant sequence of events, transverse aortic constriction (TAC) was applied to adult male Wistar rats before optogenetic modification. This modification took place 3 weeks later by intravenous delivery of adeno-associated virus vectors encoding red-activatable channelrhodopsin or Citrine for control experiments. At 8-10 weeks after TAC, VTs were induced ex vivo and in vivo, followed by programmed local illumination of the ventricular apex by a custom-made implanted multi-LED device. This resulted in effective and repetitive VT termination in the remodelled adult rat heart after optogenetic modification, leading to sustained restoration of sinus rhythm in the intact animal. Mechanistically, studies on the single cell and tissue level revealed collectively that, despite the cardiac remodelling, there were no significant differences in bioelectricity generation and subsequent transmembrane voltage responses between diseased and control animals, thereby providing insight into the observed robustness of optogenetic VT termination.
    Conclusion: Our results show that implant-based optical cardioversion of VTs is feasible in the pathologically remodelled heart in vivo after local optogenetic targeting because of preserved optical control over bioelectricity generation. These findings add novel mechanistic and translational insight into optical ventricular cardioversion.
    Mesh-Begriff(e) Animals ; Arrhythmias, Cardiac ; Cardiomyopathies ; Channelrhodopsins/genetics ; Electric Countershock ; Male ; Optogenetics/methods ; Rats ; Rats, Wistar ; Tachycardia, Ventricular
    Chemische Substanzen Channelrhodopsins
    Sprache Englisch
    Erscheinungsdatum 2021-09-15
    Erscheinungsland England
    Dokumenttyp Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 80340-6
    ISSN 1755-3245 ; 0008-6363
    ISSN (online) 1755-3245
    ISSN 0008-6363
    DOI 10.1093/cvr/cvab294
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  7. Artikel ; Online: Microbiologic quality of an untreated water sample analyzed by a novel DNA chip for simultaneous detection of microorganisms

    Filipa F. Vale / Kathy D. Saraiva-Pava / Magda S.C. Fontes / Helena Vieira

    Microbiology Research , Vol 3, Iss 1, Pp e11-e

    2012  Band 11

    Abstract: Consumption of contaminated drinking water heavily contributes to the burden of gastrointestinal waterborne diseases. Conventional detection methodologies present several shortcomings, such as indirect measure of indicator species, low throughput and ... ...

    Abstract Consumption of contaminated drinking water heavily contributes to the burden of gastrointestinal waterborne diseases. Conventional detection methodologies present several shortcomings, such as indirect measure of indicator species, low throughput and time consume. DNA chips have the potential to serve as surveillance systems for the simultaneous detection of pathogens overcoming these limitations. We have developed a DNA chip for simultaneous detection of multiple waterborne pathogens. Species specific DNA probes were implemented on a microarray, for microorganism detection. Present study reports the results of one untreated water sample analyzed by conventional methods and by the DNA chip. The results were concordant for the mandatory organisms (total coliforms, Escherichia coli , fecal enterococci) using both methods, reinforcing the utility and proof-ofconcept of the DNA chip. However, it is necessary a prior enrichment in a culture medium in order to obtain a positive signal using the DNA chip. The DNA chip may be a valuable distinctive tool for waterborne pathogens detection
    Schlagwörter DNA chip ; simultaneous microorganism’s detection ; water quality ; indicator bacteria ; waterborne pathogen ; Microbiology ; QR1-502 ; Science ; Q
    Thema/Rubrik (Code) 612 ; 500
    Sprache Englisch
    Erscheinungsdatum 2012-03-01T00:00:00Z
    Verlag PAGEPress Publications
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  8. Artikel ; Online: Ventricular TLR4 Levels Abrogate TLR2-Mediated Adverse Cardiac Remodeling upon Pressure Overload in Mice

    Elise L. Kessler / Jiong-Wei Wang / Bart Kok / Maike A. Brans / Angelique Nederlof / Leonie van Stuijvenberg / Chenyuan Huang / Aryan Vink / Fatih Arslan / Igor R. Efimov / Carolyn S. P. Lam / Marc A. Vos / Dominique P. V. de Kleijn / Magda S. C. Fontes / Toon A. B. van Veen

    International Journal of Molecular Sciences, Vol 22, Iss 11823, p

    2021  Band 11823

    Abstract: Involvement of the Toll-like receptor 4 (TLR4) in maladaptive cardiac remodeling and heart failure (HF) upon pressure overload has been studied extensively, but less is known about the role of TLR2. Interplay and redundancy of TLR4 with TLR2 have been ... ...

    Abstract Involvement of the Toll-like receptor 4 (TLR4) in maladaptive cardiac remodeling and heart failure (HF) upon pressure overload has been studied extensively, but less is known about the role of TLR2. Interplay and redundancy of TLR4 with TLR2 have been reported in other organs but were not investigated during cardiac dysfunction. We explored whether TLR2 deficiency leads to less adverse cardiac remodeling upon chronic pressure overload and whether TLR2 and TLR4 additively contribute to this. We subjected 35 male C57BL/6J mice (wildtype (WT) or TLR2 knockout (KO)) to sham or transverse aortic constriction (TAC) surgery. After 12 weeks, echocardiography and electrocardiography were performed, and hearts were extracted for molecular and histological analysis. TLR2 deficiency ( n = 14) was confirmed in all KO mice by PCR and resulted in less hypertrophy (heart weight to tibia length ratio (HW/TL), smaller cross-sectional cardiomyocyte area and decreased brain natriuretic peptide (BNP) mRNA expression, p < 0.05), increased contractility (QRS and QTc, p < 0.05), and less inflammation (e.g., interleukins 6 and 1β, p < 0.05) after TAC compared to WT animals ( n = 11). Even though TLR2 KO TAC animals presented with lower levels of ventricular TLR4 mRNA than WT TAC animals (13.2 ± 0.8 vs. 16.6 ± 0.7 mg/mm, p < 0.01), TLR4 mRNA expression was increased in animals with the largest ventricular mass, highest hypertrophy, and lowest ejection fraction, leading to two distinct groups of TLR2 KO TAC animals with variations in cardiac remodeling. This variation, however, was not seen in WT TAC animals even though heart weight/tibia length correlated with expression of TLR4 in these animals (r = 0.078, p = 0.005). Our data suggest that TLR2 deficiency ameliorates adverse cardiac remodeling and that ventricular TLR2 and TLR4 additively contribute to adverse cardiac remodeling during chronic pressure overload. Therefore, both TLRs may be therapeutic targets to prevent or interfere in the underlying molecular processes.
    Schlagwörter toll-like receptors ; TLR2 ; TLR4 ; heart failure ; pressure overload ; inflammation ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
    Thema/Rubrik (Code) 630
    Sprache Englisch
    Erscheinungsdatum 2021-10-01T00:00:00Z
    Verlag MDPI AG
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  9. Artikel ; Online: Leukocytic Toll-Like Receptor 2 Deficiency Preserves Cardiac Function And Reduces Fibrosis In Sustained Pressure Overload.

    Wang, Jiong-Wei / Fontes, Magda S C / Wang, Xiaoyuan / Chong, Suet Yen / Kessler, Elise L / Zhang, Ya-Nan / de Haan, Judith J / Arslan, Fatih / de Jager, Saskia C A / Timmers, Leo / van Veen, Toon A B / Lam, Carolyn S P / Kleijn, Dominique P V de

    Scientific reports

    2017  Band 7, Heft 1, Seite(n) 9193

    Abstract: An involement of Toll-like receptor 2 (TLR2) has been established in cardiac dysfunction after acute myocardial infarction; however, its role in chronic pressure overload is unclear. We sought to evaluate the role of TLR2 in cardiac hypertrophy, fibrosis ...

    Abstract An involement of Toll-like receptor 2 (TLR2) has been established in cardiac dysfunction after acute myocardial infarction; however, its role in chronic pressure overload is unclear. We sought to evaluate the role of TLR2 in cardiac hypertrophy, fibrosis and dysfunction in sustained pressure overload. We induced pressure overload via transverse aortic constriction (TAC) in TLR2
    Mesh-Begriff(e) Animals ; Biopsy ; Blood Pressure ; Cytokines/metabolism ; Disease Models, Animal ; Fibrosis ; Heart Diseases/etiology ; Heart Diseases/metabolism ; Heart Diseases/pathology ; Heart Diseases/physiopathology ; Heart Function Tests ; Immunohistochemistry ; Inflammation Mediators/metabolism ; Leukocytes/metabolism ; Male ; Mice ; Mice, Knockout ; Toll-Like Receptor 2/deficiency ; Ventricular Function, Left ; Ventricular Remodeling/genetics
    Chemische Substanzen Cytokines ; Inflammation Mediators ; Toll-Like Receptor 2
    Sprache Englisch
    Erscheinungsdatum 2017-08-23
    Erscheinungsland England
    Dokumenttyp Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/s41598-017-09451-3
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  10. Artikel ; Online: Eating quality of "Vitela Tradicional do Montado"-PGI veal and Mertolenga-PDO veal and beef.

    Monteiro, Ana C G / Gomes, Eduardo / Barreto, António S / Silva, Marina F / Fontes, Magda A / Bessa, Rui J B / Lemos, José P C

    Meat science

    2013  Band 94, Heft 1, Seite(n) 63–68

    Abstract: ... meat types were well discriminated based on pHu, a* and C* parameters by canonical ...

    Abstract Physicochemical and sensory characteristics were measured in veal and beef from the Portuguese Mertolenga breed having 3 quality labels as follows: Mertolenga-PDO beef and veal which apply to purebred animals and "Vitela Tradicional do Montado"-PGI veal which applies to crossbred animals. Measurements were made in longissimus lumborum muscle aged for 6days. The temperature 3h post-mortem (T3), cooking losses and Warner-Bratzler shear force (WBSF) reflected carcass weight (CW) differences between groups. The pigment content was influenced by age, with beef having higher values than veal. WBSF correlated negatively with intramuscular fat in Mertolenga-PDO beef, but not on veal. WBSF correlated positively with cooking losses and negatively with myofibrillar fragmentation index, tenderness, juiciness and overall acceptability. Cooking losses and juiciness were the main contributors for the tenderness differences. Vitela Tradicional do Montado-PGI and Mertolenga-PDO veal had lighter colour and were considered tender. The three meat types were well discriminated based on pHu, a* and C* parameters by canonical discriminant analysis.
    Mesh-Begriff(e) Age Factors ; Animals ; Body Weight ; Breeding ; Cattle ; Color ; Consumer Behavior ; Cooking ; Diet ; Humans ; Meat/analysis ; Meat/standards ; Muscle, Skeletal/metabolism ; Myofibrils ; Pigments, Biological/metabolism ; Stress, Mechanical ; Temperature ; Water
    Chemische Substanzen Pigments, Biological ; Water (059QF0KO0R)
    Sprache Englisch
    Erscheinungsdatum 2013-05
    Erscheinungsland England
    Dokumenttyp Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 753319-6
    ISSN 1873-4138 ; 0309-1740
    ISSN (online) 1873-4138
    ISSN 0309-1740
    DOI 10.1016/j.meatsci.2012.12.011
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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