22 research outputs found

    Early stages of fat crystallisation evaluated by low‐field NMR and small‐angle X‐ray scattering

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    Low‐field time‐domain nuclear magnetic resonance (NMR; 20 MHz) is commonly used in the studies of fats in the form of solid fat content (SFC) measurements. However, it has the disadvantage of low sensitivity to small amounts of crystalline material (0.5%), thus often incorrectly determining crystallisation induction times. From spin–lattice relaxation rate measurements (R1) during the isothermal crystallisation measurements of cocoa butter between 0.01 and 10 MHz using fast field cycling NMR, we learnt previously that the most sensitive frequency region is below 1 MHz. Thus, we focused on analysing our 10‐kHz data in detail, by observing the time dependence of R1 and comparing it with standard SFCNMR and SFC determinations from small‐angle X‐ray scattering (SFCSAXS). Although not reflecting directly the SFC, the R1 at this low frequency is very sensitive to changes in molecular aggregation and hence potentially serving as an alternative for determination of crystallisation induction times. Alongside R1, we also show that SFCSAXS is more sensitive to early stages of crystallisation, that is, standard SFCNMR determinations become more relevant when crystal growth starts to dominate the crystallisation process but fail to pick up earlier crystallisation steps. This paper thus demonstrates the potential of studying triacylglycerols at frequencies below 1 MHz for obtaining further understanding of the early crystallisation stages of fats and presents an alternative and complementary method to estimate SFC by SAXS

    Preclinical characterization of ISB 1342, a CD38 × CD3 T-cell engager for relapsed/refractory multiple myeloma

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    Although treatment of multiple myeloma (MM) with daratumumab significantly extends the patient's lifespan, resistance to therapy is inevitable. ISB 1342 was designed to target MM cells from patients with relapsed/refractory MM (r/r MM) displaying lower sensitivity to daratumumab. ISB 1342 is a bispecific antibody with a high-affinity Fab binding to CD38 on tumor cells on a different epitope than daratumumab and a detuned scFv domain affinity binding to CD3ε on T cells, to mitigate the risk of life-threatening cytokine release syndrome, using the Bispecific Engagement by Antibodies based on the TCR (BEAT) platform. In vitro, ISB 1342 efficiently killed cell lines with different levels of CD38, including those with a lower sensitivity to daratumumab. In a killing assay where multiple modes of action were enabled, ISB 1342 showed higher cytotoxicity toward MM cells compared with daratumumab. This activity was retained when used in sequential or concomitant combinations with daratumumab. The efficacy of ISB 1342 was maintained in daratumumab-treated bone marrow patient samples showing lower sensitivity to daratumumab. ISB 1342 induced complete tumor control in 2 therapeutic mouse models, unlike daratumumab. Finally, in cynomolgus monkeys, ISB 1342 displayed an acceptable toxicology profile. These data suggest that ISB 1342 may be an option in patients with r/r MM refractory to prior anti-CD38 bivalent monoclonal antibody therapies. It is currently being developed in a phase 1 clinical study

    Organisation structurale et moléculaire des lipides dans les aliments : impacts possibles sur leur digestion et leur assimilation par l’Homme

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    Étude de la cristallisation des lipides : Approche multi-échelle par la relaxation et la diffusion par RMN

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    The physical characteristics of the triacylglycerol (TAG) crystal networks, defined by the Solid Fat Content and the crystal structure, are determining for the mechanical and sensory properties of food containing a significant amount of fat. Low-Field NMR is presently used to determine the SFC of fats, but it does not provide information on the structure. The aim of the thesis was to develop and evaluate NMR methodologies based on the measurements of the relaxation and diffusion properties to characterize fat structure at different levels (SFC, size and shape of the crystals). The first study on pure TAG showed the possibility to distinguish the a and b polymorphic forms by the measurements of T1 and M2, independently of temperature and chain length. Different studies during which crystal thickness changed showed that T1 was sensitive to this parameter. The study of a model mixture proved that M2 was only sensitive to polymorphism, and a method for quantification of polymorphism was proposed. The study of the fat liquid phase by relaxation and diffusion provided information on the organization of the fat crystal network. NMR thus proved to be a discerning technique for the characterization of fat. It is possible to determine the SFC, but also to obtain information on polymorphism, crystal size and the organization of the TAG crystal network.Les caractéristiques physiques des réseaux formés par les cristaux de triacylglycérols (TAG), définies par le taux de solide et la structure des cristaux, sont déterminantes pour les propriétés mécaniques et sensorielles des produits alimentaires contenant une quantité significative de matière grasse. La RMN bas champ est actuellement utilisée pour déterminer le taux de solide des matières grasses, mais elle n'apporte pas pour le moment d'information structurale. L'objectif de la thèse était de développer et d'évaluer des méthodologies RMN basées sur la mesure des propriétés de relaxation et de diffusion pour caractériser la structure des TAG à différents niveaux (taux de solide, nature des cristaux, taille, forme). Une première étude sur les produits purs a permis de distinguer les formes polymorphiques a et b par la mesure du T1 et la mesure du M2, et ceci indépendamment de la température et de la longueur de chaine. Différentes études durant lesquelles l'épaisseur des cristaux variait ont permis de montrer que le T1 était sensible à ce paramètre. L'étude d'un mélange modèle a permis de prouver que le M2 était uniquement sensible au polymorphisme, et une méthode de quantification du polymorphisme a été proposée. L'étude de la phase liquide de la matière grasse par relaxation et diffusion a permis d'obtenir des informations sur la topologie du réseau de cristaux des TAG. Ainsi, la RMN s'avère être une technique pertinente pour la caractérisation de la matière grasse. En plus de la mesure du taux de solide, il est également possible d'obtenir des informations sur le polymorphisme, la taille des cristaux et l'organisation des assemblages de TAG dans le réseau de cristaux

    Étude de la cristallisation des lipides (approche multi-échelle par la relaxation et la diffusion par RMN)

    No full text
    Les caractéristiques physiques des réseaux formés par les cristaux de triacylglycérols (TAG), définies par le taux de solide et la structure des cristaux, sont déterminantes pour les propriétés mécaniques et sensorielles des produits alimentaires contenant une quantité significative de matière grasse. La RMN bas champ est actuellement utilisée pour déterminer le taux de solide des matières grasses, mais elle n'apporte pas pour le moment d'information structurale. L'objectif de la thèse était de développer et d'évaluer des méthodologies RMN pour caractériser la structure des TAG. Les paramètres RMN se sont révélés sensibles au polymorphisme (M2) et à l épaisseur des cristaux (T1). L étude de la phase liquide de la matière grasse par relaxation et diffusion a permis d obtenir des informations sur la topologie du réseau de cristaux des TAG. Ainsi, la RMN s est avérée être une technique pertinente pour la caractérisation de la matière grasse puisqu il est possible d obtenir des informations sur le polymorphisme, la taille des cristaux et l organisation des assemblages de TAG dans le réseau de cristaux.The physical characteristics of the triacylglycerol (TAG) crystal networks, defined by the Solid Fat Content and the crystal structure, are determining for the mechanical and sensory properties of food containing a significant amount of fat. Low-Field NMR is presently used to determine the SFC of fats, but it does not provide information on the structure. The aim of the thesis was to develop and evaluate NMR methodologies based on the measurements of the relaxation and diffusion properties to characterize fat structure at different levels. NMR parameters were sensitive to polymorphism (M2) and crystal size (T1). The study of the fat liquid phase by relaxation and diffusion provided information on the organization of the fat crystal network. NMR thus proved to be a discerning technique for the characterization of fat. It is possible to determine the SFC, but also to obtain information on polymorphism, crystal size and the organization of the TAG crystal network.RENNES1-BU Sciences Philo (352382102) / SudocSudocFranceF

    Influence of polymorphism on the solid fat content determined by FID deconvolution

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    One of the most important quality parameters of a fat, is its solid fat content (SFC). The standard method to determine the SFC is pNMR using a f-factor. This factor is determined with three standards. However, this contribution shows that SFC standards are not required when using deconvolution methods. At first, data acquisition is optimized. These experiments revealed that the deconvolution method worked better, if more sample is present in the detection zone of the NMR, due to a higher signal-to-noise ratio (SNR). Regarding deconvolution, a bi-Gaussian model and a model combining a Gaussian and Abragamian function are compared. Both models are able to fit the free induction decay (FID) data. Furthermore, the corresponding SFC values are comparable with the SFC values of the f-factor method when analyzing SFC standards or fats which are preprocessed using the AOCS tempering protocol. Upon evaluating the influence of the polymorphic states of cocoa butter, it became clear that the f-factor standards resemble fats containing -polymorphs. As a further consequence, the f-factor method fails when -polymorphs are present to a large extent. Overall this study shows that the deconvolution method is superior to the f-factor method since it does not require any standards and is less affected by the polymorphic state.Practical Applications: This work shows that the solid fat content (SFC) of a fat can be calculated without the use of calibration standards. If deconvolution would replace the standard used pNMR method, it could potentially reduce the preparation time for the measurements, because no calibration is necessary. Next to this, it also lowers the cost of SFC determination, because no standards should be bought. Deconvolution also gives insight in the behavior of the different components present in the sample, for example, T-2-values. There above, research toward deconvolution of pNMR signals is necessary as it could potentially also determine the presence of different fat crystal polymorphs present in samples. One of the most important quality parameters of a fat, is its solid fat content (SFC). The standard method to determine the SFC is pNMR using a f-factor. However, this contribution shows that SFC standards are not requires when using deconvolution methods. At first, data acquisition is optimized. These experiments revealed that the deconvolution method worked better, if more sample is present in the detection zone of the NMR, due to a higher signal-to-noise ratio (SNR). Regarding deconvolution, a bi-Gaussian model and a model combining a Gaussian and Abragamian function are compared. Both models are able to fit the free induction decay (FID) data
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