Heparin and the solubilization of asymmetric acetylcholinesterase

AbstractHeparin solubilizes asymmetric acetylcholinesterase, from chick skeletal muscle and retina, as a 24 S complex which is quantitatively converted to conventional asymmetric molecular forms of the enzyme (A12 and A8, either class I or class II) upon exposure to high salt. The simultaneous presence of salt and heparin in the homogenization medium selectively prevents, however, the release of class II A-forms in both muscle and retina. Heparin may generally act by displacing native proteoglycans involved in the attachment of the enzyme tail to the extracellular matrix, or its neural equivalent, being in turn removed by salt to yield typical asymmetric enzyme forms. Heparin would also appear to displace some other molecules specifically involved in the EDTA-sensitive attachment of class II tailed forms, this effect being antagonized by salt

Probabilistic methods for drug dissolution. Part 2. Modelling a soluble binary drug delivery system dissolving in vitro.

The objective of this work is to use direct Monte Carlo techniques in simulating drug delivery from compacts of complex composition, taking into consideration the special features of the in vitro dissolution environment. The paper focuses on simulating a binary system, consisting of poorly soluble drug, dispersed in a matrix of highly soluble acid excipient. At dissolution, the acid excipient develops certain mechanisms, based on local pH modifications of the medium, which strongly influence drug release. Our model directly accounts for such effects as local interactions of the dissolving components, development of wall roughness at the solid–liquid interface, moving concentration boundary layer and mass transport by advection. Results agree with experimental data and have demonstrated that when modelling dissolution in vitro, special attention must be paid to including the particular conditions of the dissolution environment

Probabilistic models for drug dissolution. Part 1. Review of Monte Carlo and stochastic cellular automata approaches.

Throughout the last decades, Monte Carlo (MC) techniques have been used in simulating various complex systems. In this paper, we investigate how MC-based methods are used in the field of Drug Delivery, indicating what aspects of the complex problems of drug dissolution and design can benefit from this particular approach. After introducing the area of modelling drug dissolution, with its different features and needs, we report and examine the existing Direct MC and Stochastic Cellular Automata modelling efforts used to simulate dissolution of pharmaceutical compacts or related phenomena. In Part 2, we enlarge on a description of our work on Direct MC, for the particular case of simulating a binary system consisting of poorly soluble drug dispersed in a matrix of highly-soluble acid excipient

Probabilistic models for drug dissolution

The focus of the material presented in this PhD thesis is the development of stochastic Direct and Inverse Monte-Carlo-based models for drug dissolution. Drug dissolution from different carriers is a complex phenomenon. Limited knowledge is available on some of the underlying constituent processes, which restricts development of mechanistic models. Monte Carlo techniques permit the treatment of certain structures and events in a probabilistic manner. The thesis examines a number of possible ways of using Monte Carlo both (1) to explore modelling for the dissolution of Drug Delivery Systems and (2) to reconstruct general system behaviour during dissolution, using noisy drug delivery data. Further, important investigations on the determination of factors responsible for noise and quantification of noise levels, are reported. In the first part of the thesis, an investigation of MC-based methods in the field of Drug Delivery is given, with the complexity of drug dissolution and design explored and the contribution of the MC approach reported. The use of Direct MC and Stochastic Cellular Automata models in the simulation of dissolution from pharmaceutical compacts or related phenomena are discussed, together with various features and requirements. The principal objective here is to extend use of Direct Monte Carlo techniques in simulating drug delivery from compacts of complex composition, taking into consideration special features of the dissolution in an in vitro environment. After examining the existing MC models for drug delivery, the need for more sophisticated models is described. Exploratory modelling is proposed in order to address the problems of dissolution related to certain drug carriers with complex internal morphology and difficult-to-predict dissolution profiles. Phenomena such as local interactions of dissolving components, development of wall-roughness at the solid-liquid interface, diffusion through occlusions and pores and moving concentration boundary layers were examined and directly accounted for in the model. As a result, new models have been developed for: i) matrix soluble drug carriers and ii) bioerodible polymeric micro- and nanospheres for controlled release of proteins. The simulations provide results in acceptable agreement with different drug release profiles obtained during laboratory experiments. The novelty of this work consists in including new features of experimental system complexity in the frame of simple and user-friendly Direct MC models, indicating that the Direct MC technique can be very helpful in exploring design parameters in the field of drug delivery. The other major axis of the thesis investigates use of Monte Carlo in data reconstruction and noise quantification. The problem posed was whether it is possible to extract detailed dynamic distributional knowledge about a dissolving pharmaceutical system composed from many small entities, when the researcher is provided with insufficient experimental data. A model based on Inverse Monte Carlo simulations was designed to exploit Bayesian principles in retrieving the desired features, such as particle size distribution. Importantly, this work demonstrates that Inverse Monte Carlo methods are capable of reconstructing underlying characteristics of drug carriers involved, even when dissolution profiles available rely on sparse data sets. The models proposed in this thesis are currently being incorporated in a largescale project in collaboration between the DCU research team and the Hospital for Special Surgery, New York. The project focuses on developing therapeutic implants with controlled drug release, specifically designed for the regeneration of severely damaged tissues

Probabilistic models for dissolution of ethylcellulose coated microspheres

In the last few decades, a number of probabilistic models for drug delivery have been developed. Of particular interest are those that model controlled release systems to provide targeted dose delivery. Controlled release is achieved by using polymers with dierent dissolution characteristics. We present here a model based on Monte Carlo and Cellular Automata approaches, for simulating drug release from coated microspheres in the gastro-intestinal tract. Controlled release is obtained using ethylcellulose as the coating polymer. Modelling features, such as the drug and coating dissolution are nontrivial, since material is non-homogenously dispersed and the dissolution exhibits complex behaviour. Important underlying mechanisms of the process, such as erosion, are described here

Effect of oregano (Origanum vulgare L. ssp. hirtum) and clove (Eugenia spp.) nanoemulsions on Zygosaccharomyces bailii survival in salad dressings

[EN] This work aimed to evaluate the in vitro effect of encapsulated oregano and clove essential oils on oil-in-water nanoemulsions against Zygosaccharomyces bailii. The antifungal efficacy of these nanoemulsions and their sensory acceptance were tested in salad dressings. Both essential oils were effective inhibitors against the target yeast, with minimal inhibitory and fungicidal concentrations of 1.75 mg/mL. In the in vitro assay done with the nanoemulsions, no yeast growth was observed for any tested essential oil concentration. In the salad dressings, all the formulations were able to reduce Z. bailii growth compared to the control, and only those samples with 1.95 mg/g of essential oil were capable of inhibiting yeast development after 4 inoculation days. The sensory acceptance of the dressing containing the nanoemulsions was similar to the control dressing in appearance, consistency and colour terms. These results evidence the antifungal activity of oregano and clove nanoemulsions against Z. bailii.Ribes-Llop, S.; Fuentes López, A.; Barat Baviera, JM. (2019). Effect of oregano (Origanum vulgare L. ssp. hirtum) and clove (Eugenia spp.) nanoemulsions on Zygosaccharomyces bailii survival in salad dressings. Food Chemistry. 295:630-636. https://doi.org/10.1016/j.foodchem.2019.05.173S63063629

Physical stability, rheology and microstructure of salad dressing containing essential oils: study of incorporating nanoemulsions

[EN] Purpose This study aims to evaluate the effect of adding oregano and clove oil-in-water (O/W) nanoemulsions on the physico-chemical, technological and microstructural properties of minimally processed salad dressings during storage at 8 degrees C and 25 degrees C. Design/methodology/approach Samples were formulated with either free or encapsulated oregano and clove essential oils in O/W nanoemulsions. Findings Noticeable differences in the physical stability and microstructure of salad dressings were observed after 11 storage days and were less marked for the samples formulated with encapsulated oregano or clove oils in the O/W nananoemulsions. Moreover, rheological measurements revealed minor changes in the viscoelastic characteristics of the salad dressings containing the O/W nanoemulsions. Originality/value These findings confirm the potential of oregano and clove O/W nanoemulsions for use in minimally processed salad dressings as stabilising and technological agents.Ribes-Llop, S.; Fuentes López, A.; Barat Baviera, JM. (2021). Physical stability, rheology and microstructure of salad dressing containing essential oils: study of incorporating nanoemulsions. British Food Journal. 123(4):1626-1642. https://doi.org/10.1108/BFJ-09-2020-0777S162616421234Ariizumi, M., Kubo, M., Handa, A., Hayakawa, T., Matsumiya, K., & Matsumura, Y. (2017). Influence of processing factors on the stability of model mayonnaise with whole egg during long-term storage. Bioscience, Biotechnology, and Biochemistry, 81(4), 803-811. doi:10.1080/09168451.2017.1281725Bae, I. Y., Oh, I.-K., Lee, S., Yoo, S.-H., & Lee, H. G. (2008). Rheological characterization of levan polysaccharides from Microbacterium laevaniformans. International Journal of Biological Macromolecules, 42(1), 10-13. doi:10.1016/j.ijbiomac.2007.08.006Burt, S. (2004). Essential oils: their antibacterial properties and potential applications in foods—a review. International Journal of Food Microbiology, 94(3), 223-253. doi:10.1016/j.ijfoodmicro.2004.03.022De Cássia da Fonseca, V., Haminiuk, C. W. I., Izydoro, D. R., Waszczynskyj, N., de Paula Scheer, A., & Sierakowski, M.-R. (2009). Stability and rheological behaviour of salad dressing obtained with whey and different combinations of stabilizers. International Journal of Food Science & Technology, 44(4), 777-783. doi:10.1111/j.1365-2621.2008.01897.xDe Melo, A. N. F., de Souza, E. L., da Silva Araujo, V. B., & Magnani, M. (2015). Stability, nutritional and sensory characteristics of French salad dressing made with mannoprotein from spent brewer’s yeast. LWT - Food Science and Technology, 62(1), 771-774. doi:10.1016/j.lwt.2014.06.050Depree, J. ., & Savage, G. . (2001). Physical and flavour stability of mayonnaise. Trends in Food Science & Technology, 12(5-6), 157-163. doi:10.1016/s0924-2244(01)00079-6Dickinson, E. (2009). Hydrocolloids as emulsifiers and emulsion stabilizers. Food Hydrocolloids, 23(6), 1473-1482. doi:10.1016/j.foodhyd.2008.08.005Espert, M., Salvador, A., & Sanz, T. (2019). Rheological and microstructural behaviour of xanthan gum and xanthan gum-Tween 80 emulsions during in vitro digestion. Food Hydrocolloids, 95, 454-461. doi:10.1016/j.foodhyd.2019.05.004Gavahian, M., Chen, Y.-M., Mousavi Khaneghah, A., Barba, F. J., & Yang, B. B. (2018). In-pack sonication technique for edible emulsions: Understanding the impact of acacia gum and lecithin emulsifiers and ultrasound homogenization on salad dressing emulsions stability. Food Hydrocolloids, 83, 79-87. doi:10.1016/j.foodhyd.2018.04.039Guerra-Rosas, M. I., Morales-Castro, J., Ochoa-Martínez, L. A., Salvia-Trujillo, L., & Martín-Belloso, O. (2016). Long-term stability of food-grade nanoemulsions from high methoxyl pectin containing essential oils. Food Hydrocolloids, 52, 438-446. doi:10.1016/j.foodhyd.2015.07.017Heyman, B., Depypere, F., Delbaere, C., & Dewettinck, K. (2010). Effects of non-starch hydrocolloids on the physicochemical properties and stability of a commercial béchamel sauce. Journal of Food Engineering, 99(2), 115-120. doi:10.1016/j.jfoodeng.2010.02.005Izidoro, D. R., Scheer, A. P., Sierakowski, M.-R., & Haminiuk, C. W. I. (2008). Influence of green banana pulp on the rheological behaviour and chemical characteristics of emulsions (mayonnaises). LWT - Food Science and Technology, 41(6), 1018-1028. doi:10.1016/j.lwt.2007.07.009Kurt, A., Cengiz, A., & Kahyaoglu, T. (2016). The effect of gum tragacanth on the rheological properties of salep based ice cream mix. Carbohydrate Polymers, 143, 116-123. doi:10.1016/j.carbpol.2016.02.018Laneuville, S. I., Turgeon, S. L., & Paquin, P. (2013). Changes in the physical properties of xanthan gum induced by a dynamic high-pressure treatment. Carbohydrate Polymers, 92(2), 2327-2336. doi:10.1016/j.carbpol.2012.11.077Ma, L., & Barbosa-Cánovas, G. V. (1995). Rheological characterization of mayonnaise. Part II: Flow and viscoelastic properties at different oil and xanthan gum concentrations. Journal of Food Engineering, 25(3), 409-425. doi:10.1016/0260-8774(94)00010-7Ma, Z., & Boye, J. I. (2013). Microstructure, Physical Stability, and Rheological Properties of Salad Dressing Emulsions Supplemented with Various Pulse Flours. Journal of Food Research, 2(2), 167. doi:10.5539/jfr.v2n2p167Ma, Z., Boye, J. I., Fortin, J., Simpson, B. K., & Prasher, S. O. (2013). Rheological, physical stability, microstructural and sensory properties of salad dressings supplemented with raw and thermally treated lentil flours. Journal of Food Engineering, 116(4), 862-872. doi:10.1016/j.jfoodeng.2013.01.024Martínez, I., Angustias Riscardo, M., & Franco, J. M. (2007). Effect of salt content on the rheological properties of salad dressing-type emulsions stabilized by emulsifier blends. Journal of Food Engineering, 80(4), 1272-1281. doi:10.1016/j.jfoodeng.2006.09.022Palanuwech, J., & Coupland, J. N. (2003). Effect of surfactant type on the stability of oil-in-water emulsions to dispersed phase crystallization. Colloids and Surfaces A: Physicochemical and Engineering Aspects, 223(1-3), 251-262. doi:10.1016/s0927-7757(03)00169-9Paraskevopoulou, D., Boskou, D., & Paraskevopoulou, A. (2007). Oxidative stability of olive oil–lemon juice salad dressings stabilized with polysaccharides. Food Chemistry, 101(3), 1197-1204. doi:10.1016/j.foodchem.2006.03.022Park, J. J., Olawuyi, I. F., & Lee, W. Y. (2020). Characteristics of low-fat mayonnaise using different modified arrowroot starches as fat replacer. International Journal of Biological Macromolecules, 153, 215-223. doi:10.1016/j.ijbiomac.2020.02.331Primacella, M., Wang, T., & Acevedo, N. C. (2019). Characterization of mayonnaise properties prepared using frozen-thawed egg yolk treated with hydrolyzed egg yolk proteins as anti-gelator. Food Hydrocolloids, 96, 529-536. doi:10.1016/j.foodhyd.2019.06.008Ribes, S., Fuentes, A., Talens, P., & Barat, J. M. (2017). Application of cinnamon bark emulsions to protect strawberry jam from fungi. LWT, 78, 265-272. doi:10.1016/j.lwt.2016.12.047Ribes, S., Fuentes, A., & Barat, J. M. (2019). Effect of oregano (Origanum vulgare L. ssp. hirtum) and clove (Eugenia spp.) nanoemulsions on Zygosaccharomyces bailii survival in salad dressings. Food Chemistry, 295, 630-636. doi:10.1016/j.foodchem.2019.05.173Román, L., Reguilón, M. P., & Gómez, M. (2018). Physicochemical characteristics of sauce model systems: Influence of particle size and extruded flour source. Journal of Food Engineering, 219, 93-100. doi:10.1016/j.jfoodeng.2017.09.024Santipanichwong, R., & Suphantharika, M. (2007). Carotenoids as colorants in reduced-fat mayonnaise containing spent brewer’s yeast β-glucan as a fat replacer. Food Hydrocolloids, 21(4), 565-574. doi:10.1016/j.foodhyd.2006.07.003SMITTLE, R. B. (2000). Microbiological Safety of Mayonnaise, Salad Dressings, and Sauces Produced in the United States: A Review. Journal of Food Protection, 63(8), 1144-1153. doi:10.4315/0362-028x-63.8.1144Sozer, N. (2009). Rheological properties of rice pasta dough supplemented with proteins and gums. Food Hydrocolloids, 23(3), 849-855. doi:10.1016/j.foodhyd.2008.03.016Srinivasan, M. (2000). The effect of sodium chloride on the formation and stability of sodium caseinate emulsions. Food Hydrocolloids, 14(5), 497-507. doi:10.1016/s0268-005x(00)00030-8Valduga, A. T., Gonçalves, I. L., Magri, E., & Delalibera Finzer, J. R. (2019). Chemistry, pharmacology and new trends in traditional functional and medicinal beverages. Food Research International, 120, 478-503. doi:10.1016/j.foodres.2018.10.091Yüceer, M., İlyasoğlu, H., & Özçelik, B. (2016). Comparison of flow behavior and physicochemical characteristics of low-cholesterol mayonnaises produced with cholesterol-reduced egg yolk. Journal of Applied Poultry Research, 25(4), 518-527. doi:10.3382/japr/pfw033Zhang, C., Quek, S. Y., Lam, G., & Easteal, A. J. (2008). The rheological behaviour of low fat soy-based salad dressing. International Journal of Food Science & Technology, 43(12), 2204-2212. doi:10.1111/j.1365-2621.2008.01852.

In vitro toxicological evaluation of mesoporous silica microparticles functionalised 1 with carvacrol and thymol

The cytotoxicity of carvacrol- and thymol- functionalised mesoporous silica microparticles (MCM-41) was assessed in the human hepatocarcinoma cell line (HepG2). Cell viability, lactate dehydrogenase (LDH) activity, reactive oxygen species (ROS) production, mitochondrial membrane potential (ΔΨm), lipid peroxidation (LPO) and apoptosis/necrosis analysis were used as endpoints. Results showed that both materials induced cytotoxicity in a time and concentration-dependent manner, being more cytotoxic than free essential oil components and bare MCM-41. This effect was caused by the cell-particle interactions and not from degradation products released to the culture media, as demonstrated in the extract dilution assays. LDH release was seen to be a less sensitive endpoint than the MTT (thiazolyl blue tetrazolium bromide) assay, suggesting impairment of the mitochondrial function as the primary cytotoxic mechanism. In vitro tests on specialised cell functions showed that exposure to sublethal concentrations of these materials did not induce ROS formation within 2-h exposure but produced LPO and ΔΨm alteration in a concentration-dependent manner when cells were exposed for 24 h. Overall, the results found in this study support the hypothesis that carvacrol- and thymol-functionalised MCM-41 microparticles induced toxicity in HepG2 cells by an oxidative stress-related mechanism that resulted in apoptosis through the mitochondrial pathway

Development of a new salmon salting smoking method and process monitoring by impedance spectroscopy

[EN] In this work two objectives were proposed: (i) to optimize a new salmon salting smoking method using vacuum packaging and (ii) to evaluate the application of impedance spectroscopy (IS) to the on-line monitoring of the process. Different processing conditions were evaluated (4 smoke flavoring (SF) salt concentrations, 3 salting times, salting in vacuum or in air). Physico-chemical analyses and IS measurements were performed with three different sensors during the process. Salting with 16 g SF salt/100 g fish in vacuum packaging provided smoked salmon similar to products currently available on the market. This new method has the advantages of reducing processing times and waste. IS measurements were carried out by three different electrodes. The most appropriate sensor for process monitoring was a needle electrode, with which robust prediction models for NaCl content, moisture and a,,, during the salting smoking process were obtained. The results showed the potential of IS as a rapid on-line monitoring method of the salmon salting smoking process. (C) 2012 Elsevier Ltd. All rights reserved.The authors gratefully acknowledge the financial support for the work reported here received from the Generalitat Valenciana (GV/2011/098) and the Universitat Politecnica de Valencia (UPV) (PAID-06-09-2940). A. Fuentes would like to thank the Campus de Excelencia Internacional at the UPV for its support. The proof-reading of this paper was funded by the UPV, Spain.Rizo Párraga, AM.; Fuentes López, A.; Fernández Segovia, I.; Masot Peris, R.; Alcañiz Fillol, M.; Barat Baviera, JM. (2013). Development of a new salmon salting smoking method and process monitoring by impedance spectroscopy. LWT - Food Science and Technology. 51(1):218-224. https://doi.org/10.1016/j.lwt.2012.09.025S21822451

Development of a novel smoke-flavoured trout product: An approach to sodium reduction and shelf life assessment

[EN] This work aimed to develop a reduced sodium smoke-flavoured trout product with similar physicochemical traits and sensory quality to commercial smoked trout. In a first phase, a reduced sodium smoke-flavoured trout product was developed by a novel smoke-flavouring process using water vapour permeable bags. In a second phase, the obtained product's microbial and physico-chemical quality was evaluated for 42 cold storage days. A smoke-flavoured trout product with similar physico-chemical characteristics and sensory acceptance to commercial smoked trout was achieved through smokeflavouring with water vapour permeable bags. Partial substitution of NaCl for KCl led to a 42% sodium reduction in the smoke-flavoured trout and did not affect its physico-chemical traits, sensory attributes and hygienic quality throughout the storage. During shelf life study, no sample exceeded the limits of acceptance proposed for physico-chemical and microbial parameters, except for mesophilic bacteria, which limited the product shelf life to 1 month.The authors gratefully acknowledge the support of Tub-Ex Aps (Taars, Denmark) for the supply of the water vapour permeable bags and for providing all the necessary technical information. Arantxa Rizo would like to thank the Universitat Politecnica de Valencia for the FPI grant.Rizo, A.; Fuentes López, A.; Fernández Segovia, I.; Barat Baviera, JM. (2017). Development of a novel smoke-flavoured trout product: An approach to sodium reduction and shelf life assessment. Journal of Food Engineering. 211:22-29. doi:10.1016/j.jfoodeng.2017.04.031S222921