Antiproliferative, genotoxic and mutagenic potential of synthetic chocolate food flavoring / Potencial antiproliferativo, genotóxico e mutagênico do aroma de chocolate sintético para alimentos

Flavoring additives are of great technological importance for the food industry. However, there is little information regarding the toxicological properties of these micro-ingredients, especially at the cellular level. The present study used meristematic root cells of Allium cepa L. to evaluate the toxicity of a liquid, aroma and flavor synthetic chocolate additive, manufactured and widely marketed throughout Brazil and exported to other countries in South America. The flavoring concentrations evaluated were 100.00; 50.00; 25.00; 1.00; 0.50 and 0.25 µL/L, where the highest concentration established was one-hundred times lower than that commercially suggested for use. The concentration 100 µL/L substantially reduced cell division of meristems within 24- and 48-hours exposure. Concentrations from 100.00 to 0.50 µL/L resulted in a significant number of prophases to the detriment of the other phases of cell division, indicating an aneugenic activity, and induced a significant number of cellular changes, with emphasis on micronuclei, nuclear buds and chromosomal breaks. Under the established analysis conditions, with the exception of concentration 0.25 µL/L, the flavoring of chocolate caused cytotoxicity, genotoxicity and mutagenicity to root meristems.

Os aditivos aromatizantes têm grande importância tecnológica para a indústria de alimentos. Contudo, poucas são as informações quanto as propriedades toxicológicas desses microingredientes, especialmente, em nível celular. No presente estudo avaliou-se, sobre as células meristemáticas de raízes de Allium cepa L., a toxicidade de um aditivo sintético líquido de aroma e sabor de chocolate, fabricado e amplamente comercializado em todo Brasil, e exportado para outros países da América do Sul. As concentrações de aromatizante avaliadas foram 100,00; 50,00; 25,00; 1,00; 0,50 e 0,25 µL/L, onde a maior concentração estabelecida foi cem vezes menor que a sugerida comercialmente para uso. Com base na interpretação dos resultados, a concentração 100 µL/L reduziu substancialmente a divisão celular dos meristemas nas 24 e 48 horas de exposição. As concentrações 100,00 a 0,50 µL/L demonstraram número significativo de prófases em detrimento as outras fases da divisão celular, indicando ação aneugênica, e induziram número significativo de alterações celulares, com ênfase a micronúcleos, broto nucleares e quebras cromossômicas. Nas condições de análises estabelecidas, com exceção a concentração 0,25 µL/L, o aromatizante de chocolate causou citotoxicidade, genotoxicidade e mutagenicidade aos meristemas radiculares.

Oleamide, a Sleep-Inducing Supplement, Upregulates Doublecortin in Hippocampal Progenitor Cells via PPARα.

BACKGROUND: Doublecortin (DCX), a microtubule associated protein, has emerged as a central biomarker of hippocampal neurogenesis. However, molecular mechanisms by which DCX is regulated are poorly understood. OBJECTIVE: Since sleep is involved with the acquisition of memory and oleamide or 9-Octadecenamide (OCT) is a sleep-inducing supplement in human, we examined whether OCT could upregulate DCX in hippocampal progenitor cells (HPCs). METHODS: We employed real-time PCR, western blot, immunostaining, chromatin immunoprecipitation, lentiviral transduction in HPCs, and the calcium influx assay. RESULTS: OCT directly upregulated the transcription of Dcx in HPCs via activation of peroxisome proliferator-activated receptor α (PPARα), a lipid-lowering transcription factor. We observed that, HPCs of Ppara-null mice displayed significant impairment in DCX expression and neuronal differentiation as compared to that of wild-type mice. Interestingly, treatment with OCT stimulated the differentiation process of HPCs in wild-type, but not Ppara-null mice. Reconstruction of PPARα in mouse Ppara-null HPCs restored the expression of DCX, which was further stimulated with OCT treatment. In contrast, a dominant-negative mutant of PPARα significantly attenuated the stimulatory effect of OCT on DCX expression and suppressed neuronal differentiation of human neural progenitor cells. Furthermore, RNA microarray, STRING, chromatin immunoprecipitation, site-directed mutagenesis, and promoter reporter assay have identified DCX as a new target of PPARα. CONCLUSION: These results indicate that OCT, a sleep supplement, directly controls the expression of DCX and suggest that OCT may be repurposed for stimulating the hippocampal neurogenesis.

Preparation and Characterization of Semi-IPN Cryogels Based on Polyacrylamide and Poly(N,N-dimethylaminoethyl methacrylate); Functionalization of Carrier with Monochlorotriazinyl-ß-cyclodextrin and Release Kinetics of Curcumin.

Curcumin (CCM) is a natural hydrophobic polyphenol known for its numerous applications in the food industry as a colorant or jelly stabilizer, and in the pharmaceutical industry due to its anti-inflammatory, antibacterial, antioxidant, anti-cancer, and anti-Alzheimer properties. However, the large application of CCM is limited by its poor solubility in water and low stability. To enhance the bioavailability of CCM, and to protect it against the external degradation agents, a novel strategy, which consists in the preparation of semi-interpenetrating polymer networks, (s-IPNs) based on poly(N,N-dimethylaminoethyl methacrylate) entrapped in poly(acrylamide) networks, by a cryogelation technique, was developed in this work. All s-IPN cryogels were characterized by SEM, EDX, FTIR, and swelling at equilibrium as a function of pH. Functionalization of semi-IPN cryogel with monochlorotriazinyl-ß-cyclodextrin (MCT-ß-CD) led to IPN cryogel. The release profile of CCM from the composite cryogels was investigated at 37 °C, in pH 3. It was found that the cumulative release increased with the increase of the carrier hydrophobicity, as a result of increasing the cross-linking degree, the content and the molar mass of PDMAEMA. Fitting Higuchi, Korsmeyer-Peppas, and first order kinetic models on the CCM release profiles indicated the diffusion as the main driving force of drug release from the composite cryogels.

Acceptance of different types of thickeners, with and without flavoring, in hospitalized patients with dysphagia - a pilot study / Aceptación de diferentes tipos de espesante, con y sin saborizante, en pacientes con disfagia hospitalizados: un estudio piloto

Introduction: the goal of this work was to evaluate the acceptance of various types of thickeners, specifically modified starch thickener and gum thickener, both with and without flavoring. Patients and methods: a randomized sample of 40 hospitalized patients with oropharyngeal dysphagia was recruited. The taste, smell, and appearance of each type of thickener were evaluated, as well as the volume of liquid ingested by the patients taking each type of thickener (modified starch thickener vs. gum thickener, both with and without flavoring).Results: the overall acceptance of gum thickener was significantly higher than that of modified starch thickener (7.45 (1.57) vs. 5.10 (2.43), respectively; p = 0.001). When a food flavor was added to the thickened water, the overall rating of the product was higher than when no flavor was added (7.70 (1.53) vs. 4.85 (2.16); p < 0.001). The difference between the daily volume of water consumed by the patients who received gum thickeners (928.33 (331.27) mL) and those who received starch thickeners (670.00 (288.35) mL) was statistically significant (p = 0.012). Patient consumption was also higher when flavoring was added as compared to when it was not (943.33 (302.45) mL) vs. (655.00 (304.60) mL; p = 0.005). Conclusion: the acceptances of the thickener and of water intake by patients with dysphagia were both significantly higher when using gum thickeners compared to starch thickeners, and when adding flavoring. (AU)

Introducción: el objetivo de este trabajo fue evaluar la aceptación de varios tipos de espesantes (almidón modificado frente a gomas) con y sin saborizante. Pacientes y métodos: se reclutaron 40 pacientes hospitalizados con disfagia orofaríngea. Se evaluaron el sabor, el olor y la apariencia de cada tipo de espesante, así como el volumen de líquido ingerido por los pacientes que tomaban cada tipo de espesante (espesante de almidón modificado vs. espesante de goma, ambos con o sin saborizante). Resultados: la aceptación general del espesante de goma fue significativamente mayor que la del almidón modificado (7,45 (1,57) vs. 5,10 (2,43); p = 0,001). Cuando se añadió un saborizante al agua espesada, la calificación general fue mejor (7,70 (1,53) frente a 4,85 (2,16); p < 0,001). La diferencia entre el volumen diario de agua consumida por los pacientes que recibieron espesantes de goma (928,33 (331,27) ml) y los que recibieron espesantes de almidón (670,00 (288,35) ml) fue estadísticamente significativa (p = 0,012). El consumo de líquido también fue mayor cuando se agregó el saborizante (943,33 (302,45) ml frente a 655,00 (304,60) ml; p = 0,005). Conclusión: la aceptación del espesante y la ingesta de agua por parte de los pacientes con disfagia fueron significativamente mayores cuando se utilizaron espesantes de goma, en comparación con los espesantes de almidón, y al agregar saborizantes. (AU)

Temporal effect of fructose supplementation at different concentrations on hepatic metabolism of Wistar rats / Efecto temporal de la suplementación de fructosa a diferentes concentraciones sobre el metabolismo hepático de ratas Wistar

Introduction: in the last few years important changes have occurred in nutritional patterns. There has been an increase in the consumption of simple carbohydrates such as fructose, which has been associated with numerous metabolic disorders, including hepatic steatosis. Materials and methods: we sought to evaluate the impact of fructose consumption, as diluted in water at different concentrations, for two time periods, on the metabolic parameters of Wistar rats using ANOVA. Results: our data indicate that both time and fructose concentration promote variations in animal body mass, and in food, water, and caloric intake. The time variable influenced the modulation of biochemical parameters such as serum concentrations of glucose and total cholesterol. Both fructose concentration and time of exposure influenced the concentrations of serum triglycerides, creatinine, AST, TNF, and IL-6. When evaluating redox status and oxidative damage markers, we observed that fructose concentration and exposure time had an effect on total glutathione levels, which decreased with an increase in concentration and time. For superoxide dismutase, we evaluated the effects of time and interaction. A significant interaction was observed for TBARS. For carbonylated proteins, exposure time was a fundamental factor in generating an effect. Conclusions: we demonstrated that fructose modulates the parameters of triglycerides and total liver cholesterol, and that time influences the number of hepatocytes. Our data suggest that fructose concentration, exposure time, and an interaction between these two parameters have a significant effect on the metabolic parameters responsible for the development of non-alcoholic fatty liver disease. (AU)

Introducción: en los últimos años se han producido cambios importantes en los patrones nutricionales. Ha habido un aumento del consumo de carbohidratos simples como la fructosa, que se ha asociado con numerosos trastornos metabólicos, incluida la esteatosis hepática. Materiales y métodos: buscamos evaluar el impacto del consumo de fructosa, diluida en agua a diferentes concentraciones, durante dos períodos de tiempo sobre los parámetros metabólicos de ratas Wistar, utilizando para ello el ANOVA. Resultados: nuestros datos indican que tanto el tiempo como la concentración de fructosa promueven variaciones en la masa corporal animal y la ingesta de alimentos, agua y calorías. La variable tiempo influyó en la modulación de parámetros bioquímicos tales como las concentraciones séricas de glucosa y colesterol total. Tanto la concentración de fructosa como el tiempo de exposición influyeron en las concentraciones séricas de triglicéridos, creatinina, AST, TNF e IL-6. Al evaluar el estado redox y los marcadores de daño oxidativo, observamos que la concentración de fructosa y el tiempo de exposición tuvieron un efecto sobre los niveles de glutatión total, que disminuyeron al aumentar la concentración y el tiempo. Para la superóxido dismutasa evaluamos los efectos del tiempo y la interacción. Se observó una interacción significativa para TBARS. Para las proteínas carboniladas, el tiempo de exposición fue un factor fundamental para generar algún efecto. Conclusiones: demostramos que la fructosa modula los parámetros de los triglicéridos y el colesterol total del hígado, y que el tiempo influye en el número de hepatocitos. Nuestros datos sugieren que la concentración de fructosa, el tiempo de exposición y cierta interacción entre estos dos parámetros tienen un efecto significativo sobre los parámetros metabólicos responsables del desarrollo de la enfermedad del hígado graso no alcohólico. (AU)

Monosodium glutamate causes hepato-cardiac derangement in male rats.

People in the fast-food era rely on pre-packaged foods and engage in limited physical activity, which leads to a shift in eating patterns. Monosodium glutamate (MSG), a dietary ingredient used in this sort of cuisine, has been found to be hazardous to both experimental animals and humans. The objective of this study was to explore at the unnecessary changes caused by consuming MSG in secret and exceeding the recommended dosage. Hence, we decided to evaluate the impact of MSG by using three different doses (200, 400, and 600 mg/kg body weight orally) for 28 days in rats. We uncovered that all three MSG dosages result in a rise in body weight, dyslipidemia, inflammatory response, and hepato-cardiac marker enzymes, all of which imply hepatic and cardiac toxicity. Furthermore, changes in redox status suggest oxidative stress, which was higher in all three MSG dosages although not as much as in the MSG-600 group when compared to control. Such effects eventually manifested themselves in tissue architecture of the liver and heart, resulting in severe hepato-cardiac derangement, but the degree of tissue damage was greater in the MSG-600 group. As a result, it is possible that MSG has a negative influence on the liver and heart. However, the MSG-600 group showed a substantial effect, indicating that MSG should not be used in food preparation. Therefore, the findings of the study may aid in the formulation of health-care strategies and serve as a warning to the general public regarding the use of MSG in daily diet.

Microencapsulation of Bioactive Ingredients for Their Delivery into Fermented Milk Products: A Review.

The popularity and consumption of fermented milk products are growing. On the other hand, consumers are interested in health-promoting and functional foods. Fermented milk products are an excellent matrix for the incorporation of bioactive ingredients, making them functional foods. To overcome the instability or low solubility of many bioactive ingredients under various environmental conditions, the encapsulation approach was developed. This review analyzes the fortification of three fermented milk products, i.e., yogurt, cheese, and kefir with bioactive ingredients. The encapsulation methods and techniques alongside the encapsulant materials for carotenoids, phenolic compounds, omega-3, probiotics, and other micronutrients are discussed. The effect of encapsulation on the properties of bioactive ingredients themselves and on textural and sensory properties of fermented milk products is also presented.

Propolis: Properties and composition, health benefits and applications in fish nutrition.

Propolis is a viscous, waxy, resinous substance that is produced from the exudates of flowers and buds by the action of salivary enzymes of honey bees. Propolis may differ in color (brown, red or green), with color being influenced by the chemical composition and age of the product. Propolis has a special distinctive odor owing to the high concentration of volatile essential oils. It is composed of 5% pollen grains, 10% essential and aromatic oils, 30% wax, 50% resin and balsams, and other minor trace substances. Natural propolis products may be useful for a range of applications in aquaculture systems instead of relying on the application of synthetic compounds to manage many ailments that affect business profitability. It has been reported in several studies that propolis enhances performance, economics, immunity response and disease resistance in different fish species. This present review discusses the functional actions of propolis and the prospects of its use as an antimicrobial, antioxidant, immune-modulatory, antiseptic, antiparasitic, anti-inflammatory and food additive in aquaculture production. In summary, propolis could be a natural supplement that has the potential to improve fish health status and immunity thereby enhancing growth and productivity of the fish industry as well as economic efficiency.

Acceptance of different types of thickeners, with and without flavoring, in hospitalized patients with dysphagia - A pilot study.

INTRODUCTION: Introduction: the goal of this work was to evaluate the acceptance of various types of thickeners, specifically modified starch thickener and gum thickener, both with and without flavoring. Patients and methods: a randomized sample of 40 hospitalized patients with oropharyngeal dysphagia was recruited. The taste, smell, and appearance of each type of thickener were evaluated, as well as the volume of liquid ingested by the patients taking each type of thickener (modified starch thickener vs. gum thickener, both with and without flavoring). Results: the overall acceptance of gum thickener was significantly higher than that of modified starch thickener (7.45 (1.57) vs. 5.10 (2.43), respectively; p = 0.001). When a food flavor was added to the thickened water, the overall rating of the product was higher than when no flavor was added (7.70 (1.53) vs. 4.85 (2.16); p < 0.001). The difference between the daily volume of water consumed by the patients who received gum thickeners (928.33 (331.27) mL) and those who received starch thickeners (670.00 (288.35) mL) was statistically significant (p = 0.012). Patient consumption was also higher when flavoring was added as compared to when it was not (943.33 (302.45) mL) vs. (655.00 (304.60) mL; p = 0.005). Conclusion: the acceptances of the thickener and of water intake by patients with dysphagia were both significantly higher when using gum thickeners compared to starch thickeners, and when adding flavoring.

INTRODUCCIÓN: Introducción: el objetivo de este trabajo fue evaluar la aceptación de varios tipos de espesantes (almidón modificado frente a gomas) con y sin saborizante. Pacientes y métodos: se reclutaron 40 pacientes hospitalizados con disfagia orofaríngea. Se evaluaron el sabor, el olor y la apariencia de cada tipo de espesante, así como el volumen de líquido ingerido por los pacientes que tomaban cada tipo de espesante (espesante de almidón modificado vs. espesante de goma, ambos con o sin saborizante). Resultados: la aceptación general del espesante de goma fue significativamente mayor que la del almidón modificado (7,45 (1,57) vs. 5,10 (2,43); p = 0,001). Cuando se añadió un saborizante al agua espesada, la calificación general fue mejor (7,70 (1,53) frente a 4,85 (2,16); p < 0,001). La diferencia entre el volumen diario de agua consumida por los pacientes que recibieron espesantes de goma (928,33 (331,27) ml) y los que recibieron espesantes de almidón (670,00 (288,35) ml) fue estadísticamente significativa (p = 0,012). El consumo de líquido también fue mayor cuando se agregó el saborizante (943,33 (302,45) ml frente a 655,00 (304,60) ml; p = 0,005). Conclusión: la aceptación del espesante y la ingesta de agua por parte de los pacientes con disfagia fueron significativamente mayores cuando se utilizaron espesantes de goma, en comparación con los espesantes de almidón, y al agregar saborizantes.

Temporal effect of fructose supplementation at different concentrations on hepatic metabolism of Wistar rats.

INTRODUCTION: Introduction: in the last few years important changes have occurred in nutritional patterns. There has been an increase in the consumption of simple carbohydrates such as fructose, which has been associated with numerous metabolic disorders, including hepatic steatosis. Materials and methods: we sought to evaluate the impact of fructose consumption, as diluted in water at different concentrations, for two time periods, on the metabolic parameters of Wistar rats using ANOVA. Results: our data indicate that both time and fructose concentration promote variations in animal body mass, and in food, water, and caloric intake. The time variable influenced the modulation of biochemical parameters such as serum concentrations of glucose and total cholesterol. Both fructose concentration and time of exposure influenced the concentrations of serum triglycerides, creatinine, AST, TNF, and IL-6. When evaluating redox status and oxidative damage markers, we observed that fructose concentration and exposure time had an effect on total glutathione levels, which decreased with an increase in concentration and time. For superoxide dismutase, we evaluated the effects of time and interaction. A significant interaction was observed for TBARS. For carbonylated proteins, exposure time was a fundamental factor in generating an effect. Conclusions: we demonstrated that fructose modulates the parameters of triglycerides and total liver cholesterol, and that time influences the number of hepatocytes. Our data suggest that fructose concentration, exposure time, and an interaction between these two parameters have a significant effect on the metabolic parameters responsible for the development of non-alcoholic fatty liver disease.

INTRODUCCIÓN: Introducción: en los últimos años se han producido cambios importantes en los patrones nutricionales. Ha habido un aumento del consumo de carbohidratos simples como la fructosa, que se ha asociado con numerosos trastornos metabólicos, incluida la esteatosis hepática. Materiales y métodos: buscamos evaluar el impacto del consumo de fructosa, diluida en agua a diferentes concentraciones, durante dos períodos de tiempo sobre los parámetros metabólicos de ratas Wistar, utilizando para ello el ANOVA. Resultados: nuestros datos indican que tanto el tiempo como la concentración de fructosa promueven variaciones en la masa corporal animal y la ingesta de alimentos, agua y calorías. La variable tiempo influyó en la modulación de parámetros bioquímicos tales como las concentraciones séricas de glucosa y colesterol total. Tanto la concentración de fructosa como el tiempo de exposición influyeron en las concentraciones séricas de triglicéridos, creatinina, AST, TNF e IL-6. Al evaluar el estado redox y los marcadores de daño oxidativo, observamos que la concentración de fructosa y el tiempo de exposición tuvieron un efecto sobre los niveles de glutatión total, que disminuyeron al aumentar la concentración y el tiempo. Para la superóxido dismutasa evaluamos los efectos del tiempo y la interacción. Se observó una interacción significativa para TBARS. Para las proteínas carboniladas, el tiempo de exposición fue un factor fundamental para generar algún efecto. Conclusiones: demostramos que la fructosa modula los parámetros de los triglicéridos y el colesterol total del hígado, y que el tiempo influye en el número de hepatocitos. Nuestros datos sugieren que la concentración de fructosa, el tiempo de exposición y cierta interacción entre estos dos parámetros tienen un efecto significativo sobre los parámetros metabólicos responsables del desarrollo de la enfermedad del hígado graso no alcohólico.

Modulation of immune functions, inflammatory response, and cytokine production following long-term oral exposure to three food additives; thiabendazole, monosodium glutamate, and brilliant blue in rats.

The food additives thiabendazole (TBZ), monosodium glutamate (MSG), and brilliant blue (BB) are commonly used in many daily-consumed food products worldwide. They are widely used in major agricultural and industrial applications. Yet, many of its toxicological aspects are still unclear, especially immune modulation. This research was therefore intended to investigate the effects of male Wistar rats' daily oral exposure for 90 days to TBZ (10 mg/kg b.wt), MSG (20 mg/kg b.wt), or BB (1.2 mg/kg b.wt) on the blood cells, immunity, and inflammatory indicators. The three tested food additives showed varying degrees of hematological alterations. Initially, megaloblastic anemia and thrombocytopenia were evident with the three tested food additives. At the same time, TBZ showed no significant changes in the leukogram element except eosinopenia. MSG induced leukopenia, lymphocytopenia, neutrophilia, and eosinophilia. BB evoked neutrophilia and lymphopenia. The immunoglobins M (IgM) and IgG were significantly reduced with the three tested food additives. In contrast, lysozyme and nitric oxide levels were elevated. A reduced considerably lymphocyte proliferation was detected with TBZ and MSG exposure without affecting the phagocytic activity. Various pathologic disturbances in splenic tissues have been detected. An obvious increase in CD4+ but a lessening in CD8+ immunolabeling was evident in TBZ and MSG groups. The cytokines, including interferon-gamma, tumor necrosis factor-alpha, and interleukin 1ß, 6, 10, and 13, were significantly upregulated in the spleen of rats exposed to TBZ, MSG, and BB. These results concluded that TBZ, MSG, and BB negatively affect hematological parameters, innate and humoral immune functions together with inflammatory responses. TBZ achieved the maximal negative impacts followed by MSG and finally with BB. Given the prevalence of these food additives, TBZ and MSG should be limited to a minimal volume use, or natural food additives should be used instead.

Sodium metabisulfite as a cytotoxic food additive induces apoptosis in HFFF2 cells.

Sodium metabisulfite (SMB), an antioxidant agent, is extensively used as a preservative in food industry. The current study was aimed to clarify its potential toxic effects on human fetal foreskin fibroblasts (HFFF2) cells, in vitro. Subsequently, MTT results illustrated that exposure to SMB significantly (p < 0.0001) decreased HFFF2 cell viability in a dose-dependent manner, and the concentration of 25 µM reduced cell survival rates to 50% as the half-maximal inhibitory concentration of SMB. It was further shown that SMB exerted this cytotoxic effect on HFFF2 cells through apoptosis induction. qRT-PCR and western blotting results showed that treatment of HFFF2 cells with this food additive led to significant upregulation of Bax, caspase 8, and caspase 9 pro-apoptotic genes and downregulation of Bcl-2 expression as a pro-survival agent. Furthermore, SMB remarkably increased caspase 3 levels and promoted its activation through cleavage in treated cells. Besides, exposure to SMB increased ROS levels and activated autophagy in treated cells, which are considered as the other indicators for cell damage. Taken together, our findings suggested that SMB could exert remarkable toxic effects on human normal cells through multiple mechanisms, including apoptosis activation, and its widespread usage in food safety should be reconsidered.

alpha-Glycosyl Isoquercitrin (AGIQ) and its lack of carcinogenicity in rasH2 mice.

alpha-Glycosyl Isoquercitrin (AGIQ), is used in Japan as a food additive and was granted generally recognized as safe (GRAS) status in 2005 (FEMA) and 2007 (FDA). The safety and toxicity information for AGIQ is sparse and therefore, the carcinogenicity potential of AGIQ was examined in the CByB6F1-Tg(HRAS)2Jic (rasH2) model. One hundred female and male rasH2 mice, each, were allocated to one of four designated dose groups; 0 (control)%, 1.5%, 3.0% or 5.0% AGIQ. Animals were administered the diets for six months and an additional 10 females and 10 males, each, were administered a positive control, N-methyl-N-nitrosourea (MNU). Body weights and clinical observations were collected. A full screen necropsy, organ weights, clinical chemistry, urinalysis and histopathology were performed. The positive control animals elicited appropriate responses specific to this strain (rasH2) of mice. There were statistically significant sporadic non-dose-dependent changes in clinical chemistries without corresponding pathological correlation. No microscopic AGIQ-related findings were noted; the range of pathology observations were all considered background findings, either specific to rasH2 mice or common to inbred strains of mice. Therefore, under the study conditions, the no-observed-adverse-effect level (NOAEL) was determined to be more than 5.0% (7215.4 mg/kg BW/day in male mice and 14685.5 mg/kg/day in female mice).

The role of the European small ruminant dairy sector in stabilising global temperatures: lessons from GWP* warming-equivalent emission metrics.

Recent calls advocate that a huge reduction in the consumption of animal products (including dairy) is essential to mitigate climate change and stabilise global warming below the 1.5 and 2°C targets. The Paris Agreement states that to stabilise temperatures we must reach a balance between anthropogenic emissions by sources and removals by sinks of greenhouse gases (GHG) in the second half of this century. Consequently, many countries have adopted overall GHG reduction targets (e.g. EU, at least 40% by 2030 compared to 1990). However, using conventional metric-equivalent emissions (CO2-e GWP100) as the basis to account for emissions does not result in capturing the effect on atmospheric warming of changing emission rates from short-lived GHG (e.g. methane: CH4), which are the main source of GHG emissions by small ruminants. This shortcoming could be solved by using warming-equivalent emissions (CO2-we, GWP*), which can accurately link annual GHG emission rates to its warming effect in the atmosphere. In our study, using this GWP* methodology and different modelling approaches, we first examined the historical (1990-2018) contribution of European dairy small ruminant systems to additional atmosphere warming levels and then studied different emission target scenarios for 2100. These scenarios allow us to envision the necessary reduction of GHG emissions from Europe's dairy small ruminants to achieve a stable impact on global temperatures, i.e. to be climatically neutral. Our analysis showed that, using this type of approach, the whole European sheep and goat dairy sector seems not to have contributed to additional warming in the period 1990-2018. Considering each subsector separately, increases in dairy goat production has led to some level of additional warming into the atmosphere, but these have been compensated by larger emission reductions in the dairy sheep sector. The estimations of warming for future scenarios suggest that to achieve climate neutrality, understood as not adding additional warming to the atmosphere, modest GHG reductions of sheep and goat GHG would be required (e.g. via feed additives). This reduction would be even lower if potential soil organic carbon (SOC) from associated pastures is considered.

Ultraprocessed Food Consumption is Strongly and Dose-Dependently Associated with Excess Body Weight in Swiss Women.

OBJECTIVE: This study investigated the association between ultraprocessed food consumption and excess body weight in a Swiss nationally representative study. METHODS: Data stem from the cross-sectional Swiss National Nutrition Survey menuCH (n = 2,057). Dietary information was collected with 24-hour dietary recalls, and food items were categorized into non-ultraprocessed or ultraprocessed using the NOVA food classification system. The following three excess body weight indicators were considered: BMI, waist circumference (WC), and a BMI-WC composite outcome. Multinomial logistic regression models stratified by sex were fitted. RESULTS: Women in the highest quintile of ultraprocessed food weight proportion had significantly higher odds of having obesity (odds ratio [OR] 3.01, 95% CI: 1.48-6.11), having abdominal obesity (OR 2.69, 95% CI: 1.43-5.05), and being in the highest category of the BMI-WC composite outcome (OR 3.28, 95% CI: 1.59-6.77). No relevant associations were observed in men. CONCLUSIONS: Ultraprocessed food weight proportion was strongly and dose-dependently associated with excess body weight in women but not in men. Further studies are required to elucidate potential mechanisms behind this association. Increasing evidence of the detrimental effect of ultraprocessed food consumption on health stresses the need to consider these products in future public health strategies.

Protective effects of the phytogenic feed additive "comfort" on growth performance via modulation of hypothalamic feeding- and drinking-related neuropeptides in cyclic heat-stressed broilers.

Identification of alternatives to antibiotics in livestock and poultry is necessary. Fueled by consumer preferences, phytogenic feed additives are increasingly used in the food system; however, their mode of action is not well defined. Here, we used broiler chickens, in which appetite and feeding behavior regulation are controlled by complex mechanisms, to determine the effect of the phytogenic feed additive "comfort" (PFA-C) as well as its underlying molecular mechanisms on growth performance in heat-stressed broiler chickens. Heat stress significantly increased birds' core body temperature, water intake, and the hypothalamic expression of heat shock protein (HSP) 70, whereas it decreased feed intake, BW, and woody breast incidence. Phytogenic feed additive "comfort" supplementation downregulated the hypothalamic expression of HSP70, reduced core body temperature, increased feed and water intake, and improved BW in HS broilers. At molecular levels, the effect of PFA-C on growth performance seemed to be mediated by modulation of hypothalamic expression of melanocortin receptor 2, arginine vasopressin, aquaporin 2, and sodium and potassium-transporting ATPase subunit beta 1 polypeptides. In summary, PFA-C supplementation ameliorates heat stress productivity losses via a potential cytoprotective effect, reduction of hypothalamic intracellular stress, and modulation of hypothalamic feeding- and drinking-related polypeptide expression.

A novel food-based foam as oral contrast agent with negative Hounsfield units for demarcation of small bowel loops on abdominal CT: tolerability and bowel distension in 25 volunteers.

BACKGROUND: Diseases of the bowel are not always displayed on conventional abdominal computed tomography (CT). The studied oral contrast agent aims to improve this. PURPOSE: To investigate whether the use of a novel oral contrast for abdominal CT enables the same diagnostic advantages as seen in magnetic resonance imaging (MRI). MATERIAL AND METHODS: Twenty-five consented volunteers drank up to 1400 mL of a stable, drinkable foam. Comments on acceptance and side effects were noted immediately and 24 h later. Foam palatability was documented through interviews, and distribution in the small bowel by Hounsfield units from the CT software. The CT results were compared with age- and sex-matched controls, pretreated according to routine. A non-enhanced abdominal CT protocol of lowest possible radiation dose was used. External referees evaluated all data obtained. RESULTS: Foam was considered odd to swallow, and fullness was reported by all volunteers after 950 mL. Five had difficulties in drinking the last 320 mL and two abstained from it. All adverse symptoms were mild. The distribution in the small bowel was on par with standard agents. Foam density revealed stability with intraluminal values of around -550 HU from stomach to terminal ileum, satisfying the requirement of a great bowel lumen-to-wall contrast. External reviewers re-evaluated all our data, and one predicted the foam to offer a potential for improved diagnostics. CONCLUSION: A CT true-negative bowel filling agent was formulated, with high acceptance, few side effects, and a potential to mimic T1-weighted MRI images.

Consumer perceptions of anticake agents on shredded Cheddar cheese.

Prepackaged natural cheese shreds are a growing consumer category. Anticake agents are applied to commercial cheese shreds to assist with shelf life and ease of use. The objective of this study was to investigate consumer perception of 3 anticake agents applied at various levels to Cheddar cheese shreds. Three common anticake agents (80% potato starch/20% cellulose blend, 100% potato starch, or potato starch/corn starch/calcium sulfate blend) were applied to duplicate lots of Cheddar cheese shreds at 1, 2, 3, 4, and 5% (wt/wt). Control Cheddar cheese shreds with no anticake were also included. Sensory properties (appearance, flavor, texture, and hot texture) were documented using a trained sensory panel (n = 8), and 3 consumer acceptance tests were also conducted. In test 1, consumers (n = 110) visually evaluated liking of cold shred appearance. In test 2, consumers (n = 100) evaluated melted shreds on a flour tortilla for overall liking and appearance, flavor, and texture liking. In test 3, consumers (n = 49) participated in a home usage test. Two-way ANOVA (anticake × anticake application rate) was used to interpret the collected data from each test. Visual appearance of shreds was the primary attribute influenced by anticake application and anticake agent. Trained panel evaluation demonstrated that the 100% potato starch anticake had minimal effects on visual appearance. The other 2 agents (80% potato starch/20% cellulose blend and potato starch/corn starch/calcium sulfate blend) showed increases in visible powder at >3% (wt/wt). Consistent with results from trained panelists, higher application rates decreased consumer appearance and color liking for Cheddar shreds with 80% potato starch/20% cellulose and potato starch/corn starch/calcium sulfate blends at >2 or 3% (wt/wt), respectively. Appearance liking of melted shreds decreased with increased anticake application percent but decreased the most for 100% potato starch anticake at greater than 1% (wt/wt) application. Overall liking, flavor liking, and texture liking attributes for melted shreds were negatively affected at >3% (wt/wt) application regardless of anticake agent used. In general, anticake agents can be applied to Cheddar cheese shreds at up to 3% (wt/wt) with minimal effect on consumer perception.

Investigating the effects of differently produced synthetic amorphous silica (E 551) on the integrity and functionality of the human intestinal barrier using an advanced in vitro co-culture model.

E 551, also known as synthetic amorphous silica (SAS), is the second most produced food additive. However, according to the re-evaluation of E 551 by the European Food Safety Authority (EFSA) in 2018, the amount of available data on the oral toxicity of food grade E 551 is still insufficient for reliable risk assessment. To close this gap, this study aimed to investigate six food-grade SAS with distinct physicochemical properties on their interaction with the intestinal barrier using advanced in vitro intestinal co-cultures and to identify potential structure-activity relationships. A mucus-secreting Caco-2/HT-29/Raji co-culture model was treated with up to 50 µg/ml SAS for 48 h, which represents a dose range relevant to dietary exposure. No effects on cell viability, barrier integrity, microvilli function or the release of inflammatory cytokine were detected after acute exposure. Slight biological responses were observed for few SAS materials on iron uptake and gene expression levels of mucin 1 and G-protein coupled receptor 120 (GPR120). There was no clear correlation between SAS properties (single or combined) and the observed biological responses. Overall, this study provides novel insights into the short-term impact of food-relevant SAS with distinct characteristics on the intestinal epithelium including a range of intestine-specific functional endpoints. In addition, it highlights the importance of using advanced intestinal co-cultures embracing relevant cell types as well as a protective mucus barrier to achieve a comprehensive understanding of the biological response of food additives at the intestinal barrier in vitro.

Development of a Web-Based Toolbox to Support Quantitative In-Vitro-to-In-Vivo Extrapolations (QIVIVE) within Nonanimal Testing Strategies.

The goal of the present study was to develop an online web-based toolbox that contains generic physiologically based kinetic (PBK) models for rats and humans, including underlying calculation tools to predict plasma protein binding and tissue:plasma distribution, to be used for quantitative in-vitro-to-in-vivo extrapolations (QIVIVE). The PBK models within the toolbox allow first estimations of internal plasma and tissue concentrations of chemicals to be made, based on the logP and pKa of the chemicals and values for intestinal uptake and intrinsic hepatic clearance. As a case study, the toolbox was used to predict oral equivalent doses of in vitro ToxCast bioactivity data for the food additives methylparaben, propyl gallate, octyl gallate, and dodecyl gallate. These oral equivalent doses were subsequently compared with human exposure estimates, as a low tier assessment allowing prioritization for further assessment. The results revealed that daily intake levels of especially propyl gallate can lead to internal plasma concentrations that are close to in vitro biological effect concentrations, particularly with respect to the inhibition of human thyroid peroxidase (TPO). Estrogenic effects were not considered likely to be induced by the food additives, as daily exposure levels of the different compounds remained 2 orders of magnitude below the oral equivalent doses for in vitro estrogen receptor activation. Overall, the results of the study show how the toolbox, which is freely accessible through www.qivivetools.wur.nl, can be used to obtain initial internal dose estimates of chemicals and to prioritize chemicals for further assessment, based on the comparison of oral equivalent doses of in vitro biological activity data with human exposure levels.