Feeding FIDO : development, validation and application of a dynamic, in vitro model of the gastrointestinal tract of the dog

To produce a complete and balanced dog diet it is necessary to know the nutritional needs of the dog as well as the availability of nutrients from the diet. Petfood manufacturers are restricted in performing (invasive) studies with animals for ethical reasons. Therefore, it is necessary to search for in vitro alternatives to these studies as explained in Chapter 1. Based on a literature study on the physiology of the GI tract of the healthy, adult dog (Chapter 2), the dynamic in vitro model for human subjects, pigs and calves, as described by Minekus (1995), was modified to mimic the physiological conditions of the dog. The model is named FIDO ( f unctional gastro i ntestinal do g model).The aim of the study was to develop the in vitro model simulating the GI tract of the dog. The model should simulate the physiological conditions in the GI tract of the dog as closely as possible. In that way luminal processes as well as physical and chemical properties of diets could be investigated. This thesis describes the developmental experiments, the validation experiments in comparison to dog studies as well as application studies.Validation of the modelTechnical validationThe study started with an extended literature review on the physiology of the stomach and small intestine of the healthy, adult dog with a special emphasis on those parameters which are relevant for the development of the dog model (Chapter 2). With respect to digestion of food, such parameters as transit times, pH values, concentrations of electrolytes and activities of enzymes are important to mimic physiological conditions as closely as possible. Data found in the literature were translated to a computer program to simulate these parameters in FIDO. The features of the model are described in Chapters 2 to 7. Based on the simulation of the physiology of the dog dry and canned dog foods were used to test the technical possibilities of the model. After some technical modifications to the gastric compartment and the pre-filters connected to the jejunal and ileal compartments, a study was performed to test the effect of particle size of dry dog food on gastric emptying. Particles≤3 mm emptied more slowly than particles≤1 mm. The effect of transit time on the availability for absorption of nitrogen and calcium of canned dog food was also investigated. Like in vivo , in FIDO less nitrogen and calcium were available for absorption with faster transit times (Chapter 3).Validation in vitro versus in vivoValidation of the model in comparison to the in vivo situation was the next step in the development of the dog model (Chapter 4). Ileal protein digestibility and availability for absorption of nitrogen of eight different dry dog foods were tested in the model. The results were compared with data found in vivo with ileally cannulated dogs, performed at the University of Illinois. The experiments proved to be very reproducible and the results found in FIDO are similar to those found in vivo in the dogs.Based on these findings and those of former experiments simulating pigs, calves and human beings, it can be concluded that the model is a suitable tool as an alternative to animal experiments in nutritional research.Application of the modelThe validation study (Chapter 3) showed a low availability for absorption of calcium in the model. Based on these results it was decided to study calcium and phosphorus availability from three commercially available canned dog foods (Chapter 4). Effects of addition of calcium-phosphorus supplements or the enzyme phytase and the effect of a lower pH in the small intestine were also included in this study. A human standard breakfast was used as a control diet, because this diet had a high calcium availability under human conditions in the diet.The results showed that the canned dog foods had a low availability for absorption for calcium (maximum 21%) and phosphorus (maximum 44%). Differences in relative availability of calcium and phosphorus were found among these diets, which can probably be explained by the source of these minerals. Also the low availability of these minerals can be attributable to the source. Another possible explanation of the low availability are the (saturated) fatty acids in the diet, which can form calcium soaps in the model.The advantage of FIDO is that the availability for absorption of calcium and other nutrients can be studied without the influence of the physiological status of the animal. The real amount absorbed by the animal, however, cannot be studied. Absorption by the animal depends on its needs and the absorption is hence dependent on two different mechanisms: passive and active absorption. To get more insight into the absorption of calcium through the intestinal wall of the dog, experiments were performed with Great Danes (8 and 20 weeks of age; in cooperation with the Veterinary Faculty of Utrecht University), FIDO and intestinal segments (Chapter 7). The effect of vitamin D was taken into account in this study by studying two levels in the diet. The three different methods ( in vivo , FIDO and intestinal segments) are complementary and can be used to get a better understanding of the regulation of calcium absorption in the dog.In Chapter 6 experiments are described to investigate the effect of gelling agents on the digestibility and availability for absorption of nutrients ('chunks in gravy' products). Three different (combinations of) gelling agents added to the gravy were used in this study in different concentrations (0.2% and 0.5%): carrageenan plus guar gum, carrageenan plus locust bean meal, and wheat starch. A diet without gelling agent was used as a control diet. Neither the gelling agent nor the concentration had any effect on digestibility of proteins and carbohydrates, availability for absorption of calcium and phosphorus, viscosity or buffering capacity in the intestinal content. From the results it can be concluded that addition of the gelling agents used does not affect the nutritional quality of the diets at the low concentrations tested.ConclusionsThe dynamic in vitro model of the GI tract of dogs simulates the physiological parameters very accurately and reproducibly. Transit time of food has an effect on digestibility and availability for absorption, just like in dogs. Also ileal protein digestibility in the model is similar to the data found in vivo . It is possible to investigate specific questions regarding dog food in this model (e.g. the effect of gelling agents on digestibility). Another important aspect is the fact that the experiments in FIDO can be performed under highly standardized condition, in contrast to in vivo studies in which biological variance among animals plays a role. This comes to expression in the reproducibility and sensitivity of the results from FIDO compared to results of in vivo studies.The dynamic in vitro model of the gastrointestinal tract of the dog is a suitable alternative to in vivo studies with respect to digestibility and availability for absorption of nutrients from different types of dog food, such as canned and dry dog foods.</p

Noninvasive monitoring of radiotherapy-induced microvascular changes using dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) in a colorectal tumor model

To examine dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) with a macromolecular contrast agent (P792) to visualize effects of radiotherapy (RT) on microvascular leakage in a colorectal cancer model.Journal Articleinfo:eu-repo/semantics/publishe

Town of Jay Annual Report Year Ending June 30, 2014

status: publishe

Stress Strengthens Memory of First Impressions of Others' Positive Personality Traits

Encounters with strangers bear potential for social conflict and stress, but also allow the formation of alliances. First impressions of other people play a critical role in the formation of alliances, since they provide a learned base to infer the other's future social attitude. Stress can facilitate emotional memories but it is unknown whether stress strengthens our memory for newly acquired impressions of other people's personality traits. To answer this question, we subjected 60 students (37 females, 23 males) to an impression-formation task, viewing portraits together with brief positive vs. negative behavior descriptions, followed by a 3-min cold pressor stress test or a non-stressful control procedure. The next day, novel and old portraits were paired with single trait adjectives, the old portraits with a trait adjective matching the previous day's behavior description. After a filler task, portraits were presented again and subjects were asked to recall the trait adjective. Cued recall was higher for old (previously implied) than the novel portraits' trait adjectives, indicating validity of the applied test procedures. Overall, recall rate of implied trait adjectives did not differ between the stress and the control group. However, while the control group showed a better memory performance for others' implied negative personality traits, the stress group showed enhanced recall for others' implied positive personality traits. This result indicates that post-learning stress affects consolidation of first impressions in a valence-specific manner. We propose that the stress-induced strengthening of memory of others' positive traits forms an important cue for the formation of alliances in stressful conditions

Recombinant human erythropoietin α modulates the effects of radiotherapy on colorectal cancer microvessels

Recent data suggest that recombinant human erythropoietin (rhEPO) modulates tumour growth and therapy response. The purpose of the present study was to examine the modulation of radiotherapy (RT) effects on tumour microvessels by rhEPO in a rat colorectal cancer model. Before and after 5 × 5 Gy of RT, dynamic contrast-enhanced -magnetic resonance imaging was performed and endothelial permeability surface product (PS), plasma flow (F), and blood volume (V) were modelled. Imaging was combined with pO2 measurements, analysis of microvessel density, microvessel diameter, microvessel fractal dimension, and expression of vascular endothelial growth factor (VEGF), hypoxia-inducible factor-1 α (HIF-1α), Bax, and Bcl-2. We found that RT significantly reduced PS and V in control rats, but not in rhEPO-treated rats, whereas F was unaffected by RT. Oxygenation was significantly better in rhEPO-treated animals, and RT induced a heterogeneous reoxygenation in both groups. Microvessel diameter was significantly larger in rhEPO animals, whereas VEGF expression was significantly lower in the rhEPO group. No differences were observed in HIF-1α, Bax, or Bcl-2 expression. We conclude that rhEPO results in spatially heterogeneous modulation of RT effects on tumour microvessels. Direct effects of rhEPO on neoplastic endothelium are likely to explain these findings in addition to indirect effects induced by increased oxygenation

Bioengineering approaches to simulate human colon microbiome ecosystem

Background Several diseases associated to colon microbial imbalance (dysbiosis), such as obesity, diabetes, inflammatory bowel disease, cardiovascular disease and cancer, are being reverted by modulation of gut microbiota composition through treatment with prebiotics and probiotics. Multiple in vitro models have been developed over the past three decades, with several experimental configurations, as they provide a quick, easy, and cost-effective approach to study the gut microbiome, as compared to troublesome and time-consuming in vivo studies. Scope and approach This review aims to provide an overview of the most relevant available in vitro models used to mimic the human colon microbiome dynamics, including macro-scale and microfluidic-based models. Main characteristics, functionalities, current applications and advantages or disadvantages of the models are discussed in order to provide useful information for end users (namely food and pharmaceutical researchers), when selecting the most appropriated model for assessing health claims and safety of novel functional food and drugs. Finally, the use of these colon models as a tool to study prebiotic and probiotic response in host-microbiota interaction is reviewed. Key findings and conclusions A wide range of in vitro models representing specific colon parts have been developed. However, none of these models can simultaneously cover all the key conditions found in the human colon (namely anatomical, physical, biochemical, and biological characteristics), as well as the complex microbiome-host interaction. Thus, there is a significant opportunity for further improvement of the models experimental setups towards more realistic operating systems, including mucosal surfaces, intestinal cells and tissues allowing microbiomehost crosstalk representation.SFRH/BD/139884/2018 from the Portuguese Foundation for Science and Technology (FCT). This study was supported by the FCT under the scope of the strategic funding of UIDB/04469/2020 unit and the Project ColOsH PTDC/BTM–SAL/30071/2017 (POCI–01–0145–FEDER–030071)info:eu-repo/semantics/publishedVersio

Demonstratives in Spatial Language and Social Interaction: An Interdisciplinary Review

This paper offers a review of research on demonstratives from an interdisciplinary perspective. In particular, we consider the role of demonstratives in current research on language universals, language evolution, language acquisition, multimodal communication, signed language, language and perception, language in interaction, spatial imagery, and discourse processing. Traditionally, demonstratives are analyzed as a particular class of spatial deictics. Yet, a number of recent studies have argued that space is largely irrelevant to deixis and that demonstratives are primarily used for social and interactive purposes. Synthesizing findings in the literature, we conclude that demonstratives are a very special class of linguistic items that are foundational to both spatial and social aspects of language and cognition