Ingestion Of Meal Research Articles

The antennal transcriptome of Triatoma infestans reveals substantial expression changes triggered by a blood meal

BackgroundTriatoma infestans is the main vector of Chagas disease in the Americas, currently transmitting it in Argentina, Paraguay, and Bolivia. Many T. infestans populations present insecticide resistance, reducing the efficiency of control campaigns. Alternative vector control methods are needed, and molecular targets mediating fundamental physiological processes can be a promising option to manipulate kissing bug behavior. Therefore, it is necessary to characterize the main sensory targets, as well as to determine whether they are modulated by physiological factors. In order to identify gene candidates potentially mediating host cue detection, the antennal transcripts of T. infestans fifth instar larvae were sequenced and assembled. Besides, we evaluated whether a blood meal had an effect on transcriptional profiles, as responsiveness to host-emitted sensory cues depends on bug starvation.ResultsThe sensory-related gene families of T. infestans were annotated (127 odorant receptors, 38 ionotropic receptors, 11 gustatory receptors, 41 odorant binding proteins, and 25 chemosensory proteins, among others) and compared to those of several other hemipterans, including four triatomine species. Several triatomine-specific lineages representing sensory adaptations developed through the evolution of these blood-feeding heteropterans were identified. As well, we report here various conserved sensory gene orthogroups shared by heteropterans. The absence of the thermosensor pyrexia, of pickpocket receptor subfamilies IV and VII, together with clearly expanded takeout repertoires, are revealed features of the molecular bases of heteropteran antennal physiology. Finally, out of 2,122 genes whose antennal expression was significantly altered by the ingestion of a blood meal, a set of 41 T. infestans sensory-related genes (9 up-regulated; 32 down-regulated) was detected.ConclusionsWe propose that the set of genes presenting nutritionally-triggered modulation on their expression represent candidates to mediate triatomine host-seeking behavior. Besides, the triatomine-specific gene lineages found represent molecular adaptations to their risky natural history that involves stealing blood from an enormously diverse set of vertebrates. Heteropteran gene orthogroups identified may represent unknown features of the sensory specificities of this largest group of hemipteroids. Our work is the first molecular characterization of the peripheral modulation of sensory processes in a non-dipteran vector of human disease.

Indispensable Amino Acid Digestibility of Moroccan Fava Bean Using the Dual Isotope Method in Healthy Adults

BackgroundAssessment of protein quality is necessary to satisfy the nutritional needs of populations across the world. In addition to indispensable amino acid (IAAs) composition, protein digestibility is a major component of IAA bioavailability, playing a crucial role in human health and affecting the linear growth of children. ObjectivesThis study aimed to evaluate IAA digestibility of fava beans, a legume widely consumed in Morocco using the dual-tracer method. Methods2H-intrinsically labeled Fava beans supplemented with 12 mg/kg BW of 13C spirulina were given to 5 healthy volunteers (3 men and 2 women), aged 25.8 ± 3.3 y, with a mean BMI of 20.0 kg/m2. The meal was spread in small portions and was given hourly throughout 7 h. Blood was sampled at baseline and hourly from 5 to 8 h after meal ingestion. IAA digestibility was evaluated by gas chromatography—combustion—isotope ratio mass spectrometry using the 2H/13C ratio in plasma IAA. Digestible indispensable amino acid ratios (DIAAR) were calculated using the scoring pattern for people older than 3 y. ResultsFava beans had an adequate level of lysine but were limiting in several IAAs, especially methionine. Under our experimental conditions, the average IAA digestibility of fava bean was 61.1% ± 5.2%. Valine had the highest digestibility (68.9% ± 4.3%) and threonine had the lowest (43.7% ± 8.2%). In consequence, the lowest DIAAR was 67% for threonine and only 47% for sulfur amino acids (SAA). ConclusionsThe present study is the first to determine the digestibility of fava bean amino acids in humans. The mean IAA digestibility was moderate, and consequently, we conclude that fava bean provides a limited amount of several IAAs, especially SAA, but adequately for lysine. Preparation and cooking methods of fava beans should be improved to increase digestibility.This study was registered at ClinicalTrials.gov as NCT04866927.

A modelling approach to hepatic glucose production estimation.

Stable isotopes are currently used to measure glucose fluxes responsible for observed glucose concentrations, providing information on hepatic and peripheral insulin sensitivity. The determination of glucose turnover, along with fasting and postprandial glucose concentrations, is relevant for inferring insulin sensitivity levels. At equilibrium (e.g. during the fasting state) the rate of glucose entering the circulation equals its rate of disappearance from the circulation. If under these conditions tracer is infused at a constant rate and Specific Activity (SA) or Tracer to Tracee (TTR) ratio is computed, the Rate of Appearance (RA) equals the Rate of Disappearance (RD) and equals the ratio between infusion rate and TTR or SA. In the post-prandial situation or during perturbation studies, however, estimation of RA and RD becomes more complex because they are not necessarily equal and, furthermore, may vary over time due to gastric emptying, glucose absorption, appearance of ingested or infused glucose, variations of EGP and glucose disappearance. Up to now, the most commonly used approach to compute RA, RD and EGP has been the single-pool model by Steele. Several authors, however, report pitfalls in the use of this method, such as "paradoxical" increase in EGP immediately after meal ingestion and "negative" rates of EGP. Different attempts have been made to reduce the impact of these errors, but the same problems are still encountered. In the present work a completely different approach is proposed, where cold and labeled [6, 6-2H2] glucose observations are simultaneously fitted and where both RD and EGP are represented by simple but reasonable functions. As an example, this approach is applied to an intra-venous experiment, where cold glucose is infused at variable rates to reproduce a desired glycaemic time-course. The goal of the present work is to show that appropriate, if simple, modelling of the whole infusion procedure together with the underlying physiological system allows robust estimation of EGP with single-tracer administration, without the artefacts produced by the Steele method.

Accuracy of Reporting Food Intakes among Primary School Children Aged 7–9 Years

BackgroundAccurate measurement of dietary intake throughout childhood is important to monitor children’s growth and development and for their long-term health. However, measuring dietary intake in children is challenging because of misreporting, difficulties in establishing portion size, and heavy reliance on proxy reporters. ObjectivesThis study aimed to determine the accuracy of self-reported food intake by primary school children aged 7–9 y. MethodsA total of 105 children (51% boys), aged 8.0 ± 0.8 y, were recruited from three primary schools in Selangor, Malaysia. Individual meal intakes during a school break time were determined using a food photography method as the reference method. The children were then interviewed the following day to assess their recall of their meal intakes the previous day. ANOVA and Kruskal-Wallis tests were used to determine mean differences in the accuracy of reporting food items and amount by age and weight status, respectively. ResultsOn average, the children achieved 85.8% match rate, 14.2% omission rate, and 3.2% intrusion rate for accuracy in reporting food items. The children also achieved 85.9% correspondence rate and 6.8% inflation ratio for accuracy in reporting food amounts. Children living with obesity had notably higher intrusion rates compared with normal weight children (10.6% vs. 1.9%) (P < 0.05). Children aged >9 y had notably higher correspondence rates, compared with children aged 7 y (93.3% vs. 78.8%) (P < 0.05). ConclusionsThe low omission and intrusion rates and the high correspondence rate indicate that primary school children aged 7–9 y are capable of self-reporting food intake accurately for a lunch meal without proxy assistance. However, to confirm children’s abilities to report their daily food intakes, further studies should be conducted to assess the accuracy of children in reporting their food intakes for more than one meal in a day.

Glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 secretion in humans: Characteristics and regulation.

Glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) are important incretin hormones. They are released from the gut after meal ingestion and potentiate glucose-stimulated insulin secretion. Their release after meal ingestion and oral glucose are well established and have been characterized previously. During recent years, knowledge of other regulatory aspects that potentially may affect GIP and GLP-1 secretion after meal ingestion have also begun to emerge. Here, the results of human studies on these novel aspects of meal- and nutrient-stimulated incretin hormone secretion are reviewed. The human literature was revisited by identifying articles in PubMed using key words GIP, GLP-1, secretion, meal, and nutrients. The results show that all macronutrients individually stimulate GIP and GLP-1 secretion. However, there was no synergistic action when given in combination. A pre-load 30 min before a meal augments the GIP and GLP-1 response. GIP and GLP-1 secretion have a diurnal variation with a higher response to an identical meal in the morning than in the afternoon. There is no difference in GIP and GLP-1 secretion whether a meal is ingested slowly or rapidly. GIP and GLP-1 secretion after dinner are the same whether or not breakfast and lunch have been ingested. The temperature of the food may be of importance for the incretin hormone response. These novel findings have increased our knowledge on the regulation of the complexity of the incretin system and are also important knowledge when designing future studies.

Selection for high growth displaces costs of digestion from SDA to SMR in divergent ecotypes of rainbow trout

AbstractTo understand the drivers of variation in digestive performance and their effects on growth, we examined relationships among food consumption, digestive metabolism, food processing efficiency, and growth rate in juveniles of fast‐growing piscivore versus slow‐growing insectivore ecotypes of rainbow trout reared at satiation rations on the same diet (i.e., commercial food pellets). Relative to slow‐growing insectivores with lower basal metabolism, and despite a much larger maximum food ration, faster‐growing piscivores presented an unexpected pattern of higher digestive efficiency through a reduction in the absolute costs of postprandial metabolism coupled with shorter or similar gut residence time and higher assimilation efficiency. These results suggest that the increase in digestive metabolism following the ingestion of larger meals can be mitigated by displacing the costs of digestion from SDA to SMR. Reducing total digestion costs (SDA + SMR) while maintaining higher assimilation efficiency may be possible through potential adaptations including (1) increased intestinal absorption capacity; (2) economies of scale that shorten gut transit time with increasing ration level; or (3) a permanently larger digestive tract that increases maintenance costs but reduces the need for cyclic upregulation and associated overhead costs.

Immune gene expression in the mosquito vector Culex quinquefasciatus during an avian malaria infection.

Plasmodium relictum is the most widespread avian malaria parasite in the world. It is listed as one of the 100 most dangerous invasive species, having been responsible for the extinction of several endemic bird species, and the near-demise of several others. Here we present the first transcriptomic study focused on the effect of P. relictum on the immune system of its vector (the mosquito Culex quinquefasciatus) at different times post-infection. We show that over 50% of immune genes identified as being part of the Toll pathway and 30%-40% of the immune genes identified within the Imd pathway are overexpressed during the critical period spanning the parasite's oocyst and sporozoite formation (8-12 days), revealing the crucial role played by both these pathways in this natural mosquito-Plasmodium combination. Comparison of infected mosquitoes with their uninfected counterparts also revealed some unexpected immune RNA expression patterns earlier and later in the infection: significant differences in expression of several immune effectors were observed as early as 30 min after ingestion of the infected blood meal. In addition, in the later stages of the infection (towards the end of the mosquito lifespan), we observed an unexpected increase in immune investment in uninfected, but not in infected, mosquitoes. In conclusion, our work extends the comparative transcriptomic analyses of malaria-infected mosquitoes beyond human and rodent parasites and provides insights into the degree of conservation of immune pathways and into the selective pressures exerted by Plasmodium parasites on their vectors.

Effect of fasting on short-term visual plasticity in adult humans.

Brain plasticity and function is impaired in conditions of metabolic dysregulation, such as obesity. Less is known on whether brain function is also affected by transient and physiological metabolic changes, such as the alternation between fasting and fed state. Here we asked whether these changes affect the transient shift of ocular dominance that follows short-term monocular deprivation, a form of homeostatic plasticity. We further asked whether variations in three of the main metabolic and hormonal pathways affected in obesity (glucose metabolism, leptin signalling and fatty acid metabolism) correlate with plasticity changes. We measured the effects of 2 h monocular deprivation in three conditions: post-absorptive state (fasting), after ingestion of a standardised meal and during infusion of glucagon-like peptide-1 (GLP-1), an incretin physiologically released upon meal ingestion that plays a key role in glucose metabolism. We found that short-term plasticity was less manifest in fasting than in fed state, whereas GLP-1 infusion did not elicit reliable changes compared to fasting. Although we confirmed a positive association between plasticity and supraphysiological GLP-1 levels, achieved by GLP-1 infusion, we found that none of the parameters linked to glucose metabolism could predict the plasticity reduction in the fasting versus fed state. Instead, this was selectively associated with the increase in plasma beta-hydroxybutyrate (B-OH) levels during fasting, which suggests a link between neural function and energy substrates alternative to glucose. These results reveal a previously unexplored link between homeostatic brain plasticity and the physiological changes associated with the daily fast-fed cycle.

Home-Prepared Meal Consumption Is Associated with Healthy Food Choices in Pregnant Women Followed Up by Primary Health Care.

The act of preparing food, especially at home, may be related to improvement in healthy eating patterns. This study analyzed the association between home-prepared meals consumption and the food markers consumption, and weight gain in pregnant women followed up in Primary Health Care in the Federal District (DF), Brazil. This is a cross-sectional study, conducted with pregnant women of all gestational ages. The characteristics of meals preparation and intake, as well as the consumption of food markers, were evaluated through structured questionnaires. Gestational weight gain was evaluated based on data recorded in the pregnant woman's booklet. Variables related to pregnancy, health, lifestyle, and socioeconomic status were analyzed as covariates. A total of 233 pregnant women were included in this study, with a mean age of 28.50 (SD = 6.32) years. Inadequate gestational weight gain was found in 46% of pregnant women. Consumption of soft drinks was 49% lower in pregnant women who prepared all meals at home. Eating home-prepared meals was inversely associated with a high score for unhealthy foods. Home-prepared meals consumption could be an effective health promotion strategy in Primary Health Care, helping to increase the chances of vegetable consumption, and decrease the consumption of soft drinks.

Artificial Pancreas: A Review of Meal Detection and Carbohydrates Counting Techniques

OBJECTIVE: The development of an artificial pancreas is an open research problem that faces the challenge of creating a control algorithm capable of dosing insulin automatically and driving blood glucose to healthy levels. Many of these approaches, including artificial intelligence, are based on techniques that could result in and undesirable outcome because most of them include neither detect meal intake or meal size information. To overcome that issue, some meal count-detection algorithms reported in scientific publications have shown not only a good performance on blood glucose regulation but fewer hypoglicemia and hyperglycemia events too. METHODS: We reviewed the most relevant authors and publications and main databases (particularly SCOPUS and Google Scholar), focusing on algorithms of detection and estimation of meal intake from multiple approaches. RESULTS: A wide range of approaches and proposals have been found. The majority of them include trials on in silico patients rather than in vivo ones. Most of procedures require as inputs glucose samples from continuous glucose monitoring devices as basal insulin and bolus as well. Most of approaches could be grouped by 2 categories: mathematical model based and not model based. CONCLUSION: A combination of methods seems to reach better results.

Magnetic Resonance Imaging and Spectroscopy Methods to Study Hepatic Glucose Metabolism and Their Applications in the Healthy and Diabetic Liver.

The liver plays an important role in whole-body glucose homeostasis by taking up glucose from and releasing glucose into the blood circulation. In the postprandial state, excess glucose in the blood circulation is stored in hepatocytes as glycogen. In the postabsorptive state, the liver produces glucose by breaking down glycogen and from noncarbohydrate precursors such as lactate. In metabolic diseases such as diabetes, these processes are dysregulated, resulting in abnormal blood glucose levels. Magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) are noninvasive techniques that give unique insight into different aspects of glucose metabolism, such as glycogenesis, glycogenolysis, and gluconeogenesis, in the liver in vivo. Using these techniques, liver glucose metabolism has been studied in regard to a variety of interventions, such as fasting, meal intake, and exercise. Moreover, deviations from normal hepatic glucose metabolism have been investigated in both patients with type 1 and 2 diabetes, as well as the effects of antidiabetic medications. This review provides an overview of current MR techniques to measure hepatic glucose metabolism and the insights obtained by the application of these techniques in the healthy and diabetic liver.

The Interindividual Variability of Phytofluene Bioavailability is Associated with a Combination of Single Nucleotide Polymorphisms.

Phytofluene is a colorless carotenoid with potential health benefits that displays a higher bioavailability compared to carotenoids such as lutein, β-carotene or lycopene. Several studies suggest its bioavailability displays an elevated interindividual variability. The aim of this work is to investigate whether a combination of SNPs is associated with this variability. Thirty-seven healthy adult males consume a test meal that provides phytofluene from a tomato puree. Phytofluene concentrations are measured at fast and in chylomicrons at regular time intervals after meal intake. Identification of the combination of SNPs that best explained the interindividual variability of the phytofluene response is assessed by partial least squares regression. There is a large interindividual variability in the phytofluene response, with CV = 88%. Phytofluene bioavailability is positively correlated with fasting plasma phytofluene concentration (r = 0.57; p = 2 × 10-4 ). A robust partial least squares regression model comprising 14 SNPs near or within 11 genes (ABCA1-rs2487059, rs2515629, and rs4149316, APOC1-rs445925, CD36-rs3211881, ELOVL5-rs6941533, FABP1-rs10185660, FADS3-rs1000778, ISX-rs130461, and rs17748559, LIPC-rs17240713, LPL-rs7005359, LYPLAL1-rs1351472, SETD7-rs11936429) explains 51% (adjusted R2 ) of the interindividual variability in phytofluene bioavailability. This study reports a combination of SNPs that is associated with a significant part of the interindividual variability of phytofluene bioavailability in a healthy male adult population.

Efficacy and Safety of Empagliflozin in Patients with Type 2 Diabetes Mellitus Fasting During Ramadan: A Real-World Study from Bangladesh.

In Bangladesh, there is a large population of Muslims with type 2 diabetes mellitus (T2DM) who fast during Ramadan. Changes in the pattern of meal and fluid intake during this long-fasting hours may increase the risk of hypoglycaemia, hyperglycaemia, and dehydration. Our key point of focus was to evaluate the efficacy and safety of Empagliflozin, a sodium-glucose co transporter 2 inhibitor (SGLT2i), in patients with T2DM while fasting during Ramadan. This was a 24-weeks, multi-centre, open-label, two-arm parallel-group study. In this prospective type of observational study, we enrolled patients taking Empagliflozin and Metformin with or without a DPP-4 inhibitor in one group (n = 274) and a parallel group (n = 219) who were treated with Metformin with or without a DPP-4 inhibitor. The primary endpoint of this study was HbA1c reduction, weight loss and the number of reported or symptomatic hypoglycemic events. In secondary endpoints, we evaluated the changes from baseline in blood pressure, estimated glomerular filtration rate (eGFR), serum creatinine, and serum electrolyte, the proportion of volume depletion (≥1 event) and incidence of other adverse events (AEs) of interest potentially related to SGLT2 inhibitor. During Ramadan, HbA1c reduction was significant in Empagliflozin arm (-0.49% vs -0.12%); [p < 0.001]. From before to the end of the study, significant weight reduction was seen in the Empagliflozin arm (-1.4 kg vs -0.09 kg); [p < 0.001]. We observed no significant increase in the incidence of hypoglycemia (0.7% vs 0.4%, p = 0.267) and volume depletion (2.6% vs 1.8%; p = 0.55) in both arm. All these milder forms events did not require any hospital admission. There was no report of serious adverse events or any discontinuation, or reduction of prescribed doses of empagliflozin during Ramadan. Empagliflozin is efficacious and safe for treating adults with T2DM during Ramadan.

Enteroendocrine Systems That Sense Nutrients in the Gut and Control the Body.

Gut hormones produced and released from enteroendocrine cells have key roles not only in nutrient digestion and absorption, but also in control of appetite, nutrient deposition and storage in the body. Several types of enteroendocrine cells sense nutrients after meal ingestion and release specific gut hormones. Understanding how gut hormone responses are controlled and in turn regulate physiological outcomes is an area of active research. In addition, the role of the endocrine system in human-physiology and in pathophysiology (obesity, diabetes, and gastrointestinal diseases) has begun being investigated. The symposium was organized to present and discuss recent advances in this research field from the aspects of bench to bedside.

Effect of Royal Palm (Roystonea regia) nut meal intake on serum biochemical indices of broilers chickens

El experimento se llevó a cabo con el objetivo de estudiar el efecto del consumo de harina de frutos de la palma real –PR– (Roystonea regia) en la bioquímica sanguínea de pollos de ceba (PC). Se utilizaron 32 animales machos de ocho a 42 días-d- de edad, que se distribuyeron según diseño completamente aleatorizado en cuatro tratamientos (T) y ocho repeticiones: control (maíz-soya) y la inclusión de harina de palmiche (HP) en 5; 10 y 15 %. Se determinaron el peso vivo (PV), indicadores digestivos y de la bioquímica sanguínea relacionados con el metabolismo proteico, de carbohidratos, de lípidos y minerales así como de funcionalidad hepática. El PV fue mayor en las aves que consumieron 15 % de HP respecto al resto de los T. Se observó aumento en las proteínas totales y el ácido úrico en los tratamientos donde se incluyó el fruto de la PR respecto al control (29,86 vs 34,78; 34,78 y 37,34 gramos·litros-1 [g·L-1]; 252,75 vs 310,63; 278,88 y 303,13 micromol·L-1 [µM·L-1]) , respectivamente. Los triglicéridos disminuyeron con la presencia del alimento alternativo (1,49 vs 1,00; 1,06 y 1,06 milimol·L-1 [mmol·L-1]), en tanto el colesterol sólo lo hizo con el 5 % de inclusión. No se observaron diferencias entre T para los indicadores del metabolismo de carbohidratos y minerales. No hubo daño en la funcionalidad hepática con los niveles que se probaron. Se concluye que el consumo de HP por PC hasta 15 % modifica indicadores de la bioquímica sanguínea relacionados con el metabolismo proteico y lipídico y no se muestran signos de daños hepáticos.

Studying iodine intake of Portuguese children school meals

Iodine is an essential trace element, and its nutritional importance is well established. The iodine content of school meals of Portuguese children aged between 6 and 10 years (collected in the metropolitan area of Lisbon) was analyzed by ICP-MS. The samples were cooked with and without iodized salt and additionally some complementary foods were purchased as supplements to the main meals or to the other meal along the day. The results report six meals per day and they suggest that at least one main meals (lunch or dinner) prepared with iodized salt is enough to reach the recommended daily iodine intake (AI), 90 µg/day, not exceeding the tolerable upper intake (UL) level of 300 µg/day. When both main meals are cooked without iodized salt, 11 % of the hypotheses present an iodine content less than 90 µg/day. However, when lunch and dinner are prepared with iodized salt, 1 % exceeds the value of the UL. The food groups with the highest levels of iodine are daily products and fish. These results presuppose a balanced diet without any dietary restrictions. So, for ideological or medical reasons, special attention must be paid to diets with some limitations, such as vegetarian, lactose or high content of proteins free diets.

The Hospital Food Experience Questionnaire Predicts Adult Patient Food Intake.

Purpose: Describe food/beverage intake among all patients and those with low meal intake and determine if the Hospital Food Experience Questionnaire (HFEQ), or its shorter version (HFEQ-sv), predicts food intake while considering patient (e.g.,gender) and hospital characteristics (e.g.,foodservice model).Methods: Cross-sectional study of 1087 adult patients from 16 hospitals in Ontario, Canada. The valid and reliable HFEQ assessed patients' meal quality perceptions. Visual estimation determined overall meal and food/beverage intake using the Comstock method. Binary logistic regressions tested the association between patient and hospital characteristics and whether HFEQ or HFEQ-sv scores added utility in predicting overall meal intake (≤50% vs. ≥75%).Results: Approximately 29% of patients consumed ≤50% of their meal. Models assessing patient and hospital characteristics and either the HFEQ or the HFEQ-sv were significant (LRT(43) = 72.25, P = 0.003; LRT(43) = 93.46, P < 0.001). Men and higher HFEQ or HFEQ-sv scores demonstrated significantly higher odds of ≥75% meal consumption. Considering HFEQ or HFEQ-sv scores explained greater variance in meal intake and resulted in better model fits.Conclusions: The HFEQ and HFEQ-sv predict patient meal intake when adjusting for covariates and add utility in understanding meal intake. Either version can be confidently used to support menu planning and food delivery to promote food intake.

Can biogenic amines cause ailments following the intake of edible mushroom meals?

Several toxicological centres have reported ailments, mainly digestive inconveniences, following the intake of provably edible mushroom species. The causes of such complaints have not been explained yet. We, therefore, tested levels of biogenic amines (BAs). Fruit bodies of widely consumed wild-growing species, Imleria badia and Suillus variegatus were stewed, then preserved by freezing or canning and stored for up to 12 months. Contents of six amines were determined in the fresh matter, in each step of preservation and during storage. Histamine (HIM) and cadaverine (CAD) were not detected at all. Putrescine (PUT) occurred in fresh fruit bodies at levels of 700–1 500 mg kg&lt;sup&gt;–1&lt;/sup&gt; dry matter (DM), however, its contents considerably decreased, particularly during stewing. Undesirable phenylethylamine (PEA) and tyramine (TYM) occurred at lower levels. Stewing, the technological step necessary in both the tested preservation treatments, reduced the contents of all the amines alike as sterilisation, whereas following storage showed a limited effect. PUT seems to be the only amine that could participate in the reported ailments.

Evaluation of Dosage and Food Effect on L-Glutamine Exposure for Sickle Cell Anemia: A Population Pharmacokinetic Analysis

Introduction: L-glutamine (Endari®) is an amino acid approved for the treatment of sickle cell disease (SCD). The mechanism of action of L-glutamine in SCD is not fully understood but believed to involve, at least partly, augmentation of the de novo synthesis of intracellular glutathione, which can protect sickle erythrocytes from oxidant injury. As an endogenous compound, the pharmacokinetics (PK) of L-glutamine have not been extensively studied, and currently recommended dosing is based on single-dose studies. It is also unclear how physiology, food intake, and dose impact L-glutamine drug exposure in patients with SCD. Our objective was to understand the PK of multiple dose L-glutamine therapy using a population PK analysis to identify factors that may inform optimal dosing of L-glutamine in children and adults with SCD. Methods: A total of 400 L-glutamine plasma concentration-time data points collected from 12 participants (NCT04684381) were available for population PK analysis. Each participant received 3 ascending oral doses (0.1 and 0.3 g/kg given BID and 0.6 g/kg given once daily) during a four-week study. Plasma L-glutamine and other amino acid levels were obtained before and after oral L-glutamine doses at each visit and quantified by ion exchange chromatography. Population PK analysis was performed using nonlinear mixed effect modeling by NONMEM 7.4 (ICON, Ellicott City, MD, USA). Multiple base model structures including one-compartment and two-compartment models were explored to describe the L-glutamine PK. In addition to the primary PK parameters clearance (CL/F) and volume of distribution (V/F), a relative bioavailability (F) was included in the modeling to account for the potential impact of dose and food on L-glutamine PK. Patient demographics and laboratory data, including body weight, body surface area, age, serum creatinine levels, urine creatinine levels, baseline glutamine level, meal intake, and dosages were evaluated as potential covariates using the stepwise selection method. The change in the objective function value (OFV) between two nested models was assumed to follow the χ2 distribution and was tested at a significance level of <0.01 (-6.64 points in OFV). The final model was evaluated by goodness-of-fit (GOF) plots and visual predictive check (VPC) analysis. For the VPC analysis, one thousand replicates of simulated datasets were generated using the final model, and the distribution of simulated observations was compared with the actual observations. Results: A one-compartment with first-order absorption model best described the oral dose L-glutamine concentration-time profiles. The data did not support the inclusion of a lag time in drug absorption, which is consistent with the observed rapid absorption. In accordance with allometric theory, body size was found to be significantly correlated with glutamine oral clearance (CL/F; where F represents bioavailability, which is not measured and therefore unknown) and volume of distribution (V/F). We therefore used allometrically scaled body weight to account for differences in body size. Dose-normalized peak concentration (Cmax) decreased with dose escalation (Figure 1), indicating capacity-limited, non-linear PK of oral L-glutamine. Covariate analysis identified that baseline glutamine levels and dosages negatively correlated with glutamine clearance, whereas food intake did not significantly impact glutamine clearance. Higher doses decreased the relative bioavailability of oral glutamine, again indicating a non-linear saturable absorption. Model evaluation indicated no systemic bias (Figure 2). The estimates of L-glutamine oral clearance and volume of distribution were 66 L/h/70 kg and 140 L/70 kg, respectively. Conclusions: This is the first report of a population PK analysis of L-glutamine in patients with SCD. We identified that higher baseline glutamine levels and higher doses were associated with lower L-glutamine clearance. In addition, increased doses reduced relative bioavailability, indicating that higher doses (>0.3 g/kg) may not provide higher drug concentrations. Food intake did not have a significant influence on glutamine clearance, implying that L-glutamine can be taken with or without food. Our findings will help to inform optimized dosing of L-glutamine for patients with SCD and potentially permit individualized PK-guided dosing to maximize treatment benefits. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Magnetic resonance imaging as a non-invasive tool to assess gastric emptying in mice.

Methods to study gastric emptying in rodents are time consuming or terminal, preventing repetitive assessment in the same animal. Magnetic resonance imaging (MRI) is a non-invasive technique increasingly used to investigate gastrointestinal function devoid of these shortcomings. Here, we evaluated MRI to measure gastric emptying in control animals and in two different models of gastroparesis. Mice were scanned using a 9.4 Tesla MR scanner. Gastric volume was measured by delineating the stomach lumen area. Control mice were scanned every 30 min after ingestion of a 0.2 g meal and stomach volume was quantified. The ability of MRI to detect delayed gastric emptying was evaluated in models of morphine-induced gastroparesis and streptozotocin-induced diabetes. Magnetic resonance imaging reproducibly detected increased gastric volume following ingestion of a standard meal and progressively decreased with a half emptying time of 59 ± 5 min. Morphine significantly increased gastric volume measured at t= 120 min (saline: 20 ± 2 vs morphine: 34 ± 5 mm3 ; n= 8-10; p< 0.001) and increased half emptying time using the breath test (saline: 85 ± 22 vs morphine: 161 ± 46 min; n= 10; p< 0.001). In diabetic mice, gastric volume assessed by MRI at t= 60 min (control: 23 ± 2 mm3 ; n= 14 vs diabetic: 26 ± 5 mm3 ; n= 18; p= 0.014) but not at t= 120 min (control: 21 ± 3 mm3 ; n= 13 vs diabetic: 18 ± 5 mm3 ; n= 18; p= 0.115) was significantly increased compared to nondiabetic mice. Our data indicate that MRI is a reliable and reproducible tool to assess gastric emptying in mice and represents a useful technique to study gastroparesis in disease models or for evaluation of pharmacological compounds.