Investigation on the influence of nematophagous fungi as feed additive on nematode infection risk of sheep and goats on pasture

Gastrointestinal nematodes in small ruminants cause high economic losses. Thus on most farms anthelmintic treatment is required. In response to increasing problems with anthelmintic resistance, biological control, for example the use of nematophagous fungi, has received significant attention. The aim of this study was to investigate the effect of Duddingtonia flagrans orally applied to small ruminants on natural infection with gastrointestinal nematodes in a field study in Northern Germany. 20 goats and 20 sheep were fed daily for 3 months with 5x105 spores of D. flagrans per kg bodyweight. Differences in body weight, faecal egg count and larval development in faeces and on pasture in comparison with same-sized control groups were analysed. After 3 months the control goats showed significantly higher mean faecal egg count than the fungus-fed group. No significant difference was found between the two sheep groups. The maximum in larval reduction in faeces was 81.3 % in the sheep groups and 67.9 % in the goat groups (not significant). At the end of the study the body weight gain in the fungus-treated groups was 1.7 kg higher in goats and 0.7 kg higher in sheep than in the control groups (not significant). Regarding the first-year-grazing goats only, the bodyweights revealed significant differences (p<0.05). No statistically significant differences were observed in pasture larval counts. In the study presented here, no clear effect of fungus could be observed. A modified feeding regimen, perhaps with permanent release boluses or feed blocks, may improve the efficacy. Furthermore, it seems that climatic conditions during the study period could have influenced the results and displayed how sensitive the fungus application may be on such parameters

Large Gliadin Peptides Detected in the Pancreas of NOD and Healthy Mice following Oral Administration

Gluten promotes type 1 diabetes in nonobese diabetic (NOD) mice and likely also in humans. In NOD mice and in non-diabetes-prone mice, it induces inflammation in the pancreatic lymph nodes, suggesting that gluten can initiate inflammation locally. Further, gliadin fragments stimulate insulin secretion from beta cells directly. We hypothesized that gluten fragments may cross the intestinal barrier to be distributed to organs other than the gut. If present in pancreas, gliadin could interact directly with the immune system and the beta cells to initiate diabetes development. We orally and intravenously administered 33-mer and 19-mer gliadin peptide to NOD, BALB/c, and C57BL/6 mice and found that the peptides readily crossed the intestinal barrier in all strains. Several degradation products were found in the pancreas by mass spectroscopy. Notably, the exocrine pancreas incorporated large amounts of radioactive label shortly after administration of the peptides. The study demonstrates that, even in normal animals, large gliadin fragments can reach the pancreas. If applicable to humans, the increased gut permeability in prediabetes and type 1 diabetes patients could expose beta cells directly to gliadin fragments. Here they could initiate inflammation and induce beta cell stress and thus contribute to the development of type 1 diabetes

The effect of protein and glycemic index on children's body composition: the DiOGenes randomized study

OBJECTIVE: To investigate the effect of protein and glycemic index (GI) on body composition among European children in the randomized, 6-month dietary intervention DiOGenes (diet, obesity, and genes) family-based study. PATIENTS AND METHODS: In the study, 827 children (381 boys and 446 girls), aged 5 to 18 years, completed baseline examinations. Families with parents who lost >= 8% of their weight during an 8-week run-in low-calorie diet period were randomly assigned to 1 of 5 ad libitum diets: low protein (LP)/low glycemic index (LGI); LP/high GI (HGI); high protein (HP)/LGI; HP/HGI; and control diet. The target difference was 15 GI U between the LGI/HGI groups and 13 protein percentage points between the LP/HP groups. There were 658 children examined after 4 weeks. Advice on food-choice modification was provided at 6 visits during this period. No advice on weight loss was provided because the focus of the study was the ability of the diets to affect outcomes through appetite regulation. Anthropometric measurements and body composition were assessed at baseline, week 4, and week 26. RESULTS: In the study, 465 children (58.1%) completed all assessments. The achieved differences between the GI and protein groups were 2.3 GI U and 4.9 protein percentage points, respectively. The LP/HGI group increased body fat percentage significantly more than the other groups (P = .040; partial eta(2) = 0.039), and the percentage of overweight/obese children in the HP/LGI group decreased significantly during the intervention (P = .031). CONCLUSIONS: Neither GI nor protein had an isolated effect on body composition. However, the LP/HGI combination increased body fat, whereas the HP/LGI combination was protective against obesity in this sample of children

Diets with high or low protein content and glycemic index for weight-loss maintenance

BACKGROUND: Studies of weight-control diets that are high in protein or low in glycemic index have reached varied conclusions, probably owing to the fact that the studies had insufficient power. METHODS: We enrolled overweight adults from eight European countries who had lost at least 8% of their initial body weight with a 3.3-MJ (800-kcal) low-calorie diet. Participants were randomly assigned, in a two-by-two factorial design, to one of five ad libitum diets to prevent weight regain over a 26-week period: a low-protein and low-glycemic-index diet, a low-protein and high-glycemic-index diet, a high-protein and low-glycemic-index diet, a high-protein and high-glycemic-index diet, or a control diet. RESULTS: A total of 1209 adults were screened (mean age, 41 years; body-mass index [the weight in kilograms divided by the square of the height in meters], 34), of whom 938 entered the low-calorie-diet phase of the study. A total of 773 participants who completed that phase were randomly assigned to one of the five maintenance diets; 548 completed the intervention (71%). Fewer participants in the high-protein and the low-glycemic-index groups than in the low-protein-high-glycemic-index group dropped out of the study (26.4% and 25.6%, respectively, vs. 37.4%; P=0.02 and P=0.01 for the respective comparisons). The mean initial weight loss with the low-calorie diet was 11.0 kg. In the analysis of participants who completed the study, only the low-protein-high-glycemic-index diet was associated with subsequent significant weight regain (1.67 kg; 95% confidence interval [CI], 0.48 to 2.87). In an intention-to-treat analysis, the weight regain was 0.93 kg less (95% CI, 0.31 to 1.55) in the groups assigned to a high-protein diet than in those assigned to a low-protein diet (P=0.003) and 0.95 kg less (95% CI, 0.33 to 1.57) in the groups assigned to a low-glycemic-index diet than in those assigned to a high-glycemic-index diet (P=0.003). The analysis involving participants who completed the intervention produced similar results. The groups did not differ significantly with respect to diet-related adverse events. CONCLUSIONS: In this large European study, a modest increase in protein content and a modest reduction in the glycemic index led to an improvement in study completion and maintenance of weight loss

A multicentre weight loss study using a low-calorie diet over 8 weeks: regional differences in efficacy across eight European cities

PRINCIPLES: The efficacy of low-calorie diets (LCDs) has not been investigated in large-scale studies or among people from different regions, who are perhaps unaccustomed to such methods of losing weight. The aim of the present study was to investigate changes in obesity measures among overweight/obese adults from eight European cities (from Northern, Central and Southern Europe) during the 8-week LCD phase of the DiOGenes study (2006–2007), a family-based, randomised, controlled dietary intervention. METHODS: 938 overweight/obese adults completed baseline examinations and underwent an 8-week LCD, providing 3.3–4.2 MJ/day to replace all meals. Anthropometric measurements and body composition were assessed at baseline and post-LCD. RESULTS: 773 (82.4%) adults (mean age, 43.1 y) completed the LCD successfully. The highest drop-out rate was observed in Southern (24.9%) and the lowest in Northern (13.3%) European cities. Overall, the LCD induced favourable changes in all outcomes, including an approximate 11.0% reduction in body weight and body fat percentage. Changes in outcomes differed significantly between regions, with North- and Central-European cities generally achieving higher percentage reductions in most anthropometric measurements assessed. Nonetheless, participants in Southern Europe reduced their body fat percentage significantly more than participants in Northern Europe (–11.8 vs. –9.5%, P = 0.017). CONCLUSIONS: The LCD significantly improved anthropometric and body composition measurements in all cities participating in DiOGenes

Blood profile of proteins and steroid hormones predicts weight change after weight loss with interactions of dietary protein level and glycemic index

Weight regain after weight loss is common. In the Diogenes dietary intervention study, high protein and low glycemic index (GI) diet improved weight maintenance. OBJECTIVE: To identify blood predictors for weight change after weight loss following the dietary intervention within the Diogenes study. DESIGN: Blood samples were collected at baseline and after 8-week low caloric diet-induced weight loss from 48 women who continued to lose weight and 48 women who regained weight during subsequent 6-month dietary intervention period with 4 diets varying in protein and GI levels. Thirty-one proteins and 3 steroid hormones were measured. RESULTS: Angiotensin I converting enzyme (ACE) was the most important predictor. Its greater reduction during the 8-week weight loss was related to continued weight loss during the subsequent 6 months, identified by both Logistic Regression and Random Forests analyses. The prediction power of ACE was influenced by immunoproteins, particularly fibrinogen. Leptin, luteinizing hormone and some immunoproteins showed interactions with dietary protein level, while interleukin 8 showed interaction with GI level on the prediction of weight maintenance. A predictor panel of 15 variables enabled an optimal classification by Random Forests with an error rate of 24±1%. A logistic regression model with independent variables from 9 blood analytes had a prediction accuracy of 92%. CONCLUSIONS: A selected panel of blood proteins/steroids can predict the weight change after weight loss. ACE may play an important role in weight maintenance. The interactions of blood factors with dietary components are important for personalized dietary advice after weight loss

Caloric restriction induces changes in insulin and body weight measurements that are inversely associated with subsequent weight regain

BACKGROUND: Successful weight maintenance following weight loss is challenging for many people. Identifying predictors of longer-term success will help target clinical resources more effectively. To date, focus has been predominantly on the identification of predictors of weight loss. The goal of the current study was to determine if changes in anthropometric and clinical parameters during acute weight loss are associated with subsequent weight regain. METHODOLOGY: The study consisted of an 8-week low calorie diet (LCD) followed by a 6-month weight maintenance phase. Anthropometric and clinical parameters were analyzed before and after the LCD in the 285 participants (112 men, 173 women) who regained weight during the weight maintenance phase. Mixed model ANOVA, Spearman correlation, and linear regression were used to study the relationships between clinical measurements and weight regain. PRINCIPAL FINDINGS: Gender differences were observed for body weight and several clinical parameters at both baseline and during the LCD-induced weight loss phase. LCD-induced changes in BMI (Spearman's ρ = 0.22, p = 0.0002) were inversely associated with weight regain in both men and women. LCD-induced changes in fasting insulin (ρ = 0.18, p = 0.0043) and HOMA-IR (ρ = 0.19, p = 0.0023) were also associated independently with weight regain in both genders. The aforementioned associations remained statistically significant in regression models taking account of variables known to independently influence body weight. CONCLUSIONS/SIGNIFICANCE: LCD-induced changes in BMI, fasting insulin, and HOMA-IR are inversely associated with weight regain in the 6-month period following weight loss

Development of a Symmetric Echo-Planar Spectroscopy Imaging Framework for Hyperpolarized 13C Imaging in a Clinical PET/MR Scanner

Here, we developed a symmetric echo-planar spectroscopic imaging (EPSI) sequence for hyperpolarized 13C imaging on a clinical hybrid positron emission tomography/magnetic resonance imaging system. The pulse sequence uses parallel reconstruction pipelines to separately reconstruct data from odd-and-even gradient echoes to reduce artifacts from gradient imbalances. The ramp-sampled data in the spatiotemporal frequency space are regridded to compensate for the chemical-shift displacements. Unaliasing of nonoverlapping peaks outside of the sampled spectral width was performed to double the effective spectral width. The sequence was compared with conventional phase-encoded chemical-shift imaging (CSI) in phantoms, and it was evaluated in a canine cancer patient with ameloblastoma after injection of hyperpolarized [1-13C]pyruvate. The relative signal-to-noise ratio of EPSI with respect to CSI was 0.88, which is consistent with the decrease in sampling efficiency due to ramp sampling. Data regridding in the spatiotemporal frequency space significantly reduced spatial blurring compared with direct fast Fourier transform. EPSI captured the spatial distributions of both metabolites and their temporal dynamics in vivo with an in-plane spatial resolution of 5 × 9 mm2 and a temporal resolution of 3 seconds. Significantly higher spatial and temporal resolution for delineating anatomical structures in vivo was achieved for EPSI metabolic maps than for CSI maps, which suffered spatiotemporal blurring. The EPSI sequence showed promising results in terms of short acquisition time and sufficient spectral bandwidth of 500 Hz, allowing to adjust the trade-off between signal-to-noise ratio and encoding speed

Protein Engineering Strategies for Sustained Glucagon-Like Peptide-1 Receptor–Dependent Control of Glucose Homeostasis

OBJECTIVE—We have developed a novel platform for display and delivery of bioactive peptides that links the biological properties of the peptide to the pharmacokinetic properties of an antibody. Peptides engineered in the MIMETIBODY platform have improved biochemical and biophysical properties that are quite distinct from those of Fc-fusion proteins. CNTO736 is a glucagon-like peptide 1 (GLP-1) receptor agonist engineered in our MIMETIBODY platform. It retains many activities of native GLP-1 yet has a significantly enhanced pharmacokinetic profile. Our goal was to develop a long-acting GLP-1 receptor agonist with sustained efficacy