A 2 year feeding study was conducted with male and female B6C3F1 mice that consumed diets containing 0, 1, 5, or 10 ppm deoxynivalenol (DON). Survivability was good and, while the test animals gained less weight with increasing levels of DON in the diet, there were no consistent toxic manifestations associated with DON consumption. There was some evidence for an increase in serum IgA and IgG in females, and there were sporadic changes noted in the clinical chemistry and hematology parameters conducted at the terminal sacrifice. However, these changes were not considered to be biologically significant. The pathology results provided statistically significant dose-related evidence for a decrease in liver preneoplastic and neoplastic lesions as the dose level of DON increased. This negative trend probably results from the known positive correlation between body weight and the appearance of spontaneous hepatic neoplasms in this strain of mouse.

The purpose of this study was to determine the effects of dietary protein intake and eating frequency on perceived appetite, satiety, and hormonal responses in overweight/obese men. Thirteen men (age 51 ± 4 years; BMI 31.3 ± 0.8 kg/m2) consumed eucaloric diets containing normal protein (79 ± 2 g protein/day; 14% of energy intake as protein) or higher protein (138 ± 3 g protein/day; 25% of energy intake as protein) equally divided among three eating occasions (3-EO; every 4 h) or six eating occasions (6-EO; every 2 h) on four separate days in randomized order. Hunger, fullness, plasma glucose, and hormonal responses were assessed throughout 11 h. No protein × eating frequency interactions were observed for any of the outcomes. Independent of eating frequency, higher protein led to greater daily fullness (P < 0.05) and peptide YY (PYY) concentrations (P < 0.05). In contrast, higher protein led to greater daily ghrelin concentrations (P < 0.05) vs. normal protein. Protein quantity did not influence daily hunger, glucose, or insulin concentrations. Independent of dietary protein, 6-EO led to lower daily fullness (P < 0.05) and PYY concentrations (P < 0.05). The 6-EO also led to lower glucose (P < 0.05) and insulin concentrations (P < 0.05) vs. 3-EO. Although the hunger-related perceived sensations and hormonal responses were conflicting, the fullness-related responses were consistently greater with higher protein intake but lower with increased eating frequency. Collectively, these data suggest that higher protein intake promotes satiety and challenge the concept that increasing the number of eating occasions enhances satiety in overweight and obese men.

Objective: This study assessed the effectiveness of a prescribed weight-loss diet with 0.8 versus 1.4 g proteinÁkg À1 day À1 on changes in weight, body composition, indices of metabolic syndrome, and resting energy expenditure (REE) in overweight and obese men. Design and Methods: Men were randomized to groups that consumed diets containing 750 kcal day À1 less than daily energy needs for weight maintenance with either normal protein (NP, n ¼ 21) or higher protein (HP, n ¼ 22) content for 12 weeks. The macronutrient distributions of the NP and HP diets were 25:60:15, and 25:50:25 percent energy from fat, carbohydrate, and protein, respectively. Assessments were made pre and post intervention. The subjects were retrospectively subgrouped into overweight and obese groups. Results and Conclusion: Both diet groups lost comparable body weight and fat. The HP group lost less lean body mass than the NP group (À1.9 6 0.3 vs. À3.0 6 0.4 kg). The effects of protein and BMI status on lean body mass loss were additive. The reductions in total cholesterol, HDL-C, triacylglycerol, glucose, and insulin, along with LDL-C, total cholesterol-to-HDL-C ratio, and HOMA-IR, were not statistically different between NP and HP. Likewise, macronutrient distributions of the diet did not affect the reductions in REE, and blood pressure. In conclusion, energy restriction effectively improves multiple clinical indicators of cardiovascular health and glucose control, and consumption of a higher-protein diet and accomplishing weight loss when overweight versus obese help men preserve lean body mass over a short period of time.

A major subset of human peripheral blood γδ T cells expresses the Vγ2Vδ2 T cell receptor (TCR) and responds to malignant or infectious diseases. We noted significant differences in the numbers of Vγ2Vδ2 T cells in blood samples from healthy Caucasian or African American (AA) donors. On average, CA donors had 3.71 ± 4.37% Vδ2 cells (as a percentage of total lymphocytes) compared to 1.18 ± 2.14% Vδ2 cells for AA donors (p < 0.0001). Age and race had the greatest impact on Vδ2 cell levels; the effect of age was similar for both racial groups. The Vδ2+ cell population was dominated, for both donor groups, by cells expressing the Vγ2-Jγ1.2 Vδ2 T cell receptor, an apparent result of strong positive selection and there was substantial overlap in the public Vγ2 clonotypes from both racial groups. Mechanisms for selection and amplification of Vδ2 cells are nearly identical for both groups, despite the significant difference in baseline levels. These data show that appropriate controls, matched for age and race, may be required for clinical studies of Vγ2Vδ2 T cells in infectious disease or cancer and raise important questions about the mechanisms regulating the levels of circulating Vδ2 cells.

Background: Chronic Kidney Disease (CKD) is associated with alterations in phosphorus excretion, and increases in fibroblast growth factor (FGF23) and parathyroid hormone (PTH). Plant protein-based phytate-bound phosphorus, is less bioavailable than that from animal sources. Our one-week study that was conducted previously showed that a nearly 100% plant protein-based diet benefits mineral metabolism in CKD; however, this diet may not be acceptable to patients. Here we hypothesize that a diet containing 70% protein from plants has similar efficacy and is tolerated by CKD patients. Methods: Thirteen subjects with CKD 3-4 received an omnivorous diet containing 70% protein from plants for 4 weeks. The primary outcome was change in 24 h urine phosphorus. Secondary outcomes were changes in serum phosphorus, FGF23, PTH, urine sodium excretion, grip strength and fat free mass. Repeated measures analysis of variance (ANOVA) was used to test differences in parameters over the 4 weeks. Results: Mean age of subjects was 54.8 years. Median eGFR was 26 (IQR 14.7) ml/min/1.73 m². Over the 4-week period, urine phosphorus significantly decreased by 215 ± 232 mg/day (p < 0.001). No significant changes in serum FGF23, phosphorus or PTH were noted. Urine sodium and titratable acid decreased significantly on the diet. Hand grip strength and fat-free mass did not change. There were two hyperkalemia events both 5.8 mEq/l, corrected by food substitutions. No other adverse events were observed. Conclusions: A 70% plant protein diet is safe, tolerated, and efficacious in lowering urine phosphorus excretion and may be an alternative to phosphate binders.

The TNF superfamily member TWEAK (TNFSF12) is a multifunctional cytokine implicated in physiological tissue regeneration and wound repair. TWEAK is initially synthesized as a membrane-anchored protein, but furin cleavage within the stalk region can generate a secreted TWEAK isoform. Both TWEAK isoforms bind to a small cell surface receptor named Fn14 (TNFRSF12A) and this interaction stimulates various cellular responses, including proliferation and migration. Fn14, like other members of the TNF receptor superfamily, is not a ligand-activated protein kinase. Instead, TWEAK:Fn14 engagement promotes Fn14 association with members of the TNFR associated factor family of adapter proteins, which triggers activation of various signaling pathways, including the classical and alternative NF-κB pathways. Numerous studies have revealed that Fn14 gene expression is significantly elevated in injured tissues and in most solid tumor types. Also, sustained Fn14 signaling has been implicated in the pathogenesis of cerebral ischemia, chronic inflammatory diseases, and cancer. Accordingly, several groups are developing TWEAK- or Fn14-targeted agents for possible therapeutic use in patients. These agents include monoclonal antibodies, fusion proteins, and immunotoxins. In this article, we provide an overview of some of the TWEAK/Fn14 axis-targeted agents currently in pre-clinical animal studies or in human clinical trials and discuss two other potential approaches to target this intriguing signaling node.

Objective-To evaluate Vγ2Vδ2 T cells in a group of HIV-infected patients who suppress HIV replication without antiretroviral therapy (natural viral suppressors, NVSs).Design-It is a cross-sectional study.Methods-We compared Vγ2Vδ2 T-cell frequency, T-cell repertoire, and responses to isopentenyl pyrophosphate stimulation between NVSs (n = 21) and HIV-uninfected controls (n = 27) and between NVSs and HIV-infected patients taking HAART with suppressed viral replication (HIV-P; n = 25).Results-NVSs had a mean frequency of 1.06 ± 0.82% CD3 + Vδ2+ cells among total lymphocytes, which was significantly higher than both control groups (HIV-negative: 0.50 ± 0.53%, P = 0.042; HIV-P: 0.34 ± 0.37%, P = 0.002). The proportion of Vγ2 chains correlating with the Vγ2-Jγ1.2 rearrangement was reduced among NVSs compared with HIV-negative controls (0.57 ± 0.06 vs. 0.32 ± 0.04; P = 0.016) but was increased compared with HIV-P patients (0.32 ± 0.04 vs. 0.22 ± 0.03; P = 0.03). NVSs had a similar baseline frequency of CD27 -/CD45RA -effector cells (19.6 ± 4.2%) compared with HIV-negative controls (20.8 ± 12.9%; P = 0.35). Conclusion-The altered γδ T-cell receptor repertoire among NVS was consistent with the known effect of HIV-1 on these cells. Uniquely among all HIV-infected groups, NVS reconstituted the γδ T-cell population, eventually reaching levels significantly above controls. This capacity to recover γδ T-cell numbers and function distinguishes individuals who control HIV-1 with and without HAART.

The purpose of this study was to determine the effects of dietary protein and eating frequency on perceived appetite and satiety during weight loss. A total of 27 overweight/obese men (age 47 ± 3 years; BMI 31.5 ± 0.7 kg/m2) were randomized to groups that consumed an energy-restriction diet (i.e., 750 kcal/day below daily energy need) as either higher protein (HP, 25% of energy as protein, n = 14) or normal protein (NP, 14% of energy as protein, n = 13) for 12 weeks. Beginning on week 7, the participants consumed their respective diets as either 3 eating occasions/day (3-EO; every 5 h) or 6 eating occasions/day (6-EO; every 2 h), in randomized order, for 3 consecutive days. Indexes of appetite and satiety were assessed every waking hour on the third day of each pattern. Daily hunger, desire to eat, and preoccupation with thoughts of food were not different between groups. The HP group experienced greater fullness throughout the day vs. NP (511 ± 56 vs. 243 ± 54 mm · 15 h; P < 0.005). When compared to NP, the HP group experienced lower late-night desire to eat (13 ± 4 vs. 27 ± 4 mm, P < 0.01) and preoccupation with thoughts of food (8 ± 4 vs. 21 ± 4 mm; P < 0.01). Within groups, the 3 vs. 6-EO patterns did not influence daily hunger, fullness, desire to eat, or preoccupation with thoughts of food. The 3-EO pattern led to greater evening and late-night fullness vs. 6-EO but only within the HP group (P < 0.005). Collectively, these data support the consumption of HP intake, but not greater eating frequency, for improved appetite control and satiety in overweight/obese men during energy-restriction-induced weight loss.