Imbalance between production and scavenging of superoxide anion results in hypertension by the inactivation of nitric oxide, and the increased oxidative stress from the resultant peroxynitrite that is produced promotes inflammatory processes such as atherosclerosis. Induction of phase 2 proteins promotes oxidant scavenging. We hypothesized that intake of dietary phase 2 protein inducers would ameliorate both hypertension and atherosclerotic changes in the spontaneously hypertensive stroke-prone rat. For 5 days͞week for 14 weeks, we fed rats 200 mg͞day of dried broccoli sprouts that contained glucoraphanin, which is metabolized into the phase 2 protein-inducer sulforaphane (Group A), sprouts in which most of the glucoraphanin was destroyed (Group B), or no sprouts (Group C). After 14 weeks of treatment, no significant differences were seen between rats in Groups B and C. Rats in Group A had significantly decreased oxidative stress in cardiovascular and kidney tissues, as shown by increased glutathione (GSH) content and decreased oxidized GSH, decreased protein nitrosylation, as well as increased GSH reductase and GSH peroxidase activities. Decreased oxidative stress correlated with better endothelial-dependent relaxation of the aorta and significantly lower (20 mm Hg) blood pressure. Tissues from Groups B and C had considerable numbers of infiltrating activated macrophages, indicative of inflammation, whereas animals in Group A had few detectable infiltrating macrophages. There is interest in dietary phase 2 protein inducers as means of reducing cancer incidence. We conclude that a diet containing phase 2 protein inducers also reduces the risk of developing cardiovascular problems of hypertension and atherosclerosis.
We determined the effects of protein supplementation immediately before (PRO-B) and after (PRO-A) resistance training (RT; 12 weeks) in older men (59-76 years), and whether this reduces deficits in muscle mass and strength compared to younger men (18-40 years). Older men were randomized to PRO-B (0.3 g/kg protein before RT + placebo after RT, n=9), PRO-A (placebo before + protein after RT, n=10), or PLA (placebo before and after RT, n=10). Lean tissue mass, muscle thickness of the elbow, knee, and ankle flexors and extensors, and leg and bench press strength were measured before and after RT and compared to databases of younger subjects (n=22-60). Myofibrillar protein degradation (3-methylhistidine) and bone resorption (cross-linked N-telopeptides) were also measured before and after RT. Lean tissue mass, muscle thickness (except ankle dorsi flexors), and strength increased with training (P<0.05), with little difference between groups. There were no changes in 3-methylhistidine or cross-linked N-telopeptides. Before RT, all measures were lower in the older compared to younger groups (P<0.05), except for elbow extensor muscle thickness. Following training, muscle thickness of the elbow flexors and ankle dorsi flexors and leg press strength were no longer different than the young, and elbow extensor muscle thickness was greater in the old men (P<0.05). Supplementation with protein before or after training has no effect on muscle mass and strength in older men. RT was sufficient to overcome deficits in muscle size of the elbow flexors and ankle dorsi flexors and leg press strength in older compared to younger men.
Supplementation with CLA during resistance training results in relatively small changes in body composition accompanied by a lessening of the catabolic effect of training on muscle protein.
Summary
Various dendritic cell (DC) populations exist that differ in phenotype and ability to present antigen to T cells. For example, plasmacytoid DCs (pDCs) are less potent T cell activators compared with conventional DCs (cDCs). Here, we compared porcine blood DCs (BDCs), containing pDCs and cDCs, and monocyte‐derived DCs (MoDC), consisting of cDCs, in their phenotype, ability to uptake antigen, activation and maturation and their ability to present antigen to autologous T cells. Pigs represent an important animal model, whose immune system in many respects closely resembles that of humans. For example, the distribution of Toll‐like receptors is similar to that of humans, in contrast to that of mice. Here we demonstrate that both populations endocytose foreign material. Following lipopolysaccharide stimulation, CD80/86 and chemokine receptor (CCR)7 expression was increased in both populations as was the expression of the chemokine ligands (CCL)‐2, CCL‐4, CCL‐20 and CXCL‐2. Although basal and post‐stimulation protein concentrations of interleukins 6 and 8 and tumour necrosis factor‐α were higher in MoDCs, protein concentrations showed a higher fold increase in BDCs. Antigen‐specific proliferation of autologous T cells was induced by MoDCs and BDCs. Interestingly, while MoDCs induced stronger proliferation in naive T cells, no difference in proliferation was observed when primed T cells were studied. These results demonstrate that isolated porcine BDCs are highly responsive to stimulation with lipopolysaccharide and are functionally able to drive primed T‐cell proliferation to the same extent as MoDCs.
The neonatal immune system is often considered as immature or impaired compared to the adult immune system. This higher susceptibility to infections is partly due to the skewing of the neonatal immune response towards a Th2 response. Activation and maturation of dendritic cells (DCs) play an important role in shaping the immune response, therefore, DCs are a target of choice for the development of efficient and protective vaccine formulations able to redirect the neonatal immune response to a protective Th1 response. As pigs are becoming more important for vaccine development studies due to their similarity to the human immune system, we decided to compare the activation and maturation of a subpopulation of porcine DCs in adult and neonatal pigs following stimulation with different TLR ligands, which are promising candidates for adjuvants in vaccine formulations. Porcine blood derived DCs (BDCs) were directly isolated from blood and consisted of a mix of conventional and plasmacytoid DCs. Following CpG ODN (TLR9 ligand) and imiquimod (TLR7 ligand) stimulation, neonatal BDCs showed higher levels of expression of costimulatory molecules and similar (CpG ODN) or higher (imiquimod) levels of IL-12 compared to adult BDCs. Another interesting feature was that only neonatal BDCs produced IFN-α after TLR7 or TLR9 ligand stimulation. Stimulation with CpG ODN and imiquimod also induced enhanced expression of several chemokines. Moreover, in a mixed leukocyte reaction assay, neonatal BDCs displayed a greater ability to induce lymphoproliferation. These findings suggest that when stimulated via TLR7 or TLR9 porcine DCs display similar if not better response than adult porcine DCs.
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