After birth the human brain is subject to major maturational changes, which are associated with changes in the biochemical composition of the brain and brain metabolism. Magnetic resonance (MR) spectroscopy has special capabilities in the analysis of in vivo metabolism. Volume-selective proton and phosphorus MR spectroscopy of the brain was performed on a 1.5-T magnet in 41 healthy children aged 1 month to 16 years. With advancing age, phosphorus spectra revealed a decrease in the ratios of phosphomonoesters (PMEs) to beta-adenosine triphosphate (ATP) and PMEs to phosphocreatine (PCr) and an increase in the ratios of phosphodiesters to beta-ATP, PCr to beta-ATP, and PCr to inorganic phosphate (Pi). No significant changes were observed in Pi/beta-ATP and pH. No changes occurred after the age of 3 years. Proton spectroscopy revealed an increase in the ratios of N-acetylaspartate (NAA) to choline (Ch) and NAA to creatine (Cr) and a decrease in Ch/Cr with increasing age. The most rapid changes were noted during the first 3 years of life, but changes were still observed at the age of 16 years.

Apigenin and its structural analogues chrysin and luteolin were used to evaluate their capacity to inhibit the production of pro-inflammatory cytokines by lipopolysaccharide (LPS)-stimulated human peripheral blood mononuclear cells (PBMC). Furthermore, flowcytometric analysis was performed to compare the effects of apigenin, chrysin, luteolin, quercetin and naringenin on the different cell types present in PBMC. LPS-stimulated PBMC were cultured in the presence of the flavonoids and TNFalpha, IL-1beta and IL-6 were measured in the supernatants. In parallel, metabolic activity of the PBMC was determined by measuring succinate dehydrogenase activity. Apigenin, chrysin and luteolin dose-dependently inhibited both pro-inflammatory cytokine production and metabolic activity of LPS-stimulated PBMC. With increasing concentration of apigenin, chrysin or luteolin the monocytes/macrophages disappeared as measured by flowcytometry. This also appeared to occur in the non-LPS-stimulated PBMC. At the same time there was an increase in dead cells. T- and B-lymphocytes were not affected. Quercetin and naringenin had virtually no effects on cytokines, metabolic activity or on the number of cells in the studied cell populations. In conclusion, monocytes were specifically eliminated in PBMC by apigenin, chrysin or luteolin treatment in vitro at low concentrations (around 8 microM), in which apigenin appeared to be the most potent.

Cancer cachexia is characterised by metabolic alterations leading to loss of adipose tissue and lean body mass and directly compromises physical performance and the quality of life of cancer patients. In a murine cancer cachectic model, the effects of dietary supplementation with a specific combination of high protein, leucine and fish oil on weight loss, muscle function and physical activity were investigated. Male CD2F1 mice, 6 -7 weeks old, were divided into body weight-matched groups: (1) control, (2) tumourbearing, and (3) tumour-bearing receiving experimental diets. Tumours were induced by s.c. inoculation with murine colon adenocarcinoma (C26) cells. Food intake, body mass, tumour size and 24 h-activity were monitored. Then, 20 days after tumour/ vehicle inoculation, the animals were killed and muscle function was tested ex vivo. Tumour-bearing mice showed reduced carcass, muscle and fat mass compared with controls. EDL muscle performance and total daily activity were impaired in the tumour-bearing mice. Addition of single nutrients resulted in no or modest effects. However, supplementation of the diet with the all-in combination of high protein, leucine and fish oil significantly reduced loss of carcass, muscle and fat mass (loss in mass 45, 52 and 65% of TB-con, respectively (Po0.02)) and improved muscle performance (loss of max force reduced to 55 -64% of TB-con (Po0.05)). Moreover, total daily activity normalised after intervention with the specific nutritional combination (50% of the reduction in activity of TB-con (Po0.05)). In conclusion, a nutritional combination of high protein, leucine and fish oil reduced cachectic symptoms and improved functional performance in cancer cachectic mice. Comparison of the nutritional combination with its individual modules revealed additive effects of the single components provided.

BACKGROUND Thrombus regression in heparin-treated, acute deep venous thrombosis of the lower extremity is poorly documented in the literature; different rates of thrombus resolution and recanalization are reported. METHODS AND RESULTS In a prospective follow-up study, duplex scanning was used to evaluate the thrombus regression in patients with documented acute femoropopliteal thrombosis. Eighty vein segments in 20 legs of 18 patients were subjected to repeat duplex scans at 1, 3, 6, 12, and 26 weeks after diagnosis; 49 segments showed thrombus at diagnosis. The popliteal vein showed the highest thrombus load at diagnosis, followed in descending order by the superficial femoral, profunda femoris, and common femoral vein segments (p less than 0.001). Thrombus regression was significant (p less than 0.001) in all segments and proceeded at an exponential rate that was equal in the different vein segments of the upper leg. Both thrombus resolution and recanalization appeared to be a function of the initial thrombus load and could not be related to individual vein segments. Recanalization was seen in 23 of 31 initially occluded segments and occurred within the first 6 weeks after diagnosis in 20 of 23 segments. Extension of thrombus despite anticoagulant therapy was observed in 15 vein segments and was not related to the initial thrombosis score (p = 0.1) or individual vein segments (p = 0.23). Thrombus extension in seven patients with prethrombotic conditions was not different (p = 0.9) from the other patients. CONCLUSIONS Duplex scanning is an important noninvasive tool to quantify thrombus regression in acute deep venous thrombosis in detail without unnecessary discomfort to the patient.

Immune modulatory effects of EPA and DHA are well described. However, these fatty acids must be effectively incorporated into cell membrane phospholipids to modify cell function. To address the absence of human data regarding short-term incorporation, the present study investigated the incorporation of EPA and DHA into white blood cells (WBC) at different time points during 1 wk of supplementation with a medical food, which is high in protein and leucine and enriched with fish oil and specific oligosaccharides. Additionally, the effects on ex vivo immune function were determined. In a single-arm, open label study, 12 healthy men and women consumed 2 × 200 mL of medical food providing 2.4 g EPA, 1.2 g DHA, 39.7 g protein (including 4.4 g L-leucine), and 5.6 g oligosaccharides daily. Blood samples were taken at d 0 (baseline), 1, 2, 4, and 7. Within 1 d of nutritional intervention, the percentage of EPA in phospholipids of WBC increased from 0.5% at baseline to 1.3% (P < 0.001). After 1 wk, the percentage of EPA rose to 2.8% (P < 0.001). Additionally, the production of proinflammatory cytokines in LPS-stimulated whole blood cultures was significantly increased within 1 wk. Nutritional supplementation with a fish oil-enriched medical food significantly increased the percentage of EPA in phospholipids of WBC within 1 wk. Simultaneously, ex vivo immune responsiveness to LPS increased significantly. These results hold promise for novel applications such as fast-acting nutritional interventions in cancer patients, which should be investigated in future studies.