Reduced arginine availability and nitric oxide synthesis in cancer is related to impaired endogenous arginine synthesis.

Reduced plasma arginine (ARG) concentrations are found in various types of cancer. ARG and its product nitric oxide (NO) are important mediators in the immune function and the defense against tumour cells. It remains unclear whether the diminished systemic ARG availability in cancer is related to insufficient endogenous ARG synthesis, negatively affecting NO synthesis, and whether a dietary amino acid mixture is able to restore this. In 13 patients with advanced non-small cell lung cancer (NSCLC) and 11 healthy controls, whole body ARG and CIT (citrulline) rates of appearance were measured by stable isotope methodology before and after intake of a mixture of amino acids as present in whey protein. The conversions of CIT to ARG (indicator of de novo ARG synthesis) and ARG to CIT (marker of NO synthesis), and ARG clearance (reflecting ARG disposal capacity) were calculated. Plasma isotopic enrichments and amino acid concentrations were measured by LC-MS/MS. Conversions of CIT to ARG and ARG to CIT (P<0.05), and CIT rate of appearance (P=0.07) were lower in NSCLC. ARG rate of appearance and clearance were comparable suggesting no enhanced systemic ARG production and disposal capacity in NSCLC. After intake of the mixture, ARG rate of appearance and concentration increased (P<0.001), and ARG to CIT conversion was restored in NSCLC. In conclusion, an impaired endogenous ARG synthesis plays a role in the reduced systemic ARG availability and NO synthesis in advanced NSCLC. Nutritional approaches may restore systemic ARG availability and NO synthesis in cancer, but the clinical implication remains unclear.

Trabecular, but not cortical, bone tissue protein synthesis rates are lower in the femoral head when compared to the proximal femur following an intracapsular hip fracture.

BACKGROUND: All musculoskeletal tissues are in a constant state of turnover, with a dynamic equilibrium between tissue protein synthesis and breakdown rates. The synthesis of protein allows musculoskeletal tissues to heal following injury. Yet, impaired tissue healing is observed following certain injuries, such as geriatric hip fractures. It is assumed that the regenerative properties of femoral head bone tissue are compromised following an intracapsular hip fracture and therefore hip replacement surgery is normally performed. However, the actual impact on in vivo bone protein synthesis rates has never been determined. DESIGN: In the present study, 10 patients (age: 79 ± 10 y, BMI: 24 ± 4 kg/m2) with an acute (<24 h) intracapsular hip fracture received a primed continuous intravenous infusion of L-[ring-13C6]-phenylalanine before and throughout their hip replacement surgery. Trabecular and cortical bone tissue from both the femoral head and proximal femur were sampled during surgery to assess protein synthesis rates of affected (femoral head) and unaffected (proximal femur) bone tissue, respectively. In addition, tissue samples of gluteus maximus muscle, synovium, ligamentum teres, and femoral head cartilage were collected. Tissue-specific protein synthesis rates were assessed by measuring L-[ring-13C6]-phenylalanine incorporation in tissue protein. RESULTS: Femoral head trabecular bone protein synthesis rates (0.056 [0.024-0.086] %/h) were lower when compared to proximal femur trabecular bone protein synthesis rates (0.081 [0.056-0.118] %/h; P = 0.043). Cortical bone protein synthesis rates did not differ between the femoral head and proximal femur (0.041 [0.021-0.078] and 0.045 [0.028-0.073] %/h, respectively; P > 0.05). Skeletal muscle, synovium, ligamentum teres, and femoral head cartilage protein synthesis rates averaged 0.080 [0.048-0.089], 0.093 [0.051-0.130], 0.121 [0.110-0.167], and 0.023 [0.015-0.039] %/h, respectively. CONCLUSION: In contrast to the general assumption that the femoral head is avital after an intracapsular displaced hip fracture in the elderly, our data show that bone protein synthesis is still ongoing in femoral head bone tissue during the early stages following an intracapsular hip fracture in older patients. Nonetheless, trabecular bone protein synthesis rates are lower in the femoral head when compared to the proximal femur in older patients following an acute intracapsular hip fracture. Trial register no: NL9036.

Basal protein synthesis rates differ between vastus lateralis and rectus abdominis muscle.

BACKGROUND: In vivo muscle protein synthesis rates are typically assessed by measuring the incorporation rate of stable isotope labelled amino acids in skeletal muscle tissue collected from vastus lateralis muscle. It remains to be established whether muscle protein synthesis rates in the vastus lateralis are representative of muscle protein synthesis rates of other muscle groups. We hypothesized that post-absorptive muscle protein synthesis rates differ between vastus lateralis and rectus abdominis, pectoralis major, or temporalis muscle in vivo in humans. METHODS: Twenty-four patients (62 ± 3 years, 42% female), scheduled to undergo surgery, participated in this study and underwent primed continuous intravenous infusions with l-[ring-13 C6 ]-phenylalanine. During the surgical procedures, serum samples were collected, and muscle tissue was obtained from the vastus lateralis as well as from the rectus abdominis, pectoralis major, or temporalis muscle. Fractional mixed muscle protein synthesis rates (%/h) were assessed by measuring the incorporation of l-[ring-13 C6 ]-phenylalanine into muscle tissue protein. RESULTS: Serum l-[ring-13 C6 ]-phenylalanine enrichments did not change throughout the infusion period. Post-absorptive muscle protein synthesis rates calculated based upon serum l-[ring-13 C6 ]-phenylalanine enrichments did not differ between vastus lateralis and rectus abdominis (0.032 ± 0.004 vs. 0.038 ± 0.003%/h), vastus lateralis and pectoralis major, (0.025 ± 0.003 vs. 0.022 ± 0.005%/h) or vastus lateralis and temporalis (0.047 ± 0.005 vs. 0.043 ± 0.005%/h) muscle, respectively (P > 0.05). When fractional muscle protein synthesis rates were calculated based upon tissue-free l-[ring-13 C6 ]-phenylalanine enrichments as the preferred precursor pool, muscle protein synthesis rates were significantly higher in rectus abdominis (0.089 ± 0.008%/h) compared with vastus lateralis (0.054 ± 0.005%/h) muscle (P < 0.01). No differences were observed between fractional muscle protein synthesis rates in vastus lateralis and pectoralis major (0.046 ± 0.003 vs. 0.041 ± 0.008%/h) or vastus lateralis and temporalis (0.073 ± 0.008 vs. 0.083 ± 0.011%/h) muscle, respectively. CONCLUSIONS: Post-absorptive muscle protein synthesis rates are higher in rectus abdominis when compared with vastus lateralis muscle. Post-absorptive muscle protein synthesis rates do not differ between vastus lateralis and pectoralis major or temporalis muscle. Protein synthesis rates in muscle tissue samples obtained during surgery do not necessarily represent a good proxy for appendicular skeletal muscle protein synthesis rates.

Both basal and post-prandial muscle protein synthesis rates, following the ingestion of a leucine-enriched whey protein supplement, are not impaired in sarcopenic older males.

BACKGROUND: Studying the muscle protein synthetic response to food intake in elderly is important, as it aids the development of interventions to combat sarcopenia. Although sarcopenic elderly are the target group for many of these nutritional interventions, no studies have assessed basal or post-prandial muscle protein synthesis rates in this population. OBJECTIVE: To assess the basal and post-prandial muscle protein synthesis rates between healthy and sarcopenic older men. DESIGN: A total of 15 healthy (69 ± 1 y) and 15 sarcopenic (81 ± 1 y) older men ingested a leucine-enriched whey protein nutritional supplement containing 21 g of protein, 9 g of carbohydrate, and 3 g of fat. Stable isotope methodology combined with frequent collection of blood and muscle samples was applied to assess basal and post-prandial muscle protein fractional synthetic rates. Handgrip strength, muscle mass, and gait speed were assessed to identify sarcopenia, according to international criteria. RESULTS: Basal mixed muscle protein fractional synthetic rates (FSR) averaged 0.040 ± 0.005 and 0.032 ± 0.003%/h (mean ± SEM) in the sarcopenic and healthy group, respectively (P = 0.14). Following protein ingestion, FSR increased significantly to 0.055 ± 0.004 and 0.053 ± 0.004%/h in the post-prandial period in the sarcopenic (P = 0.003) and healthy groups (P < 0.001), respectively, with no differences between groups (P = 0.45). Furthermore, no differences were observed between groups in muscle protein synthesis rates during the early (0.058 ± 0.007 vs 0.060 ± 0.008%/h, sarcopenic vs healthy, respectively) and late (0.052 ± 0.004 vs 0.048 ± 0.003%/h) stages of the post-prandial period (P = 0.93 and P = 0.34, respectively). CONCLUSIONS: Basal muscle protein synthesis rates are not lower in sarcopenic older men compared to healthy older men. The ingestion of 21 g of a leucine-enriched whey protein effectively increases muscle protein synthesis rates in both sarcopenic and healthy older men. Public trial registry number: NTR3047.

Characterisation of fatty acid metabolism in different insulin-resistant phenotypes by means of stable isotopes.

The obese insulin resistant and/or prediabetic state is characterised by systemic lipid overflow, mainly driven by an impaired lipid buffering capacity of adipose tissue, and an impaired capacity of skeletal muscle to increase fat oxidation upon increased supply. This leads to the accumulation of bioactive lipid metabolites in skeletal muscle interfering with insulin sensitivity via various mechanisms. In this review, the contribution of dietary v. endogenous fatty acids to lipid overflow, their extraction or uptake by skeletal muscle as well as the fractional synthetic rate, content and composition of the muscle lipid pools is discussed in relation to the development or presence of insulin resistance and/or an impaired glucose metabolism. These parameters are studied in vivo in man by combining a dual stable isotope methodology with [2H2]- and [U-13C]-palmitate tracers with the arterio-venous balance technique across forearm muscle and biochemical analyses in muscle biopsies. The insulin-resistant state is characterised by an elevated muscle TAG extraction, despite similar supply, and a reduced skeletal muscle lipid turnover, in particular after intake of a high fat, SFA fat meal, but not after a high fat, PUFA meal. Data are placed in the context of current literature, and underlying mechanisms and implications for long-term nutritional interventions are discussed.

The 15N isotope to evaluate fertilizer nitrogen absorption efficiency by the coffee plant

The use of the 15N label for agronomic research involving nitrogen (N) cycling and the fate of fertilizer-N is well established, however, in the case of long term experimentation with perennial crops like citrus, coffee and rubber tree, there are still shortcomings mainly due to large plant size, sampling procedures, detection levels and interferences on the system. This report tries to contribute methodologically to the design and development of 15N labeled fertilizer experiments, using as an example a coffee crop fertilized with 15N labeled ammonium sulfate, which was followed for two years. The N of the plant derived from the fertilizer was studied in the different parts of the coffee plant in order to evaluate its distribution within the plant and the agronomic efficiency of the fertilizer application practice. An enrichment of the fertilizer-N of the order of 2 percent 15N abundance was sufficient to study N absorption rates and to establish fertilizer-N balances after one and two years of coffee cropping. The main source of errors in the estimated values lies in the inherent variability among field replicates and not in the measurements of N contents and 15N enrichments of plant material by mass-spectrometry.

O uso do traçador 15N em pesquisas agronômicas que envolvem o ciclo do nitrogênio (N) e o destino do N do fertilizante está bem estabelecido, entretanto, para o caso de experimentação com plantas perenes como citrus, café e seringueira, ainda existem limitações devidas ao porte das plantas, à amostragem, aos níveis de detecção e à interferência no sistema. Este estudo procura contribuir metodologicamente no delineamento experimental e no desenvolvimento desse tipo de experimentação, em condições de campo, fazendo uso, por dois anos, do experimento de uma cultura de café adubada com fertilizante marcado com 15N. O N da planta derivado do fertilizante foi estudado nas diferentes partes da planta de café para determinar sua distribuição dentro dela e a eficiência agronômica da prática de adubação. Um enriquecimento do N do fertilizante da ordem de 2 por cento em abundância de 15N foi suficiente para estudar taxas de absorção de N e estabelecer balanços do N do fertilizante depois de um e dois anos de cultivo. A principal fonte de erros dos valores estimados está na variabilidade agronômica das repetições e não na precisão das medidas de conteúdo de N e de enriquecimento em 15N por espectrometria de massa.