Sodium L-Aspartate Supplementation Improves Repeated-Sprint Performance.

Aspartate supplementation has been reported to improve endurance performance by facilitating the tricarboxylic acid cycle flux. The present study was performed to investigate the effects of aspartate supplementation on repeated-sprint performance and blood pH. Following an overnight fast, fourteen healthy males completed three sets of 10 × 6 s maximal sprints after consuming sodium L-aspartate (ASP) or placebo (PLA), in a double-blind manner. Both supplements were taken twice on each test day (2 × 4.5 g). Exercise performance (e.g., cadence and power output) and blood variables (e.g., pH and plasma amino acid levels) were measured. The ASP trial evidenced significantly higher plasma aspartate concentration during the first (ASP, 45.3 ± 9.2 µM; PLA, 6.1 ± 0.8 µM) and the second exercise sets (ASP, 24.2 ± 4.5 µM; PLA, 6.6 ± 0.9 µM) and peak cadence during the second set (ASP, 153 ± 3 rpm; PLA, 152 ± 3 rpm) compared with the PLA trial (all p < 0.05). The peak power output during the second exercise set (ASP, 743 ± 32 W; PLA, 734 ± 31 W; p = 0.060) and the blood pH immediately before (ASP, 7.280 ± 0.020; PLA, 7.248 ± 0.016; p = 0.087) and after the third exercise set (ASP, 7.274 ± 0.019; PLA, 7.242 ± 0.018; p = 0.093) tended to be higher in the ASP than in the PLA trial. In conclusion, ASP supplementation partially improved repeated-sprint performance (peak cadence during the second exercise set). However, it did not affect the mean power output.

Effects of Capsinoids on Daily Physical Activity, Body Composition and Cold Hypersensitivity in Middle-Aged and Older Adults: A Randomized Study.

Sedentary/inactive lifestyle leads middle-aged and older adults to metabolic syndrome and frailty. Capsinoids from nonpungent chili pepper cultivar have been reported to reduce body fat mass, promote metabolism, and improve unidentified complaints of chills. Additionally, they have an anti-inflammation effect; therefore, we hypothesized that continuous oral ingestion of capsinoids alleviates age-related inflammation in the brain and improves the physical activity (PA) in middle-aged and older adults. In our double-blind human study, 69 participants (17 male, 52 female; mean age: 74.1 ± 7.7 years; range: 52-87 years) were administered either 9 mg of capsinoids which were extracted from pepper fruit variety CH-19 Sweet (Capsicum anuum L.) (CP group), or a placebo (PL group) daily over a 3 month period. In an animal study, PA and inflammation-related mRNA expression in the brain were examined in 5-week (young) and 53-week (old) aged mice fed a diet with or without 0.3% dihydrocapsiate, a type of capsinoids, for 12 weeks. In a human study, capsinoids intake did not increase the amount of light-to-moderate PA less than 6.0 metabolic equivalents (METs) (CP: 103.0 ± 28.2 at baseline to 108.2 ± 28.3 at 12 weeks; PL: 104.6 ± 19.8 at baseline to 115.2 ± 23.6 at 12 weeks, METs × hour/week); however, in participants exhibiting an inactive lifestyle, it showed significant increase (CP: 84.5 ± 17.2 at baseline to 99.2 ± 24.9 at 12 weeks; PL: 99.7 ± 23.3 at baseline to 103.8 ± 21.9 at 12 weeks). The energy expenditure in physical activity also improved in the inactive CP group (CP: 481.2 ± 96.3 at baseline to 562.5 ± 145.5 at 12 weeks; PL: 536.8 ± 112.2 at baseline to 598.6 ± 127.6 at 12 weeks; kcal/day). In all participants, CP showed reduced waist circumference, percent body fat, and visceral fat volume; in addition, chills were eased in subjects aged 80 years and older. The older mice fed capsinoids showed increased locomotion activity, decreased inflammation, and oxidative stress in the brain. The results suggest that the continuous oral ingestion of capsinoids gains PA through anti-inflammation effect in the brain as well as reduces fat accumulation and chills in inactive and older humans.

Pharmacokinetics and cerebral distribution of glycine administered to rats.

High doses of glycine have been reported to improve negative schizophrenic symptoms, suggesting that ingested glycine activates glutamatergic transmission via N-methyl-D-aspartate (NMDA) receptors. However, the pharmacokinetics of administered glycine in the brain has not been evaluated. In the present study, the time- and dose-dependent distributions of administered glycine were investigated from a pharmacokinetic viewpoint. Whole-body autoradiography of radiolabeled glycine was performed, and time-concentration curves for glycine and serine in plasma, cerebrospinal fluid (CSF), and brain tissues were obtained. Furthermore, pharmacokinetic parameters were calculated. For a more detailed analysis, the amount of glycine uptake in the brain was evaluated using the brain uptake index method. Radiolabeled glycine was distributed among periventricular organs in the brain. Oral administration of 2 g/kg of glycine significantly elevated the CSF glycine concentration above the ED50 value for NMDA receptors. The glycine levels in CSF were 100 times lower than those in plasma. Glycine levels were elevated in brain tissue, but with a slower time-course than in CSF. Serine, a major metabolite of glycine, was elevated in plasma, CSF, and brain tissue. Glycine uptake in brain tissue increased in a dose-dependent manner. Time-concentration curves revealed that glycine was most likely transported via the blood-CSF barrier and activated NMDA receptors adjacent to the ventricles. The pharmacokinetic analysis and the brain uptake index for glycine suggested that glycine was transported into brain tissue by passive diffusion. These results provide further insight into the potential therapeutic applications of glycine.

Different efficacy of CT screening for lung cancer according to histological type: analysis of Japanese-smoker cases detected using a low-dose CT screen.

The efficacy of CT screening for lung cancers is still a controversial issue, although one of the recently publicized large randomized controlled trials of this methodology, the National Lung Screening Trial (NLST), reported a decrease in the lung cancer-specific mortality for heavy smokers. We here performed case-matched comparative analyses, as a retrospective study, of three lung cancer arms detected by CT screen, X-ray screen, and by individual analysis of the clinicopathological features and outcomes in smokers from a symptomatic-prompted group of patients. We also considered the impacts of various potential biases in this cohort. The total study cohort comprised 136 patients in the CT screen group, 263 in the X-ray screen group and 254 in the symptomatic-prompted group. The ratio of stage IA cancers in the CT screen group was 67.7% and the ratio of advanced cases (i.e. stages IIIB+IV) was 12.5%. The percentage of bronchioloalveolar carcinoma (BAC) was 28.7% in the CT screen group. The 5-year survival rates were 82.4% in the CT screen group, 38.0% in the X-ray screen group and 17.8% in the symptomatic-prompted group. CT screening was found to be an independent prognostic factor for lung cancer even when BAC cases were eliminated (HR 0.35, P<0.01). Based on our sub-analysis by individual histological sub-type, CT screen lung cancer cases had a better survival rate than non-screened patients, which included adenocarcinoma, squamous cell carcinoma and large/small cell carcinoma. However, by multi-variant analysis a CT scan would not be expected to reduce the risk of lung cancer mortality in patients with large/small cell carcinoma, although would be expected to reduce the risk of lung cancer death by 80% in cases of both adenocarcinoma and squamous cell carcinoma. In conclusion, our current findings indicate that CT screening for lung cancer is an effective strategy for smokers and that patients with adenocarcinoma and squamous cell carcinoma of all variant histological types may benefit from this test. In this regard, early stage large/small cell carcinomas are insufficiently detected by the existing annual screening system.

Efficacy of CT screening for lung cancer in never-smokers: analysis of Japanese cases detected using a low-dose CT screen.

CT-screening for lung cancer is fairly widely used for both smokers and never-smokers in East Asia because the mortality rate for never-smokers due to this cancer is relatively high in this region. We performed comparative analyses, as a retrospective study, on three lung cancer arms detected by CT-screen, X-ray-screen, and via analysis of clinicopathological features and outcomes in never-smokers from a symptomatic-prompted group of patients. The total study cohort comprised 218 patients in CT group, 160 in X-ray group, and 82 in symptomatic-prompted group. The percentage of bronchioloalveolar carcinoma (BAC) was 65.1% in CT-screen group. The ratio of stage IA tumors in CT-screen group was 88.5% and the ratio of advanced cases (i.e. stages IIIB+IV) was 2.3%. The 5-year-survival rates were 95.0% in CT-screen, 73.0% in X-ray-screen and 40.0% in symptomatic-prompted group. We performed further sub-analysis which excluded pure BACs (i.e. Noguchi types A and B) or pure GGOs within a 10mm diameter because this is indicative of a very favorable prognosis. Based on this sub-analysis the number of the subjects in each group became 76 in CT group; 140 in X-ray group and 77 in symptomatic-prompted group. The principal characteristics of the patients such as age and sex became almost even in the three arms. In CT-screen subgroup, the ratio of stage IA cancer was 69.7% and of advanced cases was 6.6%. This advanced ratio was lower than both X-ray-screen (22.1%) and symptomatic-prompted (61.9%) groups. The 5-year-survival rates were 89.9% among CT-screen group patients, 72.6% for X-ray screen cases and 39.1% in symptomatic-prompted group. A CT-screen was found to be one of the independent prognostic factors for lung cancer (HR, 0.28; 95% CI, 0.12-0.72) and based on this would be expected to reduce the risk of lung cancer death by 78% compared with non-screened cases. In conclusion, CT will improve the survival rate and decrease the rate of advanced cancers in never-smokers via the existing annual screening system. CT-screening is also an independent prognostic improvement factor in never-smokers, and will therefore reduce the risk of lung cancer death.

[A case of primary pulmonary leiomyosarcoma showing rapid growth and fatal outcome].

An 80-year-old man was admitted to our hospital with a 4.0 x 2.0 cm shadow accompanied by calcification, found on chest CT scans on a health check. The shadow was located in the left lower lobe (S10), and was attached to the pleura. A transbronchial biopsy did not yield a definitive diagnosis. A percutaneous needle biopsy yielded a diagnosis of leiomyosarcoma. A general examination did not show any metastatic lesions in other areas. However, the tumor grew rapidly, with pleural effusion, and therefore he was treated only by palliative therapy. He died from respiratory failure 90 days after onset. The primary site of the tumor was determined to be intrapulmonary area by radiographic and autopsy findings. We report a rare primary pulmonary leiomyosarcoma showing rapid growth and fatal outcome.

Prediction of the metabolic interaction of nateglinide with other drugs based on in vitro studies.

Nateglinide is an antidiabetic agent metabolized by CYP2C9 and CYP3A4; hence inhibitors of these CYP isozymes may interact with nateglinide. There are, however, only limited in vitro data on how to predict drug-drug interactions in vivo. We examined the effects of 18 drugs that may be prescribed together with nateglinide (metformin, buformin, aspirin, gemfibrozil, simvastatin, pioglitazone, rosiglitazone, carbamazepine, clarithromycin, gliclazide, clofibrate, fluconazole, bezafibrate, phenylbutazone, nifedipine, famotidine, ibuprofen and miconazole) on the conversion of nateglinide to its major metabolite (N-[trans-4-(1-hydroxy-1-methylethyl)-cyclohexanecarbonyl]-D-phenylalanine) using human liver microsomes. Eight compounds showed a<50% inhibitory effect and we estimated the K(i) values for the remaining 10 compounds. Except for fluconazole and miconazole, 1+I(in, max, u)/K(i) calculated from the K(i) values, was approximately 1 and thus the possibility of a drug-drug interaction was considered low. The value for fluconazole suggested the risk of interaction and agreed with the results of clinical studies in which the AUC of nateglinide increased by 48% when it was co-administered with fluconazole. The present study showed that nateglinide metabolism would hardly be affected by the drugs used in this study, except for miconazole and fluconazole that are potent inhibitors of multiple isoforms of CYPs.

Nitric oxide inhibitor altitude-dependently elevates pulmonary arterial pressure in high-altitude adapted yaks.

We studied the effect of N(w)-nitro-L-arginine (NLA) on yak pulmonary vascular tone in a climatic (hypobaric/hyperbaric adjusted) chamber. Five young male yaks that had been born and reared at an altitude greater than 3800 m a.s.l. were used. After measuring control values, 20 mg/kg of NLA was administered via the jugular vein to each animal, and pulmonary hemodynamics and blood gases were repeatedly measured at simulated altitudes of 0, 2260 and 4500 m. The mean PaO2 decreased in an altitude-dependent manner, whereas there was no change in mean pulmonary arterial pressure (mPAP) or mean cardiac output (mCO). NLA significantly increased mPAP, and mean pulmonary vascular resistance (mPVR), and decreased CO at each tested altitude, and greater increases in mPAP and mPVR by NLA were observed at the higher elevations. We conclude that augmented endogenous NO production, especially at higher altitudes, accounts for the low pulmonary vascular tone observed in high-altitude adapted yaks.

Blunted effect of the Kv channel inhibitor on pulmonary circulation in Tibetan sheep: a model for studying hypoxia and pulmonary artery pressure regulation.

OBJECTIVE: The aim of this study was to assess the effect of 4-aminopyridine, a Kv channel inhibitor, on the pulmonary circulation of Tibetan sheep. It has been reported that chronic hypoxia downregulates the 4-aminopyridine (4AP)-sensitive Kv channel (which governs the membrane potential (Em) of pulmonary vascular smooth muscle cells in pulmonary vessels) without a change in 4AP sensitivity. METHODOLOGY: Pulmonary haemodynamic indices and blood gas analyses were measured in six young male animals in an altitude chamber that was adjusted to simulated altitudes of 0 m, 2260 m, and 4500 m. Drip infusion of 4AP, 10 mg/h for 3 h, was started and continued during the study. RESULTS: With the increase in altitude mean pulmonary artery pressure increased and mean PaO(2) decreased. 4AP had no effect on the levels of mean PPA, mean pulmonary artery wedge pressure, cardiac output, and mean PaO(2), mean PaCO(2), and mean pH at any altitude but tended to alter heart rate and mean arterial pressure at altitudes of 2260 m and 4500 m. CONCLUSION: It is concluded that the 4AP-sensitive Kv channel does not play a role in pulmonary vascular tone in high-altitude active Tibetan sheep. Their pulmonary vascular oxygen sensing appears not to involve Kv channels.