Supplementation-induced change in muscle carnosine is paralleled by changes in muscle metabolism, protein glycation and reactive carbonyl species sequestering.

Carnosine is a performance-enhancing food supplement with a potential to modulate muscle energy metabolism and toxic metabolites disposal. In this study we explored interrelations between carnosine supplementation (2 g/day, 12 weeks) induced effects on carnosine muscle loading and parallel changes in (i) muscle energy metabolism, (ii) serum albumin glycation and (iii) reactive carbonyl species sequestering in twelve (M/F=10/2) sedentary, overweight-to-obese (BMI: 30.0+/-2.7 kg/m2) adults (40.1+/-6.2 years). Muscle carnosine concentration (Proton Magnetic Resonance Spectroscopy; 1H-MRS), dynamics of muscle energy metabolism (Phosphorus Magnetic Resonance Spectroscopy; 31P-MRS), body composition (Magnetic Resonance Imaging; MRI), resting energy expenditure (indirect calorimetry), glucose tolerance (oGTT), habitual physical activity (accelerometers), serum carnosine and carnosinase-1 content/activity (ELISA), albumin glycation, urinary carnosine and carnosine-propanal concentration (mass spectrometry) were measured. Supplementation-induced increase in muscle carnosine was paralleled by improved dynamics of muscle post-exercise phosphocreatine recovery, decreased serum albumin glycation and enhanced urinary carnosine-propanal excretion (all p<0.05). Magnitude of supplementation-induced muscle carnosine accumulation was higher in individuals with lower baseline muscle carnosine, who had lower BMI, higher physical activity level, lower resting intramuscular pH, but similar muscle mass and dietary protein preference. Level of supplementation-induced increase in muscle carnosine correlated with reduction of protein glycation, increase in reactive carbonyl species sequestering, and acceleration of muscle post-exercise phosphocreatine recovery.

The potential impact of sleep-related movement disorders on stroke risk: a population-based longitudinal study.

BACKGROUND: Sleep-related movement disorders (SRMD) have been shown to increase the risk of cardiovascular diseases. However, the relationship between SRMD and stroke remains unclear. AIM: To explore the relationship between SRMD and stroke in the general population. DESIGN: Two cohorts of patients with SRMD and without SRMD were followed up for the occurrence of hemorrhagic and ischemic stroke. METHODS: The study cohort enrolled 604 patients who were initially diagnosed as SRMD between 2000 and 2005. 2,416 age- and sex-matched patients without prior stroke were selected as the comparison cohort. A Cox-proportional hazard regression analysis was performed for multivariate adjustment. RESULTS: Patients with SRMD had a higher risk for developing all-cause stroke [adjusted hazard ratio (HR) = 2.29, 95% confidence interval (CI) = 1.42-3.80]. Patients of below 45 years old had the greatest stroke risk (HR = 4.03, 95% CI = 3.11-5.62), followed by patients aged ≥65 years (HR = 2.64, 95% CI = 1.12-3.44) and 45-64 years (HR = 1.07, 95% CI = 1.02-1.71). The age-stratified analysis suggested that the increased risk of hemorrhagic stroke was more significant than ischemic stroke among all age groups. Furthermore, males with SRMD were at greater risk to develop all-cause stroke (HR = 2.98, 95% CI = 1.74-4.50) than that of females (HR = 1.94, 95% CI = 1.01-3.77). CONCLUSIONS: Patients with SRMD were found to have an increased risk of all-cause stroke along with a higher possibility of hemorrhagic stroke over ischemic stroke.

Handling leachate from glass cullet stockpiles.

Mixed glass cullet (crushed recycled glass containers) is stockpiled uncovered before use as roadway construction aggregate or daily cover in landfills. Rainwater that leaches through the stockpiles dissolves and suspends contaminants such as those from food residuals and paper labels. The objective of this study was to determine leachate quantity and quality from cullet stockpiles as a basis for development of Best Management Practices (BMPs). Four 35-tonne field stockpiles were set up for leachate analysis and to determine the effects of mechanical turning treatment on the leachate. Field-collected leachate and laboratory-generated washwater of cullet (water:cullet=3:1 by weight) were both analyzed for basic wastewater parameters, which showed pollutant levels comparable to or higher than those of untreated domestic wastewater or urban stormwater. While organic contamination decreased substantially (e.g., washwater BOD>95% reduction), TKN and total-phosphorus levels in leachate ranged between 11.6-154mgL(-1) and 1.6-12.0mgL(-1), respectively, and remained comparable to levels found in untreated domestic wastewater after four months. Turning enhanced the degradation of the organic constituents inside the stockpiles, which was confirmed by elevated temperatures. Based on this study, leachate from glass cullet stockpiles should not be released to surface water. For leachate from long-term cullet stockpiles, release to groundwater should be only done after treatment to reduce nitrogen levels.

Influence of temperature on the ontogenetic expression of neural development-related genes from developing tilapia brain expressed sequence tags.

The developing central neural circuits in teleosts are genetically controlled and temperature-initiated. We compiled a list of transcripts expressed in the developing tilapia (Oreochromis mossambicus) brain using expressed sequence tags derived from the developing brain, and investigated genes with thermosensitive ontogenetic expression. Of 1084 clones, 893 were unique genes, 445 of which were known. Fourteen of the latter were neural development-related, and the ontogenetic expression of nine was temperature-influenced. Discs large homolog 5, myelin expression factor 2, plasticity-related protein-2, tsc2 gene product-related genes, and an inhibitor of differentiation protein 2 (Id2) were differentially temperature-influenced according to their developmental stages. Endothelial differentiation-related factor 1, midkine-related growth factor b, and mitogen-activated protein kinase 14b were specifically influenced by elevated temperature, and beta-catenin-like isoform 1 by lower temperature. Neural development-related genes, particularly those with thermosensitive ontogenetic expression, might be important for developing central neural circuits in teleosts.

Comparative anti-caries effects of tablet and liquid fluorides in cleft children.

Children with cleft lip and/or palate are at a higher risk for developing caries of the primary incisors compared with non-cleft children. To determine whether fluoride in tablet or liquid form would be more efficacious with children with cleft lip and/or palate, a two-year clinical investigation was conducted to test the anti-caries effects. One-hundred and fifteen cleft children (59 boys and 56 girls) between 22 and 26 months old were randomly selected into control, tablet and liquid fluoride groups. The amount of administered fluoride was 0.25 mg F daily in non-fluoridated Taiwan. Dental examinations were conducted using mirrors and #23 explorers. Caries were assessed using the DMF index in the baseline, first year and second year. The results showed that children in the tablet and liquid groups had a significantly lower DMFT increment than in the control group (p < 0.05). In the DMFS index, children in the liquid group showed a significantly lower caries increment than in the control group (p < 0.01), and children in the tablet group presented a borderline, but non-significant statistical difference when compared with the control group (p = 0.065). No significant statistical difference was found in either DMFT or DMFS between tablet and liquid fluoride administrations (p = 0.521 and p = 0.383, respectively). It is concluded that dietary fluoride supplements in liquid form show efficacy in reducing early childhood caries in the cleft children. Liquid fluoride showed slightly better numerical anti-caries effect than tablet fluoride, which is possibly due to its ease of administration with small children.

Arecoline cytotoxicity on human oral mucosal fibroblasts related to cellular thiol and esterase activities.

Betel quid (BQ) chewing is associated with an increased risk of oral submucous fibrosis (OSF) and oral cancer in India and many south-east Asian countries. Recently, we have shown that arecoline is cytotoxic to cultured human oral mucosal fibroblasts. This study investigated protective effects of various agents against the cytotoxicity of arecoline and its mechanisms. Arecoline, at concentrations of 0.2 and 0.4 mM, decreased the cell numbers by 38% and 63%, respectively. At a concentration of 2 mM, N-acetyl-L-cysteine [a glutathione (GSH) synthesis precursor] could prevent arecoline-induced cytotoxicity. The decrease in cell numbers was reduced to 17% relative to control. Extracellular addition of esterase at a concentration of 0.1 U/ml could almost completely protect the oral mucosal fibroblast (OMF) from arecoline-induced cytotoxicity. Arecoline is a muscarinic receptor agonist. However, atropine, a muscarinic receptor antagonist was unable to protect the cells from arecoline cytotoxicity at a concentration of 10 microM. Pretreatment of OMF with 50 microM buthionine sulfoximine (a cellular GSH synthesis inhibitor) or 0.5 mM diethylmaleate (a cellular GSH depleting agent) potentiated the cytotoxic effects of arecoline. These results indicate that cytotoxicity of arecoline on OMF is associated with cellular GSH levels and esterase activities. Factors that induce the GSH synthesis or esterase activity of oral mucosal cells can be used for future chemoprevention of BQ chewing-related lesions.

Effects of estradiol on the serotonin secretion and turnover in the hypothalamus of male tilapia, Oreochromis mossambicus, in vitro.

The effects of estradiol on the secretion and turnover of serotonin in the hypothalamic fragments of male tilapia, Oreochromis mossambicus, were studied using a static incubation system. The quantitative analysis of serotonin and its related metabolite, 5-hydroxyindoleacetic acid, were performed by high-performance liquid chromatography with electrochemical detection. The hypothalamic fragments were incubated with 17 beta-estradiol at a concentration of 2 x 10(-8), 8 x 10(-8), 2 x 10(-7), 4 x 10(-7), or 4 x 10(-6) g/ml. The low dose of estradiol, 2 x 10(-8) g/ml, had no effect on the concentration of serotonin and 5-hydroxyindoleacetic acid or serotonin turnover in the hypothalamic incubation media. The moderate doses of estradiol 8 x 10(-8) and 2 x 10(-7) g/ml, increased the concentrations of serotonin and 5-hydroxyindoleacetic acid in the hypothalamic incubation media, but had no effect on the serotonin turnover. The high doses of estradiol, 4 x 10(-7) and 4 x 10(-6) g/ml, did not alter the serotonin concentration in the hypothalamic incubation media, but increased the 5-hydroxyindoleacetic acid concentration and serotonin turnover. These results demonstrate that the moderate dose of estradiol increases the serotonin activity by increasing the serotonin concentration, whereas the high dose of estradiol increases the serotonin activity by increasing the ratio of 5-hydroxyindoleacetic acid and serotonin. However, the serotonin concentration is homeostatically maintained in the extracellular fluid of hypothalamus under the high dose of E2 treatment.

Effects of estradiol treatment on responses of rat preoptic warm sensitive neurons to progesterone in vitro.

Single unit activity was recorded extracellularly in preoptic slice preparations from ovariectomized female rats. The rats were pretreated daily with (1) estradiol benzoate (20 micrograms/0.1 ml sesame oil) for 3 consecutive days just prior to the experiment (OVX+E72h), (2) sesame oil (OVX+Oil), or (3) untreated (OVX). In the preparations from OVX rats, 12 (50%) of 24 warm-sensitive neurons were inhibited and 2 (8%) were excited by the application of progesterone (P) in perfusion medium (30 ng/ml). In OVX+Oil preparations, 4 (40%) of 10 warm-sensitive neurons were inhibited and none was excited by P. In OVX+E72h preparations, however, only 4 (10%) were inhibited by P and 16 (38%) of 42 warm-sensitive neurons were excited. When Ru38486, a P-receptor antagonist, was applied together with P, no excitation was observed in warm-sensitive neurons in OVX+E72h preparations. These findings suggest that the P-induced excitation of preoptic warm sensitive neurons is mediated through the estrogen-induced P-receptors.

Anti-inflammatory effect of saikogenin A.

Saikogenin A, an anti-inflammatory drug, is present in the crude extract of a Chinese herbal plant called Tsai-Fu. Saikogenin A was less effective in adrenalectomized rats than in normal rats in reducing the carrageenin-induced edema. Serum corticosterone and ACTH were increased in the saikogenin A-treated rats, supporting the view that stimulation of hypothalamopituitary-adrenal system is responsible for the anti-inflammatory effect of saikogenin A. This is further supported by the findings that saikogenin A did not affect the spontaneous release of corticosterone but it facilitated the ACTH-induced release. In addition, cyclic AMP in isolated pituitary and adrenal glands was increased by saikogenin A. A role for cyclic AMP as the second messenger is thus considered. Otherwise, the direct action of saikogenin A on the process of inflammation cannot be ruled out because saikogenin A also functioned in the adrenalectomized rats and it inhibited the release of histamine induced by compound 48/80. Reduction of the vascular permeability was also observed in the saikogenin A-treated rats. These results suggest that the anti-inflammatory action of saikogenin A are due to an increase in corticosterone caused by the release of ACTH and a direct effect on the process of inflammation.