A novel red grape cells complex: health effects and bioavailability of natural resveratrol.

In this study, we present a novel product consisted of red grape cells (RGC) grown in culture and evaluated its effect on human LDL oxidation (in vitro) and inflammatory stress (in an in vivo rat model). We analyzed RGC for its polyphenols content and characterized RGC-derived resveratrol (RES) and its properties; and finally, we characterized the pharmacokinetic profile of RGC-RES in human plasma. RGC has demonstrated a strong inhibitory effect on LDL oxidation with IC50 as low as 8.0 µg/ml. RGC significantly reduced rats inflamed paw size induced by carrageenan injection. LC/MS analysis has shown that the main polyphenol in RGC was RES with one hexose moiety. The human pharmacokinetic analysis (clinicaltrials.gov NCT01747252) revealed relatively high bioavailability and two distinctly separated plasma concentration peaks at 1 and 5 h. The present study demonstrates antioxidant and anti-inflammatory traits of RGC that warrants further research in both pre-clinical and clinical settings.

Effects of prolonged-release melatonin and zolpidem on postural stability in older adults.

OBJECTIVES: A prolonged-release formulation of melatonin (PR-M) is indicated for insomnia in patients aged 55 years and older. Because hypnotics result in impairments of body sway, it was important to evaluate the effect of 2 mg PR-M on postural stability in older adults at night. METHODS: Twenty-four healthy volunteers (12 women, 12 men, aged 55-64 years) completed a randomized, double-blind, single-dose, three-way crossover study of postural stability of PR-M 2 mg, zolpidem 10 mg (active control) or placebo. Subjects were tested for body sway 30 min before, 1.5 and 4 h after dosing. Parameters tested were the area of the 95% confidence ellipse enclosing the center of pressure (COP; [A95]) and COP path length. RESULTS: Zolpidem significantly increased the A95 (both eyes conditions at all time points) and path length of COP. PR-M had no effect on A95 (both "eyes closed" and "eyes open" conditions at all time points) compared with placebo and increased COP path length by 10% at 4 h post-dose in open but not closed eyes condition. No serious adverse events were observed. CONCLUSIONS: In older adults, evening PR-M intake did not impair postural stability during the night. The postural instability with zolpidem demonstrated assay sensitivity and validated the outcome.

Efficacy and safety of prolonged-release melatonin for insomnia in middle-aged and elderly patients with hypertension: a combined analysis of controlled clinical trials.

BACKGROUND: Add-on prolonged-release melatonin (PRM) in antihypertensive therapy has been shown to ameliorate nocturnal hypertension. Hypertension is a major comorbidity among insomnia patients. The efficacy and safety of PRM for primary insomnia in patients aged 55 years and older who are treated with antihypertensive drugs were evaluated. METHODS: Post hoc analysis of pooled antihypertensive drug-treated subpopulations from four randomized, double-blind trials of PRM and placebo for 3 weeks (N[PRM] = 195; N[placebo] = 197) or 28 weeks (N[PRM] = 157; N[placebo] = 40). Efficacy measurements included Leeds Sleep Evaluation Questionnaire scores of quality of sleep and alertness and behavioral integrity the following morning after 3 weeks, and sleep latency (daily sleep diary) and Clinical Global Impression of Improvement (CGI-I) after 6 months of treatment. Safety measures included antihypertensive drug-treated subpopulations from these four and three additional single-blind and open-label PRM studies of up to 1 year (N[PRM] = 650; N[placebo] = 632). RESULTS: Quality of sleep and behavior following wakening improved significantly with PRM compared with placebo (P < 0.0001 and P < 0.0008, respectively). Sleep latency (P = 0.02) and CGI-I (P = 0.0003) also improved significantly. No differences were observed between PRM and placebo groups in vital signs, including daytime blood pressure at baseline and treatment phases. The rate of adverse events normalized per 100 patient-weeks was lower for PRM (3.66) than for placebo (8.53). CONCLUSIONS: The findings demonstrate substantive and sustained efficacy of PRM in primary insomnia patients treated with antihypertensive drugs. PRM appears to be safe for insomnia in patients with cardiovascular comorbidity.

A novel methodology to estimate the evolution of construction waste in construction sites.

This paper focuses on the accumulation of construction waste generated throughout the erection of new residential buildings. A special methodology was developed in order to provide a model that will predict the flow of construction waste. The amount of waste and its constituents, produced on 10 relatively large construction sites (7000-32,000 m(2) of built area) was monitored periodically for a limited time. A model that predicts the accumulation of construction waste was developed based on these field observations. According to the model, waste accumulates in an exponential manner, i.e. smaller amounts are generated during the early stages of construction and increasing amounts are generated towards the end of the project. The total amount of waste from these sites was estimated at 0.2m(3) per 1m(2) floor area. A good correlation was found between the model predictions and actual data from the field survey.

Steroidal and gonadal effects on neural cell proliferation in vitro in an adult songbird.

Neurogenesis in the adult songbird brain occurs along the ventricular zone (VZ), a specialized cell layer surrounding the lateral ventricles. To examine the acute effects of sex steroids on VZ cell proliferation, male and female adult zebra finch brain slices containing the VZ were exposed to 5-bromo-2'-deoxyuridine-5'-monophosphate (BrdU) in vitro. Slices from one hemisphere served as the control, while contralateral slices were treated with steroids, steroidogenic enzyme inhibitors or gonadal tissue itself. There were no significant effects on VZ cell proliferation in either sexes by acute exposure to 17beta-estradiol (E2), dihydrotestosterone (DHT), a cocktail of four sex steroids, and inhibitors of sex steroid synthesis (aminoglutethimide, ketoconazole, and fadrozole), or by activation of a mitochondrial cholesterol transporter. By contrast, dehydroepiandrosterone (DHEA) suppressed VZ cell proliferation in males, but not females, replicating previous observations involving treatments with corticosterone and RU-486. This suggests that DHEA suppresses proliferation in males via a glucocorticoid receptor-related mechanism. These results suggest that neurosteroidogenesis per se has little effect on acute VZ cell proliferation. Co-incubation with an ovary of female, but not male, slices significantly increased VZ cell proliferation; testicular tissue had no impact on proliferation in males or females. This suggests a role for a non-steroidal ovarian factor on adult female VZ cell proliferation. We also have evidence that previously reported sex-differences in BrdU-labeling along the adult VZ (males>females) result from a more rapid loss of cells in females. Sex differences in steroid action and cell death along the VZ may contribute to the maintenance of the sexually dimorphic song system.

11beta-hydroxysteroid dehydrogenase type 2 in zebra finch brain and peripheral tissues.

The enzyme 11betaHSD2 inactivates glucocorticoids by synthesizing metabolites that bind poorly to mineralocorticoid and glucocorticoid receptors. Oscine songbirds (Passeriformes) are important models for investigating stress hormone effects on brain and behavior but nothing is known about 11betaHSD2 activity in the songbird brain. We measured 11betaHSD2 mRNA expression and enzymatic activity in brain of adult and developing male and female zebra finches. Since 11betaHSD2 plays an important role in GC metabolism in some peripheral organs we measured mRNA and catalytic activity also in the adult liver, kidney colon and gonads. 11betaHSD2 mRNA was detected in all brain regions examined with expression in the cerebellum and hypothalamus greater in females than in males; expression in ovaries was greater than in testes. No differences were detected in the other peripheral tissues. Catalytic activity of 11betaHSD2 could be measured in brain, but at low levels and no sex differences were measured in any region tested. Because 11betaHSD2 protects mineralocorticoid sensitive tissues from inappropriate CORT action, we also measured mineralocorticoid receptor (MR) expression in adult brain kidney and liver. MR mRNA was detected in all tissues with similar levels of expression in neural and peripheral tissues. The wide distribution of 11betaHSD2 and MR throughout the songbird brain suggests that concentrations of glucocorticoids may be locally regulated in brain to modulate their actions on MR and possibly also glucocorticoid receptors (GR). Notable differences between mRNA expression and activity point to post-transcriptional regulation of the 11betaHSD2 enzyme.

Limb muscles are androgen targets in an acrobatic tropical bird.

Spectacular athleticism is a conspicuous feature of many animal courtship displays yet surprisingly little is known about androgen dependence of skeletal muscles underlying these displays. Testosterone (T) acts through androgen receptors (ARs) to stimulate muscular male Golden-collared manakins of Panama to perform a remarkably athletic courtship display that includes loud wingsnaps generated by the rapid and forceful lifting of the wings. We tested the hypothesis that androgen sensitivity, reflected in the expression levels of AR mRNA, is a muscular adaptation supporting these courtship displays. Quantitative PCR showed substantially greater AR mRNA expression in all limb muscles of wild male and female manakins compared with two other avian species that do not perform athletic displays, zebra finches and ochre-bellied flycatchers. AR expression levels in the massive skeletal muscles were comparable with the minute oscine syringeal muscle but greater than levels in nonmuscular androgen targets that did not differ across species. Compared with zebra finches, male manakins also had greater activity of the T-activating enzyme 5 alpha-reductase in a wing-lifting muscle. In addition, low levels of estrogen receptor alpha (ER) mRNA were detected in all muscles of control, T-treated, and estradiol-treated manakins. Treatment of manakins with T, but not estradiol, significantly increased skeletal muscle ER expression, suggesting that ER expression is AR-dependent. These results confirm manakin limb muscles as important androgen targets where T may act to promote the speed, force, and/or endurance required for the manakin display. Androgen-sensitive muscular phenotypes may adapt males of many species to perform impressive athletic displays.

Sex differences in cell proliferation and glucocorticoid responsiveness in the zebra finch brain.

Neural proliferation is a conserved property of the adult vertebrate brain. In mammals, stress reduces hippocampal neuronal proliferation and the effect is stronger in males than in females. We tested the effects of glucocorticoids on ventricular zone cell proliferation in adult zebra finches where neurons are produced that migrate to and incorporate within the neural circuits controlling song learning and performance. Adult male zebra finches sing and have an enlarged song circuitry; females do not sing and the song circuit is poorly developed. Freshly prepared slices from adult males and females containing the lateral ventricles were incubated with the mitotic marker BrdU with or without steroid treatments. BrdU-labeled cells were revealed immunocytochemically and all labeled cells within the ventricular zone were counted. We identified significantly higher rates of proliferation along the ventricular zone of males than in females. Moreover, acute administration of corticosterone significantly reduced proliferation in males with no effects in females. This effect in males was replicated by RU-486, which appears to act as an agonist of the glucocorticoid receptor in the songbird brain. The corticosterone effect was reversed by Thiram, which disrupts corticosterone action on the glucocorticoid receptor. Sex differences in proliferation and responses to stress hormones may contribute to the sexually dimorphic and seasonal growth of the neural song system of songbirds.

Utilization of industrial by-products for the production of controlled low strength materials (CLSM).

Industrial by-products were used for the production of controlled low-strength material (CLSM). CLSM, also known as 'flowable fill' is used as a replacement of compacted soil in cases where the application of the latter is difficult or impossible. The low mechanical requirements (compared with structural concrete) enable the use of industrial by-products for the production of CLSM. In this study cement kiln dust, asphalt dust, coal fly ash, coal bottom ash and quarry waste were tested for the possibility of producing CLSM with large proportions of those wastes. The results showed that in most cases, CLSM with good properties could be made with significant amounts of dust (25-50%w), especially when the dust has some cementing or pozzolanic potential as do fly ash and cement kiln dust.