Functional food, blood lipids and cardiovascular disease. Part 2: prebiotics and synbiotics

For the past 20 years, the focuses of public health strategies for reducing the risk of cardiovascular disease (CVD) have been aimed at lowering cholesterol levels. However, recent findings have highlighted not only cholesterol but also triacylglycerol as a lipid risk factor for CVD. Dietary strategies which are able to reduce these Circulating lipid levels, but which are able to offer longterm efficacy comparable with effective drug treatments, are currently being sought. One dietary strategy that has been proposed to benefit the lipid profile involves the supplementation of the diet with probiotics (Part 1) prebiotics and synbiotics (Part 2), which are mechanisms to improve the health of the host by supplementation and/or fortification of certain health promoting gut bacteria. Probiotics in the form of fermented milk products have been shown to have cholesterol-lowering properties, whereas non-digestible fermentable prebiotics have been shown to reduce triacylglycerol levels in animal studies, However, in human studies, there have been inconsistent findings with respect to changes in lipid levels with both prebiotics and probiotics although on the whole there have been favourable outcomes.

Gas-phase rate coefficients for the reactions of nitrate radicals with (Z)-pent-2-ene, (E)-pent-2-ene, (Z)-hex-2-ene, (E)-hex-2-ene, (Z)-hex-3-ene, (E)-hex-3-ene and (E)-3-methylpent-2-ene at room temperature

Rate coefficients for reactions of nitrate radicals (NO3) with (Z)-pent-2-ene, (E)-pent-2-ene, (Z)-hex-2-ene, (E)-hex-2-ene, (Z)-hex-3-ene, (E)-hex-3-ene and (E)-3-methylpent-2-ene were determined to be (6.55 +/- 0.78) x 10(-13) cm(3) molecule(-1) s(-1), (3.78 +/- 0.45) x 10(-13) cm(3) molecule(-1) s(-1), (5.30 +/- 0.73) x 10(-13) cm(3) molecule(-1) s(-1), (3.83 +/- 0.47) x 10(-13) cm(3) molecule(-1) s(-1), (4.37 +/- 0.49) x 10(-13) cm(3) molecule(-1) s(-1), (3.61 +/- 0.40) x 10(-13) cm(3) molecule(-1) s(-1) and (8.9 +/- 1.5) x 10(-12) cm(3) molecule(-1) s(-1), respectively. We performed kinetic experiments at room temperature and atmospheric pressure using a relative-rate technique with GC-FID analysis. The experimental results demonstrate a surprisingly large cis-trans (Z-E) effect, particularly in the case of the pent-2-enes, where the ratio of rate coefficients is ca. 1.7. Rate coefficients are discussed in terms of electronic and steric influences, and our results give some insight into the effects of chain length and position of the double bond on the reaction of NO3 with unsaturated hydrocarbons. Atmospheric lifetimes were calculated with respect to important oxidants in the troposphere for the alkenes studied, and NO3-initiated oxidation is found to be the dominant degradation route for (Z)-pent-2-ene, (Z)-hex-3-ene and (E)-3-methylpent-2-ene.

Modulation of pro-survival Akt/protein kinase B and ERK1/2 signaling cascades by quercetin and its in vivo metabolites underlie their action on neuronal viability

Much recent interest has focused on the potential of flavonoids to interact with intracellular signaling pathways such as with the mitogen-activated protein kinase cascade. We have investigated whether the observed strong neurotoxic potential of quercetin in primary cortical neurons may occur via specific and sensitive interactions within neuronal mitogen-activated protein kinase and Akt/protein kinase B (PKB) signaling cascades, both implicated in neuronal apoptosis. Quercetin induced potent inhibition of both Akt/PKB and ERK phosphorylation, resulting in reduced phosphorylation of BAD and a strong activation of caspase-3. High quercetin concentrations (30 microM) led to sustained loss of Akt phosphorylation and subsequent Akt cleavage by caspase-3, whereas at lower concentrations (<10 microM) the inhibition of Akt phosphorylation was transient and eventually returned to basal levels. Lower levels of quercetin also induced strong activation of the pro-survival transcription factor cAMP-responsive element-binding protein, although this did not prevent neuronal damage. O-Methylated quercetin metabolites inhibited Akt/PKB to lesser extent and did not induce such strong activation of caspase-3, which was reflected in the lower amount of damage they inflicted on neurons. In contrast, neither quercetin nor its O-methylated metabolites had any measurable effect on c-Jun N-terminal kinase phosphorylation. The glucuronide of quercetin was not toxic and did not evoke any alterations in neuronal signaling, probably reflecting its inability to enter neurons. Together these data suggest that quercetin and to a lesser extent its O-methylated metabolites may induce neuronal death via a mechanism involving an inhibition of neuronal survival signaling through the inhibition of both Akt/PKB and ERK rather than by an activation of the c-Jun N-terminal kinase-mediated death pathway.

Timing and structure of the 8.2 kyr B.P. event inferred from δ18O records of stalagmites from China, Oman, and Brazil

Oxygen isotope records of stalagmites from China and Oman reveal a weak summer monsoon event, with a double-plunging structure, that started 8.21 ± 0.02 kyr B.P. An identical but antiphased pattern is also evident in two stalagmite records from eastern Brazil, indicating that the South American Summer Monsoon was intensified during the 8.2 kyr B.P. event. These records demonstrate that the event was of global extent and synchronous within dating errors of <50 years. In comparison with recent model simulations, it is plausible that the 8.2 kyr B.P. event can be tied in changes of the Atlantic Meridional Overturning Circulation triggered by a glacial lake draining event. This, in turn, affected North Atlantic climate and latitudinal position of the Intertropical Convergence Zone, resulting in the observed low-latitude monsoonal precipitation patterns.

Uncoupling protein 2 and 3 gene polymorphisms and their association with type 2 diabetes in asian indians

BACKGROUND: this study examined the association of -866G/A, Ala55Val, 45bpI/D, and -55C/T polymorphisms at the uncoupling protein (UCP) 3-2 loci with type 2 diabetes in Asian Indians. METHODS: a case-control study was performed among 1,406 unrelated subjects (487 with type 2 diabetes and 919 normal glucose-tolerant [NGT]), chosen from the Chennai Urban Rural Epidemiology Study, an ongoing population-based study in Southern India. The polymorphisms were genotyped using polymerase chain reaction-restriction fragment length polymorphism and direct sequencing. Haplotype frequencies were estimated using an expectation-maximization algorithm. Linkage disequilibrium was estimated from the estimates of haplotypic frequencies. RESULTS: the genotype (P = 0.00006) and the allele (P = 0.00007) frequencies of Ala55Val of the UCP2 gene showed a significant protective effect against the development of type 2 diabetes. The odds ratios (adjusted for age, sex, and body mass index) for diabetes for individuals carrying Ala/Val was 0.72, and that for individuals carrying Val/Val was 0.37. Homeostasis insulin resistance model assessment and 2-h plasma glucose were significantly lower among Val-allele carriers compared to the Ala/Ala genotype within the NGT group. The genotype (P = 0.02) and the allele (P = 0.002) frequencies of -55C/T of the UCP3 gene showed a significant protective effect against the development of diabetes. The odds ratio for diabetes for individuals carrying CT was 0.79, and that for individuals carrying TT was 0.61. The haplotype analyses further confirmed the association of Ala55Val with diabetes, where the haplotypes carrying the Ala allele were significantly higher in the cases compared to controls. CONCLUSIONS: Ala55Val and -55C/T polymorphisms at the UCP3-2 loci are associated with a significantly reduced risk of developing type 2 diabetes in Asian Indians.

Synthesis and antiviral properties of spirocyclic [1,2,3]-triazolooxazine nucleosides

An efficient synthesis of spirocyclic triazolooxazine nucleosides is described. This was achieved by the conversion of β-D-psicofuranose to the corresponding azido-derivative, followed by alkylation of the primary alcohol with a range of propargyl bromides - obtained via Sonogashira chemistry. The products of these reactions underwent 1,3-dipolar addition smoothly to generate the protected spirocyclic adducts. These were easily deprotected to give the corresponding ribose nucleosides. The library of compounds obtained was investigated for its antiviral activity, using MHV (Mouse Hepatitis Virus) as a model wherein derivative 3f showed the most promising activity and tolerability.

Mesomorphic behaviour in copoly(ester-imide)s of poly(butylene-2,6-naphthalate) (PBN)

Copolycondensation of N,N’-bis(4-hydroxybutyl)-biphenyl-3,4,3',4'-tetracarboxylic diimide at 20 and 25 mol% with bis(4-hydroxybutyl)-2,6-naphthalate produces PBN-based copoly(ester-imide)s that not only crystallise but also form a (smectic) mesophase upon cooling from the melt. Incorporation of 25 mol% imide in PBN causes the glass transition temperature (measured by DSC) to rise from 51 to 74 °C, a significant increase relative to PBN. Furthermore, increased storage- (G'), loss- (G'') and elastic (E) moduli are observed for both copoly(ester-imide)s when compared to PBN itself. Structural analysis of the 20 mol% copolymer by X-ray powder and fibre diffraction, interfaced to computational modelling, suggests a crystal structure related to that of α-PBN, in space group P-1, with cell dimensions a = 4.74, b = 6.38, c = 14.45 Å, α = 106.1, β = 122.1, γ = 97.3°, ρ = 1.37 g cm-3.

Clinical comparison between the bleaching efficacy of 37% peroxide carbamide gel mixed with sodium perborate with established intracoronal bleaching agent

Objective. The aim was to evaluate the bleaching efficacy of sodium perborate/37% carbamide peroxide paste and traditional sodium perborate/distilled water for intracoronal bleaching. Study design. Thirty patients with dark anterior teeth were divided into 2 groups (n = 15): group A: sodium perborate/ distilled water; and group B: sodium perborate/37% carbamide peroxide paste. The bleaching treatment limited each patient to the maximum of 4 changes of the bleaching agent. Initial and final color shades were measured using the Vita Lumin shade guide. Results. Data was analyzed with Wilcoxon test for initial and final comparison according to the bleaching agent, demonstrating efficacy of the bleaching treatment with both agents. Mann-Whitney test was used for comparison of the efficacy of the bleaching agents, showing that there was no significant difference between them. Conclusion. The sodium perborate/37% carbamide peroxide association for intracoronal bleaching has proven to be as effective as sodium perborate/distilled water. (Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2009; 107: e43-e47)

Health in Brazil 2 Maternal and child health in Brazil: progress and challenges

In the past three decades, Brazil has undergone rapid changes in major social determinants of health and in the organisation of health services. In this report, we examine how these changes have affected indicators of maternal health, child health, and child nutrition. We use data from vital statistics, population censuses, demographic and health surveys, and published reports. In the past three decades, infant mortality rates have reduced substantially, decreasing by 5.5% a year in the 1980s and 1990s, and by 4.4% a year since 2000 to reach 20 deaths per 1000 livebirths in 2008. Neonatal deaths account for 68% of infant deaths. Stunting prevalence among children younger than 5 years decreased from 37% in 1974-75 to 7% in 2006-07. Regional differences in stunting and child mortality also decreased. Access to most maternal-health and child-health interventions increased sharply to almost universal coverage, and regional and socioeconomic inequalities in access to such interventions were notably reduced. The median duration of breastfeeding increased from 2.5 months in the 1970s to 14 months by 2006-07. Official statistics show stable maternal mortality ratios during the past 10 years, but modelled data indicate a yearly decrease of 4%, a trend which might not have been noticeable in official reports because of improvements in death registration and the increased number of investigations into deaths of women of reproductive age. The reasons behind Brazil`s progress include: socioeconomic and demographic changes (economic growth, reduction in income disparities between the poorest and wealthiest populations, urbanisation, improved education of women, and decreased fertility rates), interventions outside the health sector (a conditional cash transfer programme and improvements in water and sanitation), vertical health programmes in the 1980s (promotion of breastfeeding, oral rehydration, and immunisations), creation of a tax-funded national health service in 1988 (coverage of which expanded to reach the poorest areas of the country through the Family Health Program in the mid-1990s); and implementation of many national and state-wide programmes to improve child health and child nutrition and, to a lesser extent, to promote women`s health. Nevertheless, substantial challenges remain, including overmedicalisation of childbirth (nearly 50% of babies are delivered by caesarean section), maternal deaths caused by illegal abortions, and a high frequency of preterm deliveries.

Aquaporin 2 expression increased by glucagon in normal rat inner medullary collecting ducts

Yano Y, Cesar KR, Araujo M, Rodrigues Jr. AC, Andrade LC, Magaldi AJ. Aquaporin 2 expression increased by glucagon in normal rat inner medullary collecting ducts. Am J Physiol Renal Physiol 296: F54-F59, 2009. First published October 1, 2008; doi: 10.1152/ajprenal.90367.2008.-It is well known that Glucagon (Gl) is released after a high protein diet and participates in water excretion by the kidney, principally after a protein meal. To study this effect in in vitro perfused inner medullary collecting ducts (IMCD), the osmotic water permeability (Pf; mu m/s) at 37 degrees C and pH 7.4 in normal rat IMCDs (n = 36) perfused with Ringer/HCO(3) was determined. Gl (10(-7) M) in absence of Vasopressin (AVP) enhanced the Pf from 4.38 +/- 1.40 to 11.16 +/- 1.44 mu m/s (P < 0.01). Adding 10(-8), 10(-7), and 10(-6) M Gl, the Pf responded in a dose-dependent manner. The protein kinase A inhibitor H8 blocked the Gl effect. The specific Gl inhibitor, des-His(1)-[Glu(9)] glucagon (10(-7) M), blocked the Gl-stimulated Pf but not the AVP-stimulated Pf. There occurred a partial additional effect between Gl and AVP. The cAMP level was enhanced from the control 1.24 +/- 0.39 to 59.70 +/- 15.18 fm/mg prot after Gl 10(-7) M in an IMCD cell suspension. The immunoblotting studies indicated an increase in AQP2 protein abundance of 27% (cont 100.0 +/- 3.9 vs. Gl 127.53; P = 0.0035) in membrane fractions extracted from IMCD tubule suspension, incubated with 10(-6) M Gl. Our data showed that 1) Gl increased water absorption in a dose-dependent manner; 2) the anti-Gl blocked the action of Gl but not the action of AVP; 3) Gl stimulated the cAMP generation; 4) Gl increased the AQP2 water channel protein expression, leading us to conclude that Gl controls water absorption by utilizing a Gl receptor, rather than a AVP receptor, increasing the AQP2 protein expression.

Prevalence and nonrandom distribution of exonic mutations in interferon regulatory factor 6 in 307 families with Van der Woude syndrome and 37 families with popliteal pterygium syndrome

Purpose: Interferon regulatory factor 6 encodes a member of the IRF family of transcription factors. Mutations in interferon regulatory factor 6 cause Van der Woude and popliteal pterygium syndrome, two related orofacial clefting disorders. Here, we compared and contrasted the frequency and distribution of exonic Mutations in interferon regulatory factor 6 between two large geographically distinct collections of families with Van der Woude and between one collection of families with popliteal pterygium syndrome. Methods: We performed direct sequence analysis of interferon regulatory factor 6 exons oil samples from three collections, two with Van der Woude and one with popliteal pterygium syndrome. Results: We identified mutations in interferon regulatory factor 6 exons in 68% of families in both Van der Woude collections and in 97% of families with popliteal pterygium syndrome. In sum, 106 novel disease-causing variants were found. The distribution of mutations in the interferon regulatory factor 6 exons in each collection was not random; exons 3, 4, 7, and 9 accounted for 80%. In the Van der Woude collections, the mutations were evenly divided between protein truncation and missense, whereas most mutations identified in the popliteal pterygium syndrome collection were missense. Further, the missense mutations associated with popliteal pterygium syndrome were localized significantly to exon 4, at residues that are predicted to bind directly to DNA. Conclusion: The nonrandom distribution of mutations in the interferon regulatory factor 6 exons suggests a two-tier approach for efficient mutation screens for interferon regulatory factor 6. The type and distribution of mutations are consistent with the hypothesis that Van der Woude is caused by haploinsufficiency of interferon regulatory factor 6. Oil the other hand, the distribution of popliteal pterygium syndrome-associated mutations suggests a different, though not mutually exclusive, effect oil interferon regulatory factor 6 function. Genet Med 2009:11(4):241-247.

Elevated CO(2) increases photosynthesis, biomass and productivity, and modifies gene expression in sugarcane

Because of the economical relevance of sugarcane and its high potential as a source of biofuel, it is important to understand how this crop will respond to the foreseen increase in atmospheric [CO(2)]. The effects of increased [CO(2)] on photosynthesis, development and carbohydrate metabolism were studied in sugarcane (Saccharum ssp.). Plants were grown at ambient (similar to 370 ppm) and elevated (similar to 720 ppm) [CO(2)] during 50 weeks in open-top chambers. The plants grown under elevated CO(2) showed, at the end of such period, an increase of about 30% in photosynthesis and 17% in height, and accumulated 40% more biomass in comparison with the plants grown at ambient [CO(2)]. These plants also had lower stomatal conductance and transpiration rates (-37 and -32%, respectively), and higher water-use efficiency (c.a. 62%). cDNA microarray analyses revealed a differential expression of 35 genes on the leaves (14 repressed and 22 induced) by elevated CO(2). The latter are mainly related to photosynthesis and development. Industrial productivity analysis showed an increase of about 29% in sucrose content. These data suggest that sugarcane crops increase productivity in higher [CO(2)], and that this might be related, as previously observed for maize and sorghum, to transient drought stress.

Matrix metalloproteinases cleave the beta(2)-adrenergic receptor in spontaneously hypertensive rats

Rodrigues SF, Tran ED, Fortes ZB, Schmid-Schonbein GW. Matrix metalloproteinases cleave the beta(2)-adrenergic receptor in spontaneously hypertensive rats. Am J Physiol Heart Circ Physiol 299: H25-H35, 2010. First published April 9, 2010; doi:10.1152/ajpheart.00620.2009.-We recently observed the enhanced serine and matrix metalloproteinase (MMP) activity in the spontaneously hypertensive rat (SHR) compared with its normotensive Wistar-Kyoto (WKY) rat and the cleavage of membrane receptors in the SHR by MMPs. We demonstrate in vivo that MMP-7 and MMP-9 injection leads to a vasoconstrictor response in microvessels of rats that is blocked by a specific MMP inhibitor (GM-6001, 1 mu M). Multiple pathways may be responsible. Since the beta(2)-adrenergic receptor (beta(2)-AR) is susceptible to the action of endogenous MMPs, we hypothesize that MMPs in the plasma of SHRs are able to cleave the extracellular domain of the beta(2)-AR. SHR arterioles respond in an attenuated fashion to beta(2)-AR agonists and antagonists. Aorta and heart muscle of control Wistar rats were exposed for 24 h (37 C) to fresh plasma of male Wistar and WKY rats and SHRs with and without doxycycline (30 mu M) and EDTA (10 mM) to reduce MMP activity. The density of extracellular and intracellular domains of beta(2)-AR was determined by immunohistochemistry. The density of the extracellular domain of beta(2)-AR is reduced in aortic endothelial cells and cardiac microvessels of SHRs compared with that of WKY or Wistar rats. Treatment of the aorta and the heart of control Wistar rats with plasma from SHRs, but not from WKY rats, reduced the number of extracellular domains, but not intracellular domains, of beta(2)-AR in aortic endothelial cells and cardiac microvessels. MMP inhibitors (EDTA and doxycycline) prevented the cleavage of the extracellular domain. Thus MMPs may contribute to the reduced density of the extracellular domain of beta(2)-AR in blood vessels and to the increased arteriolar tone of SHRs compared with normotensive rats.