Bradykinin -induced vasodilatation : Role of age, ACE1-inhibitory peptide, mas- and bradykinin receptors

Bradykinin exerts its vascular actions via two types of receptors, the non-constitutively expressed bradykinin receptor type 1 (BR1) and the constitutive type 2 receptor (BR2). Bradykinin-induced vasorelaxation is age-dependent, a phenomenon related to the varying amounts of BR1 and BR2 in the vasculature. Isoleucine-proline-proline (Ile-Pro-Pro), a bioactive tripeptide, lowers elevated blood pressure and improves impaired endothelium-dependent vasorelaxation in hypertensive rats. It inhibits angiotensin converting enzyme 1 (ACE1). Other mechanisms of action have also been postulated. The aims of the study were to clarify the underlying mechanisms of the age-dependency of bradykinin-induced vasodilatation such as the roles of the two bradykinin receptors, themas-receptor and synergism with Ile-Pro-Pro. The vascular response studies were conducted using mesenteric artery and aorta rings from normotensive 6 wk. (young) and 22 wk. (old) Wistar rats. Cumulative dosing of acetylcholine, bradykinin and angiotensin(1-7) (Ang(1-7))were tested in phenylephrine-induced vasoconstriction with or without 10 min pre-incubation with antagonists against BR1-, BR2- or mas-receptors,Ang(1-7) or ACE1-inhibitors captopril and Ile-Pro-Pro. The bradykinin-induced vasorelaxation in vitro was age-dependent and it was improved by pre incubation with Ile-Pro-Pro, especially in old rats with endothelial dysfunction. The mas-receptor antagonist, D-Pro7-Ang(1-7) abolished bradykinin-induced relaxation totally. Interestingly, BR1 and BR2 antagonists only slightly reduced bradykinin-induced vasorelaxation, as an evidence for the involvement of other mechanisms in addition to receptor activation. In conclusion, bradykinin-induced vasorelaxation was age -dependent and He-Pro-Pro improved it. Mas receptor antagonist abolished relaxation while bradykinin receptor antagonist only slightly reduced it, suggesting that bradykinin-induced vasorelaxation is regulated also by other mechanisms than the classical BR1/BR2 pathway. (C) 2016 Elsevier Inc: All rights reserved.Peer reviewe

Bovine serum albumin as the dominant form of dietary protein reduces subcutaneous fat mass, plasma leptin and plasma corticosterone in high fat-fed C57/BL6J mice

Acknowledgements The authors thank Harriett Schellekens from the University College Cork and Paula O’Connor from Teagasc Moorepark Food Research Centre for their assistance in procuring laboratory space and equipment. The present study was funded by Teagasc. B. L. M. was funded by the Walsh Fellowship Program. J. R. S. was supported by a 1000-talents professorship from the Chinese government. The funding bodies had no input on the design of the study or in the interpretation of the data.Peer reviewedPublisher PD

Fine-resolution mapping of microforms of a boreal bog using aerial images and waveform-recording LiDAR

Boreal bogs are important stores and sinks of atmospheric carbon whose surfaces are characterised by vegetation microforms. Efficient methods for monitoring their vegetation are needed because changes in vegetation composition lead to alteration in their function such as carbon gas exchange with the atmosphere. We investigated how airborne image and waveform-recording LiDAR data can be used for 3D mapping of microforms in an open bog which is a mosaic of pools, hummocks with a few stunted pines, hollows, intermediate surfaces and mud-bottom hollows. The proposed method operates on the bog surface, which is reconstructed using LiDAR. The vegetation was classified at 20 cm resolution. We hypothesised that LiDAR data describe surface topography, moisture and the presence and depth of field-layer vegetation and surface roughness; while multiple images capture the colours and texture of the vegetation, which are influenced by directional reflectance effects. We conclude that geometric LiDAR features are efficient predictors of microforms. LiDAR intensity and echo width were specific to moisture and surface roughness, respectively. Directional reflectance constituted 4-34 % of the variance in images and its form was linked to the presence of the field layer. Microform-specific directional reflectance patterns were deemed to be of marginal value in enhancing the classification, and RGB image features were inferior to LiDAR variables. Sensor fusion is an attractive option for fine-scale mapping of these habitats. We discuss the task and propose options for improving the methodology.Peer reviewe

A novel Bayesian approach to quantify clinical variables and to determine their spectroscopic counterparts in 1H NMR metabonomic data

<p>Abstract</p> <p>Background</p> <p>A key challenge in metabonomics is to uncover quantitative associations between multidimensional spectroscopic data and biochemical measures used for disease risk assessment and diagnostics. Here we focus on clinically relevant estimation of lipoprotein lipids by ¹H NMR spectroscopy of serum.</p> <p>Results</p> <p>A Bayesian methodology, with a biochemical motivation, is presented for a real ¹H NMR metabonomics data set of 75 serum samples. Lipoprotein lipid concentrations were independently obtained for these samples via ultracentrifugation and specific biochemical assays. The Bayesian models were constructed by Markov chain Monte Carlo (MCMC) and they showed remarkably good quantitative performance, the predictive R-values being 0.985 for the very low density lipoprotein triglycerides (VLDL-TG), 0.787 for the intermediate, 0.943 for the low, and 0.933 for the high density lipoprotein cholesterol (IDL-C, LDL-C and HDL-C, respectively). The modelling produced a kernel-based reformulation of the data, the parameters of which coincided with the well-known biochemical characteristics of the ¹H NMR spectra; particularly for VLDL-TG and HDL-C the Bayesian methodology was able to clearly identify the most characteristic resonances within the heavily overlapping information in the spectra. For IDL-C and LDL-C the resulting model kernels were more complex than those for VLDL-TG and HDL-C, probably reflecting the severe overlap of the IDL and LDL resonances in the ¹H NMR spectra.</p> <p>Conclusion</p> <p>The systematic use of Bayesian MCMC analysis is computationally demanding. Nevertheless, the combination of high-quality quantification and the biochemical rationale of the resulting models is expected to be useful in the field of metabonomics.</p

A possible optical counterpart to the old nearby pulsar J0108-1431

The multi-wavelength study of old (>100 Myr) radio pulsars holds the key to understanding the long-term evolution of neutron stars, including the advanced stages of neutron star cooling and the evolution of the magnetosphere. Optical/UV observations are particularly useful for such studies because they allow one to explore both thermal and non-thermal emission processes. In particular, studying the optical/UV emission constrains temperature of the bulk of the neutron star surface, too cold to be measured in X-ray observations.Aim of this work is to identify the optical counterpart of the very old (166 Myr) radio pulsar J0108-1431. We have re-analyzed our original VLT observations (Mignani et al. 2003), where a very faint object was tentatively detected close to the radio position, near the edge of a field galaxy. We found that the backward extrapolation of the PSR J0108-1431 proper motion recently measured by CHANDRA(Pavlov et al. 2008) nicely fits the position of this object. Based on that, we propose it as a viable candidate for the optical counterpart to PSR J0108-1431. The object fluxes (U =26.4+/-0.3; B =27.9; V >27.8) are consistent with a thermal spectrum with a brightness temperature of 9X10^4 K (for R = 13 km at a distance of 130 pc), emitted from the bulk of the neutron star surface. New optical observations are required to confirm the optical identification of PSR J0108-1431 and measure its spectrum.Comment: 5 pages, 4 figures, submitted to A&

Evidence for local aldosterone synthesis in the large intestine of the mouse

Aldosterone, the main physiological mineralocorticoid, regulates sodium and potassium balance in the distal convoluted tubule of the kidney. Aldosterone is synthesized from cholesterol in the adrenal cortex in a sequence of enzymatic steps. Recently however, several tissues or cells e.g. brain, heart, blood vessels, kidneys and adipocytes have been shown to possess capability to produce aldosterone locally, and there is some evidence that this occurs also in the intestine. Colon expresses mineralocorticoid receptors and is capable of synthesizing corticosterone, the second last intermediate on the route to aldosterone from cholesterol. Based on such reports and on our preliminary finding, we hypothesized that aldosterone could be synthesized locally in the intestine and therefore we measured the concentration of aldosterone as well as the protein and gene expression of aldosterone synthase (CYP11B2), an enzyme responsible on aldosterone synthesis, from the distal section of the gastrointestinal tract of 10-week-old Balb/c male mice. It is known that sodium deficiency regulates aldosterone synthesis in adrenal glands, therefore we fed the mice with low (0.01%), normal (0.2%) and high-sodium (1.6%) diets for 14 days. Here we report that, aldosterone was detected in colon and cecum samples. Measurable amounts of CYP11B2 protein were detected by Western blot and Elisa analysis from both intestinal tissues. We detected CYP1182 gene expression from the large intestine along with immunohistochemical findings of CYP11B2 in colonic wall. Sodium depletion increased the aldosterone concentration in plasma compared to control and high-sodium groups as well as in the intestine compared to mice fed with the high-sodium diet. To summarize, this study further supports the presence of aldosterone and the enzyme needed to produce this mineralocorticoid in the murine large intestine.Peer reviewe

SPEAR Far Ultraviolet Spectral Images of the Cygnus Loop

We present far-ultraviolet (FUV) spectral images, measured at C IV 1550, He II 1640, Si IV+O IV] 1400, and O III] 1664, of the entire Cygnus Loop, observed with the Spectroscopy of Plasma Evolution from Astrophysical Radiation (SPEAR) instrument, also known as FIMS. The spatial distribution of FUV emission generally corresponds with a limb-brightened shell, and is similar to optical, radio and X-ray images. The features found in the present work include a ``carrot'', diffuse interior, and breakout features, which have not been seen in previous FUV studies. Shock velocities of 140-160 km/s is found from a line ratio of O IV] to O III], which is insensitive not only to resonance scattering but also to elemental abundance. The estimated velocity indicates that the fast shocks are widespread across the remnant. By comparing various line ratios with steady-state shock models, it is also shown that the resonance scattering is widespread.Comment: 13 pages, 3 figures, 1 table, accepted for publication in ApJ

Yoghurt containing galacto-oligosaccharides, prunes and linseed reduces the severity of mild constipation in elderly subjects

Peer reviewe

Effects of Soluble Corn Fiber Alone or in Synbiotic Combination with Lactobacillus rhamnosus GG and the Pilus-Deficient Derivative GG-PB12 on Fecal Microbiota, Metabolism, and Markers of immune Function : A Randomized, Double-Blind, Placebo-Controlled, Crossover Study in Healthy Elderly (Saimes Study)

Background: The aging process leads to a potential decline in immune function and adversely affects the gut microbiota. To date, many in vitro and in vivo studies focused on the application of synbiotics (prebiotics combined with probiotics) as a promising dietary approach to affect gut microbiota composition and improved functioning of the immune system. However, studies using synbiotic preparations often have the limitation that it remains unclear whether any effect observed is a result of the prebiotic or probiotic or a synergistic effect of the combined supplement. Objectives: We investigated the effects of a probiotic Lactobacillus rhamnosus GG and pilus-deficient L. rhamnosus GG-PB12 combined with Promitor (TM) Soluble Corn Fiber (SCF, a candidate prebiotic) on fecal microbiota, metabolism, immunity, and blood lipids in healthy elderly persons. A prospective, double-blind, placebo controlled, randomized, single-centered, crossover study in 40 healthy elderly subjects (aged 60-80 years) was carried out. Volunteers were randomized to consume either probiotic and prebiotic as synbiotic, prebiotic or placebo (maltodextrin) during 3 weeks. Three-week washout periods separated all the treatments. We assessed effects upon blood lipids, glucose, cytokines, natural killer (NK) cell activity, phenotype, and intestinal microbiota composition. SCF decreased IL-6, which was not observed with the synbiotics. Results: Consumption of L. rhamnosus GG combined with SCF increased NK cell activity compared to baseline in females and the older group. In the fecal microbiota analyses, the strongest community shifts were due to L. rhamnosus GG combined with SCF and SCF treatments. L. rhamnosus GG combined with SCF and L. rhamnosus GG-PB12 combined with SCF significantly increased the genus Parabacteroides. L. rhamnosus GG combined with SCF and SCF increased concentrations of Ruminococcaceae Incertae Sedis. Oscillospira and Desulfovibrio slightly decreased in the L. rhamnosus GG combined with SCF group, whereas Desulfovibrio decreased also in the L. rhamnosus GG-PB12 combined with SCF group. L. rhamnosus GG combined with SCF reduced total cholesterol and LDL-cholesterol in volunteers with initially elevated concentrations. C-reactive protein significantly decreased during L. rhamnosus GG-PB12 combined with SCF intervention compared to baseline. Conclusion: In conclusion, the synbiotic combination of L. rhamnosus GG with SCF showed a tendency to promote innate immunity by increasing NK cell activity in elderly women and in 70 to 80-year-old volunteers and decreased TC and LDL-c in hyper-cholesterolemic patients. In addition, L. rhamnosus GG-PB12 combined with SCF demonstrated an increase in NK cell activity compared to SCF alone in older volunteers. We also found significant positive effects on the immune response, evidenced by a decrease of the pro-inflammatory cytokine IL-6. Therefore, dietary intervention with L. rhamnosus GG combined with SCF could be of importance in elderly as an attractive option for enhancement of both the microbial and immune systems.Peer reviewe

Antibiotics in early life associate with specific gut microbiota signatures in a prospective longitudinal infant cohort

BACKGROUND The effects of antibiotics on infant gut microbiota are unclear. We hypothesized that the use of common antibiotics results in long-term aberration in gut microbiota. METHODS Antibiotic-naive infants were prospectively recruited when hospitalized because of a respiratory syncytial virus infection. Composition of fecal microbiota was compared between those receiving antibiotics during follow-up (prescribed at clinicians' discretion because of complications such as otitis media) and those with no antibiotic exposure. Fecal sampling started on day 1, then continued at 2-day intervals during the hospital stay, and at 1, 3 and 6 months at home. RESULTS One hundred and sixty-three fecal samples from 40 patients (median age 2.3 months at baseline; 22 exposed to antibiotics) were available for microbiota analyses. A single course of amoxicillin or macrolide resulted in aberration of infant microbiota characterized by variation in the abundance of bifidobacteria, enterobacteria and clostridia, lasting for several months. Recovery from the antibiotics was associated with an increase in clostridia. Occasionally, antibiotic use resulted in microbiota profiles associated with inflammatory conditions. CONCLUSIONS Antibiotic use in infants modifies especially bifidobacterial levels. Further studies are warranted whether administration of bifidobacteria will provide health benefits by normalizing the microbiota in infants receiving antibiotics.Peer reviewe