ACE-versus chymase-dependent angiotensin II generation in human coronary arteries: a matter of efficiency?

OBJECTIVE: The objective of this study was to investigate ACE- and chymase-dependent angiotensin I-to-II conversion in human coronary arteries (HCAs). METHODS AND RESULTS: HCA rings were mounted in organ baths, and concentration-response curves to angiotensin II, angiotensin I, and the chymase-specific substrate Pro(11)-D-Ala(12)-angiotensin I (PA-angiotensin I) were constructed. All angiotensins displayed similar efficacy. For a given vasoconstriction, bath (but not interstitial) angiotensin II during angiotensin I and PA-angiotensin I was lower than during angiotensin II, indicating that interstitial (and not bath) angiotensin II determines vasoconstriction. PA-angiotensin I increased interstitial angiotensin II less efficiently than angiotensin I. Separate inhibition of ACE (with captopril) and chymase (with C41 or chymostatin) shifted the angiotensin I concentration-response curve approximately 5-fold to the right, whereas a 10-fold shift occurred during combined ACE and chymase inhibition. Chymostatin, but not captopril and/or C41, reduced bath angiotensin II and abolished PA-Ang I-induced vasoconstriction. Perfused HCA segments, exposed luminally or adventitially to angiotensin I, released angiotensin II into the luminal and adventitial fluid, respectively, and this release was blocked by chymostatin. CONCLUSIONS: Both ACE and chymase contribute to the generation of functionally active angiotensin II in HCAs. However, because angiotensin II loss in the organ bath is chymase-dependent, ACE-mediated conversion occurs more efficiently (ie, closer to AT(1) receptors) than chymase-mediated conversion

The Antioxidant Potential of the Mediterranean Diet in Patients at High Cardiovascular Risk: An In-Depth Review of the PREDIMED

Cardiovascular disease (CVD) is the leading global cause of death. Diet is known to be important in the prevention of CVD. The PREDIMED trial tested a relatively low-fat diet versus a high-fat Mediterranean diet (MedDiet) for the primary prevention of CVD. The resulting reduction of the CV composite outcome resulted in a paradigm shift in CV nutrition. Though many dietary factors likely contributed to this effect, this review focuses on the influence of the MedDiet on endogenous antioxidant systems and the effect of dietary polyphenols. Subgroup analysis of the PREDIMED trial revealed increased endogenous antioxidant and decreased pro-oxidant activity in the MedDiet groups. Moreover, higher polyphenol intake was associated with lower incidence of the primary outcome, overall mortality, blood pressure, inflammatory biomarkers, onset of new-onset type 2 diabetes mellitus (T2DM), and obesity. This suggests that polyphenols likely contributed to the lower incidence of the primary event in the MedDiet groups. In this article, we summarize the potential benefits of polyphenols found in the MedDiet, specifically the PREDIMED cohort. We also discuss the need for further research to confirm and expand the findings of the PREDIMED in a non-Mediterranean population and to determine the exact mechanisms of action of polyphenols

Kinetics of exciton photoluminescence in type-II semiconductor superlattices

The exciton decay rate at a rough interface in type-II semiconductor superlattices is investigated. It is shown that the possibility of recombination of indirect excitons at a plane interface essentially affects kinetics of the exciton photoluminescence at a rough interface. This happens because of strong correlation between the exciton recombination at the plane interface and at the roughness. Expressions that relate the parameters of the luminescence kinetics with statistical characteristics of the rough interface are obtained. The mean height and length of roughnesses in GaAs/AlAs superlattices are estimated from the experimental data.Comment: 3 PostScript figure

Screening of antioxidant properties of the apple juice using the front-face synchronous fluorescence and chemometrics

Fluorescence spectroscopy is gaining increasing attention in food analysis due to its higher sensitivity and selectivity as compared to other spectroscopic techniques. Synchronous scanning fluorescence technique is particularly useful in studies of multi-fluorophoric food samples, providing a further improvement of selectivity by reduction in the spectral overlapping and suppressing light-scattering interferences. Presently, we study the feasibility of the prediction of the total phenolics, flavonoids, and antioxidant capacity using front-face synchronous fluorescence spectra of apple juices. Commercial apple juices from different product ranges were studied. Principal component analysis (PCA) applied to the unfolded synchronous fluorescence spectra was used to compare the fluorescence of the entire sample set. The regression analysis was performed using partial least squares (PLS1 and PLS2) methods on the unfolded total synchronous and on the single-offset synchronous fluorescence spectra. The best calibration models for all of the studied parameters were obtained using the PLS1 method for the single-offset synchronous spectra. The models for the prediction of the total flavonoid content had the best performance; the optimal model was obtained for the analysis of the synchronous fluorescence spectra at Delta lambda = 110 nm (R (2) = 0.870, residual predictive deviation (RPD) = 2.7). The optimal calibration models for the prediction of the total phenolic content (Delta lambda = 80 nm, R (2) = 0.766, RPD = 2.0) and the total antioxidant capacity (Delta lambda = 70 nm, R (2) = 0.787, RPD = 2.1) had only an approximate predictive ability. These results demonstrate that synchronous fluorescence could be a useful tool in fast semi-quantitative screening for the antioxidant properties of the apple juices.info:eu-repo/semantics/publishedVersio

Translational Cancer Research: Balancing Prevention and Treatment to Combat Cancer Globally

Cancer research is drawing on the human genome project to develop new molecular-targeted treatments. This is an exciting but insufficient response to the growing, global burden of cancer, particularly as the projected increase in new cases in the coming decades is increasingly falling on developing countries. The world is not able to treat its way out of the cancer problem. However, the mechanistic insights from basic science can be harnessed to better understand cancer causes and prevention, thus underpinning a complementary public health approach to cancer control. This manuscript focuses on how new knowledge about the molecular and cellular basis of cancer, and the associated high-throughput laboratory technologies for studying those pathways, can be applied to population-based epidemiological studies, particularly in the context of large prospective cohorts with associated biobanks to provide an evidence base for cancer prevention. This integrated approach should allow a more rapid and informed translation of the research into educational and policy interventions aimed at risk reduction across a population

Metabolomics to unveil and understand phenotypic diversity between pathogen populations

Visceral leishmaniasis is caused by a parasite called Leishmania donovani, which every year infects about half a million people and claims several thousand lives. Existing treatments are now becoming less effective due to the emergence of drug resistance. Improving our understanding of the mechanisms used by the parasite to adapt to drugs and achieve resistance is crucial for developing future treatment strategies. Unfortunately, the biological mechanism whereby Leishmania acquires drug resistance is poorly understood. Recent years have brought new technologies with the potential to increase greatly our understanding of drug resistance mechanisms. The latest mass spectrometry techniques allow the metabolome of parasites to be studied rapidly and in great detail. We have applied this approach to determine the metabolome of drug-sensitive and drug-resistant parasites isolated from patients with leishmaniasis. The data show that there are wholesale differences between the isolates and that the membrane composition has been drastically modified in drug-resistant parasites compared with drug-sensitive parasites. Our findings demonstrate that untargeted metabolomics has great potential to identify major metabolic differences between closely related parasite strains and thus should find many applications in distinguishing parasite phenotypes of clinical relevance

First principles study of the origin and nature of ferromagnetism in (Ga,Mn)As

The properties of diluted Ga$_{1-x}$Mn$_x$As are calculated for a wide range of Mn concentrations within the local spin density approximation of density functional theory. M\"ulliken population analyses and orbital-resolved densities of states show that the configuration of Mn in GaAs is compatible with either 3d$^5$ or 3d$^6$, however the occupation is not integer due to the large $p$-$d$ hybridization between the Mn $d$ states and the valence band of GaAs. The spin splitting of the conduction band of GaAs has a mean field-like linear variation with the Mn concentration and indicates ferromagnetic coupling with the Mn ions. In contrast the valence band is antiferromagnetically coupled with the Mn impurities and the spin splitting is not linearly dependent on the Mn concentration. This suggests that the mean field approximation breaks down in the case of Mn-doped GaAs and corrections due to multiple scattering must be considered. We calculate these corrections within a simple free electron model and find good agreement with our {\it ab initio} results if a large exchange constant ($N\beta=-4.5$eV) is assumed.Comment: 15 pages, 14 figure

Metabolomics methods for the synthetic biology of secondary metabolism

Many microbial secondary metabolites are of high biotechnological value for medicine, agriculture, and the food industry. Bacterial genome mining has revealed numerous novel secondary metabolite biosynthetic gene clusters, which encode the potential to synthesize a large diversity of compounds that have never been observed before. The stimulation or “awakening” of this cryptic microbial secondary metabolism has naturally attracted the attention of synthetic microbiologists, who exploit recent advances in DNA sequencing and synthesis to achieve unprecedented control over metabolic pathways. One of the indispensable tools in the synthetic biology toolbox is metabolomics, the global quantification of small biomolecules. This review illustrates the pivotal role of metabolomics for the synthetic microbiology of secondary metabolism, including its crucial role in novel compound discovery in microbes, the examination of side products of engineered metabolic pathways, as well as the identification of major bottlenecks for the overproduction of compounds of interest, especially in combination with metabolic modeling. We conclude by highlighting remaining challenges and recent technological advances that will drive metabolomics towards fulfilling its potential as a cornerstone technology of synthetic microbiology

Validation of a Mass Spectrometry Method To Quantify Oak Ellagitannins in Wine Samples

[EN] Detection and individual quantification of oak wood ellagitannins in oak barrel aged red wine samples are difficult mainly due to their low levels and the similarity between their structures. In this work, a quantification method using mass spectrometry has been developed and validated to quantify wine ellagitannins after sample fractionation with a previously reported method. The use of an internal standard is a requirement to correct mass signal variability. (−)-Gallocatechin, among the different tested compounds, was the only one that proved to be a suitable internal standard making possible the accurate and individual quantification of the main oak wood ellagitannins. The developed methodology has been used to detect and quantify these ellagitannins in different Spanish commercial wines, proving its usefulness