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Purpose To differentiate the plasma metabolomic profile of patients with age related macular degeneration (AMD) from that of controls, by Nuclear Magnetic Resonance (NMR) spectroscopy. Methods: Two cohorts (total of 396 subjects) representative of central Portugal and Boston, USA phenotypes were studied. For each cohort, subjects were grouped according to AMD stage (early, intermediate and late). Multivariate analysis of plasma NMR spectra was performed, followed by signal integration and univariate analysis. Results: Small changes were detected in the levels of some amino acids, organic acids, dimethyl sulfone and specific lipid moieties, thus providing some biochemical information on the disease. The possible confounding effects of gender, smoking history and age were assessed in each cohort and found to be minimal when compared to that of the disease. A similar observation was noted in relation to age-related comorbidities. Furthermore, partially distinct putative AMD metabolite fingerprints were noted for the two cohorts studied, reflecting the importance of nutritional and other lifestyle habits in determining AMD metabolic response and potential biomarker fingerprints. Notably, some of the metabolite changes detected were noted as potentially differentiating controls from patients diagnosed with early AMD. Conclusion: For the first time, this study showed metabolite changes in the plasma of patients with AMD as compared to controls, using NMR. Geographical origins were seen to affect AMD patients´ metabolic profile and some metabolites were found to be valuable in potentially differentiating controls from early stage AMD patients. Metabolomics has the potential of identifying biomarkers for AMD, and further work in this area is warranted.

ABSTRACT Diabetic patients show a high susceptibility to oral diseases of inflammatory, catabolic and chronic nature with potential impact on saliva composition. In this study, our purpose was to characterize type 1 diabetes-induced alterations in the salivary peptidome aiming to find prospective biomarkers for type 1 diabetes oral health evaluation. Peptidomic analysis of saliva from controls ( n = 5) and type 1 diabetic patients ( n = 5) were performed by liquid chromatography followed by mass spectrometry. The proteolytic activity and metalloproteinases expression was accessed by zymography and slot blot analysis, respectively. Data evidenced a significant increase in the percentage of peptides in diabetic patients paralleled by a higher proteolytic activity, compared with healthy individuals. The nonsalivary gland protein fragments identified in saliva were mainly derived from collagen and extracellular matrix proteins, namely collagen type I. The cleavage site frequency analysis showed significant differences between healthy and type 1 diabetic individuals, highlighting the activity of proteases such as matrix metalloproteinase-9 and cathepsin D. Our results highlight salivary collagen fragments as potential biomarkers to follow up diabetes-related oral damage. Copyright © 2011 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

The impacts of salt stress and inoculation in in vitro grapevine (Vitis vinifera L.) growth, nutrient accumulation, osmoregulation, photosynthesis and membrane integrity were evaluated. One month exposure to 100mM NaCl as well as to inoculation with Phaeomoniella chlamydospora reduced relative growth rate (RGR) and induced senescence in grapevine plants, shown by: (1) decrease of Ψ π without osmoregulation, (2) decrease of chlorophyll content and fluorescence, (3) loss of membrane integrity and (4) nutritional disorders. To assess putative changes in structural and/or non-structural carbohydrates induced by these two stress conditions, alcohol insoluble residues from the roots, stems and leaves were also characterised by FT-IR and GC with respect to the sugar composition. The referred organs were distinguished based on: (1) higher proportion of uronic acid residues in leaves which diagnose the presence of pectic polysaccharides (wavenumbers 1100, 1150 and 1018cm−1 in FT-IR spectra), (2) higher proportion of xylose and glucose on stems and FT-IR spectra diagnostic of xylose-rich polysaccharides (1041cm−1) and cellulose (1060cm−1), (3) higher proportion of glucose residues, xylose and arabinose on roots and a FT-IR spectra characteristic of xylose-rich polysaccharides (1041cm−1). The main alterations induced by salt stress and inoculation were more visible in leaves, where the content of uronic acid decreased showing that changes in cell wall composition occurred, mostly at the pectic fraction. Besides, an accumulation of insoluble glucose was found, and FT-IR spectra showed that this glucose-based material was starch (maximum absorption at 998cm−1), accumulated as a non-specific response to salt stress and P. chlamydospora inoculation. [Copyright &y& Elsevier]

An abstract of the article "NMR metabonomic study of lung cancer: metabolic profiling of tissues," by Ana M. Gil, Brian J Goodfellow, Isabel M. Carreira is presented.

1D and 2D 800 MHz high-resolution nuclear magnetic resonance spectroscopy of human amniotic fluid (HAF) enabled the identification of ∼50 metabolites. In addition, liquid chromatography-NMR and diffusion ordered spectroscopy (DOSY) allowed signal overlap to be reduced and the characterization of higher molecular weight (Mw) components, respectively. Indeed, the DOSY spectrum of a Mw >10 kDa HAP fraction enabled three protein families, differing in average Mw, to be detected and may therefore be of potential value in the study of disorder-related variations in HAF protein profiles. The effects of freeze-drying, storage at -20 or -70 °C, and freeze-thawing cycles on HAF compositional stability were investigated, as well as stability at room temperature (to account for overnight data acquisition runs). These data are the basis for establishing statistically validated correlations between HAF NMR data and any physiological disorders of the fetus/mother. Freeze-drying caused signal loss for urea, ethanol, and compounds resonating at 2.22 and 1.17 ppm. Storage at -70 °C or lower is recommended since only minor compositional changes were observed, affecting mainly acetate and pyruvate. Freeze-thaw cycles did not cause significant compositional changes, and room-temperature stability studies indicated a 4-5 h maximum period of handling/acquisition time to ensure HAP stability. [ABSTRACT FROM AUTHOR]

Pressure overload-induced hypertrophy compromises cardiac stretch-induced compliance (SIC) after acute volume overload (AVO). We hypothesized that SIC could be enhanced by physiological hypertrophy induced by pregnancy's chronic volume overload. This study evaluated SIC-cardiac adaptation in pregnant women with or without cardiovascular risk (CVR) factors. Thirty-seven women (1st trimester, 1 st T) and a separate group of 31 (3rd trimester, 3 rd T) women [healthy or with CVR factors (obesity and/or hypertension and/or with gestational diabetes)] underwent echocardiography determination of left ventricular end-diastolic volume (LVEDV) and E/e' before (T0), immediately after (T1), and 15 min after (T2; SIC) AVO induced by passive leg elevation. Blood samples for NT-proBNP quantification were collected before and after the AVO. Acute leg elevation significantly increased inferior vena cava diameter and stroke volume from T0 to T1 in both 1 st T and 3 rd T, confirming AVO. LVEDV and E/e' also increased immediately after AVO (T1) in both 1 st T and 3 rd T. SIC adaptation (T2, 15 min after AVO) significantly decreased E/e' in both trimesters, with additional expansion of LVEDV only in the 1 st T. NT-pro-BNP increased slightly after AVO but only in the 1 st T. CVR factors, but not parity or age, significantly impacted SIC cardiac adaptation. A distinct functional response to SIC was observed between 1 st T and 3 rd T, which was influenced by CVR factors. The LV of 3 rd T pregnant women was hypertrophied, showing a structural limitation to dilate with AVO, whereas the lower LV filling pressure values suggest increased diastolic compliance. NEW & NOTEWORTHY The sudden increase of volume overload triggers an acute myocardial stretch characterized by an immediate rise in contractility by the Frank-Starling mechanism, followed by a progressive increase known as the slow force response. The present study is the first to characterize echocardiographically the stretch-induced compliance (SIC) mechanism in the context of physiological hypertrophy induced by pregnancy. A distinct functional adaptation to SIC was observed between first and third trimesters, which was influenced by cardiovascular risk factors.

Objectives: To compare 7-year survival and freedom from reoperation, as well as early clinical and hemodynamic outcomes, after surgical aortic valve replacement (SAVR) with mechanical or bioprosthetic valves in patients aged 50-70 years., Methods: single-center retrospective cohort study including adults aged 50-70 years who underwent SAVR in 2012 with a mechanical or bioprosthetic valve. Median follow-up was 7 years. Univariable analyses were performed using Kaplan-Meier curves and Log-Rank tests for survival and freedom from reoperation analyses. Multivariable time-to-event analyses were conducted using Cox Regression., Results: Of a total of 193 patients, 76 (39.4%) received mechanical valves and 117 (60.6%) received bioprosthetic valves. A trend for better survival was found for mechanical prostheses when adjusting for EuroSCORE II (HR: 0.35; 95%CI: 0.12-1.02, p=0.054), but using a backward stepwise Cox regression prosthesis type was not retained by the model as an independent predictor of survival. Moreover, mechanical prostheses showed trends for higher freedom from reoperation (100% vs. 95.5%, Log-Rank, p=0.076), higher median EuroSCORE II (2.52% vs. 1.95%, p=0.06) and early mortality (7.9% vs. 2.6%, p=0.086). However, after adjusting for EuroSCORE II, there was no significant difference in early mortality (OR: 2.3, 95%CI: 0.5-10.5, p=0.272). Regarding hemodynamic performance at follow-up echocardiogram, there were no differences other than left ventricular mass regression, which was not as pronounced in the mechanical group (-12% vs. -21%, p=0.002)., Conclusion: Mechanical and bioprosthetic aortic valves prostheses showed similar mid-term survival in the 50-70 age group. Further prospective and larger studies are needed to provide evidence-based recommendations on this topic.

This work aims at characterizing the metabolic profile of human lung cancer, to gain new insights into tumor metabolism and to identify possible biomarkers with potential diagnostic value in the future. Paired samples of tumor and noninvolved adjacent tissues from 12 lung tumors have been directly analyzed by (1)H HRMAS NMR (500/600 MHz) enabling, for the first time to our knowledge, the identification of over 50 compounds. The effect of temperature on tissue stability during acquisition time has also been investigated, demonstrating that analysis should be performed within less than two hours at low temperature (277 K), to minimize glycerophosphocholine (GPC) and phosphocholine (PC) conversion to choline and reduce variations in some amino acids. The application of Principal Component Analysis (PCA) and Hierarchical Cluster Analysis (HCA) to the standard 1D (1)H spectra resulted in good separation between tumor and control samples, showing that inherently different metabolic signatures characterize the two tissue types. On the basis of spectral integration measurements, lactate, PC, and GPC were found to be elevated in tumors, while glucose, myo-inositol, inosine/adenosine, and acetate were reduced. These results show the valuable potential of HRMAS NMR-metabonomics for investigating the metabolic phenotype of lung cancer.