Folate catabolites in spot urine as non-invasive biomarkers of folate status during habitual intake and folic acid supplementation.

Folate status, as reflected by red blood cell (RCF) and plasma folates (PF), is related to health and disease risk. Folate degradation products para-aminobenzoylglutamate (pABG) and para-acetamidobenzoylglutamate (apABG) in 24 hour urine have recently been shown to correlate with blood folate. Since blood sampling and collection of 24 hour urine are cumbersome, we investigated whether the determination of urinary folate catabolites in fasted spot urine is a suitable non-invasive biomarker for folate status in subjects before and during folic acid supplementation. Immediate effects of oral folic acid bolus intake on urinary folate catabolites were assessed in a short-term pre-study. In the main study we included 53 healthy men. Of these, 29 were selected for a 12 week folic acid supplementation (400 µg). Blood, 24 hour and spot urine were collected at baseline and after 6 and 12 weeks and PF, RCF, urinary apABG and pABG were determined. Intake of a 400 µg folic acid bolus resulted in immediate increase of urinary catabolites. In the main study pABG and apABG concentrations in spot urine correlated well with their excretion in 24 hour urine. In healthy men consuming habitual diet, pABG showed closer correlation with PF (rs = 0.676) and RCF (rs = 0.649) than apABG (rs = 0.264, ns and 0.543). Supplementation led to significantly increased folate in plasma and red cells as well as elevated urinary folate catabolites, while only pABG correlated significantly with PF (rs = 0.574) after 12 weeks. Quantification of folate catabolites in fasted spot urine seems suitable as a non-invasive alternative to blood or 24 hour urine analysis for evaluation of folate status in populations consuming habitual diet. In non-steady-state conditions (folic acid supplementation) correlations between folate marker (RCF, PF, urinary catabolites) decrease due to differing kinetics

Dataset supporting paper 'Dietary n-3 polyunsaturated fatty acids alter the number, fatty acid profile and coagulatory activity of circulating and platelet-derived extracellular vesicles'

This dataset includes all reports and summaries of raw data supporting the results presented in the paper "Dietary n-3 polyunsaturated fatty acids alter the number, fatty acid profile and coagulatory activity of circulating and platelet-derived extracellular vesicles". The objective of this paper is to investigate whether daily supplementation of participants at moderate risk of (cardiovascular diseases) CVDs with 1.8 g/d of fish oil-derived n-3 polyunsaturated fatty acids (PUFAs) altered the generation, composition and function of circulating and platelet-derived extracellular vesicles (EVs). Data about EVs parameters include: i. the numbers, and size of circulating total EVs and in vitro generated platelet-derived EVs (PDEVs) measured by Nanoparticle Tracking Analysis (NTA); ii. the numbers of EV subpopulations (i.e. phosphatidylserine-positive EVs (PS+EVs), PDEVs, endothelial-derived EVs (EDEVs)) and PS expression on PDEVs generated in vitro from platelets measured by flow cytometry (FCM); iii. the procoagulatory activity of circulating EVs (in vitro thrombogenic potential in activating tissue factor-dependent thrombin generation) measured by thrombin generation assay. The coagulatory behaviour of PDEVs generated in vitro from platelets measured by thrombin generation, clot formation, fibrinolysis and in vivo thrombus formation assays. Data about conventional cardiovascular risk markers include i. body mass index (BMI) measured by Tanita; ii. blood pressure measured by upper arm blood pressure monitor; iii. plasma lipid profile (i.e. triacylglycerol (TAG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and glucose concentrations measured by iLab. Data about thrombogenic markers include: i. plasma platelet aggregation measured by 96-well high-throughput aggregometry; ii. plasma thrombin generation measured by thrombin generation assay; iii. plasma clot growth and fibrinolysis measured by thrombodynamics analyzer

Effects of peripheral neuropathy on exercise capacity and quality of life in patients with chronic obstructive pulmonary diseases

Introduction: Chronic obstructive pulmonary diseases (COPD) have some systemic effects including systemic inflammation, nutritional abnormalities, skeletal muscle dysfunction, and cardiovascular, skeletal and neurological disorders. Some studies have reported the presence of peripheral neuropathy (PNP) at an incidence of 28-94% in patients with COPD. Our study aimed to identify whether PNP affects exercise performance and quality of life in COPD patients. Material and methods: Thirty mild-very severe patients with COPD (male/female = 29/1, mean age = 64 +/- 10 years) and 14 normal subjects (male/female = 11/5, mean age = 61 +/- 8 years) were included in the present study. All subjects underwent pulmonary function testing (PFT), cardiopulmonary exercise testing, electroneuromyography and short form 36 (SF-36). Results: Peak oxygen uptake (PeakVO(2)) was lower in COPD patients (115 +/- 0.53 l/min) than healthy subjects (2.02 +/- 0.46 l/min) (p = 0.0001). There was no PUP in healthy subjects while 16 (53%) of the COPD patients had PNP. Forced expiratory volume in 1 s (FEV1) and PeakVO(2) were significantly different between patients with PNP and those without (p = 0.009, p = 0.03 respectively). Quality of life of patients with PNP was lower than that of patients without PNP (p < 0.05). Conclusions: The present study demonstrates the exercise limitation in COPD patients with PUP Thus, presence of PNP has a poor effect on exercise capacity and quality of life in patients with COPD. Furthermore, treatment modalities for PNP can be recommended to these patients in order to improve exercise capacity and quality of life.Wo

Diagnostic value of BNP in diastolic heart failure

Dijastoličko zatajivanje srca zahvaća otprilike 40-50% bolesnika koji imaju znakove i simptome zatajivanja srca. BNP (engl. brain natriureticpeptide, moždani natrijuretski peptid; B-tip natrijuretskog peptida) je srčani neurohormon koji izlučuju mišićne stanice klijetke kao odgovor na povećan tlak ili volumen na kraju dijastole. Sve brojniji dokazi pokazali su da su koncentracije BNP povećane u slučaju zatajivanja srca, te da su te koncentracije osobito važne kod diferencijalne dijagnoze dispneje. Koncentracije BNP su povećane kod dijastoličkog, no obično su niže nego kod sistoličkog zatajivanja srca. Koncentracije BNP su u uzajamnoj vezi sa stupnjem dijastoličke disfunkcije, te su blago povišene među bolesnicima sa simptomima poremećenog opuštanja srčanog mišića, a najviše su među onima s restriktivnim tipom punjenja. Kod asimptomatičnih bolesnika s blagim oblikom dijastoličke disfunkcije, koncentracije BNP mogu biti unutar granica referentnog raspona. U ovom preglednom članku raspravljamo o dijagnostičkoj vrijednosti BNP u dijagnostici dijastoličkog zatajivanja srca.Diastolic heart failure affects approximately 40%-50% of patients presenting with signs and symptoms of heart failure. Brain natriuretic peptide (BNP) is a cardiac neurohormone secreted from ventricular myocytes in response to increased end-diastolic pressure or volume. Accumulating evidence showed that BNP concentrations are increased in heart failure, and it is especially important in the differential diagnosis of dyspnea. BNP concentrations are increased in diastolic heart failure, but they are typically lower in diastolic than that in systolic heart failure. BNP concentrations are correlated with the stage of diastolic dysfunction, being mild-moderately elevated among patients with evidence of impaired relaxation and highest among those with a restrictive filling pattern. In asymptomatic patients with mild degree of diastolic dysfunction BNP concentrations may be within normal range. In this review we discuss the diagnostic value of BNP in diastolic heart failure

Circulating Extracellular Vesicles Are Strongly Associated With Cardiovascular Risk Markers

Data Availability Statement: The datasets presented in this study can be found in an online repository, which is the University of Reading Research Data Archive at https://doi.org/10.17864/1947.000366.Copyright © 2022 Zhou, Bozbas, Allen-Redpath and Yaqoob. Background: Extracellular vesicles (EVs) are submicron membrane-bound vesicles released from various cells, which are emerging as a potential novel biomarker in cardiovascular diseases (CVDs) due to their procoagulatory and prothrombotic properties. However, there is little information about the relationships between circulating EVs and conventional and thrombogenic risk markers of CVDs. Objective: To investigate the relationships between circulating EVs, conventional cardiovascular risk markers and thrombogenic markers in subjects with moderate risk of CVDs. Design: Subjects (n = 40) aged 40-70 years with moderate risk of CVDs were recruited and assessed for body mass index, blood pressure and plasma lipid profile, as well as platelet aggregation, clot formation, thrombin generation and fibrinolysis. Numbers of circulating EVs were assessed by Nanoparticle Tracking Analysis and flow cytometry. A range of assays were used to assess the procoagulatory activity of plasma and circulating EVs. Results: Circulating EV numbers were positively associated with body mass index, blood pressure, plasma triacylglycerol concentration and overall CVD risk. Higher circulating EV numbers were also associated with increased thrombin generation and enhanced clot formation, and EVs isolated from subjects with moderate CVD risk promoted thrombin generation ex vivo. Higher numbers of endothelial-derived EVs were associated with a greater tendency for clot lysis. Plasma triacylglycerol concentration and diastolic blood pressure independently predicted circulating EV numbers, and EV numbers independently predicted aspects of thrombin generation and clot formation and 10-year CVD risk. Conclusion: Circulating EVs were strongly associated with both conventional and thrombogenic risk markers of CVDs, and also with overall CVD risk, highlighting a potentially important role for EVs in CVDs.Biotechnology and Biological Sciences Research Council (BBSRC) and the Diet and Health Research Industry Club (DRINC) (Research Grant BB/N021185/1)

Application of Response Surface Methodology for Optimization of Copper Removal Using a Novel Polymeric Adsorbent

Depending on the increase in the world population, the need for consumption and industrial resources is increasing day by day. In the wastewater caused by industrial production, a serious amount of heavy metals and water pollution caused by inorganic dyestuffs occur. In this study, graphene nanoplate/natural zeolite/sodium alginate bio-composite adsorbent was prepared and copper removal from wastewater by adsorption method was investigated. The characterization of the adsorbent was carried out by Fourier transform infrared spectroscopy, scanning electron microscopy, X-ray diffraction and Brunauer-Emmett-Teller. In addition to batch adsorption tests, isotherm, kinetic and thermodynamic studies, experimental optimization was carried out with experimental parameters determined by the surface response methodology. Four experimental parameters (adsorbent dosage, metal concentration, solution pH, and contact time) were evaluated in a versatile way to determine the efficiency of heavy metal adsorption. The highest copper removal was obtained as 92.9% and 91.4%, respectively, in the experimental and model study at the adsorbent dosage of 0.5 g, the solution pH of 4.5, and the copper concentration of 20 ppm. The parametric results was meet with the optimization results with an R-2 value of 0.9834. The three most commonly used adsorption isotherms at 25 degrees C were calculated. The high R-2 value was found to be 0.9834 for the Langmuir isotherm model. It was determined that the adsorption kinetics matched the pseudo-second-order kinetics.Coordinator of Chemical Engineering Laboratory of Kocaeli University,Chemical Engineering DepartmentThe authors would like to thank the Coordinator of Chemical Engineering Laboratory of Kocaeli University, Chemical Engineering Department for their support

Circulating extracellular vesicles are strongly associated with cardiovascular risk markers

Background: Extracellular vesicles (EVs) are submicron membrane-bound vesicles released from various cells, which are emerging as a potential novel biomarker in cardiovascular diseases (CVDs) due to their procoagulatory and prothrombotic properties. However, there is little information about the relationships between circulating EVs and conventional and thrombogenic risk markers of CVDs. Objective: To investigate the relationships between circulating EVs, conventional cardiovascular risk markers and thrombogenic markers in subjects with moderate risk of CVDs. Design: Subjects (n=40) aged 40-70 years with moderate risk of CVDs were recruited and assessed for body mass index, blood pressure and plasma lipid profile, as well as platelet aggregation, clot formation, thrombin generation and fibrinolysis. Numbers of circulating EVs were assessed by Nanoparticle Tracking Analysis and flow cytometry. A range of assays were used to assess the procoagulatory activity of plasma and circulating EVs. Results: Circulating EV numbers were positively associated with body mass index, blood pressure, plasma triacylglycerol concentration and overall CVD risk. Higher circulating EV numbers were also associated with increased thrombin generation and enhanced clot formation, and EVs isolated from subjects with moderate CVD risk promoted thrombin generation ex vivo. Higher numbers of endothelial-derived EVs were associated with a greater tendency for clot lysis. Plasma triacylglycerol concentration and diastolic blood pressure independently predicted circulating EV numbers, and EV numbers independently predicted aspects of thrombin generation and clot formation and 10-year CVD risk. Conclusion: Circulating EVs were strongly associated with both conventional and thrombogenic risk markers of CVDs, and also with overall CVD risk, highlighting a potentially important role for EVs in CVDs

Przepływ w gałęzi przedniej zstępującej lewej tętnicy wieńcowej u pacjentów z marskością wątroby

Introduction. Although cardiac function appears normal in patients with cirrhosis at rest, cardiac function deteriorates in these patients under stress conditions. Decreased cardiac function against stress may be due to coronary microvascular dysfunction in these patients. In this study, we aimed to evaluate coronary microvascular dysfunction in patients with cirrhosis by measuring coronary flow reserve (CFR) by transthoracic echocardiography. Materials and methods. Thirty-eight patients with cirrhosis and 32 healthy subjects (as control group) were examined. In addition to standard two-dimesional (2D) and Doppler echocardiography, coronary flow velocity was measured by pulsed-wave Doppler from the middle to the distal part of the left anterior descending artery at the beginning and after dipyridamole infusion in the hyperemic state. CFR was measured as the ratio of hyperemic peak diastolic flow rate to basal peak diastolic flow rate. Results. CFR was significantly lower in the cirrhosis group than in the control group (2.01 ± 0.31 and 2.84 ± 0.62; p < 0.0001). Increasing age, increasing myocardial mass, high aspartate aminotransferase and alanine aminotransferase, low hemoglobin, high C-reactive protein, decreased cholesterol and platelet levels were found to be associated with the reduction in CFR. Among all these factors only, the hemoglobin level and age were independent determinants of impaired CFR. Conclusions. Impaired CFR in patients with cirrhosis promotes coronary microvascular dysfunction. The coronary microvascular dysfunction can potentially contribute to the development of cirrhotic cardiomyopathy.Wstęp. Chociaż czynność serca u pacjentów z marskością wątroby oceniana w spoczynku wydaje się prawidłowa, to w warunkach wysiłku fizycznego lub obciążenia farmakologicznego ulega ona pogorszeniu. Zaburzenie czynności serca podczas obciążenia może być spowodowane dysfunkcją mikrokrążenia wieńcowego u tych chorych. Celem badania była ocena dysfunkcji mikrokrążenia wieńcowego u pacjentów z marskością wątroby przez pomiar rezerwy przepływu wieńcowego (CRF) za pomocą echokardiografii przezklatkowej. Materiał i metody. Do badania włączono 38 chorych z marskością wątroby i 32 osoby zdrowe (grupa kontrolna). Oprócz standardowej echokardiografii dwuwymiarowej (2D) i echokardiografii doplerowskiej prędkość przepływu wieńcowego w odcinkach środkowym i dystalnym gałęzi przedniej lewej tętnicy zstępującej zmierzono za pomocą badania dopplerowskiego metodą fali pulsacyjnej bezpośrednio przed wlewem dipirydamolu i po nim. Rezerwę przepływu wieńcowego mierzono jako stosunek maksymalnego przepływu rozkurczowego w obciążeniu do maksymalnego przepływu rozkurczowego w spoczynku. Wyniki. Rezerwa przepływu wieńcowego była istotnie niższa w grupie z marskością wątroby niż w grupie kontrolnej (2,01 ± 0,31 i 2,84 ± 0,62; p &lt; 0,0001). Stwierdzono, że ze zmniejszeniem CFR wiązały się: wiek, zwiększenie masy mięśnia sercowego, wysoka aktywność aminotransferaz asparaginianowej i alaninowej, niskie stężenie hemoglobiny, wysokie stężenie białka C-reaktywnego, obniżone stężenie cholesterolu i zmniejszona liczba płytek krwi. Jednak tylko stężenie hemoglobiny i wiek były niezależnymi determinantami zmniejszonej CFR. Wnioski. Zmniejszenie CFR u chorych z marskością wątroby sprzyja dysfunkcji mikrokrążenia wieńcowego, która może prowadzić do rozwoju kardiomiopatii wątrobowej (marskiej)

Mode of induction of platelet-derived extracellular vesicles is a critical determinant of their phenotype and function

Platelet-derived extracellular vesicles (PDEVs) are the most abundant amongst all types of EVs in the circulation. However, the mechanisms leading to PDEVs release, their role in coagulation and phenotypic composition are poorly understood. PDEVs from washed platelets were generated using different stimuli and were characterised using nanoparticle tracking analysis. Procoagulant properties were evaluated by fluorescence flow cytometry and calibrated automated thrombography. EVs from plasma were isolated and concentrated using a novel protocol involving a combination of size exclusion chromatography and differential centrifugation, which produces pure and concentrated EVs. Agonist stimulation enhanced PDEV release, but did not alter the average size of EVs compared to those produced by unstimulated platelets. Agonist stimulation led to lower negatively-charged phospholipid externalization in PDEVs, which was reflected in the lower procoagulant activity compared to those generated without agonist stimulation. Circulating EVs did not have externalized negatively-charged phospholipids. None of the 4 types of EVs presented tissue factor. The mechanism by which PDEV formation is induced is a critical determinant of its phenotype and function. Importantly, we have developed methods to obtain clean, concentrated and functional EVs derived from platelet-free plasma and washed platelets, which can be used to provide novel insight into their biological functions