The significance of determination of symmetric-L-dimethylarginine and N-terminal pro B type natriuretic peptide in chronic kidney disease patients and renal tranplant recipiens

Cilj studije je bio da se ispita značaj određivanja simetričnog dimetil-L-arginina (SDMA) i N-terminalnog fragmenta natriuretskog propeptida B-tipa (NT-proBNP) kod bolesnika sa hroničnom bubrežnom insuficijencijom (HBI) i bolesnika sa transplantiranim bubregom (RT) za detekciju bubrežne, endotelne i dijastolne disfunkcije. U studiju je uključeno 98 HBI i 52 RT bolesnika. Kontrolnu grupu je činilo 88 zdravih osoba (43 muškarca i 45 žena) bez znakova kardiovaskularne i bubrežne bolesti koji su po polu i godinama upareni sa bolesnicima.Bolesnici sa HBI imali su značajno višu vrednost SDMA u odnosu na RT bolesnike (p<0.001). NT-proBNP je takoĎe bio viši kod HBI bolesnika ali bez statističke značajnosti. Korelaciona analiza izmeĎu NTproBNP, SDMA i drugih parametara bubrežne funkcije je pokazala statističku značajnost naročito sa brzinom glomerularne filtracije (GFR), albuminom, ureom, kreatininom, godinama i dužinom trajanja bolesti. Ispitali smo promene ispitivanih parametara u odnosu na dijastolnu disfunkciju leve komore koja je procenjena na osnovu Dopler ehokardiografije. Dijastolna disfunkcija je definisana kao E:A ratio <1. U RT grupi, posle korekcije u odnosu na trajanje bolesti, koncentracije SDMA i NTproBNP kod bolesnika sa dijastolnom disfunkcijom su bile znajno više nego kod bolesnika bez dijastolne disfunkcije (F= 7.478, P<0.011; F=2.631,p<0.017). Posle korekcije u odnosu na GFR, vrednosti SDMA i NT-proBNP se nisu značajno razlikovale. Kod bolesnika sa HBI, korigovane vrednosti SDMA i NT-proBNP u odnosu na GFR su bile više kod bolesnika sa dijastolnom disfunkcijom u odnosu na bolesnike bez dijastolne disfunkcije ali ne značajno. Da bi ispitali uticaj endotelne funkcije na ispitivane parametre bolesnici sa HBI i RT bolesnici su na osnovu protokom posredovane vazodilatacije brahijalne arterije zavisne od endotela (FMD) podeljeni u dve grupe. Kod HBI bolesnika ultrasenzitivni Creaktivni protein (hs-CRP), interleukin-6 (IL-6), serumski amiloid - A (SAA) i SDMA su bili značajno viši u grupi sa oštećenom FMD u odnosu na neoštećenu. Logistička regresiona analiza je pokazala da su, posle korekcije u odnosu na GFR, povišeni hs- CRP i SDMA udruženi sa oštećenom FMD kod HBI i RT bolesnika...The aim of the study was to explore the clinical usefulness of N-terminal pro Btype natriuretic peptide (NT-proBNP) and symmetric dimethyl-L-arginine (SDMA) for detection of renal, endothelial and left ventricular (LV) diastolic dysfunction in chronic kidney disease patients (CKD) and renal transplant recipients (RT). We included 98 CKD and 52 RT recipients. The control group 88 (43 men and 45 women) consisted of healthy individuals with no history of cardiovascular and renal disease , matched to the patients according to age and gender. In our study, CKD patients have statistically higher levels of SDMA than RT patients (p<0.001). NTproBNP was also higher within CKD patients but without statistical significance. Correlation analysis between NT-proBNP, SDMA and other parameters of renal function shows significant association, especially GFR, albumin, urea, creatinin, age and duration of disease. We evaluated the changes of examined parameters according to left ventricular diastolic dysfunction witch is assessed using pulsed-wave Doppler ultrasound. Diastolic dysfunction was defined when the E:A ratio was<1. In RT group, after adjusting for duration of disease NT-proBNP and SDMA concentrations in patients with diastolic dysfunction were significantly higher than the corresponding values in patient without diastolic dysfunction (F= 7.478, P<0.011; F=2.631,p<0.017), but after adjustment for GFR, NT-proBNP and SDMA levels were not significantly different. In CKD patients adjusted NT-proBNP and SDMA values for GFR were nonsignificantly higher in patient with diastolic dysfunction than in patient without diastolic dysfunction. To evaluate the effect of endothelial function on the examined parameters CKD and RT patients were stratified according to brachial artery flow-mediated dilation (FMD, endothelium-dependent). In CKD patients high sensitive C-reactive protein (hs- CRP), interleukin-6 (IL-6), serum amyloid - A (SAA) and SDMA were significantly higher in those with impaired FMD. Logistic regression analysis showed that high hs- CRP and SDMA were associated with impaired FMD in CKD and RT patients, after adjustment for GFR..

Distinct effects of virgin coconut oil supplementation on the glucose and lipid homeostasis in non-diabetic and alloxan-induced diabetic rats

Non-diabetic and alloxan-induced diabetic rats were fed with standard laboratory food enriched with 20% virgincoconut oil for 16 weeks. In non-diabetic animals coconut oil improved insulin sensitivity and ability to controlglycaemia and decreased the serum triglycerides for almost 50% in comparison with controls. Supplementationwith coconut oil caused liver steatosis in both non-diabetic and diabetic animals. However, the severity ofsteatosis was lower in diabetic animals compared to non-diabetic animals. Coconut oil had no effects on hearthistology, ascending and abdominal aorta wall thickening and atherosclerotic plaques development neither innon-diabetic nor in diabetic animals. While alloxan treatment caused Type I diabetes in rats, supplementationwith coconut oil in combination with the alloxan unexpectedly resulted in Type II diabetes. The development ofsevere insulin resistance and deterioration in serum lipid profile implied that the use of coconut oil is contra-indicated in diabetic condition

Određivanje holesterola u membrani eritrocita

Quantification of cholesterol in biological membranes is an important step toward understanding of metabolism of intracellular cholesterol, composition of cell membrane and plasma lipid profile. The aim of our study was to optimize the method for determination of cholesterol in erythrocyte membrane and then to use this method in the determination of cholesterol concentration in erythrocyte membrane in the studied group of blood samples. Cholesterol in erythrocyte membrane was determined in dry lipid extract of erythrocyte membrane by the enzymatic manual CHOD-PAP method. Cholesterol in erythrocyte membrane and plasma lipid parameters (total cholesterol HDL-cholesterol, LDL-cholesterol and triglycerides) were determined in blood samples of 58 females, obtained by routine health control. Lipid parameters were determined by standard biochemical methods. We examined the relationship between cholesterol in erythrocyte membrane and other plasma lipid parameters as well as other atherogenic risk factors (BMI, blood pressure). Optimization of the method for determination of cholesterol in erythrocyte membrane was based on the observation that primary cholesterol standards prepared by dissolving crystal cholesterol cannot be used due to the interference of the dissolved dry extract in organic solvents with the enzymatic reagent. Commercial standard solutions of cholesterol were used for calibration because they contain detergents for solubilisation of the dry extract in enzymatic reagent. The obtained mean value for cholesterol in erythrocyte membrane, as mmol/L erythrocyte is 4.44 ± 1.019; median 4.65 5-th percentile is 2.70, and 95-th percentile is 6.26. In the examined female group we tested cholesterol concentration in erythrocyte membrane according to age. Two groups were formed (females below and above 50 years) using nonparametric t-test no statistically significant difference was found between these two age groups (p>0.05), while plasma lipid parameters of total cholesterol, triglycerides and LDL-cholesterol were different in the examined groups (p lt 0.05). By Spearmen nonparametric correlation method we found no statistically significant correlation between cholesterol in erythrocyte membrane and other atherogenic risk factors.Određivanje membranskog holesterola je važan stepen u utvrđivanju povezanosti intracelularnog metabolizma holesterola, sastava ćelijske membrane i plazmatskog lipidnog profila. Prvi cilj ovog rada je bio optimizacija metode za određivanje membranskog holesterola što je podrazumevalo izbor standarda i primenu enzimskog testa. Holesterol u membrani eritrocita određivan je ručno u suvom lipidnom ekstraktu membrane, enzimskom CHOD-PAP metodom firme Randox. Optimizirana metoda je primenjena za određivanje koncentracija holesterola u membrani eritrocita kod 58 žena kojima je krv uzeta na rutinskom sistematskom pregledu. U ispitivanim uzorcima određen je i serumski lipidni profil standardnim biohemijskim metodama. Ispitivane žene su podeljene u dve starosne grupe: na mlađe od 50 godina i na starije od 50 godina. Ispitan je i stepen povezanosti između membranskog holesterola sa jedne strane i plazmatskih lipida i drugih faktora rizika za aterosklerozu (starosti, BMI, sistolni i dijastolni pritisak) sa druge strane. Optimizacijom metode za određivanje membranskog holesterola došlo se do zaključka da se ne mogu koristiti primarni standardni rastvori holesterola dobijeni rastvaranjem kristalnog holesterola u organskom rastvaraču zbog slabe rastvorljivosti suvog ekstrakta u enzimskom reagensu i uticaja pojedinih rastvarača na bojenu reakciju. Za kalibraciju treba koristiti komercijalne standardne rastvore holesterola jer sadrže deterdžente koji omogućavaju rastvorljivost suvog ekstrakta. U ispitivanoj populaciji dobijena srednja vrednosti za holesterol u membrani eritrocita (izražene kao mmol/L eritrocita) iznosi 4,44 ± 1,019, mediana 4,65, 5-ti procenat iznosi 2,70, a 95-ti procenat je 6,26. Poređenjem ispitivanih parametara između dve starosne grupe za holesterol u eritrocitnoj membrani nije bilo značajne razlike (p>0,05) dok je za ukupan holesterol, LDL-holesterol i trigliceride ova razlika bila statistički značajna (p lt 0,05). Primenom Spearmanove neparametarske korelacije nije nađena statistički značajna korelacija između membranskog holesterola i drugih faktora rizika za aterosklerozu

Matrix Metalloproteinase-9 and Tissue Inhibitor of Matrix Metalloproteinase-1 in Sepsis after Major Abdominal Surgery

Background. The role of matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) in sepsis after major abdominal surgery and sepsis-associated organ dysfunction is unexplored. Materials and Methods. Fifty-three patients with sepsis after major abdominal surgery were compared to 50 operated and 50 nonoperated controls. MMP-9, TIMP-1, biomarkers of inflammation, kidney and liver injury, coagulation, and metabolic disorders were measured daily during 96 h following diagnosis of sepsis and once in controls. MMP-9/TIMP-1 ratios and disease severity scores were calculated. Use of vasopressors/inotropes, mechanical ventilation, and survival were recorded. Results. Septic patients had lower MMP-9 and MMP-9/TIMP-1 ratios but higher TIMP-1 levels compared to controls. AUC-ROC for diagnosis of sepsis was 0.940 and 0.854 for TIMP-1 and 0.924 and 0.788 for MMP-9/TIMP-1 ratio (sepsis versus nonoperated and sepsis versus operated controls, resp.). Lower MMP-9 and MMP-9/TIMP-1 ratio and higher TIMP-1 levels were associated with shorter survival. MMP-9, TIMP-1, and MMP-9/TIMP-1 ratio correlated with biomarkers of inflammation, kidney and liver injury, coagulation, metabolic disorders, and disease severity scores. Use of vasopressors/inotropes was associated with higher TIMP-1 levels. Conclusions. MMP-9, TIMP-1, and MMP-9/TIMP ratio were good diagnostic or prognostic biomarkers of sepsis after major abdominal surgery and were linked to sepsis-associated organ dysfunction

Bolest nealkoholne masne jetre kao metabolička posledica opstruktivne apneje u snu

Obstructive sleep apnea (OSA) as a worldwide prevalent condition carries risk for cardiovascular and metabolic diseases, ultimately increasingoverall mortality rates. Non-alcoholic fatty liver disease (NAFLD) can be considered as the primary metabolic disease, but also as a coexisting OSA comorbidity. Although prevalence of NAFLD covers quarter of world population, it increases with OSA presence. It can be speculated that chronic intermittent hypoxia (CIH) and sympathetic nervous system overactivity are involved in NAFLD pathogenesis and progression from simple steatosis throughsteatohepatitis to fibrosis. CIH provides the environment for liveroxidative stress, inflammation and increases the expression of genes involved in cholesterol and fatty acids synthesis. Catecholamines increase β-oxidation in liver and release free fatty acids from adipose tissue in plasma which inhibit insulin effects. Obesity and insulin resistance as key playersin NAFLD development and advancement, deepen vicious circle of oxidative stress, inflammation and dyslipidemia. If not treated, OSA in NAFLD patients has been associated with inflammation, hepatocytes’ necrosis, and fibrosis. Continuous positive airway pressure (CPAP) represents gold standard for OSA therapy, allowing the unimpeded air passage through upper parts of respiratory system. However, it has been demonstrated that CPAP therapyhave beneficial effects on cardiometabolic outcomes and slowliver degenerationOpstruktivna apneja u snu (OSA) kao oboljenje prevalentno u svetu nosi rizik za nastanak kardiovaskularnih i metaboličkih bolesti, povećavajući ukupnu smrtnost. Bolest nealkoholne masne jetre (eng. non-alcoholic fatty liver disease -NAFLD) se može smatrati primarnom metaboličkom bolešću, ali kao i komorbiditet OSA. Iako prevalenca NAFLD obuhvata četvrtinu svetske populacije, ona se povećava sa prisustvom OSA. Pretpostavlja se da su hronična intermitentna hipoksija (eng. chronic intermittent hypoxia -CIH) i prekomerna aktivnost simpatičkog nervnog sistema uključeni u patogenezu NAFLD i progresiju od steatoze preko steatohepatitisa do fibroze. U jetri CIH stvara uslove za oksidativni stres, inflamaciju i povećava ekspresiju gena koji učestvuju u sintezi holesterola i masnih kiselina. Kateholamini stimulišu b-oksidaciju masnih kiselina u jetri i oslobađaju slobodne masne kiseline iz masnog tkiva u plazmu, koje inhibiraju dejstva insulina. Gojaznost i insulinska rezistencija kao ključni faktori u razvoju i napredovanju NAFLD produbljuju začarani krug oksidativnog stresa, inflamacije i dislipidemije. Ako se ne leči, OSA kod pacijenata sa NAFLD je povezana sa inflamacijom, nekrozom hepatocita i fibrozom. Kontinuirani pozitivni pritisak vazduha (eng. continuous positive airway pressure -CPAP) predstavlja zlatni standard u terapiji OSA, koji omogućava neometani prolaz vazduha kroz gornje delove respiratornog sistema. Međutim, CPAP terapija je pokazala da ima povoljne efekte na kardiometaboličke ishode i da usporava degeneraciju jetre

Biomarkeri prehipertenzije

Prehypertension, which was defined as a systolic blood pressure (SBP) between 120 and 139 mmHg or a diastolic blood pressure (DBP) between 80 and 89 mmHg is shown to be associated with a twofold higher risk of cardiovascular disease (CVD) in addition to a higher risk of developing hypertension. We examined the association between CVD biomarkers and prehypertension in 99 adults who were free of hypertension. We measured concentrations of lipid parameters, high sensitivity serum C-reactive protein, uric acid (UA), fibrinogen and colected demografic data. The SBP positively correlated with body mass index (BMI), waist-to-hip ratio (WHR), triglycerides and UA and negatively with high density lipoprotein cholesterol and apolipoprotein A-I concentrations. There was independent association of higher WHR with higher SBP (standardized coefficients β = 0.483; p=0.002). The ordinal regression analysis revealed that WHR (β = 9.380, p =0.004) and UA concentration (β = 0.006, p = 0.013) were predictors of higher blood pressure (BP). Higher BP in asymptomatic parsons is associated with abdominal obesity. Lifestyle modifications, especially WHR reduction, should be recommended to individuals with prehypertension. Therapy with positive effect on BP and UA concentration may improve CVD management. These should be further investigated in longitudinal population-based studies.Osobe sa sistolnim krvnim pritiskom (SKP) između 120 i 139 mm Hg i dijastolnim krvnim pritiskom (DKP) od 80 do 89 mm Hg ili sa prehipertenzijom imaju dva puta veću verovatnoću razvoja kardiovaskularnih bolesti (KVB) i veći rizik za razvoj hipertenzije. U ovoj studiji ispitivana je veza biomarkera KVB sa prehipertenzijom. U istraživanje je uključeno 99 normotenzivnih osoba. Određivane su koncentracije lipidnih parametara, visoko osetljivog C reaktivnog proteina, mokraćne kiseline (MK), fibrinogena i demografske karakteristike pacijenata. Utvrđena je pozitivna veza SKP sa indeksom telesne mase (ITM) i odnosom struka i kuka (indeks S/K) i negativna korelacija sa koncentracijama holesterola u lipoproteinima visoke gustine i apolipoproteina A-I. Takođe, visoke vrednosti indeksa S/K nezavisno od ostalih parametara doprinose povećanju SKP (standardizovani koeficijent β = 0.483; p=0.002). Veći indeks S/K (β = 9.380, p =0.004) i viša koncentracija MK (β = 0.006, p = 0.013) povećavaju verovatnoću pojave viših vrednosti krvnog pritiska (KP). Kod normotenzivnih osoba više vrednosti KP su u vezi sa abdominalnom gojaznošću, pa cilj preventivnih mera treba da bude smanjenje indeksa S/K. Buduće studije bi pored proučavanja efekata lekova na smanjenje KP, trebalo da ispitaju uticaj tih lekova na koncetraciju MK, u cilju nalaženja novih mogućnosti za smanjenje rizika za KVB

Lack of association between low HDL-cholesterol and elevated circulating cellular adhesion molecules in normolipidemic CAD patients and healthy subjects

High plasma HDL-cholesterol (HDL-c) is a well-established protective factor in coronary artery disease (CAD). One of its potential protective mechanisms is the inhibition of the cytokine-induced upregulation of expression of cellular adhesion molecules (CAMs). High sCAM levels were found to be associated with low HDL-c in some studies performed mostly in hyperlipidemic subjects, but this association has not yet been investigated in CAD patients. In addition, conflicting results were obtained from in vitro studies that explored the proposed HDL effect on cytokine-induced CAM expression. The aim of the present case-control study was to investigate whether low HDL-c values are associated with CAM overexpression in normolipidemic CAD patients and healthy individuals, matched according to age and gender. Plasma HDL-c, sICAM-1, sVCAM-1, and sE-selectin were measured in 37 normolipidemic patients with angiographically verified coronary artery disease and in 52 healthy normolipidemic subjects. The sCAM values obtained in the subjects (patients or controls) with low HDL-c levels ( lt 1.03 mmol/L) were compared with the values in the subjects with high HDL-c (>= 1.03 mmol/L). No significant difference was found between sICAM-1, sVCAM-1, and E-selectin values obtained in subjects with low and high HDL-c, either among the patients or the healthy controls. In conclusion, low HDL-c levels are not associated with CAM overexpression in normolipidemic CAD patients and healthy subjects

Telomere-telomerase system status in patients with acute myocardial infarction with ST-segment elevation – relationship with oxidative stress

Introduction: Telomeres are protective chromosomal ends. Short telomeres are a proven biomarker of biological aging. We aimed to find an association of telomere length and telomerase activity in circulating leukocytes and thromboaspirates of patients with acute myocardial infarction. Furthermore, association of the telomere-telomerase system with oxidative stress markers (as common risk factors for coronary artery disease (CAD)) was tested. Material and methods: Patients were selected from the patients admitted to the intensive care unit with acute myocardial infarction with ST-segment elevation (STEMI), with the following inclusion criteria – STEMI patients between 18 and 80 years old of both genders and candidates for primary percutaneous coronary intervention, with infarction pain present for a maximum of 12 h. In all the patients leukocyte telomere length, telomerase activity and scores related to oxidative-stress status (Protective, Damage and OXY) were evaluated. Results: Patients were divided into different groups: with stable angina pectoris (AP) (n = 22), acute myocardial infarction with: STEMI (n = 93), non-obstructive coronary arteries (MINOCA) (n = 7), blood vessel rupture (n = 6) at three time points, and compared to the group of 84 healthy subjects. Telomerase activity was significantly higher in all CAD sub-groups compared to the control group (AP = 0.373 (0.355–0.386), STEMI = 0.375 (0.349–0.395), MINOCA = 0.391 (0.366–0.401), blood vessel rupture = 0.360 (0.352–0.385) vs. CG = 0.069 (0.061–0.081), p < 0.001), while telomeres were significantly shorter in STEMI, MINOCA and blood vessel rupture groups compared to the control group (STEMI = 1.179 (0.931–1.376), MINOCA = 1.026 (0.951–1.070), blood vessel rupture = 1.089 (0.842–1.173) vs. CG = 1.329 (1.096–1.624), p = 0.030]. Values of OXY score were significantly higher in STEMI and MINOCA patients compared to the control group and AP patients (5.83 (4.55–7.54) and 10.28 (9.19–10.72) vs. 4.94 (3.29–6.18) and 4.18 (2.58–4.86), p < 0.001). Longer telomeres and higher telomerase activity were found in thromboaspirates, compared to the peripheral blood leukocytes in the same patients (1.25 (1.01–1.84) vs. 1.18 (0.909–1.516), p = 0.036; and 0.366 (0.367–0.379) vs. 0.366 (0.367–0.379), p < 0.001, respectively). In addition, telomere length and telomerase activity had good diagnostic ability to separate STEMI patients from healthy persons. Conclusions: Leukocyte telomere length and telomerase activity can differentiate CAD patients from healthy persons, and relate CAD to oxidative stress

Smaller HDL particles are associated with absence of obstructive coronary artery disease in stable angina pectoris patients

Background A research on novel cardiovascular risk factors is mainly focused on patients with clinically verified coronary artery disease (CAD), while less is known about their presence in symptomatic patients, but without angiographically proven occlusion of coronary arteries. The aim of this study was to compare plasma low-density lipoprotein (LDL) and high-density lipoprotein (HDL) size and subclasses in stable angina patients with and without significant obstructive CAD. Methods LDL and HDL subclasses were analysed in 100 stable angina patients with >= 50% of obstruction and 40 patients with less than 50% of luminal narrowing, as assessed by coronary angiography. Results Patients with lt 50% of obstruction had reduced mean HDL size and higher proportion of small HDL particles (P lt 0.05). HDL size and proportion of small HDL particles were significant and independent predictors of obstructive CAD (P lt 0.05, respectively). Conclusions Stable angina patients wit

Low Paraoxonase 1 Activity Predicts Mortality in Surgical Patients with Sepsis

Introduction. State of severe oxidative stress is encountered in sepsis. Paraoxonase 1 (PON1) protects against oxidative stress but also undergoes inactivation upon that condition. We investigated PON1 activity in surgical patients with sepsis in relation to oxidative stress status, inflammation, disease severity, and survival. Methods. Prospective observational study. Sixty-nine surgical patients with sepsis were compared to 69 age/sex matched healthy controls. PON1 paraoxonase and diazoxonase activities, selected biochemical, hematological and oxidative stress parameters were measured on admission to ICU and 24, 48, 72, and 96 hours later. Disease severity scores were calculated daily. Results. Septic patients had significantly lower PON1 activities compared to control group at all time points. PON1 activities had good capacity to differentiate septic patients from healthy controls. Low PON1 activities were associated with higher disease severity scores and higher risk of death. Correlation between PON1 activity and markers of inflammation failed to reach significance. Decrease in PON1 activity was correlated with an increase in reducing components in plasma. Conclusion. Our study demonstrated lower PON1 activity in surgical patients with sepsis compared to healthy controls. PON1 activity also reflected severity of the disease. Low PON1 activity was associated with higher mortality of surgical patients with sepsis