Povezanost inzulinu sličnog faktora rasta tip 1 i intrauterinog rasta

Insulin-like growth factor 1 (IGF-1) is a regulator of intrauterine growth, and circulating concentrations are reduced in intrauterine growth-restricted fetuses. The aim of our study was to investigate the relationship between IGF-1 levels in newborns and intrauterine growth, expressed as birth weight (BW). The research was designed as a cross-sectional study. The study included 71 premature newborns, gestational age (GA) ≤33 weeks. Quantitative determination of IGF-1 was performed in the 33rd post-menstrual week (pmw) to make the measurements more comparable. We used an enzyme-bound immunosorbent test for quantitative determination of IGF-1. Our results showed the mean IGF-1 level in premature newborns in 33rd pmw to be 23.1±4.56 (range 15.44-39.75) μg/L. There was no difference in IGF-1 values between male (23.1±4.98 μg/L) and female (23.1±4.87 μg/L) newborns. Tere was no significant difference in the average IGF-1 levels between male and female newborns with BW 50th percentile for GA either (p>0.50). Only BW <33rd percentile newborns had a statistically significantly lower IGF-1 level compared to newborns with greater BW. Based on our results, it is concluded that serum IGF-1 level reflects intrauterine growth only in BW <33rd percentile newborns. This fact could be used for further therapeutic purposes.Inzulinu sličan faktor rasta (IGF-1) je jedan od čimbenika koji utječu na intrauterini rast. Serumske razine IGF-1 su smanjene u fetusima s intrauterinim zastojem rasta. Cilj našega istraživanja bio je ispitati odnos između razine IGF-1 u nedonoščadi i intrauterinog rasta izraženog kao porođajna težina (PT). Istraživanje je provedeno kao presječna studija. U studiju je bilo uključeno 71 nedonošče gestacijske dobi (GD) ≤33 tjedna. Kvantitativno određivanje IGF-1 provedeno je u 33. postmenstruacijskom tjednu (pmt) radi bolje usporedivosti rezultata. Za kvantitativno određivanje IGF-1 rabili smo enzimski imunosorbentni test. Naši rezultati pokazali su da je srednja razina IGF-1 u nedonoščadi u 33. pmt iznosila 23,1±4,56 (raspon 15,44-39,75) μg/L. Nije bilo razlike u vrijednostima IGF-1 između muške (23,1±4,98 μg/L) i ženske (23,1±4,87 μg/L) nedonoščadi. Također nije bilo značajne razlike u srednjim razinama IGF-1 između nedonoščadi s PT 50. percentila za GD (p>0,50). Nedonoščad s niskom PT (<33. percentila) imala su statistički značajno nižu razinu IGF-1. Na temelju naših rezultata može se zaključiti da serumska razina IGF-1 odražava intrauterini rast samo u nedonoščadi male PT (<33. percentila), što bi mogao biti koristan podatak za buduću uporabu IGF-1 u terapijske svrhe

Evaluation of different formulas for LDL-C calculation

<p>Abstract</p> <p>Background</p> <p>Friedewald's formula for the estimation of LDL-C concentration is the most often used formula in clinical practice. A recent formula by Anandaraja and colleagues for LDL-C estimation still needs to be evaluated before it is extensively applied in diagnosis. In the present study we validated existing formulas and derived a more accurate formula to determine LDL-C in a Serbian population.</p> <p>Methods</p> <p>Our study included 2053 patients with TG ≤ 4.52 mmol/L. In an initial group of 1010 patients, Friedewald's and Anandaraja's formulas were compared to a direct homogenous method for LDL-C determination. The obtained results allowed us to modify Friedewald's formula and apply it in a second group of patients.</p> <p>Results</p> <p>The mean LDL-C concentrations were 3.9 ± 1.09 mmol/L, 3.63 ± 1.06 mmol/L and 3.72 ± 1.04 mmol/L measured by a direct homogenous assay (D-LDL-C), calculated by Friedewald's formula (F-LDL-C) and calculated by Anandaraja's formula (A-LDL-C), respectively in the 1010 patients. The Student's paired t-test showed that D-LDL-C values were significantly higher than F-LDL-C and A-LDL-C values (p < 0.001). The Passing-Bablok regression analysis indicated good correlation between calculated and measured LDL-Cs (r > 0.89). Using lipoprotein values from the initial group we modified Friedewald's formula by replacing the term 2.2 with 3. The new modified formula for LDL-C estimation (S-LDL-C) showed no statistically significant difference compared to D-LDL-C. The absolute bias between these two methods was -0.06 ± 0.37 mmol/L with a high correlation coefficient (r = 0.96).</p> <p>Conclusions</p> <p>Our modified formula for LDL-C estimation appears to be more accurate than both Friedewald's and Anandaraja's formulas when applied to a Serbian population.</p

Natural and natural-like polyphenol compounds: in vitro antioxidant activity and potential for therapeutic application

Introduction Phenols are a large family of natural and synthetic compounds with known antioxidant activity. The aim of this study was to preform an in vitro screening of natural and natural-like phenol monomers and their C2-symetric dimers (hydroxylated biphenyls) in order to identify those representatives which pharmacophores have the strongest antioxidant and the lowest prooxidant activity. Material and methods Antioxidative properties of 36 compounds (monomers and their C2-symmetric dimers) were evaluated in vitro. Different (red/ox) assays were used to measure their total oxidative potential (TOP), their total antioxidative capacity (TAC), the pro-oxidative-antioxidant balance (PAB) and total SH-group content (SHG) in a biologically relevant environment. The Pro-oxidative Score, Antioxidative Score and the Oxy Score were also calculated. Trolox, a water soluble analogue of α- tocopherol was used as a positive control. Results In an assay consisting of pooled human serum 6 of the 36 compounds indicated significant antioxidant activity (compounds 6, 7, 12, 13, 26, and 27) whereas 4 indicated extremely weak antioxidant activity (compounds 2, 29, 30, and 31). Within the 36 compounds comprising of zingerone, dehydrozingerone, aurone, chalcone, magnolol derivatives, in both monomeric and dimeric forms, the 2 compounds that indicated the highest antioxidant activity were dehydrozingerone derivatives (compounds 6 and 12). Trolox’s activity was found between the strong and weak antioxidant compounds analysed in our study. Conclusions In this study selected dehydrozingerones were identified as good candidates for in-depth testing of their biological behaviour and for possible precursors for the synthesis of novel polyphenolic molecules with potential therapeutic applications

Sex Bias in Pathogenesis of Autoimmune Neuroinflammation: Relevance for Dimethyl Fumarate Immunomodulatory/Anti-oxidant Action

In the present study, upon showing sexual dimorphism in dimethyl fumarate (DMF) efficacy to moderate the clinical severity of experimental autoimmune encephalomyelitis (EAE) in Dark Agouti rats, cellular and molecular substrate of this dimorphism was explored. In rats of both sexes, DMF administration from the day of immunization attenuated EAE severity, but this effect was more prominent in males leading to loss of the sexual dimorphism observed in vehicle-administered controls. Consistently, in male rats, DMF was more efficient in diminishing the number of CD4+ T lymphocytes infiltrating spinal cord (SC) and their reactivation, the number of IL-17+ T lymphocytes and particularly cellularity of their highly pathogenic IFN-gamma+GM-CSF+IL-17+ subset. This was linked with changes in SC CD11b+CD45+TCR alpha beta- microglia/proinflammatory monocyte progeny, substantiated in a more prominent increase in the frequency of anti-inflammatory phygocyting CD163+ cells and the cells expressing high surface levels of immunoregulatory CD83 molecule (associated with apoptotic cells phagocytosis and implicated in downregulation of CD4+ T lymphocyte reactivation) among CD11b+CD45+TCR alpha beta- cells in male rat SC. These changes were associated with greater increase in the nuclear factor (erythroid-derived 2)-like 2 expression in male rats administered with DMF. In accordance with the previous findings, DMF diminished reactive nitrogen and oxygen species generation and consistently, SC level of advanced oxidation protein products, to the greater extent in male rats. Overall, our study indicates sex-specificity in the sensitivity of DMF cellular and molecular targets and encourages sex-based clinical research to define significance of sex for action of therapeutic agents moderating autoimmune neuroinflammation-/oxidative stress-related nervous tissue damage

Factorial Analysis of the Cardiometabolic Risk Influence on Redox Status Components in Adult Population

Different byproducts of oxidative stress do not always lead to the same conclusion regarding its relationship with cardiometabolic risk, since controversial results are reported so far. The aim of the current study was to examine prooxidant determinant ((prooxidant-antioxidant balance (PAB)) and the marker of antioxidant defence capacity (total sulphydryl groups (tSHG)), as well as their ratio (PAB/tSHG) in relation to different cardiometabolic risk factors in the cohort of adult population. Additionally, we aimed to examine the joint effect of various cardiometabolic parameters on these markers, since to our knowledge, there are no studies that investigated that issue. A total of 292 participants underwent anthropometric measurements and venipuncture procedure for cardiometabolic risk factors assessment. Waist-to-height ratio (WHtR), body mass index, visceral adiposity index (VAI), and lipid accumulation product (LAP) were calculated. Principal component analysis (PCA) grouped various cardiometabolic risk parameters into different factors. This analysis was used in the subsequent binary logistic regression analysis to estimate the predictive potency of the factors towards the highest PAB and tSHG values. Our results show that triglycerides, VAI, and LAP were positively and high density lipoprotein cholesterol (HDL-c) were negatively correlated with tSHG levels and vice versa with PAB/tSHG index, respectively. On the contrary, there were no independent correlations between each cardiometabolic risk factor and PAB. PCA revealed that obesity-renal function-related factor (i.e., higher WHtR, but lower urea and creatinine) predicts both high PAB (OR=1.617, 95% CI (1.204-2.171), P<0.01) and low tSHG values (OR=0.443, 95% CI (0.317-0.618), P<0.001), while obesity-dyslipidemia-related factor (i.e., lower HDL-c and higher triglycerides, VAI, and LAP) predicts high tSHG values (OR=2.433, 95% CI (1.660-3.566), P<0.001). In conclusion, unfavorable cardiometabolic profile was associated with higher tSHG values. Further studies are needed to examine whether increased antioxidative capacity might be regarded as a compensatory mechanism due to free radicals’ harmful effects

Comparison of two RNA isolation methods for determination of SOD1 and SOD2 gene expression in human blood and mononuclear cells

468-474In the current study, two RNA isolation techniques were compared and their abilities to produce high-quality RNA were evaluated. mRNA expression profiles of SOD1 (Cu/Zn superoxide dismutase) and SOD2 (Mn superoxide dismutase) genes were measured by real-time PCR. From a pool of fresh human citrate-whole blood and ten healthy individuals, RNA was isolated with the TRIzol™ extraction method (TRI) and with the ABI PRISMTM 6100 Nucleic AcidPrepStation (ABI). The concentration and purity of RNA extracts were determined spectrophotometrically. RNA integrity was evaluated by electrophoresis on a 1% agarose gel. PCR was performed on a 7500 Real-Time PCR System. The student’s t-test was applied to compare normally distributed variables. Both protocols gave similar RNA quantities when adjusted to the initial blood volume. Relative quantification values obtained from the TRI method for SOD1 were significantly higher (p<0.01) and for SOD2 were significantly lower (p<0.05) as compared to those obtained from the ABI method, respectively. Coefficients of variation (CV) for gene expression parameters in SOD1 and SOD2 analyses were lower when the TRI method was used. The TRI method was generally more consistent in yielding pure RNA in comparison to the ABI and better reproducibility in gene expression analyses was apparent. </span

Antioxidative Effects of Black Currant and Cornelian Cherry Juices in Different Tissues of an Experimental Model of Metabolic Syndrome in Rats

A Western-style diet, rich in fat and simple sugars, is the main risk factor for a significant number of chronic diseases and disorders, as well as for a progression of metabolic syndrome (MetS). One of the key mechanisms involved in MetS development is increased oxidative stress caused by the accumulation of body fat. Some dietary polyphenols have shown a protective role in preventing oxidative-stress-induced damage. We investigated the difference in the oxidative response of plasma, liver, and visceral adipose tissue in rats fed with a high-fat high-fructose (HFF) diet for ten weeks, and the effectiveness of polyphenol-rich juices (black currant (BC) and cornelian cherry (CC)) in HFF-diet-induced oxidative stress prevention. The most prominent impact of the HFF diet on redox parameters was recorded in the liver, whereas adipose tissue showed the most potent protection mechanisms against oxidative stress. Consumption of both juices decreased advanced oxidation protein product (AOPP) level in plasma, increased paraoxonase1 (PON1) activity in the liver, and significantly decreased total oxidative status (TOS) in adipose tissue. BC exerted stronger antioxidative potential than CC and decreased the superoxide anion radical (O2•−) level in the liver. It also reduced TOS, total antioxidative status (TAS), and malondialdehyde (MDA) concentration in adipose tissue. The multiple linear regression analysis has shown that the best predictors of MetS development, estimated through the increase in visceral adiposity, were superoxide dismutase (SOD), AOPP, TOS, and TAS. The consumption of polyphenol-rich juices may provide a convenient approach for the systemic reduction of oxidative stress parameters