A specific feature of dyslipidemia in pregnancy is increased high-density lipoprotein (HDL) cholesterol concentration, which is probably associated with maternal endothelium protection. However, ...preeclampsia is most often associated with low HDL cholesterol, and the mechanisms behind this change are scarcely explored. We aimed to investigate changes in HDL metabolism in risky pregnancies and those complicated by late-onset preeclampsia. We analyze cholesterol synthesis (cholesterol precursors: desmosterol, 7-dehydrocholesterol, and lathosterol) and absorption markers (phytosterols: campesterol and β-sitosterol) within HDL particles (NCS
), the activities of principal modulators of HDL cholesterol's content, and major HDL functional proteins levels in mid and late pregnancy. On the basis of the pregnancy outcome, participants were classified into the risk group (RG) (70 women) and the preeclampsia group (PG) (20 women). HDL cholesterol was lower in PG in the second trimester compared to RG (
< 0.05) and followed by lower levels of cholesterol absorption markers (
< 0.001 for campesterol
and
< 0.05 for β-sitosterol
). Lowering of HDL cholesterol between trimesters in RG (
< 0.05) was accompanied by a decrease in HDL phytosterol content (
< 0.001), apolipoprotein A-I (apoA-I) concentration (
< 0.05), and paraoxonase 1 (PON1) (
< 0.001), lecithin-cholesterol acyltransferase (LCAT) (
< 0.05), and cholesterol ester transfer protein (CETP) activities (
< 0.05). These longitudinal changes were absent in PG. Development of late-onset preeclampsia is preceded by the appearance of lower HDL cholesterol and NCS
in the second trimester. We propose that reduced capacity for intestinal HDL synthesis, decreased LCAT activity, and impaired capacity for HDL-mediated cholesterol efflux could be the contributing mechanisms resulting in lower HDL cholesterol.
Linkage between bis(2-ethylhexyl) phthalate (DEHP), dibutyl phthalate (DBP), and bisphenol A (BPA) co-exposure and type 2 diabetes mellitus (T2DM), as well as ability of multi-strained probiotic to ...reduce DEHP, DBP and BPA mixture-induced oxidative damage in rat pancreas were investigated. The Comparative Toxicogenomics Database, Cytoscape software and ToppGene Suite were used for data-mining. Animals were sorted into seven groups (n = 6): (1) Control group: corn oil, (2) P: probiotic: Saccharomyces boulardii + Lactobacillus rhamnosus + Lactobacillus plantarum LP 6595 + Lactobacillus plantarum HEAL9; (3) DEHP: 50 mg/kg b.w./day, (4) DBP: 50 mg/kg b.w./day, (5) BPA: 25 mg/kg b.w./day, and (6) MIX: 50 mg/kg b.w./day DEHP + 50 mg/kg b.w/day DBP + 25 mg/kg b.w./day BPA; (7) MIX + P. Rats were sacrificed after 28 days of oral exposure. In silico investigation highlighted 44 DEHP, DBP and BPA mutual genes linked to the T2DM, while apoptosis and oxidative stress were highlighted as the main mechanisms of DEHP, DBP and BPA mixture-linked T2DM. In vivo experiment confirmed the presence of significant changes in redox status parameters (TOS, SOD and SH groups) only in the MIX group, indicating possible additive effects, while probiotic ameliorated mixture-induced redox status changes in rat pancreatic tissue.
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•MIX (DEHP, DBP and BPA): 44 mutual genes linked to T2DM.•Apoptosis and oxidative stress – the most probable mechanisms of MIX-linked T2DM.•Significant redox status parameters changes (TOS, SOD and SH) only in the MIX group.•Polybiotic ameliorated MIX-induced redox status changes in rat pancreatic tissue.
Background/Aim. Dietary intake of n-3 long-chain polyunsaturated fatty acids (LC-PUFA) is important in prevention and treatment of different diseases. In general population, the average intake of n-3 ...LC-PUFA is often significantly lower than recommended levels. Fish lipids are rich sources of these fatty acids, of which the most important are eicosapentaenoic (20:5 n-3, EPA) and docosahexaenoic (22:6 n-3, DHA) fatty acids. This study was designed to determine and compare fat, fatty acids and lipid quality indices in 10 commercial fish species available on the Serbian market, as well as relation between their price and nutritional value. Methods. Freshwater fish originated from the Danube River in the Belgrade Region, while seawater fish were mostly from the Adriatic Sea. A gas chromatography method was used to define fatty acids in 40 fish samples after lipid extraction. Cost-minimization analysis was conducted to assess the economic utility. Results. Seawater fish had a significantly higher value of flash lipid quality compared to the freshwater fish (p < 0.05). Value of hypercholesterolaemic fatty acids (OFA) for the freshwater group was 18.70 (17.40?21.30) while the seawater group had a similar range of values 18.90 (17.55?22.75). Hypocholesterolaemic fatty acids (DFA) also showed similar ranges for both groups: 68.80 (66?70.20) for freshwater and 68.40 (64.85?73.05) for seawater group. The ratio of DHA/EPA ranged from 1.8 for sardine samples and up to 10 for tuna samples, indicating that the amount of DHA in natural samples exceeds the amount of EPA in many cases. The values of atherogenic (AI) and thrombogenic index (TI) were lower than 1 for all analysed samples. Conclusion. Sardine and mackerel had the highest content of n-3 LC-PUFA and presented the least expensive sources of EPA and DHA. The low values of AI and TI obtained from studied fish indicate its benefits from a health point of view.
Non-cholesterol sterols (NCS) are promising biomarkers for estimation of cholesterol homeostasis properties. In addition, determination of NCS in high-density lipoprotein (HDL) fraction (HDL-NCS) ...could provide information on cholesterol efflux. However, matrix effects interfere in liquid chromatography-mass spectrometry (LC-MS) analysis of NCS, thereby impairing the method sensitivity. The aims of this study were development, optimization and validation of LC-MS method for quantification of NCS in serum and HDL-NCS. Additionally, matrix effect interferences and methods application in individual serum samples were examined.
HDL precipitating reagent was used for HDL isolation. Matrix effect was examined by comparing different surrogates by simple regression analysis. Validation was conducted according to the FDA-ICH guideline. 20 healthy volunteers were recruited for testing of method application.
The observed matrix effect was 30%, and matrix comparison showed that cholesterol was the dominant contributor to the matrix effect. Cholesterol concentration was adjusted by construction of the calibration curve for serum and HDL fraction (5 mmol/L and 2.5 mmol/L, respectively). The intraand interrun variabilities for NCSs were 4.7-10.3% for serum NCS and 3.6-13.6% for HDLNCS and 4.6-9.5% for serum NCSs and 2.5-9.8% for HDL-NCS, respectively. Recovery studies showed satisfactory results for NCSs: 89.8-113.1% for serum NCS and 85.3-95.8% for HDL-NCS.
The method was successfully developed and optimized. The matrix interference was solved by customising calibration curves for each method and sample type. The measurement of NCS in HDL fraction was proposed for the first time as potentially useful procedure in biomedical researches.
Metabolic disorders in pregnancy, particularly gestational diabetes mellitus (GDM), are associated with an increased risk for adverse pregnancy outcome and long-term cardiometabolic health of mother ...and child. This study analyzed changes of serum cholesterol synthesis and absorption markers during the course of high-risk pregnancies, with respect to the development of GDM. Possible associations of maternal lipid biomarkers with neonatal characteristics were also investigated. The study included 63 women with high risk for development of pregnancy complications. Size and proportions of small low-density (LDL) and high-density lipoprotein (HDL) particles were assessed across trimesters (T1−T3), as well as concentrations of cholesterol synthesis (lathosterol, desmosterol) and absorption markers (campesterol, β-sitosterol). During the study, 15 women developed GDM, while 48 had no complications (non-GDM). As compared to the non-GDM group, women with GDM had significantly higher triglycerides in each trimester, while having a lower HDL-C level in T3. In addition, they had significantly lower levels of β-sitosterol in T3 (p < 0.05). Cholesterol synthesis markers increased across trimesters in both groups. A decrease in serum β-sitosterol levels during the course of pregnancies affected by GDM was observed. The prevalence of small-sized HDL decreased in non-GDM, while in the GDM group remained unchanged across trimesters. Newborn’s size in the non-GDM group was significantly higher (p < 0.01) and inversely associated with proportions of both small, dense LDL and HDL particles (p < 0.05) in maternal plasma in T1. In conclusion, high-risk pregnancies affected by GDM are characterized by altered cholesterol absorption and HDL maturation. Advanced lipid testing may indicate disturbed lipid homeostasis in GDM.
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) less than or equal to33 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+ or -4.56 (range 15.44-39.75) microg/L. There was no difference in IGF-1 values between male (23.1+ or -4.98 microg/L) and female (23.1+ or -4.87 microg/L) newborns. There was no significant difference in the average IGF-1 levels between male and female newborns with BW <50th and 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 reffects intrauterine growth only in BW <33rd percentile newborns. This fact could be used for further therapeutic purposes. Key words: Infant, newborn; Insulin-like growth factor I; Fetal growth retardation; Cross-sectional studies
BACKGROUND AND AIMSObstructive sleep apnea (OSA) is closely linked to obesity and related adverse metabolic changes, including dyslipidemia. However, it is not clear whether OSA is an independent ...contributing factor to dyslipidemia, or the observed association is a reflection of a concomitant presence of obesity. Additionally, dyslipidemia is usually evaluated through measurement of parameters of routine lipid status, while more precise evaluation of lipid homeostasis is rarely performed in OSA. In this study, we analyzed markers of cholesterol synthesis and absorption in patients with OSA with respect to the presence of obesity and the disease severity. METHODS AND RESULTSThis study enrolled 116 OSA patients. Concentrations of non-cholesterol sterols (NCS), measured by LC-MS/MS, were used as markers of cholesterol synthesis and absorption. Apnea-hypopnea index (AHI) and oxygen saturation (SaO2) were utilized as markers of OSA severity. Serum lipid status parameters were determined by routine enzymatic methods. Markers of cholesterol synthesis were increased (P = 0.005), whilst markers of cholesterol absorption decreased (P = 0.001) in obese OSA patients. Cholesterol synthesis/absorption ratio was elevated in obese subjects (P < 0.001). Concentration of cholesterol synthesis marker lathosterol was significantly higher in subjects with severe OSA (P = 0.014) and we observed a trend of decreased cholesterol absorption in these patients. AHI was revealed as an independent determinant of lathosterol concentration (P = 0.022). CONCLUSIONSOur results suggest that the presence of obesity and severe forms of OSA is characterized by elevated endogenous cholesterol synthesis. AHI was singled out as an independent determinant of the serum level of cholesterol synthesis marker lathosterol.
- Premature infants are susceptible to oxidative stress that causes neonatal disease such as retinopathy of prematurity (ROP). Oxidative stress is an imbalance between the production of pro-oxidants ...and the ability of the body to detoxify their harmful effects by antioxidants. The proliferative phase 2 ROP occurs at around 33
postmenstrual week (pmw). The purpose of our study was to evaluate the pro-oxidant/antioxidant status in preterm infants at 33
pmw. The study included 59 premature infants. ROP was classified according to the International Classification of Retinopathy of Prematurity. Total oxidative status (TOS), total antioxidant status (TAS), malondialdehyde (MDA) and paraoxonase 1 (PON1) activity were determined spectrophotometrically. The values of the pro-oxidants TOS and MDA were significantly higher in infants with ROP as compared to infants without ROP (p<0.05 both). There were no significant differences in the values of TAS and PON1 between the infants with and without ROP. According to study results, TOS and MDA are good markers of oxidative stress, whereas TAS and PON1 activity are unreliable in assessing antioxidant protection.
Vitamin D deficiency is repeatedly reported in colorectal cancer (CRC). Since cholesterol and vitamin D share common precursor 7-dehydrocholesterol (7-DHC), it would be important to explore the ...associations of key vitamin D metabolites and serum lipid parameters in patients with high and low grade CRC. The aim of this study was to analyze relationships between serum 25(OH)D3, 24,25(OH)2D3 and 7-DHC levels and serum lipids in patients with CRC, and to evaluate their potential for prediction of risk for development of high grade CRC.
We recruited 82 patients CRC and 77 controls. 7-DHC, 25(OH)D3 and 24,25(OH)2D3 were quantified by LC-MS/MS methods.
7-DHC, 25(OH)D3 and vitamin D metabolic ratio (VDMR) were significantly lower in CRC patients than in control group (P<0.001, P<0.010, P<0.050 and P<0.050, respectively). 25(OH)D3 levels were higher in patients with grade I CRC when compared to grade II (P<0.050). All vitamin D metabolites positively correlated with total cholesterol (TC) concentration in CRC patients. 25(OH)D3 was significant predictor of increased CRC risk (P<0.010). After adjustment for TC concentration, 25(OH)D3 lost its predictive abilities. However, 25(OH)D3 remained significant predictor of poorly differentiated type of cancer (P<0.050).
We found significant positive association between vitamin D status and serum total cholesterol. Although low 25(OH)D3 was found to be a significant risk factor for CRC development, the obtained results primarily suggest profound impact of cholesterol level on vitamin D status in CRC. However, our results suggest that low 25(OH)D3 might independently contribute to development of poorly differentiated tumor.
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