An Evaluation of Plasma TNF, VEGF-A, and IL-6 Determination as a Risk Marker of Atherosclerotic Vascular Damage in Early-Onset CAD Patients.

Background: The pathogenesis of atherosclerosis is multifactorial and diverse. Pro-inflammatory cytokines are involved in these processes. It is suggested that inflammation may represent a novel and modifiable risk factor for cardiovascular disease. Therefore, this study aimed to gain insight into the relationship between plasma concentrations of TNF, VEGF, IL-6, and radiological parameters of atherosclerosis progression in patients with early-onset coronary artery disease (CAD). Methods: Seventy clinically stable patients were included in the study group. The age range for men was no more than 50 years, while for women, it was no more than 55 years. Fasting blood samples were obtained for plasma TNF, VEGF, and IL-6 protein measurements. Plasma cytokine concentrations were measured via ELISA. Doppler ultrasound of the carotid and peripheral arteries was performed in all patients. Results: After Bonferroni correction, there were no significant correlations between any cytokine and radiological parameters of atherosclerosis progression in our patients. Conclusions: The determination of plasma TNF, IL-6, and VEGF levels may not be a reliable marker for the vascular condition, and the measurement of these cytokines in plasma cannot replace the classical radiological examination of the vessels.

Polymorphisms in GP6, PEAR1A, MRVI1, PIK3CG, JMJD1C, and SHH Genes in Patients with Unstable Angina.

INTRODUCTION: Coronary artery disease (CAD) is a significant public health problem because it is one of the major causes of death worldwide. Several studies have investigated the associations between CAD and polymorphisms in genes connected with platelet aggregation and the risk of venous thromboembolism. AIM: In this study, we examined the associations between polymorphisms in GP6 (rs1671152), PEAR1A (rs12566888), MRVI1 (rs7940646), PIK3CG (rs342286), JMJD1C (rs10761741), SHH (rs2363910), and CAD in the form of unstable angina as well as selected clinical and biochemical parameters. The study enrolled 246 patients with diagnosed unstable angina and 189 healthy controls. RESULTS: There were no significant differences in the distribution of the studied polymorphisms between the patients with unstable angina and the controls. In patients with the GP6 rs1671152 GG genotype, we observed increased BMI values and an increased frequency of type 2 diabetes diagnosis. CONCLUSIONS: The results of this study suggest a lack of association between GP6 (rs1671152), PEAR1A (rs12566888), MRVI1 (rs7940646), PIK3CG (rs342286), JMJD1C (rs10761741), SHH (rs2363910), and unstable angina. The results indicate an association between GP6 (rs1671152) and type 2 diabetes.

The Multifunctionality of CD36 in Diabetes Mellitus and Its Complications-Update in Pathogenesis, Treatment and Monitoring.

CD36 is a multiligand receptor contributing to glucose and lipid metabolism, immune response, inflammation, thrombosis, and fibrosis. A wide range of tissue expression includes cells sensitive to metabolic abnormalities associated with metabolic syndrome and diabetes mellitus (DM), such as monocytes and macrophages, epithelial cells, adipocytes, hepatocytes, skeletal and cardiac myocytes, pancreatic ß-cells, kidney glomeruli and tubules cells, pericytes and pigment epithelium cells of the retina, and Schwann cells. These features make CD36 an important component of the pathogenesis of DM and its complications, but also a promising target in the treatment of these disorders. The detrimental effects of CD36 signaling are mediated by the uptake of fatty acids and modified lipoproteins, deposition of lipids and their lipotoxicity, alterations in insulin response and the utilization of energy substrates, oxidative stress, inflammation, apoptosis, and fibrosis leading to the progressive, often irreversible organ dysfunction. This review summarizes the extensive knowledge of the contribution of CD36 to DM and its complications, including nephropathy, retinopathy, peripheral neuropathy, and cardiomyopathy.

Fluoride Content in Alcoholic Drinks.

The aim of the study was to determine the role of alcoholic drinks as a potential source of dietary fluoride by means of measuring fluoride levels in selected alcoholic drinks available on the Polish market that are also diverse in terms of the percentage content of ethanol. The study was conducted on 48 types of drinks with low, medium, and high alcohol content available on the Polish market and offered by various manufacturers, both Polish and foreign. Fluoride concentrations in individual samples were measured by potentiometric method with a fluoride ion-selective electrode. The highest fluoride levels were determined in the lowest percentage drinks (less than 10 % v/v ethanol), with the lowest fluoride levels observed in the highest percentage drinks (above 40 % v/v ethanol). In terms of types of alcoholic drinks, the highest fluoride levels were determined in beers and wines, while the lowest levels were observed in vodkas. These data confirm the fact that alcoholic beverages need to be considered as a significant source of fluoride delivered into the body.

CD36 gene is associated with thickness of atheromatous plaque and ankle-brachial index in patients with early coronary artery disease.

BACKGROUND: CD36 is a multifunctional molecule engaged in the removal of oxidised LDL from plasma. It is unclear whether mutation of the CD36 gene protects against, or increases, the risk of hypercholesterolaemia, atherosclerosis and its complications. AIM: To search for associations between the CD36 gene polymorphisms and radiological markers of atherosclerosis progress in Caucasian patients with coronary artery disease (CAD) diagnosed at a young age. METHODS: The study group comprised 70 patients with early CAD. Doppler ultrasound of carotid and peripheral arteries was carried out and genomic DNA was isolated from each patient. RESULTS: We found two single nucleotide substitutions in introns (IVS3-6 T/C - rs3173798 and IVS4-10 G/A - rs3211892) and two synonymous polymorphisms in exon 6 (G573A - rs5956 and A591T). The allele frequencies were: 10.7% for the IVS3-6C, 3.6% for the IVS4-10A, 3.6% for the 573A, and 2.1% for the 591T. The 573A allele of CD36 rs5956 polymorphism is associated with low thickness of atheromatous plaque. The 591T allele is associated with lower ankle-brachial index. CONCLUSIONS: The 573A allele has a protective effect against atherosclerosis development and the 591T allele is a cardiovascular risk factor. Assessment of their functional implications requires further research.

Polymorphism of the CD36 Gene and Cardiovascular Risk Factors in Patients with Coronary Artery Disease Manifested at a Young Age.

This study investigates potential associations between CD36 gene variants and the presence of risk factors in Caucasians with coronary artery disease (CAD) manifested at a young age. The study group consisted of 90 patients; the men were ≤ 50 years old and the women were ≤ 55 years old. Amplicons of exons 4 and 5 including fragments of introns were analyzed by DHPLC. Two polymorphisms were found: IVS3-6 T/C (rs3173798) and IVS4-10 G/A (rs3211892). The C allele of the IVS3-6 T/C polymorphism was associated with higher prevalence of obesity and diabetes, higher hsCRP, lower Lp(a) serum concentrations, and younger age at myocardial infarction. The A allele of the IVS4-10 G/A polymorphism was associated with older age of myocardial infarction and higher white blood cell count. The functional role of CD36 polymorphisms in CAD development needs further research.

Analysis of human CD36 gene sequence alterations in the oxidized low-density lipoprotein-binding region using denaturing high-performance liquid chromatography.

Denaturing high-performance liquid chromatography (DHPLC) has been employed as a prescreening tool to reduce the amount of DNA sequencing. It could be a simple and cost-effective screening method for mutations and polymorphisms in exons 4, 5, and 6 of the CD36 gene, which encode the protein region responsible for the removal of oxidized low-density lipoprotein. Genomic DNA was isolated from 306 Caucasian infants of Polish origin. Six single-nucleotide substitutions were detected by DHPLC and confirmed by direct sequencing. The A591T, G550A, and C572T alterations have not been described so far. Each of two nonsynonymous substitutions (Asp184Asn, Pro191Leu) was found in one subject (0.2% minor allele frequency). The results suggest that nonsynonymous alterations in the analyzed CD36 region are rare in Caucasians. DHPLC is a specific and cost-effective technique that may prove to be particularly useful for the identification of polymorphisms and mutations in the CD36 gene.

Molecular basis of human CD36 gene mutations.

CD36 is a transmembrane glycoprotein of the class B scavenger receptor family. The CD36 gene is located on chromosome 7 q11.2 and is encoded by 15 exons. Defective CD36 is a likely candidate gene for impaired fatty acid metabolism, glucose intolerance, atherosclerosis, arterial hypertension, diabetes, cardiomyopathy, Alzheimer disease, and modification of the clinical course of malaria. Contradictory data concerning the effects of antiatherosclerotic drugs on CD36 expression indicate that further investigation of the role of CD36 in the development of atherosclerosis may be important for the prevention and treatment of this disease. This review summarizes current knowledge of CD36 gene structure, splicing, and mutations and the molecular, metabolic, and clinical consequences of these phenomena.

Shell of snail Helix aspersa maxima (Helicidae) as a protection of bioaccumulation toxic sodium fluoride in soft tissue.

The aim of this work was to determine the extent of bioaccumulation of sodium fluorides in tissues of snails under strictly controlled conditions, and also to determine resistance and tolerance to sodium fluoride load in these organisms. The study was performed on snails removed from aestivation. Quantitation of fluoride levels was done in soft tissues (foot, hepatopancreas) and shells of mature snails. Results show that long exposure to sodium fluoride pollution at a low level results in accumulation principally in the soft tissues of the snails. Because of the possibility of fluoride accumulation in the foot, the number of snails used for culinary purposes must be controlled, as it can potentially cause chronic toxemia caused by this trace element. Results also show that the shells of snails offer protection against the bioaccumulation of toxic fluoride in the soft tissue. The Helix aspersa maxima snail is characterised by high resistance and tolerance to fluoride load. Fluoride levels in soft tissues of the snail cannot serve as an indicator for biomonitoring purposes. In contrast, levels in the shell rose significantly with the concentration of fluoride and can be used in biomonitoring of sodium fluoride pollution.

[The influence of some trace elements on bioaccumulation in tissues and bioenergetic metabolism of the edible snail Helix aspersa maxima as determined by HPLC of purine derivatives]. / Wplyw niektórych pierwiastków sladowych na biokumulacje w tkankach oraz na przemiany bioenergetyczne u slimaka jadalnego Helix aspersa maxima na podstawie oznaczen pochodnych purynowych metoda HPLC.

UNLABELLED: The aim of this work was to determine the bioaccumulation of fluoride and some metals (Cu, Zn, Pb) in tissues of snails under strictly controlled conditions expecting with this approach to verify the hypothesis that snails are suitable for the monitoring of environmental hazards. Additionally, the toxicity of fluorides administered orally on the energy balance of the snail's foot was investigated basing on concentrations of nucleosides, nucleotides and their products measured with high-performance liquid chromatography (HPLC). Two parallel snail cultures were started. The effect of dose on tissue levels of fluoride and metals was studied in the first part of the experiment. The second part served to study the effects of fluoride on energy metabolism of foot muscle (Tab. 1). Quantitation of fluoride and metal levels was done in soft tissues (foot, hepatopancreas) and shells of snails. Qualitative and quantitative analysis of purine compounds was performed in slices of foot. Fluoride concentrations in pulverized shells were measured using an ion-selective electrode. Gas chromatography served to determine fluoride concentrations in soft tissues (hepatopancreas and foot). Concentrations of metals were determined spectrophotometrically. Fluoride and metal content was calculated basing on weight of the pulverized sample. Purines were measured in foot muscle slices with high-performance liquid chromatography (HPLC). Concentrations were adjusted for protein content of sample. Concentrations of the following nucleosides, nucleotides and their products were determined: ATP, ADP, AMP, Ado (adenosine), GTP, GDP, GMP, Guo (guanosine), Hyp (hypoxanthine), IMP, Ino (inosine), Xan (xanthine), Urd (uridine), UA (uric acid), NAD+, and NADP (Fig. 1.). Statistical analysis was done with non-parametric test of Kruskal-Wallis, Mann-Whitney U-test and Spearman Rank Correlation Coefficient. CONCLUSIONS: 1. Accumulation in the shell was significantly increased at the lowest concentration of fluoride, but levels remained below those in the foot or hepatopancreas. It can be inferred that due to low sensitivity, accumulation of fluoride in soft tissues is not a suitable indicator for biomonitoring purposes. Shells seem to be more suited for this aim. 2. Due to low sensitivity, accumulation of metals in soft tissues is not a suitable indicator for biomonitoring purposes. 3. Fluoride had a statistically significant effect on the energy metabolism in muscle, especially on the content of AMP and GMP (Fig. 3, 4). The content of adenylate derivatives was increased (Fig. 3, 4) and phosphorylation of ADP to ATP was inhibited (Fig. 2, 5). 4. An increase in TAN and AEC with 1330 mg F-/kg seems to result from inhibition by fluoride of energy-consuming processes (Fig. 5). 5. In cases of high levels of fluoride it seems reasonable to measure the content of AMP, GMP, Guo or the value of AEC which appear to serve as universal indicators of depressed metabolic function (Fig. 3, 4, 5, 6).